PRP and Articular Cartilage: A Clinical Update

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Antonio Marmotti

2015-01-01

Full Text Available The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis. Recent evidences in literature have shown that PRP may be helpful both as an adjuvant for surgical treatment of cartilage defects and as a therapeutic tool by intra-articular injection in patients affected by osteoarthritis. In this review, the authors introduce the trophic and anti-inflammatory properties of PRP and the different products of the available platelet concentrates. Then, in a complex scenario made of a great number of clinical variables, they resume the current literature on the PRP applications in cartilage surgery as well as the use of intra-articular PRP injections for the conservative treatment of cartilage degenerative lesions and osteoarthritis in humans, available as both case series and comparative studies. The result of this review confirms the fascinating biological role of PRP, although many aspects yet remain to be clarified and the use of PRP in a clinical setting has to be considered still exploratory.

Intra-articular laser treatment plus Platelet Rich Plasma (PRP) significantly reduces pain in many patients who had failed prior PRP treatment

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Prodromos, Chadwick C.; Finkle, Susan; Dawes, Alexander; Dizon, Angelo

2018-02-01

INTRODUCTION: In our practice Platelet Rich Plasma (PRP) injections effectively reduce pain in most but not all arthritic patients. However, for patients who fail PRP treatment, no good alternative currently exists except total joint replacement surgery. Low level laser therapy (LLLT) on the surface of the skin has not been helpful for arthritis patients in our experience. However, we hypothesized that intra-articular laser treatment would be an effective augmentation to PRP injection and would increase its efficacy in patients who had failed prior PRP injection alone. METHODS: We offered Intra-articular Low Level Laser Therapy (IAL) treatment in conjunction with repeat PRP injection to patients who had received no benefit from PRP injection alone at our center. They were the treatment group. They were not charged for PRP or IAL. They also served as a historical control group since they had all had failed PRP treatment alone. 28 patients (30 joints) accepted treatment after informed consent. 22 knees, 4 hips, 2 shoulder glenohumeral joints and 1 first carpo-metacarpal (1st CMC) joint were treated RESULTS: All patients were followed up at 1 month and no adverse events were seen from the treatment. At 6 months post treatment 46% of patients had good outcomes, and at 1 year 17% still showed improvement after treatment. 11 patients failed treatment and went on to joint replacement. DISCUSSION: A single treatment of IAL with PRP salvaged 46% of patients who had failed PRP treatment alone, allowing avoidance of surgery and good pain control.

Experimental Models of Inherited PrP Prion Diseases.

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Watts, Joel C; Prusiner, Stanley B

2017-11-01

The inherited prion protein (PrP) prion disorders, which include familial Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia, constitute ∼10%-15% of all PrP prion disease cases in humans. Attempts to generate animal models of these disorders using transgenic mice expressing mutant PrP have produced variable results. Although many lines of mice develop spontaneous signs of neurological illness with accompanying prion disease-specific neuropathological changes, others do not. Furthermore, demonstrating the presence of protease-resistant PrP species and prion infectivity-two of the hallmarks of the PrP prion disorders-in the brains of spontaneously sick mice has proven particularly challenging. Here, we review the progress that has been made toward developing accurate mouse models of the inherited PrP prion disorders. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Platlet Rich Plasma (PRP) Improves Fat Grafting Outcomes.

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Modarressi, Ali

2013-01-01

Autologous fat transfer offers many qualities of a ideal soft tissue filler. Main advantages of fat grafting ensue from the fact that the lipoaspirate tissue is an abundant source of regenerative pluripotential cells. However, the reported rates of fat cell survival vary greatly in the medical literature (10-90%). Different techniques of harvesting, processing, and reinjecting the fat cells are so claimed to be responsible for these differences, without any agreement concerning the best way to process. To address this important disadvantage, we propose the addition of autologous platelet rich plasma (PRP) which is known as a natural reservoir of growth factors stimulating tissue repair and regeneration. This approach is completely autologous and immediately employed without any type of preconditioning. Platelets rich plasma (PRP) preparation included bleeding of 8 ml of blood from patient's peripheral vein in Regen Lab© tubes containing sodium citrate anticoagulant. The whole blood was centrifugated at 1500 g during 3 min. As Regen-tubes contained a special gel separator, 99 % of red blood cells were discarded from the plasma at the bottom of the gel, and >90% of platelets were harvested in 4 ml of plasma on the top of the gel, called the platelet-rich plasma (PRP). The purified fat prepared by Coleman technique was mixed with different amount of PRP for in vitro, in vivo (mice) and clinical experiments: >50% of PRP for skin rejuvenation, superficial scars correction, infraorbital region, ..., and for 20% of PRP with 80% of purified fat for deep filler indication (nasolabial folds, lips, or soft tissue defect). In vitro studies demonstrated that PRP increased fat cells survival rate and stem cells differentiation. Animal models showed that fat graft survival rate was significantly increased by addition of PRP. Several clinical cases confirmed the improvement of wound healing and fat grafting survival in facial reconstruction and aesthetic cases by association of

Portable Radiation Package (PRP) Instrument Handbook

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Reynolds, R Michael [Remote Measurements and Research Company, Seattle, WA (United States)

2017-08-03

The Portable Radiation Package (PRP) was developed to provide basic radiation information in locations such as ships at sea where proper exposure is remote and difficult, the platform is in motion, and azimuth alignment is not fixed. Development of the PRP began at Brookhaven National Laboratory (BNL) in the mid-1990s and versions of it were deployed on ships in the U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Climate Research Facility’s Nauru-99 project. The PRP was deployed on ships in support of the National Aeronautics and Space Administration (NASA) Sensor Intercomparison for Marine Biological and Interdisciplinary Ocean Studies (SIMBIOS) program. Over the years the measurements have remained the same while the post-processing data analysis, especially for the FRSR, has evolved. This document describes the next-generation Portable Radiation Package (PRP2) that was developed for the DOE ARM Facility, under contract no. 9F-31462 from Argonne National Laboratory (ANL). The PRP2 has the same scientific principles that were well validated in prior studies, but has upgraded electronic hardware. The PRP2 approach is completely modular, both in hardware and software. Each sensor input is treated as a separate serial stream into the data collection computer. In this way the operator has complete access to each component of the system for purposes of error checking, calibration, and maintenance. The resulting system is more reliable, easier to install in complex situations, and more amenable to upgrade.

Periodontal tissue regeneration with PRP incorporated gelatin hydrogel sponges

International Nuclear Information System (INIS)

Nakajima, Dai; Tabata, Yasuhiko; Sato, Soh

2015-01-01

Gelatin hydrogels have been designed and prepared for the controlled release of the transforming growth factor (TGF-b1) and the platelet-derived growth factor (PDGF-BB). PRP (Platelet rich plasma) contains many growth factors including the PDGF and TGF-b1. The objective of this study was to evaluate the regeneration of periodontal tissue following the controlled release of growth factors in PRP. For the periodontal ligament cells and osteoblast, PRP of different concentrations was added. The assessment of DNA, mitochondrial activity and ALP activity were measured. To evaluate the TGF-β1 release from PRP incorporated gelatin sponge, amounts of TGF-β1 in each supernatant sample were determined by the ELISA. Transplantation experiments to prepare a bone defect in a rat alveolar bone were an implanted gelatin sponge incorporated with different concentration PRP. In DNA assay and MTT assay, after the addition of PRP to the periodontal ligament cells and osteoblast, the cell count and mitochondrial activity had increased the most in the group with the addition of 5  ×  PRP. In the ALP assay, after the addition of PRP to the periodontal ligament cells, the cell activity had increased the most in the group with the addition of 3  ×  PRP. In the transplantation, the size of the bone regenerated in the defect with 3  ×  PRP incorporated gelatin sponge was larger than that of the other group. (paper)

Periodontal tissue regeneration with PRP incorporated gelatin hydrogel sponges.

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Nakajima, Dai; Tabata, Yasuhiko; Sato, Soh

2015-10-20

Gelatin hydrogels have been designed and prepared for the controlled release of the transforming growth factor (TGF-b1) and the platelet-derived growth factor (PDGF-BB). PRP (Platelet rich plasma) contains many growth factors including the PDGF and TGF-b1. The objective of this study was to evaluate the regeneration of periodontal tissue following the controlled release of growth factors in PRP. For the periodontal ligament cells and osteoblast, PRP of different concentrations was added. The assessment of DNA, mitochondrial activity and ALP activity were measured. To evaluate the TGF-β1 release from PRP incorporated gelatin sponge, amounts of TGF-β1 in each supernatant sample were determined by the ELISA. Transplantation experiments to prepare a bone defect in a rat alveolar bone were an implanted gelatin sponge incorporated with different concentration PRP. In DNA assay and MTT assay, after the addition of PRP to the periodontal ligament cells and osteoblast, the cell count and mitochondrial activity had increased the most in the group with the addition of 5  ×  PRP. In the ALP assay, after the addition of PRP to the periodontal ligament cells, the cell activity had increased the most in the group with the addition of 3  ×  PRP. In the transplantation, the size of the bone regenerated in the defect with 3  ×  PRP incorporated gelatin sponge was larger than that of the other group.

Cytosolic PrP Can Participate in Prion-Mediated Toxicity

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Thackray, Alana M.; Zhang, Chang; Arndt, Tina

2014-01-01

ABSTRACT Prion diseases are characterized by a conformational change in the normal host protein PrPC. While the majority of mature PrPC is tethered to the plasma membrane by a glycosylphosphatidylinositol anchor, topological variants of this protein can arise during its biosynthesis. Here we have generated Drosophila transgenic for cytosolic ovine PrP in order to investigate its toxic potential in flies in the absence or presence of exogenous ovine prions. While cytosolic ovine PrP expressed in Drosophila was predominantly detergent insoluble and showed resistance to low concentrations of proteinase K, it was not overtly detrimental to the flies. However, Drosophila transgenic for cytosolic PrP expression exposed to classical or atypical scrapie prion inocula showed a faster decrease in locomotor activity than similar flies exposed to scrapie-free material. The susceptibility to classical scrapie inocula could be assessed in Drosophila transgenic for panneuronal expression of cytosolic PrP, whereas susceptibility to atypical scrapie required ubiquitous PrP expression. Significantly, the toxic phenotype induced by ovine scrapie in cytosolic PrP transgenic Drosophila was transmissible to recipient PrP transgenic flies. These data show that while cytosolic PrP expression does not adversely affect Drosophila, this topological PrP variant can participate in the generation of transmissible scrapie-induced toxicity. These observations also show that PrP transgenic Drosophila are susceptible to classical and atypical scrapie prion strains and highlight the utility of this invertebrate host as a model of mammalian prion disease. IMPORTANCE During prion diseases, the host protein PrPC converts into an abnormal conformer, PrPSc, a process coupled to the generation of transmissible prions and neurotoxicity. While PrPC is principally a glycosylphosphatidylinositol-anchored membrane protein, the role of topological variants, such as cytosolic PrP, in prion-mediated toxicity and

Redox induces diverse effects on recombinant human wild-type PrP and mutated PrP with inserted or deleted octarepeats.

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Shi, Qi; Chen, Cao; Zhang, Bao-Yun; Zhou, Wei; Xiao, Kang; Dong, Xiao-Ping

2018-04-01

Normal prion protein (PrP) contains two cysteines at amino acids 179 and 214, which may form intra‑ and interpeptide disulfide bonds. To determine the possible effects of this disulfide bridge on the biochemical features of PrP, prokaryotic recombinant human wild‑type PrP (PG5), and mutated PrPs with seven extra octarepeats (PG12) or with all five octarepeats removed (PG0), were subjected to redox in vitro. Sedimentation assays revealed a large portion of aggregation in redox‑treated PG5, but not in PG0 and PG12. Circular dichroism analysis detected increased β‑sheet and decreased α‑helix in PG5 subjected to redox, increased random‑coil and decreased β‑sheet in PG0, and increased random‑coil, but limited changes to β‑sheet content, in PG12. Thioflavin T fluorescence tests indicated that fluorescent value was increased in PG5 subjected to redox. In addition, proteinase K (PK) digestions indicated that PK resistance was stronger in PG12 and PG0 compared with in PG5; redox enhanced the PK resistance of all three PrP constructs, particularly PG0 and PG12. These data indicated that formation of a disulfide bond induces marked alterations in the secondary structure and biochemical characteristics of PrP. In addition, the octarepeat region within the PrP peptide markedly influences the effects of redox on the biochemical phenotypes of PrP, thus highlighting the importance of the number of octarepeats in the biological functions of PrP.

Glycan-deficient PrP stimulates VEGFR2 signaling via glycosaminoglycan.

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Gao, Zhenxing; Zhang, Huixia; Hu, Fei; Yang, Liheng; Yang, Xiaowen; Zhu, Ying; Sy, Man-Sun; Li, Chaoyang

2016-06-01

Whether the two N-linked glycans are important in prion, PrP, biology is unresolved. In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. Compared to fully-glycosylated PrP, glycan-deficient PrP preferentially partitions to lipid raft. In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. Accordingly, CHO cells expressing glycan-deficient PrP lacking the GAG binding motif or cells treated with heparinase to remove GAG show diminished Akt signaling. Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. CHO cells bearing glycan-deficient PrP also exhibit enhanced cellular adhesion and migration. Based on these findings, we propose a model in which glycan-deficient PrP, GAG, and VEGFR2 interact, activating VEGFR2 and resulting in changes in cellular behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

PRP in OA knee - update, current confusions and future options.

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Dhillon, Mandeep S; Patel, Sandeep; John, Rakesh

2017-01-01

Positive results have been uniformly observed by various researchers for platelet-rich plasma (PRP) in early osteoarthritis (OA) knee in the past few years. PRP has clearly demonstrated its supremacy in comparison to hyaluronic acid (HA) and placebo in various clinical trials and is undoubtedly the best option available for symptomatic treatment in early OA. The release of growth factors from PRP occurs immediately and lasts for around three weeks and the clinical effect tends to wane down by the end of the year. Prolonged and sustained release of growth factors from platelets could possibly help in much better biological healing and sustained clinical effects. PRP in combination with biocompatible carriers could be one way of achieving this. Gelatin hydrogel PRP and chitosan PRP seem to be promising based on early in vitro studies and animal studies. PRP in combination with hyaluronic acid also seems to be additive. This article intends to discuss the present status of the PRP, confusions surrounding its use, upcoming trends and ideas for improvising PRP for use early OA knees based on available evidence. © The Authors, published by EDP Sciences, 2017.

Purification and Fibrillation of Full-Length Recombinant PrP

OpenAIRE

Makarava, Natallia; Baskakov, Ilia V.

2012-01-01

Misfolding and aggregation of prion protein (PrP) is related to several neurodegenerative diseases in humans such as Creutzfeldt–Jacob disease, fatal familial insomnia, and Gerstmann–Straussler–Sheinker disease. Certain applications in prion area require recombinant PrP of high purity and quality. Here, we report an experimental procedure for expression and purification of full-length mammalian PrP. This protocol has been proved to yield PrP of extremely high purity that lac...

The differential effects of leukocyte-containing and pure platelet-rich plasma (PRP) on tendon stem/progenitor cells - implications of PRP application for the clinical treatment of tendon injuries.

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Zhou, Yiqin; Zhang, Jianying; Wu, Haishan; Hogan, MaCalus V; Wang, James H-C

2015-09-15

Platelet-rich plasma (PRP) is widely used to treat tendon injuries in clinics. These PRP preparations often contain white blood cells or leukocytes, and the precise cellular effects of leukocyte-rich PRP (L-PRP) on tendons are not well defined. Therefore, in this study, we determined the effects of L-PRP on tendon stem/progenitor cells (TSCs), which play a key role in tendon homeostasis and repair. TSCs isolated from the patellar tendons of rabbits were treated with L-PRP or P-PRP (pure PRP without leukocytes) in vitro, followed by measuring cell proliferation, stem cell marker expression, inflammatory gene expression, and anabolic and catabolic protein expression by using immunostaining, quantitative real-time polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay, respectively. Cell proliferation was induced by both L-PRP and P-PRP in a dose-dependent manner with maximum proliferation at a 10 % PRP dose. Both PRP treatments also induced differentiation of TSCs into active tenocytes. Nevertheless, the two types of PRP largely differed in several effects exerted on TSCs. L-PRP induced predominantly catabolic and inflammatory changes in differentiated tenocytes; its treatment increased the expression of catabolic marker genes, matrix metalloproteinase-1 (MMP-1), MMP-13, interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α), and their respective protein expression and prostaglandin E2 (PGE 2) production. In contrast, P-PRP mainly induced anabolic changes; that is, P-PRP increased the gene expression of anabolic genes, alpha-smooth muscle actin (α-SMA), collagen types I and III. These findings indicate that, while both L-PRP and P-PRP appear to be "safe" in inducing TSC differentiation into active tenocytes, L-PRP may be detrimental to the healing of injured tendons because it induces catabolic and inflammatory effects on tendon cells and may prolong the effects in healing tendons. On the other hand, when P-PRP is used to

Interaction between 14-3-3β and PrP influences the dimerization of 14-3-3 and fibrillization of PrP106-126.

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Han, Jun; Song, Qin-Qin; Sun, Peng; Zhang, Jin; Wang, Xu; Song, Juan; Li, Gong-Qi; Liu, Ying-Hui; Mei, Guo-Yong; Shi, Qi; Tian, Chan; Chen, Cao; Gao, Chen; Zhao, Bo; Dong, Xiao-Ping

2014-02-01

Proteins of the 14-3-3 family are universal participate in multiple cellular processes. However, their exact role in the pathogenesis of prion diseases remains unclear. In this study, we proposed that human PrP was able to form molecular complex with 14-3-3β. The domains responsible for the interactions between PrP and 14-3-3β were mapped at the segments of amino acid (aa) residues 106-126 within PrP and aa 1-38 within 14-3-3β. Homology modeling revealed that the key aa residues for molecular interaction were D22 and D23 in 14-3-3β as well as K110 in PrP. Mutations in these aa residues inhibited the interaction between the two proteins in vitro. Our results also showed that recombinant PrP encouraged 14-3-3β dimer formation, whereas PrP106-126 peptide inhibited it. Recombinant 14-3-3β disaggregated the mature PrP106-126 fibrils in vitro. Moreover, the PrP-14-3-3 protein complexes were observed in the brain tissues of normal and scrapie agent 263K infected hamsters. Colocalization of PrP and 14-3-3 was seen in the cytoplasm of human neuroblastoma cell line SH-SY5Y, as well as human cervical cancer cell line HeLa transiently expressing full-length human PrP. Our current data suggest the neuroprotection of PrPC and neuron damage caused by PrPSc may be associated with their functions of 14-3-3 dimerization regulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Identification of PrP sequences essential for the interaction between the PrP polymers and Aβ peptide in a yeast-based assay

OpenAIRE

Rubel, Aleksandr A; Ryzhova, Tatyana A; Antonets, Kirill S; Chernoff, Yury O; Galkin, Alexey P

2013-01-01

Alzheimer disease is associated with the accumulation of oligomeric amyloid β peptide (Aβ), accompanied by synaptic dysfunction and neuronal death. Polymeric form of prion protein (PrP), PrPSc, is implicated in transmissible spongiform encephalopathies (TSEs). Recently, it was shown that the monomeric cellular form of PrP (PrPC), located on the neuron surface, binds Aβ oligomers (and possibly other β-rich conformers) via the PrP23–27 and PrP90–110 segments, acting as Aβ receptor. On the other...

PRP as an Adjunct to Rotator Cuff Tendon Repair.

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Barber, F Alan

2018-06-01

Arthroscopic rotator cuff repair is a commonly performed repair. Technical developments provide surgeons the tools to create biomechanically robust repairs. How can the biological response mirror the strong and stable surgery? Platelet-rich plasma (PRP) is a supraphysiological platelet concentration which may positively augment rotator cuff healing. Not all PRPs are the same. High leukocyte levels and thrombin activation may be detrimental to tendon healing. Thrombin activation triggers an immediate release of growth factors and may actually inhibit some parts of the healing response. Clear differences exist between liquid PRP (products released within hours after activation) and solid fibrin PRP which slowly releases factors over days. The heterogenicity data and grouping liquid and solid PRP together make systematic reviews confusing. Solid PRP fibrin constructs are often associated with increased tendon healing. PRP fibrin matrix offers the greatest promise for improving clinical success after rotator cuff tendon repair.

PrP aggregation can be seeded by pre-formed recombinant PrP amyloid fibrils without the replication of infectious prions.

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Barron, Rona M; King, Declan; Jeffrey, Martin; McGovern, Gillian; Agarwal, Sonya; Gill, Andrew C; Piccardo, Pedro

2016-10-01

Mammalian prions are unusual infectious agents, as they are thought to consist solely of aggregates of misfolded prion protein (PrP). Generation of synthetic prions, composed of recombinant PrP (recPrP) refolded into fibrils, has been utilised to address whether PrP aggregates are, indeed, infectious prions. In several reports, neurological disease similar to transmissible spongiform encephalopathy (TSE) has been described following inoculation and passage of various forms of fibrils in transgenic mice and hamsters. However, in studies described here, we show that inoculation of recPrP fibrils does not cause TSE disease, but, instead, seeds the formation of PrP amyloid plaques in PrP-P101L knock-in transgenic mice (101LL). Importantly, both WT-recPrP fibrils and 101L-recPrP fibrils can seed plaque formation, indicating that the fibrillar conformation, and not the primary sequence of PrP in the inoculum, is important in initiating seeding. No replication of infectious prions or TSE disease was observed following both primary inoculation and subsequent subpassage. These data, therefore, argue against recPrP fibrils being infectious prions and, instead, indicate that these pre-formed seeds are acting to accelerate the formation of PrP amyloid plaques in 101LL Tg mice. In addition, these data reproduce a phenotype which was previously observed in 101LL mice following inoculation with brain extract containing in vivo-generated PrP amyloid fibrils, which has not been shown for other synthetic prion models. These data are reminiscent of the "prion-like" spread of aggregated forms of the beta-amyloid peptide (Aβ), α-synuclein and tau observed following inoculation of transgenic mice with pre-formed seeds of each misfolded protein. Hence, even when the protein is PrP, misfolding and aggregation do not reproduce the full clinicopathological phenotype of disease. The initiation and spread of protein aggregation in transgenic mouse lines following inoculation with pre

Singlet ground-state fluctuations in praseodymium observed by muon spin relaxation in PrP and PrP0.9

International Nuclear Information System (INIS)

Noakes, D R; Waeppling, R; Kalvius, G M; Jr, M F White; Stronach, C E

2005-01-01

Muon spin relaxation (μSR) in the singlet ground-state compounds PrP and PrP 0.9 reveals the unusual situation of a Lorentzian local field distribution with fast-fluctuation-limit strong-collision dynamics, a case that does not show motional narrowing. Contrary to publications by others, where PrP 0.9 was asserted to have vacancy-induced spin-glass freezing, no spin-glass freezing is seen in PrP 0.9 or PrP down to ≤100mK. This was confirmed by magnetization measurements on these same samples. In both compounds, the muon spin relaxation rate does increase as temperature decreases, demonstrating increasing strength of the paramagnetic response. A Monte Carlo model of fluctuations of Pr ions out of their crystalline-electric-field singlet ground states into their magnetic excited states (and back down again) produces the strong-collision-dynamic Lorentzian relaxation functions observed at each individual temperature but not the observed temperature dependence. This model contains no exchange interaction, and so predicts decreasing paramagnetic response as the temperature decreases, contrary to the temperature dependence observed. Comparison of the simulations to the data suggests that the exchange interaction is causing the system to approach magnetic freezing (by mode softening), but fails to complete the process

HGF mediates the anti-inflammatory effects of PRP on injured tendons.

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Jianying Zhang

Full Text Available Platelet-rich plasma (PRP containing hepatocyte growth factor (HGF and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2.

HGF Mediates the Anti-inflammatory Effects of PRP on Injured Tendons

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Zhang, Jianying; Middleton, Kellie K.; Fu, Freddie H.; Im, Hee-Jeong; Wang, James H-C.

2013-01-01

Platelet-rich plasma (PRP) containing hepatocyte growth factor (HGF) and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP) however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2. PMID:23840657

Cytosolically expressed PrP GPI-signal peptide interacts with mitochondria.

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Guizzunti, Gianni; Zurzolo, Chiara

2015-01-01

We previously reported that PrP GPI-anchor signal peptide (GPI-SP) is specifically degraded by the proteasome. Additionally, we showed that the point mutation P238S, responsible for a genetic form of prion diseases, while not affecting the GPI-anchoring process, results in the accumulation of PrP GPI-SP, suggesting the possibility that PrP GPI-anchor signal peptide could play a role in neurodegenerative prion diseases. We now show that PrP GPI-SP, when expressed as a cytosolic peptide, is able to localize to the mitochondria and to induce mitochondrial fragmentation and vacuolarization, followed by loss in mitochondrial membrane potential, ultimately resulting in apoptosis. Our results identify the GPI-SP of PrP as a novel candidate responsible for the impairment in mitochondrial function involved in the synaptic pathology observed in prion diseases, establishing a link between PrP GPI-SP accumulation and neuronal death.

The influence of training on the attentional blink and psychological refractory period.

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Garner, K G; Tombu, M N; Dux, P E

2014-05-01

A growing body of research suggests that dual-task interference in sensory consolidation (e.g., the attentional blink, AB) and response selection (e.g., the psychological refractory period, PRP) stems from a common central bottleneck of information processing. With regard to response selection, it is well known that training reduces dual-task interference. We tested whether training that is known to be effective for response selection can also reduce dual-task interference in sensory consolidation. Over two experiments, performance on a PRP paradigm (Exp. 1) and on AB paradigms (differing in their stimuli and task demands, Exps. 1 and 2) was examined after participants had completed a relevant training regimen (T1 practice for both paradigms), an irrelevant training regimen (comparable sensorimotor training, not related to T1 for both tasks), a visual-search training regimen (Exp. 2 only), or after participants had been allocated to a no-training control group. Training that had shown to be effective for reducing dual-task interference in response selection was also found to be effective for reducing interference in sensory consolidation. In addition, we found some evidence that training benefits transferred to the sensory consolidation of untrained stimuli. Collectively, these findings show that training benefits can transfer across cognitive operations that draw on the central bottleneck in information processing. These findings have implications for theories of the AB and for the design of cognitive-training regimens that aim to produce transferable training benefits.

An introduction to application of Platelet Rich Plasma (PRP in skin rejuvenation

Directory of Open Access Journals (Sweden)

Mahnaz Banihashemi

2014-04-01

Full Text Available Platelet-rich plasma (PRP is an autologous concentration of human platelets contained in a small volume of plasma characterized by haemostatic and tissue repairing effects. Tissue repairing effects and being enriched by various kind of growth factors, has made them the focus of attention for different procedures. PRP has been effective in bony defects, wound healing and recently for aesthetic procedures in plastic surgery. The purpose of this review is to evaluate and summarize the applications of PRP in the dermatology literature, with particular focus on rejuvenizaton process, advances and limitations of current PRP therapies. We studied literature related to PRP therapy, these include regeneration of soft tissue, skin aging mechanisms, as well as wound healing. Some studies have shown promising results, with favorable outcomes about PRP clinical application for skin rejuvenization. This article summarizes our current understanding regarding photoaging process and the role of PRP in the skin rejuvenization process. PRP has been shown to be useful in skin rejuvenization. Further studies are needed to elucidate both basic and clinical aspects of PRP therapies. In particular, platelet preparation methods, different application methods, platelet mechanism of action in rejuvenation field, interactions with the skin components, long-term efficacy and safety are necessary to be determined.

CONTAMINATED PROBLEMATIC SKIN WOUNDS IN DIABETIC PATIENTS TREATED WITH AUTOLOGOUS PLATELET-RICH PLASMA (PRP: A case series study

Directory of Open Access Journals (Sweden)

Tsvetan Sokolov

2016-03-01

Full Text Available OBJECTIVE: To study the effect of platelet-rich plasma (PRP on contaminated problematic skin ulcers in patients with diabetes. MATERIAL AND METHODS: A total of 6 patients had been treated within the period from 2012 to 2014; they had various types of problematic wounds and diabetes type 2. Patients’ distribution by sex was as follows: 1 man and 5 women; mean age- 68 years. Ulcer types: acute (2 patients, hard-to-heal (2 patients and chronic (2 patients ulcers. The mean size of the skin and soft tissue defect was 9,5 cm2. Pathogenic microflora was isolated in 4 patients - S. aureus in three and Е. Coli in one. Based on a scheme developed by us, all cases were treated by administering platelet-rich plasma, derived by PRGF Endoret system. Follow-up period was within 4 – 6 months (4,5 on average. We used platelet rich plasma derived by PRGF Endoret system, applied on the wound bed on a weekly basis. RESULTS: Application of PRP allowed successful closure of all wounds. There were no complications associated with treatment of PRP. Epithelialization of the wound took 15 weeks on average for all patients. One patient presented with hyperkeratosis. Initial score of followed wounds, based on the scales are as follows: Total wound score – 10 p. Total anatomic score – 8 p. Total score – 15 p. at the initial stage. At the end of the treatment period scores were as follows - 0 p., which means excellent results CONCLUSION: We believe that the application of PRP may become optimal therapy in the treatment of contaminated problematic wounds in diabetic patients. PRP not only stimulates wound healing, but also has antimicrobial properties, which may contribute to the prevention of infections.

Performance related pay (PRP) to social workers in Danish Job Centres

DEFF Research Database (Denmark)

Flensborg Jensen, Maya; Rosdahl, Anders

This paper discusses two issues: - Why has some Danish local employment administrations introduced performance related pay (PRP) for social workers while others have not? - Does PRP to social workers imply better efforts to bring long-term recipients of social assistance into employment?......This paper discusses two issues: - Why has some Danish local employment administrations introduced performance related pay (PRP) for social workers while others have not? - Does PRP to social workers imply better efforts to bring long-term recipients of social assistance into employment?...

PRP for Degenerative Cartilage Disease: A Systematic Review of Clinical Studies.

Science.gov (United States)

Laver, Lior; Marom, Niv; Dnyanesh, Lad; Mei-Dan, Omer; Espregueira-Mendes, João; Gobbi, Alberto

2017-10-01

To explore the utilization of platelet-rich plasma (PRP) for degenerative cartilage processes and evaluate whether there is sufficient evidence to better define its potential effects. Systematic literature reviews were conducted in PubMed/MEDLINE and Cochrane electronic databases till May 2015, using the keywords "platelet-rich plasma OR PRP OR autologous conditioned plasma OR ACP AND cartilage OR chondrocyte OR chondrogenesis OR osteoarthritis (OA) OR arthritis." The final result yielded 29 articles. Twenty-six studies examined PRP administration for knee OA and 3 involved PRP administration for hip OA. The results included 9 prospective randomized controlled trials (RCTs) (8 knee and 1 hip), 4 prospective comparative studies, 14 case series, and 2 retrospective comparative studies. Hyaluronic acid (HA) was used as a control in 11 studies (7 RCTs, 2 prospective comparative studies, and 2 retrospective cohort). Overall, all RCTs reported on improved symptoms compared to baseline scores. Only 2 RCTs-one for knee and one for hip-did not report significant superiority of PRP compared to the control group (HA). Nine out of 11 HA controlled studies showed significant better results in the PRP groups. A trend toward better results for PRP injections in patients with early knee OA and young age was observed; however, lack of uniformity was evident in terms of indications, inclusion criteria, and pathology definitions in the different studies. Current clinical evidence supports the benefit in PRP treatment for knee and hip OA, proven to temporarily relieve pain and improve function of the involved joint with superior results compared with several alternative treatments. Further research to establish the optimal preparation protocol and characteristics of PRP injections for OA is needed.

[Platelet rich plasma (PRP): potentialities and techniques of extraction].

Science.gov (United States)

Pacifici, L; Casella, F; Maggiore, C

2002-01-01

This paper describes the various techniques of platelet-rich plasma (PRP) extraction codified in recent years and their use potential is evaluated. PRP is one of the techniques with which at the moment it is attempted to modulate and facilitate the cure of a wound. The use of PRP is based on the theoretical premise that by concentrating platelets the effects of the growth factors (PDGF, TGF-beta, IGF-I and -II) so released will be increased. Marx's original technique is described above all. This prescribes the sampling of a unit of blood (450-500 ml) and the use of a cell separator. We then analysed the technique of Marx and Hannon in which the quantity of blood sampled is reduced to 150 ml, and the two simplified techniques of the Sacchi and Bellanda group. Finally, a new PRP extraction technique is described. We conclude that platelet gel allows access to autologous growth factors which by definition are neither toxic nor immunogenic and are capable of accelerating the normal processes of bone regeneration. PRP can thus be considered a useful instrument for increasing the quality and final quantity of regenerated bone in oral and maxillo-facial surgery operations.

Recommendations for the Involvement of Patient Research Partners (PRP) in OMERACT Working Groups. A Report from the OMERACT 2014 Working Group on PRP.

Science.gov (United States)

Cheung, Peter P; de Wit, Maarten; Bingham, Clifton O; Kirwan, John R; Leong, Amye; March, Lyn M; Montie, Pam; Scholte-Voshaar, Marieke; Gossec, Laure

2016-01-01

Patient participation in research is increasing; however, practical guidelines to enhance this participation are lacking. Specifically within the Outcome Measures in Rheumatology (OMERACT) organization, although patients have participated in OMERACT meetings since 2002, consensus about the procedures for involving patients in working groups has not been formalized. The objective is to develop a set of recommendations regarding patient research partner (PRP) involvement in research working groups. We conducted a systematic literature review on recommendations/guidelines of PRP involvement in research; elaborated a structured consensus process involving multiple participants to develop a set of recommendations; and sought endorsement of recommendations by OMERACT. In the 18 articles included in the literature review, there was general agreement on the broad concepts for recommendations covering PRP involvement in research although they were heterogeneous in detail. Most considered PRP involvement in all phases of research with early engagement, training, and support important, but details on the content were scarce. This review informed a larger consensus-building process regarding PRP inclusion in OMERACT research. Three overarching principles and 8 recommendations were developed, discussed, and refined at OMERACT 2014. The guiding principles were endorsed during the OMERACT plenary session. These recommendations for PRP involvement in OMERACT research reinforce the importance of patient participation throughout the research process as integral members. Although the applicability of the recommendations in other research contexts should be assessed, the generalizability is expected to be high. Future research should evaluate their implementation and their effect on outcome development.

PrP N-terminal domain triggers PrPSc-like aggregation of Dpl

International Nuclear Information System (INIS)

Erlich, Paul; Cesbron, Jean-Yves; Lemaire-Vieille, Catherine; Curt, Aurelie; Andrieu, Jean-Pierre; Schoehn, Guy; Jamin, Marc; Gagnon, Jean

2008-01-01

Transmissible spongiform encephalopathies are fatal neurodegenerative disorders thought to be transmitted by self-perpetuating conformational conversion of a neuronal membrane glycoprotein (PrP C , for 'cellular prion protein') into an abnormal state (PrP Sc , for 'scrapie prion protein'). Doppel (Dpl) is a protein that shares significant biochemical and structural homology with PrP C . In contrast to its homologue PrP C , Dpl is unable to participate in prion disease progression or to achieve an abnormal PrP Sc -like state. We have constructed a chimeric mouse protein, composed of the N-terminal domain of PrP C (residues 23-125) and the C-terminal part of Dpl (residues 58-157). This chimeric protein displays PrP-like biochemical and structural features; when incubated in presence of NaCl, the α-helical monomer forms soluble β-sheet-rich oligomers which acquire partial resistance to pepsin proteolysis in vitro, as do PrP oligomers. Moreover, the presence of aggregates akin to protofibrils is observed in soluble oligomeric species by electron microscopy

CD36 participates in PrP(106-126-induced activation of microglia.

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Mohammed Kouadir

Full Text Available Microglial activation is a characteristic feature of the pathogenesis of prion diseases. The molecular mechanisms that underlie prion-induced microglial activation are not very well understood. In the present study, we investigated the role of the class B scavenger receptor CD36 in microglial activation induced by neurotoxic prion protein (PrP fragment 106-126 (PrP(106-126. We first examined the time course of CD36 mRNA expression upon exposure to PrP(106-126 in BV2 microglia. We then analyzed different parameters of microglial activation in PrP(106-126-treated cells in the presence or not of anti-CD36 monoclonal antibody (mAb. The cells were first incubated for 1 h with CD36 monoclonal antibody to block the CD36 receptor, and were then treated with neurotoxic prion peptides PrP(106-126. The results showed that PrP(106-126 treatment led to a rapid yet transitory increase in the mRNA expression of CD36, upregulated mRNA and protein levels of proinflammatory cytokines (IL-1β, IL-6 and TNF-α, increased iNOS expression and nitric oxide (NO production, stimulated the activation of NF-κB and caspase-1, and elevated Fyn activity. The blockade of CD36 had no effect on PrP(106-126-stimulated NF-κB activation and TNF-α protein release, abrogated the PrP(106-126-induced iNOS stimulation, downregulated IL-1β and IL-6 expression at both mRNA and protein levels as well as TNF-α mRNA expression, decreased NO production and Fyn phosphorylation, reduced caspase-1 cleavage induced by moderate PrP(106-126-treatment, but had no effect on caspase-1 activation after treatment with a high concentration of PrP(106-126. Together, these results suggest that CD36 is involved in PrP(106-126-induced microglial activation and that the participation of CD36 in the interaction between PrP(106-126 and microglia may be mediated by Src tyrosine kinases. Our findings provide new insights into the mechanisms underlying the activation of microglia by neurotoxic prion peptides

Structural and functional analysis of the human spliceosomal DEAD-box helicase Prp28

Energy Technology Data Exchange (ETDEWEB)

Möhlmann, Sina [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany); Mathew, Rebecca [Max-Planck-Institute for Biophysical Chemistry, Am Fassberg, 37077 Göttingen (Germany); Neumann, Piotr; Schmitt, Andreas [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany); Lührmann, Reinhard [Max-Planck-Institute for Biophysical Chemistry, Am Fassberg, 37077 Göttingen (Germany); Ficner, Ralf, E-mail: rficner@uni-goettingen.de [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany)

2014-06-01

The crystal structure of the helicase domain of the human spliceosomal DEAD-box protein Prp28 was solved by SAD. The binding of ADP and ATP by Prp28 was studied biochemically and analysed with regard to the crystal structure. The DEAD-box protein Prp28 is essential for pre-mRNA splicing as it plays a key role in the formation of an active spliceosome. Prp28 participates in the release of the U1 snRNP from the 5′-splice site during association of the U5·U4/U6 tri-snRNP, which is a crucial step in the transition from a pre-catalytic spliceosome to an activated spliceosome. Here, it is demonstrated that the purified helicase domain of human Prp28 (hPrp28ΔN) binds ADP, whereas binding of ATP and ATPase activity could not be detected. ATP binding could not be observed for purified full-length hPrp28 either, but within an assembled spliceosomal complex hPrp28 gains ATP-binding activity. In order to understand the structural basis for the ATP-binding deficiency of isolated hPrp28, the crystal structure of hPrp28ΔN was determined at 2.0 Å resolution. In the crystal the helicase domain adopts a wide-open conformation, as the two RecA-like domains are extraordinarily displaced from the productive ATPase conformation. Binding of ATP is hindered by a closed conformation of the P-loop, which occupies the space required for the γ-phosphate of ATP.

Ubiquitin Ligase gp78 Targets Unglycosylated Prion Protein PrP for Ubiquitylation and Degradation

OpenAIRE

Shao, Jia; Choe, Vitnary; Cheng, Haili; Tsai, Yien Che; Weissman, Allan M.; Luo, Shiwen; Rao, Hai

2014-01-01

Prion protein PrP is a central player in several devastating neurodegenerative disorders, including mad cow disease and Creutzfeltd-Jacob disease. Conformational alteration of PrP into an aggregation-prone infectious form PrPSc can trigger pathogenic events. How levels of PrP are regulated is poorly understood. Human PrP is known to be degraded by the proteasome, but the specific proteolytic pathway responsible for PrP destruction remains elusive. Here, we demonstrate that the ubiquitin ligas...

Enhanced Osteogenic Differentiation of Mesenchymal Stem Cells on Electrospun PES/PVA/PRP Nanofibrous Scaffolds.

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Kashef-Saberi, Mahshid Sadat; Roodbari, Nasim Hayati; Parivar, Kazem; Vakilian, Saeid; Hanee-Ahvaz, Hana

2018-03-28

Over the last few decades, great advancements have been achieved in the field of bone tissue engineering (BTE). Containing a great number of growth factors needed in the process of osteogenesis, platelet rich plasma (PRP) has gained a great deal of attention. However, due to the contradictory results achieved in different studies, its effectiveness remains a mystery. Therefore, in this study, we investigated in vitro performance of co-electrospun PRP/poly ether sulfone/poly(vinyl) alcohol (PRP/PES/PVA) composite scaffolds for the osteogenic differentiation of human adipose-derived mesenchymal stem cells. The activated PRP was mixed with PVA solution to be used alongside PES solution for the electrospinning process. Fourier transform infrared spectroscopy, scanning electron microscopy and tensile tests were performed to evaluate the scaffolds. After confirmation of sustained release of protein, osteogenic potential of the co-electrospun PRP/polymer scaffolds was evaluated by measuring relative gene expression, calcium content, and alkaline phosphatase (ALP) activity. Alizarin red and Hematoxylin and Eosin staining were performed as well. The results of ALP activity and calcium content demonstrated the effectiveness of PRP when combined with PRP-incorporated scaffold in comparison with the other tested groups. In addition, the results of tensile mechanical testing indicated that addition of PRP improves the mechanical properties. Taking these results into account, it appears PES/PVA/PRP scaffold treated with PRP 5% enhances osteogenic differentiation most. In conclusion, incorporation of PRP into electrospun PES/PVA scaffold in this study had a positive influence on osteogenic differentiation of AdMSCs, and thus it may have great potential for BTE applications.

Matrix metalloproteinase content and activity in low-platelet, low-leukocyte and high-platelet, high-leukocyte platelet rich plasma (PRP) and the biologic response to PRP by human ligament fibroblasts.

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Pifer, Matthew A; Maerz, Tristan; Baker, Kevin C; Anderson, Kyle

2014-05-01

concentration (P = .002) compared with controls, but no difference in MMP-3 concentration was found. At 48 hours, there was a significantly higher concentration of MMP-9 in the cell culture media of ACP-treated cells compared with GPS-treated cells (P = .003). PRP prepared as both ACP and GPS contains MMP-2, -3, and -9, which is released over a period of at least 6 days. Furthermore, a large proportion of these MMPs are in their active form, and MMP activity is dependent on platelet count within the PRP preparation. Once exposed to ligament fibroblasts, both ACP and GPS cause the fibroblasts to release MMPs, most notably 24 hours after PRP exposure, and this release is dependent on prior IL-1β stimulation. The results of this study demonstrate that PRP therapy delivers ng/mL-range concentrations of catabolic proteases, which could perpetuate inflammation and inhibit tissue healing.

PRP: The Proven Solution for Cleaning Up Oil Spills

Science.gov (United States)

2006-01-01

The basic technology behind PRP is thousands of microcapsules, tiny balls of beeswax with hollow centers. Water cannot penetrate the microcapsule s cell, but oil is absorbed right into the beeswax spheres as they float on the water s surface. This way, the contaminants, chemical compounds that originally come from crude oil such as fuels, motor oils, or petroleum hydrocarbons, are caught before they settle. PRP works well as a loose powder for cleaning up contaminants in lakes and other ecologically fragile areas. The powder can be spread over a contaminated body of water or soil, and it will absorb contaminants, contain them in isolation, and dispose of them safely. In water, it is important that PRP floats and keeps the oil on the surface, because, even if oil exposure is not immediately lethal, it can cause long-term harm if allowed to settle. Bottom-dwelling fish exposed to compounds released after oil spills may develop liver disease, in addition to reproductive and growth problems. This use of PRP is especially effective for environmental cleanup in sensitive areas like coral reefs and mangroves.

Acetylcholinesterase triggers the aggregation of PrP 106-126

International Nuclear Information System (INIS)

Pera, M.; Roman, S.; Ratia, M.; Camps, P.; Munoz-Torrero, D.; Colombo, L.; Manzoni, C.; Salmona, M.; Badia, A.; Clos, M.V.

2006-01-01

Acetylcholinesterase (AChE), a senile plaque component, promotes amyloid-β-protein (Aβ) fibril formation in vitro. The presence of prion protein (PrP) in Alzheimer's disease (AD) senile plaques prompted us to assess if AChE could trigger the PrP peptides aggregation as well. Consequently, the efficacy of AChE on the PrP peptide spanning-residues 106-126 aggregation containing a coumarin fluorescence probe (coumarin-PrP 106-126) was studied. Kinetics of coumarin-PrP 106-126 aggregation showed a significant increase of maximum size of aggregates (MSA), which was dependent on AChE concentration. AChE-PrP 106-126 aggregates showed the tinctorial and optical amyloid properties as determined by polarized light and electronic microscopy analysis. A remarkable inhibition of MSA was obtained with propidium iodide, suggesting that AChE triggers PrP 106-126 and Aβ aggregation through a similar mechanism. Huprines (AChE inhibitors) also significantly decreased MSA induced by AChE as well, unveiling the potential interest for some AChE inhibitors as a novel class of potential anti-prion drugs

Comparison of hyaluronic acid and PRP intra-articular injection with combined intra-articular and intraosseous PRP injections to treat patients with knee osteoarthritis.

Science.gov (United States)

Su, Ke; Bai, Yuming; Wang, Jun; Zhang, Haisen; Liu, Hao; Ma, Shiyun

2018-05-01

The aim of this study was to evaluate the benefit provided by intraosseous infiltration combined with intra-articular injection of platelet-rich plasma to treat mild and moderate stages of knee joint degeneration (Kellgren-Lawrence score II-III) compared with other treatments, specifically intra-articular injection of PRP and of HA. Eighty-six patients with grade II to grade III knee OA according to the Kellgren-Lawrence classification were randomly assigned to intra-articular combined with intraosseous injection of PRP (group A), intra-articular PRP (group B), or intra-articular HA (group C). Patients in group A received intra-articular combined with intraosseous injection of PRP (administered twice, 2 weeks apart). Patients in group B received intra-articular injection of PRP every 14 days. Patients in group C received a series of five intra-articular injections of HA every 7 days. All patients were evaluated using the Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities (WOMAC) score before the treatment and at 1, 3, 6, 12, and 18 months after treatment. There were significant improvements at the end of the 1st month. Notably, group A patients had significantly superior VAS and WOMAC scores than were observed in groups B and C. The VAS scores were similar in groups B and group C after the 6th month. Regarding the WOMAC scores, groups B and C differed at the 1st, 3rd, 6th, and 12th months; however, no significant difference was observed at the 18th month. The combination of intraosseous with intra-articular injections of PRP resulted in a significantly superior clinical outcome, with sustained lower VAS and WOMAC scores and improvement in quality of life within 18 months.

Comparison of the Efficacy of Homologous and Autologous Platelet-Rich Plasma (PRP) for Treating Androgenic Alopecia.

Science.gov (United States)

Ince, Bilsev; Yildirim, Mehmet Emin Cem; Dadaci, Mehmet; Avunduk, Mustafa Cihat; Savaci, Nedim

2018-02-01

Androgenetic alopecia (AGA), the most common cause of hair loss in both sexes, accounts for 95% of all cases of hair loss. Although the literature has suggested that both nonactivated (n-PRP) and activated autologous (a-PRP) PRP can be used to treat AGA, we did not find any study investigating the use of homologous PRP (h-PRP) for this purpose. Also, to the best of our knowledge, there are no studies comparing the efficacy of h-PRP, a-PRP, or n-PRP on AGA therapy. The aim of this study was to compare the increase in hair density, average number of platelets, complications, preparation, and duration of application in the treatment of AGA using a-PRP, n-PRP, and h-PRP. Between 2014 and 2015, we studied male patients who had experienced increased hair loss in the last year. Patients were divided into three groups: Group 1 received n-PRP, Group 2 received active PRP, and Group 3 received h-PRP. For Group 1, PRP was prepared by a single centrifugation prepared from the patient's own blood. For Group 2, the PRP was prepared from the patient's own blood, but a second centrifugation was applied for platelet activation with calcium chloride. For Group 3, the PRP was prepared from pooled platelets with the same blood group as the patient from the blood center. PRP was injected at 1, 2, and 6 months. The hair density (n/cm 2 ) of each patient before and after injection was calculated. Each patient was assigned a fixed evaluation point at the time of application to calculate hair density. At 2, 6, and 12 months after the first treatment, the increase in hair density was calculated as 11.2, 26.1, and 32.4%, respectively, in Group 1; 8.1, 12.5, and 20.8%, respectively, in Group 2; and 16.09, 36.41, and 41.76%, respectively, in Group 3. The increase in hair density was statistically significantly greater in Group 1 than in Group 2 and more so in Group 3 than in both groups among all controls (p PRP was greater than with autologous PRP groups. We believe that h-PRP therapy can

Contingent capture of visual-spatial attention depends on capacity-limited central mechanisms: evidence from human electrophysiology and the psychological refractory period.

Science.gov (United States)

Brisson, Benoit; Leblanc, Emilie; Jolicoeur, Pierre

2009-02-01

It has recently been demonstrated that a lateralized distractor that matches the individual's top-down control settings elicits an N2pc wave, an electrophysiological index of the focus of visual-spatial attention, indicating that contingent capture has a visual-spatial locus. Here, we investigated whether contingent capture required capacity-limited central resources by incorporating a contingent capture task as the second task of a psychological refractory period (PRP) dual-task paradigm. The N2pc was used to monitor where observers were attending while they performed concurrent central processing known to cause the PRP effect. The N2pc elicited by the lateralized distractor that matched the top-down control settings was attenuated in high concurrent central load conditions, indicating that although involuntary, the deployment of visual-spatial attention occurring during contingent capture depends on capacity-limited central resources.

Mechanical and Controlled PRP Injections in Patients Affected by Androgenetic Alopecia.

Science.gov (United States)

Gentile, Pietro; Garcovich, Simone; Scioli, Maria Giovanna; Bielli, Alessandra; Orlandi, Augusto; Cervelli, Valerio

2018-01-27

23 patients (18 male and 5 female) aged 21-70 years who displayed male pattern hair loss (MPHL) in Stage 1 to Stage 5 as determined by the Norwood-Hamilton classification scale, and female pattern hair loss (FPHL) in Stage 1 to Stage 2 as determined by the Ludwig classification scale, were treated with non-activated autologous platelet-rich plasma (A-PRP). Autologous blood (55 mL) was harvested using sodium citrate as an anticoagulant. A-PRP (23 mL) was produced for all cases using a closed system according to the transfusion service protocol. Following centrifugation (260 x g for 10 min) the A-PRP was inserted in a laser light selector device, and after the centrifugation, 9 mL of A-PRP was collected. The scalp of the patients affected by androgenetic alopecia (AGA) was divided into four areas (frontal, parietal, vertex, and occipital); local anesthesia was not performed. Interfollicular A-PRP injections (0.2 mL x cm 2 ) were performed by controlled and mechanical injections scheduled at a depth of 5 mm using a medical injector gun. Treatment sessions were performed with a 30-day interval. For each patient, three treatment sessions were performed. PRP was injected in the androgen-related areas of scalp affected by hair loss. Placebo (normal saline solution) was loaded in another syringe (10 mL) and injected on the adjacent side in a similar fashion.

Impact of local anaesthetics and needle calibres used for painless PRP injections on platelet functionality.

Science.gov (United States)

Bausset, Olivier; Magalon, Jeremy; Giraudo, Laurent; Louis, Marie-Laure; Serratrice, Nicolas; Frere, Corrine; Magalon, Guy; Dignat-George, Françoise; Sabatier, Florence

2014-01-01

The platelet-rich plasma (PRP) is an autologous biotherapy commonly used for its healing properties. Once activated, platelets released a real "cocktail" of growth factor and cytokines implied in numerous regenerative processes. However the impact of medical practices associated to PRP therapeutic use on platelets functionality remains poorly known. we evaluated the in vitro effects of two commonly used local anesthetics (Xylocaine(*) and Naropin(*)) on PRP functionality. We also investigated the quantity and quality of PRP that passed through the smallest gauge needle commercialized. PRP from 9 healthy volunteers were prepared using our previously described home made purification protocol. Platelet aggregation capacity was evaluated by aggregometry assays and the growth factor release was determined by ELISA after platelet activation. We also evaluated the platelet activation status, reactivity and stability of platelets by flow cytometry using the P-selectin expression marker. the association of local anaesthetics with PRP injections resulted in a significant decrease of platelets functionality, assessed by their capacity of aggregating. Local anaesthetics did not interfere with the growth factor release. The different needle sizes and calibres tested for PRP injections did not influence the platelet functionality. the use of local anaesthetics to prevent pain during PRP injections could compromise the therapeutic potential of PRP. These results suggest using carefully local anaesthetics or limiting their use as often is possible. To minimize injection pain, we recommend using 30 G needles. These data will lead to clinical recommendations for painless and controlled PRP injections.

Platelet-rich plasma (PRP) treatment of sports-related severe acute hamstring injuries.

Science.gov (United States)

Guillodo, Yannick; Madouas, Gwénaelle; Simon, Thomas; Le Dauphin, Hermine; Saraux, Alain

2015-01-01

hamstring injury is the most common musculoskeletal disorder and one of the main causes of missed sporting events. Shortening the time to return to play (TTRTP) is a priority for athletes and sports medicine practitioners. platelet-rich plasma (PRP) injection at the site of severe acute hamstring injury increases the healing rate and shortens the TTRTP. Cohort study. all patients with ultrasonography and MRI evidence of severe acute hamstring injury between January 2012 and March 2014 were offered PRP treatment. Those who accepted received a single intramuscular PRP injection within 8 days post-injury; the other patients served as controls. The same standardized rehabilitation program was used in both groups. A physical examination and ultrasonography were performed 10 and 30 days post-injury, then a phone interview 120 days post-injury, to determine the TTRTP at the pre-injury level. of 34 patients, 15 received PRP and 19 did not. Mean TTRTP at the pre-injury level was 50.9±10.7 days in the PRP group and 52.8±15.7 days in the control group. The difference was not statistically significant. a single intramuscular PRP injection did not shorten the TTRTP in sports people with severe acute hamstring injuries.

What About the Rheological Properties of PRP/Microfat Mixtures in Fat Grafting Procedure?

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Ghazouane, R; Bertrand, B; Philandrianos, C; Veran, J; Abellan, M; Francois, P; Velier, M; Orneto, C; Piccerelle, P; Magalon, J

2017-10-01

Fat grafting has emerged as a reference procedure in daily plastic surgery practice. Unpredictable fat resorption is the main clinical problem. For this purpose, the addition of PRP to enhance fat revascularization is now an easy and popular procedure. However, no consensus exists regarding the respective volume of fat and PRP used to obtain the ideal mixture. This study investigated the rheological properties of microfat mixed with different proportions of PRP. Results obtained were compared with commercialized hyaluronic acid fillers. Microfat and PRP preparations were performed using standardized techniques. Lipoaspirate residue and blood were obtained from six patients undergoing aesthetic facial microlipofilling. Elastic modulus G' and tan δ (proportion of elasticity versus fluidity) were obtained for the following conditions: microfat alone and microfat mixed with 10, 30 or 50% of PRP. An expected decrease in elastic modulus was observed by adding increase volumes of PRP. Two groups of products with different rheological properties were considered based on statistical differences highlighted regarding the value of G'. Mean tan δ varied from 0.20 ± 0.04 (microfat alone) to 0.28 ± 0.08 (50% microfat/50% PRP). Microfat mixed with 10% of PRP presents consistency comparable to stiffer fillers, whereas microfat mixed with 30 or 50% corresponds to softer fillers. Rheological differences were highlighted given the proportion of PRP added to the microfat. Further studies assessing the impact of increased doses of platelets in microfat/PRP mixtures on clinical outcomes should also be investigated. Our findings will help clinicians to choose a mixture that meets their specific needs for a given indication. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Semisynthetic prion protein (PrP) variants carrying glycan mimics at position 181 and 197 do not form fibrils.

Science.gov (United States)

Araman, Can; Thompson, Robert E; Wang, Siyao; Hackl, Stefanie; Payne, Richard J; Becker, Christian F W

2017-09-01

The prion protein (PrP) is an N -glycosylated protein attached to the outer leaflet of eukaryotic cell membranes via a glycosylphosphatidylinositol (GPI) anchor. Different prion strains have distinct glycosylation patterns and the extent of glycosylation of potentially pathogenic misfolded prion protein (PrP Sc ) has a major impact on several prion-related diseases (transmissible spongiform encephalopathies, TSEs). Based on these findings it is hypothesized that posttranslational modifications (PTMs) of PrP influence conversion of cellular prion protein (PrP C ) into PrP Sc and, as such, modified PrP variants are critical tools needed to investigate the impact of PTMs on the pathogenesis of TSEs. Here we report a semisynthetic approach to generate PrP variants modified with monodisperse polyethyleneglycol (PEG) units as mimics of N-glycans. Incorporating PEG at glycosylation sites 181 and 197 in PrP induced only small changes to the secondary structure when compared to unmodified, wildtype PrP. More importantly, in vitro aggregation was abrogated for all PEGylated PrP variants under conditions at which wildtype PrP aggregated. Furthermore, the addition of PEGylated PrP as low as 10 mol% to wildtype PrP completely blocked aggregation. A similar effect was observed for synthetic PEGylated PrP segments comprising amino acids 179-231 alone if these were added to wildtype PrP in aggregation assays. This behavior raises the question if large N-glycans interfere with aggregation in vivo and if PEGylated PrP peptides could serve as potential therapeutics.

Genetic human prion disease modelled in PrP transgenic Drosophila.

Science.gov (United States)

Thackray, Alana M; Cardova, Alzbeta; Wolf, Hanna; Pradl, Lydia; Vorberg, Ina; Jackson, Walker S; Bujdoso, Raymond

2017-09-20

Inherited human prion diseases, such as fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD), are associated with autosomal dominant mutations in the human prion protein gene PRNP and accumulation of PrP Sc , an abnormal isomer of the normal host protein PrP C , in the brain of affected individuals. PrP Sc is the principal component of the transmissible neurotoxic prion agent. It is important to identify molecular pathways and cellular processes that regulate prion formation and prion-induced neurotoxicity. This will allow identification of possible therapeutic interventions for individuals with, or at risk from, genetic human prion disease. Increasingly, Drosophila has been used to model human neurodegenerative disease. An important unanswered question is whether genetic prion disease with concomitant spontaneous prion formation can be modelled in Drosophila We have used pUAST/PhiC31-mediated site-directed mutagenesis to generate Drosophila transgenic for murine or hamster PrP (prion protein) that carry single-codon mutations associated with genetic human prion disease. Mouse or hamster PrP harbouring an FFI (D178N) or fCJD (E200K) mutation showed mild Proteinase K resistance when expressed in Drosophila Adult Drosophila transgenic for FFI or fCJD variants of mouse or hamster PrP displayed a spontaneous decline in locomotor ability that increased in severity as the flies aged. Significantly, this mutant PrP-mediated neurotoxic fly phenotype was transferable to recipient Drosophila that expressed the wild-type form of the transgene. Collectively, our novel data are indicative of the spontaneous formation of a PrP-dependent neurotoxic phenotype in FFI- or CJD-PrP transgenic Drosophila and show that inherited human prion disease can be modelled in this invertebrate host. © 2017 The Author(s).

PrP Conformational Transitions Alter Species Preference of a PrP-specific antibody

NARCIS (Netherlands)

Zou, W.Q.; Langeveld, J.P.M.; Xiao, X.; Chen, S.; McGeer, P.L.; Yuan, J.; Payne, M.C.; Kang, H.E.; McGeehan, J.M.; Sy, M.S.; Greenspan, N.S.; Kaplan, D.; Wang, G.X.; Parchi, P.; Hoover, E.A.; Kneale, G.; Telling, G.; Surewicz, W.; Kong, Q.; Guo, J.

2010-01-01

The epitope of the 3F4 antibody most commonly used in human prion disease diagnosis is believed to consist of residues Met-Lys-His-Met (MKHM) corresponding to human PrP-(109–112). This assumption is based mainly on the observation that 3F4 reacts with human and hamster PrP but not with PrP from

PLATELET-RICH PLASMA (PRP FOR THE TREATMENT OF PROBLEMATIC SKIN WOUNDS

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Tsvetan Sokolov

2016-12-01

Full Text Available OBJECTIVE: To show platelet-rich plasma (PRP application of problematic skin wounds and to evaluate the results from the treatment. MATERIAL AND METHODS: A total of 31 patients with problematic skin wounds had been treated at the clinic for a period of five years (from May 2010 to September 2015 with the following patient sex ratio: male patients– 13 and female patients– 18. Average age– 46,5 (22-82. Patients with Type 2 Diabetes– 10, with decubitus ulcers– 2, traumatic– 29, with infection– 12, acute– 15, chronic– 16. Based on a scheme developed by us, all cases were treated by administering platelet-rich plasma, derived by PRGF Endoret system. Follow-up period was within 4 – 6 months (4,5 on average. We used platelet rich plasma derived by PRGF Endoret system, applied on the wound bed on a weekly basis. RESULTS: The results have been evaluated based on the following functional scoring systems - Total wound score, Total anatomic score and Total score (20. The baseline values at the very beginning of the follow-up period were as follows: Total wound score – 10 p.; Total anatomic score – 8 p., Total score – 15 p. By the end of the treatment period the score was 0 p., which means excellent results, i.e. complete healing of the wounds. CONCLUSION: We believe that the application of PRP may become optimal therapy in the treatment of difficult to heal wounds around joints, bone, subject tendons, plantar surface of the foot, etc., as it opens new perspectives in the field of human tissue regeneration.

A call for a standard classification system for future biologic research: the rationale for new PRP nomenclature.

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Mautner, Kenneth; Malanga, Gerard A; Smith, Jay; Shiple, Brian; Ibrahim, Victor; Sampson, Steven; Bowen, Jay E

2015-04-01

Autologous cell therapies including platelet-rich plasma (PRP) and bone marrow concentrate (BMC) are increasingly popular options for soft tissue and joint-related diseases. Despite increased clinical application, conflicting research has been published regarding the efficacy of PRP, and few clinical publications pertaining to BMC are available. Preparations of PRP (and BMC) can vary in many areas, including platelet concentration, number of white blood cells, presence or absence of red blood cells, and activation status of the preparation. The potential effect of PRP characteristics on PRP efficacy is often not well understood by the treating clinician, and PRP characteristics, as well as the volume of PRP delivered, are unfortunately not included in the methods of many published research articles. It is essential to establish a standard reporting system for PRP that facilitates communication and the interpretation and synthesis of scientific investigations. Herein, the authors propose a new PRP classification system reflecting important PRP characteristics based on contemporary literature and recommend adoption of minimal standards for PRP reporting in scientific investigations. Widespread adoption of these recommendations will facilitate interpretation and comparison of clinical studies and promote scientifically based progress in the field of regenerative medicine. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Is PRP useful in alveolar cleft reconstruction? Platelet-rich plasma in secondary alveoloplasty.

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Luaces-Rey, Ramon; Arenaz-Búa, Jorge; Lopez-Cedrún-Cembranos, José-Luis; Herrero-Patiño, Susana; Sironvalle-Soliva, Sheyla; Iglesias-Candal, Emma; Pombo-Castro, María

2010-07-01

Cleft lip and palate is a congenital facial malformation with an established treatment protocol. Mixed dentition period is the best moment for correct maxillary bone defect with an alveoloplasty. The aim of this surgical procedure is to facilitate dental eruption, re-establish maxillary arch, close any oro-nasal communication, give support to nasal ala, and in some cases allow dental rehabilitation with osteointegrated implants. Twenty cleft patients who underwent secondary alveoloplasty were included. In 10 of them autogenous bone graft were used and in other 10 autogenous bone and platelet-rich plasma (PRP) obtained from autogenous blood. Bone formation was compared by digital orthopantomography made on immediate post-operatory and 3 and 6 months after the surgery. No significant differences were found between both therapeutic groups on bone regeneration. We do not find justified the use of PRP for alveoloplasty in cleft patients' treatment protocol.

Kartogenin with PRP promotes the formation of fibrocartilage zone in the tendon-bone interface.

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Zhou, Yiqin; Zhang, Jianying; Yang, Jinsong; Narava, Manoj; Zhao, Guangyi; Yuan, Ting; Wu, Haishan; Zheng, Nigel; Hogan, MaCalus V; Wang, James H-C

2017-12-01

Treatment of tendon-bone junction injuries is a challenge because tendon-bone interface often heals poorly and the fibrocartilage zone, which reduces stress concentration, at the interface is not formed. In this study, we used a compound called kartogenin (KGN) with platelet-rich plasma (PRP) to induce the formation of fibrocartilage zone in a rat tendon graft-bone tunnel model. The experimental rats received KGN-PRP or PRP injections in the tendon graft-bone tunnel interface. The control group received saline. After 4, 8 and 12 weeks, Safranin O staining of the tendon graft-bone tunnels revealed abundant proteoglycans in the KGN-PRP group indicating the formation of cartilage-like transition zone. Immunohistochemical and immuno-fluorescence staining revealed collagen types I (Col-I) and II (Col-II) in the newly formed fibrocartilage zone. Both fibrocartilage zone formation and maturation were healing time dependent. In contrast, the PRP and saline control groups had no cartilage-like tissues and minimal Col-I and Col-II staining. Some gaps were also present in the saline control group. Finally, pull-out strength in the KGN-PRP-treated group at 8 weeks was 1.4-fold higher than the PRP-treated group and 1.6-fold higher than the saline control group. These findings indicate that KGN, with PRP as a carrier, promotes the formation of fibrocartilage zone between the tendon graft and bone interface. Thus, KGN-PRP may be used as a convenient cell-free therapy in clinics to promote fibrocartilage zone formation in rotator calf repair and anterior cruciate ligament reconstruction, thereby enhancing the mechanical strength of the tendon-bone interface and hence the clinical outcome of these procedures. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting.

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Mohssen Hakimi

Full Text Available One possible alternative to the application of autologous bone grafts represents the use of autologous bone marrow concentrate (BMC. The purpose of our study was to evaluate the potency of autologous platelet-rich plasma (PRP in combination with BMC. In 32 mini-pigs a metaphyseal critical-size defect was surgically created at the proximal tibia. The animals were allocated to four treatment groups of eight animals each (1. BMC+CPG group, 2. BMC+CPG+PRP group, 3. autograft group, 4. CPG group. In the BMC+CPG group the defect was filled with autologous BMC in combination with calcium phosphate granules (CPG, whereas in the BMC+CPG+PRP group the defect was filled with the composite of autologous BMC, CPG and autologous PRP. In the autograft group the defect was filled with autologous cancellous graft, whereas in the CPG group the defect was filled with CPG solely. After 6 weeks radiological and histomorphometrical analysis showed significantly more new bone formation in the BMC+CPG+PRP group compared to the BMC+CPG group and the CPG group. There were no significant differences between the BMC+CPG+PRP group and the autograft group. In the PRP platelets were enriched significantly about 4.7-fold compared to native blood. In BMC the count of mononuclear cells increased significantly (3.5-fold compared to the bone marrow aspirate. This study demonstrates that the composite of BMC+CPG+PRP leads to a significantly higher bone regeneration of critical-size defects at the proximal tibia in mini-pigs than the use of BMC+CPG without PRP. Furthermore, within the limits of the present study the composite BMC+CPG+PRP represents a comparable alternative to autologous bone grafting.

Expressions of pathologic markers in PRP based chondrogenic differentiation of human adipose derived stem cells.

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Pakfar, Arezou; Irani, Shiva; Hanaee-Ahvaz, Hana

2017-02-01

Optimization of the differentiation medium through using autologous factors such as PRP is of great consideration, but due to the complex, variable and undefined composition of PRP on one hand and lack of control over the absolute regulatory mechanisms in in vitro conditions or disrupted and different mechanisms in diseased tissue microenvironments in in vivo conditions on the other hand, it is complicated and rather unpredictable to get the desired effects of PRP making it inevitable to monitor the possible pathologic or undesired differentiation pathways and therapeutic effects of PRP. Therefore, in this study the probable potential of PRP on inducing calcification, inflammation and angiogenesis in chondrogenically-differentiated cells was investigated. The expressions of chondrogenic, inflammatory, osteogenic and angiogenic markers from TGFβ or PRP-treated cells during chondrogenic differentiation of human adipose-derived stem cells (ADSCs) was evaluated. Expressions of Collagen II (Col II), Aggrecan, Sox9 and Runx2 were quantified using q-RT PCR. Expression of Col II and X was investigated by immunocytochemistry as well. Glycosaminoglycans (GAGs) production was also determined by GAG assay. Possible angiogenic/inflammatory potential was determined by quantitatively measuring the secreted VEGF, TNFα and phosphorylated VEGFR2 via ELISA. In addition, the calcification of the construct was monitored by measuring ALP activity and calcium deposition. Our data showed that PRP positively induced chondrogenesis; meanwhile the secretion of angiogenic and inflammatory markers was decreased. VEGFR2 phosphorylation and ALP activity had a decreasing trend, but tissue mineralization was enhanced upon treating with PRP. Although reduction in inflammatory/angiogenic potential of the chondrogenically differentiated constructs highlights the superior effectiveness of PRP in comparison to TGFβ for chondrogenic differentiation, yet further improvement of the PRP

Split face comparative study of microneedling with PRP versus microneedling with vitamin C in treating atrophic post acne scars

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Simran Chawla

2014-01-01

Full Text Available Introduction: Acne scars are largely preventable complications of acne. 95% of the scars occur over the face thus impacting the quality of life. Correction of scars is the priority for acne patients. Materials and Methods: Thirty patients with post acne atrophic facial scars attending the OPD during the period from April to October 2013 were offered four sittings of microneedling with PRP on one side and microneedling with vitamin C on other side of the face at an interval of 1 month. Results: Twenty-seven out of the total 30 patients completed the treatment schedule. Two patients were lost to follow up and one dropped out of the study due to severe PIH. Mean age of the patients was 27.5 years. Out of 30 patients, 23 achieved reduction in scarring by one or two grades. Excellent response was seen in five (18.5% patients with platelet-rich plasma (PRP as compared to two (7% patients who received treatment with vitamin C according to physician′s assessment. As far as up gradation by 1 score is considered, i.e., good response, it was similar in both cases. Vitamin C did not prove to be as efficacious as PRP since 10 (37% patients had poor response in vitamin C-treated area compared to only 6 (22.2% patients who underwent PRP therapy, but vitamin C proved to be efficacious in dealing with post inflammatory hyper-pigmentation secondary to acne. Patients were more satisfied with PRP as compared to vitamin C. The results were evaluated and statistical analysis was done using SPSS 16.0.2. Conclusions: Overall results were better with microneedling and PRP. Vitamin C combined with microneedling also showed improvement with respect to firmness and smoothness of skin; as well as post inflammatory hyper-pigmentation. Microneedling combined with PRP proved to be good in treating boxcar and rolling scars but had limited efficacy in dealing with ice pick scars.

Recombinant PrP and Its Contribution to Research on Transmissible Spongiform Encephalopathies.

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Charco, Jorge M; Eraña, Hasier; Venegas, Vanessa; García-Martínez, Sandra; López-Moreno, Rafael; González-Miranda, Ezequiel; Pérez-Castro, Miguel Ángel; Castilla, Joaquín

2017-12-14

The misfolding of the cellular prion protein (PrP C ) into the disease-associated isoform (PrP Sc ) and its accumulation as amyloid fibrils in the central nervous system is one of the central events in transmissible spongiform encephalopathies (TSEs). Due to the proteinaceous nature of the causal agent the molecular mechanisms of misfolding, interspecies transmission, neurotoxicity and strain phenomenon remain mostly ill-defined or unknown. Significant advances were made using in vivo and in cellula models, but the limitations of these, primarily due to their inherent complexity and the small amounts of PrP Sc that can be obtained, gave rise to the necessity of new model systems. The production of recombinant PrP using E. coli and subsequent induction of misfolding to the aberrant isoform using different techniques paved the way for the development of cell-free systems that complement the previous models. The generation of the first infectious recombinant prion proteins with identical properties of brain-derived PrP Sc increased the value of cell-free systems for research on TSEs. The versatility and ease of implementation of these models have made them invaluable for the study of the molecular mechanisms of prion formation and propagation, and have enabled improvements in diagnosis, high-throughput screening of putative anti-prion compounds and the design of novel therapeutic strategies. Here, we provide an overview of the resultant advances in the prion field due to the development of recombinant PrP and its use in cell-free systems.

Splicing Factor Prp8 Interacts With NES(AR) and Regulates Androgen Receptor in Prostate Cancer Cells.

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Wang, Dan; Nguyen, Minh M; Masoodi, Khalid Z; Singh, Prabhpreet; Jing, Yifeng; O'Malley, Katherine; Dar, Javid A; Dhir, Rajiv; Wang, Zhou

2015-12-01

Androgen receptor (AR) plays a pivotal role in the development of primary as well as advanced castration-resistant prostate cancer. Previous work in our lab identified a novel nuclear export signal (NES) (NES(AR)) in AR ligand-binding domain essential for AR nucleocytoplasmic trafficking. By characterizing the localization of green fluorescence protein (GFP)-tagged NES(AR), we designed and executed a yeast mutagenesis screen and isolated 7 yeast mutants that failed to display the NES(AR) export function. One of those mutants was identified as the splicing factor pre-mRNA processing factor 8 (Prp8). We further showed that Prp8 could regulate NES(AR) function using short hairpin RNA knockdown of Prp8 coupled with a rapamycin export assay in mammalian cells and knockdown of Prp8 could induce nuclear accumulation of GFP-tagged AR in PC3 cells. Prp8 expression was decreased in castration-resistant LuCaP35 xenograft tumors as compared with androgen-sensitive xenografts. Laser capture microdissection and quantitative PCR showed Prp8 mRNA levels were decreased in human prostate cancer specimens with high Gleason scores. In prostate cancer cells, coimmunoprecipitation and deletion mutagenesis revealed a physical interaction between Prp8 and AR mainly mediated by NES(AR). Luciferase assay with prostate specific antigen promoter-driven reporter demonstrated that Prp8 regulated AR transcription activity in prostate cancer cells. Interestingly, Prp8 knockdown also increased polyubiquitination of endogenous AR. This may be 1 possible mechanism by which it modulates AR activity. These results show that Prp8 is a novel AR cofactor that interacts with NES(AR) and regulates AR function in prostate cancer cells.

Characterization of barley Prp1 gene and its expression during seed development and under abiotic stress.

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Jiang, Qian-Tao; Liu, Tao; Ma, Jian; Wei, Yu-Ming; Lu, Zhen-Xiang; Lan, Xiu-Jin; Dai, Shou-Fen; Zheng, You-Liang

2011-10-01

The pre-mRNA processing (Prp1) gene encodes a spliceosomal protein. It was firstly identified in fission yeast and plays a regular role during spliceosome activation and cell cycle. Plant Prp1 genes have only been identified from rice, Sorghum and Arabidopsis thaliana. In this study, we reported the identification and isolation of a novel Prp1 gene from barley, and further explored its expressional pattern by using real-time quantitative RTPCR, promoter prediction and analysis of microarray data. The putative barley Prp1 protein has a similar primary structure features to those of other known Prp1 protein in this family. The results of amino acid comparison indicated that Prp1 protein of barley and other plant species has a highly conserved 30 termnal region while their 50 sequences greatly varied. The results of expressional analysis revealed that the expression level of barley Prp1 gene is always stable in different vegetative tissues, except it is up-regulated at the mid- and late stages of seed development or under the condition of cold stress. This kind of expressional pattern for barley Prp1 is also supported by our results of comparison of microarray data from barley, rice and Arabidopsis. For the molecular mechanism of its expressional pattern, we conclude that the expression of Prp1 gene may be up-regulated by the increase of pre-mRNAs and not be constitutive or ubiquitous.

CLINICAL RESULTS FROM THE TREATMENT OF CHRONIC SKIN WOUNDS WITH PLATELET RICH PLASMA (PRP

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Pencho Kossev

2015-12-01

Full Text Available PURPOSE: To show platelet rich plasma (PRP application of chronic skin wounds and to evaluate the results from the treatment. MATERIAL AND METHODS: A total of 14 patients with problematic skin wounds had been treated at the clinic for a period of five years (from May 2009 to December 2014 with the following patient sex ratio: male patients - 5 and female patients - 9. Average age - 48,5 (30-76. Patients with Type 2 Diabetes - 4, with decubitus ulcers - 6, traumatic - 8, with infection - 5. Based on a scheme developed by us, all cases were treated by administering platelet-rich plasma, derived by PRGF Endoret system. Follow-up period was within 4 - 6 months (4,5 on average. RESULTS: The results have been evaluated based on the following functional scoring systems - Total wound score, Total anatomic score and Total score (20. The baseline values at the very beginning of the follow-up period were as follows: Total wound score - 12 p.; Total anatomic score - 10 p., Total score - 17 p. By the end of the treatment period the score was 0 p., which means excellent results, i.e. complete healing of the wounds. CONCLUSION: We believe that the application of PRP may become optimal therapy in the treatment of difficult to heal wounds around joints, bone, subject tendons, plantar surface of the foot, etc., as it opens new perspectives in the field of human tissue regeneration.

Can platelet-rich plasma (PRP) improve bone healing? A comparison between the theory and experimental outcomes.

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Malhotra, Angad; Pelletier, Matthew H; Yu, Yan; Walsh, William R

2013-02-01

The increased concentration of platelets within platelet-rich plasma (PRP) provides a vehicle to deliver supra-physiologic concentrations of growth factors to an injury site, possibly accelerating or otherwise improving connective tissue regeneration. This potential benefit has led to the application of PRP in several applications; however, inconsistent results have limited widespread adoption in bone healing. This review provides a core understanding of the bone healing mechanisms, and corresponds this to the factors present in PRP. In addition, the current state of the art of PRP preparation, the key aspects that may influence its effectiveness, and treatment outcomes as they relate specifically to bone defect healing are presented. Although PRP does have a sound scientific basis, its use for bone healing appears only beneficial when used in combination with osteoconductive scaffolds; however, neither allograft nor autograft appear to be appropriate carriers. Aggressive processing techniques and very high concentrations of PRP may not improve healing outcomes. Moreover, many other variables exist in PRP preparation and use that influence its efficacy; the effect of these variables should be understood when considering PRP use. This review includes the essentials of what has been established, what is currently missing in the literature, and recommendations for future directions.

Mouse homologue of yeast Prp19 interacts with mouse SUG1, the regulatory subunit of 26S proteasome

International Nuclear Information System (INIS)

Sihn, Choong-Ryoul; Cho, Si Young; Lee, Jeong Ho; Lee, Tae Ryong; Kim, Sang Hoon

2007-01-01

Yeast Prp19 has been shown to involve in pre-mRNA splicing and DNA repair as well as being an ubiquitin ligase. Mammalian homologue of yeast Prp19 also plays on similar functional activities in cells. In the present study, we isolated mouse SUG1 (mSUG1) as binding partner of mouse Prp19 (mPrp19) by the yeast two-hybrid system. We confirmed the interaction of mPrp9 with mSUG1 by GST pull-down assay and co-immunoprecipitation assay. The N-terminus of mPrp19 including U-box domain was associated with the C-terminus of mSUG1. Although, mSUG1 is a regulatory subunit of 26S proteasome, mPrp19 was not degraded in the proteasome-dependent pathway. Interestingly, GFP-mPrp19 fusion protein was co-localized with mSUG1 protein in cytoplasm as the formation of the speckle-like structures in the presence of a proteasome inhibitor MG132. In addition, the activity of proteasome was increased in cells transfected with mPrp19. Taken together, these results suggest that mPrp19 involves the regulation of protein turnover and may transport its substrates to 26S proteasome through mSUG1 protein

Effects of platelet rich plasma (PRP) on human gingival fibroblast, osteoblast and periodontal ligament cell behaviour.

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Kobayashi, Eizaburo; Fujioka-Kobayashi, Masako; Sculean, Anton; Chappuis, Vivianne; Buser, Daniel; Schaller, Benoit; Dőri, Ferenc; Miron, Richard J

2017-06-02

The use of platelet rich plasma (PRP, GLO) has been used as an adjunct to various regenerative dental procedures. The aim of the present study was to characterize the influence of PRP on human gingival fibroblasts, periodontal ligament (PDL) cells and osteoblast cell behavior in vitro. Human gingival fibroblasts, PDL cells and osteoblasts were cultured with conditioned media from PRP and investigated for cell migration, proliferation and collagen1 (COL1) immunostaining. Furthermore, gingival fibroblasts were tested for genes encoding TGF-β, PDGF and COL1a whereas PDL cells and osteoblasts were additionally tested for alkaline phosphatase (ALP) activity, alizarin red staining and mRNA levels of osteoblast differentiation markers including Runx2, COL1a2, ALP and osteocalcin (OCN). It was first found that PRP significantly increased cell migration of all cells up to 4 fold. Furthermore, PRP increased cell proliferation at 3 and 5 days of gingival fibroblasts, and at 3 days for PDL cells, whereas no effect was observed on osteoblasts. Gingival fibroblasts cultured with PRP increased TGF-β, PDGF-B and COL1 mRNA levels at 7 days and further increased over 3-fold COL1 staining at 14 days. PDL cells cultured with PRP increased Runx2 mRNA levels but significantly down-regulated OCN mRNA levels at 3 days. No differences in COL1 staining or ALP staining were observed in PDL cells. Furthermore, PRP decreased mineralization of PDL cells at 14 days post seeding as assessed by alizarin red staining. In osteoblasts, PRP increased COL1 staining at 14 days, increased COL1 and ALP at 3 days, as well as increased ALP staining at 14 days. No significant differences were observed for alizarin red staining of osteoblasts following culture with PRP. The results demonstrate that PRP promoted gingival fibroblast migration, proliferation and mRNA expression of pro-wound healing molecules. While PRP induced PDL cells and osteoblast migration and proliferation, it tended to have

Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration.

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Albanese, Antonino; Licata, Maria E; Polizzi, Bianca; Campisi, Giuseppina

2013-06-13

Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed

Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration

Science.gov (United States)

2013-01-01

Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed

A comparison between platelet-rich plasma (PRP and hyaluronate acid on the healing of cartilage defects.

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Ji Liu

Full Text Available Platelet-rich plasma (PRP has offered great promise for the treatment of cartilage degradation, and has been proved to have positive effects on the restoration of cartilage lesions. But no comparative work has been done between PRP and hyaluronate acid (HA concerning their restoring effect on cartilage defect, especially by means of animal experiments and histologic assessments. The purpose of the study was to compare the therapeutic effects of P-PRP and HA on osteoarthritis in rabbit knees. Thirty rabbits were used to establish the animal models by creating a cartilage defect of 5 mm in diameter on the condyles of the femurs, and were randomly divided into three groups: the P-PRP group, HA group and the control group. Then each group was treated with P-PRP, HA or saline solution, respectively. Six and twelve weeks later the rabbits were sacrificed and the samples were collected. The platelet number, the concentrations of growth factors of P-PRP and whole blood, and the IL-1β concentration in the joint fluid were investigated, and the histological assessment of the cartilage were performed according to Mankin's scoring system. Micro-CT was also used to evaluate the restoration of subchondral bone. The platelet concentration in P-PRP is 6.8 fold of that in the whole blood. The IL-1β level in the P-PRP group was lower than in the HA group (p<0.01 and in the control group (p<0.01. The restoration of the defected cartilage as well as the subchondral bone was better in the P-PRP group than in the HA group or the control group (P<0.05. Our data showed that P-PRP is better than HA in promoting the restoration of the cartilage and alleviating the arthritis caused by cartilage damage.

DEPA classification: a proposal for standardising PRP use and a retrospective application of available devices.

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Magalon, J; Chateau, A L; Bertrand, B; Louis, M L; Silvestre, A; Giraudo, L; Veran, J; Sabatier, F

2016-01-01

Significant biological differences in platelet-rich plasma (PRP) preparations have been highlighted and could explain the large variability in the clinical benefit of PRP reported in the literature. The scientific community now recommends the use of classification for PRP injection; however, these classifications are focused on platelet and leucocyte concentrations. This presents the disadvantages of (1) not taking into account the final volume of the preparation; (2) omitting the presence of red blood cells in PRP and (3) not assessing the efficiency of production. On the basis of standards classically used in the Cell Therapy field, we propose the DEPA (Dose of injected platelets, Efficiency of production, Purity of the PRP, Activation of the PRP) classification to extend the characterisation of the injected PRP preparation. We retrospectively applied this classification on 20 PRP preparations for which biological characteristics were available in the literature. Dose of injected platelets varies from 0.21 to 5.43 billion, corresponding to a 25-fold increase. Only a Magellan device was able to obtain an A score for this parameter. Assessments of the efficiency of production reveal that no device is able to recover more than 90% of platelets from the blood. Purity of the preparation reveals that a majority of the preparations are contaminated by red blood cells as only three devices reach an A score for this parameter, corresponding to a percentage of platelets compared with red blood cells and leucocytes over 90%. These findings should provide significant help to clinicians in selecting a system that meets their specific needs for a given indication.

Transmission Properties of Human PrP 102L Prions Challenge the Relevance of Mouse Models of GSS.

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Asante, Emmanuel A; Grimshaw, Andrew; Smidak, Michelle; Jakubcova, Tatiana; Tomlinson, Andrew; Jeelani, Asif; Hamdan, Shyma; Powell, Caroline; Joiner, Susan; Linehan, Jacqueline M; Brandner, Sebastian; Wadsworth, Jonathan D F; Collinge, John

2015-07-01

Inherited prion disease (IPD) is caused by autosomal-dominant pathogenic mutations in the human prion protein (PrP) gene (PRNP). A proline to leucine substitution at PrP residue 102 (P102L) is classically associated with Gerstmann-Sträussler-Scheinker (GSS) disease but shows marked clinical and neuropathological variability within kindreds that may be caused by variable propagation of distinct prion strains generated from either PrP 102L or wild type PrP. To-date the transmission properties of prions propagated in P102L patients remain ill-defined. Multiple mouse models of GSS have focused on mutating the corresponding residue of murine PrP (P101L), however murine PrP 101L, a novel PrP primary structure, may not have the repertoire of pathogenic prion conformations necessary to accurately model the human disease. Here we describe the transmission properties of prions generated in human PrP 102L expressing transgenic mice that were generated after primary challenge with ex vivo human GSS P102L or classical CJD prions. We show that distinct strains of prions were generated in these mice dependent upon source of the inoculum (either GSS P102L or CJD brain) and have designated these GSS-102L and CJD-102L prions, respectively. GSS-102L prions have transmission properties distinct from all prion strains seen in sporadic and acquired human prion disease. Significantly, GSS-102L prions appear incapable of transmitting disease to conventional mice expressing wild type mouse PrP, which contrasts strikingly with the reported transmission properties of prions generated in GSS P102L-challenged mice expressing mouse PrP 101L. We conclude that future transgenic modeling of IPDs should focus exclusively on expression of mutant human PrP, as other approaches may generate novel experimental prion strains that are unrelated to human disease.

Experimental conditions and monitoring items of the prototype repository project (PRP). Research document

International Nuclear Information System (INIS)

Sugita, Yutaka; Ito, Akira; Kawakami, Susumu

2003-03-01

Various experiments are ongoing in the underground research facility 'the Hard Rock Laboratory (HRL)' of SKB in Sweden for the geological disposal of the high-level radioactive waste. International joint project Prototype Repository Project (PRP) is one of the experiments in the HRL which has some engineered barrier systems and to study the coupled behavior happening in and around the engineered barrier system. JNC has joined this international joint project PRP to obtain the information of the coupled behavior on such systematic engineered barrier system and to apply the JNC's coupled THMC analytical code to the prediction and back analysis of the PRP. The analytical code will be verified through these analyses in this project. JNC can apply the verified analytical code to assess the coupled behavior in Japan. This report summarizes the experimental conditions and monitoring items of the PRP. (author)

Comparison of the effect of activated or non-activated PRP in various concentrations on osteoblast and fibroblast cell line proliferation.

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Vahabi, Surena; Yadegari, Zahra; Mohammad-Rahimi, Hossein

2017-09-01

Platelet-rich plasma (PRP) contains growth factors which positively affect cell proliferation, cell differentiation, chemotaxis and intracellular matrix synthesis. All these processes are involved in wound healing and tissue regeneration; thus, PRP as a source of growth factors can be used in periodontal regenerative therapies. The purpose of the present study was to assess the effect of various concentrations of activated and non-activated PRP on proliferation of osteoblasts and fibroblasts in vitro. PRP was obtained from three healthy volunteers. 75, 50, 25, and 10% concentrations of f PRP were prepared by dilution in Dulbecco's modified Eagle's medium. In activated PRP groups, PRP concentrations were activated by adding calcium gluconate. Human gingival fibroblast (HGF) cell line and MG-63 (osteosarcoma) human osteoblast-like cell line were used in the study. The MTT proliferation assay was used to assess the effect of different types of PRP concentrates on proliferation of HGF and MG-63 cells, in 24, 48 and 72 h. After 24, 48, and 72 h, the proliferation rate of both cell lines was higher in the positive control group, except in 72 h in HGF cell lines, that 10% non-activated PRP group and 10 and 25% activated PRP groups has higher proliferation rate than the positive control group, which it was not significant. Proliferation rate in cells with 10% activated PRP was highest among samples containing PRP. The current study failed to show the significant effect of activated or non-activated PRP on proliferation of HGFs or MG-63 osteoblast-like cells. However, our results showed that activated PRP had a greater effect than non-activated PRP.

Early Delivery of Misfolded PrP from ER to Lysosomes by Autophagy

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Cortes, Constanza J.; Qin, Kefeng; Norstrom, Eric M.; Green, William N.; Bindokas, Vytautas P.; Mastrianni, James A.

2013-01-01

Prion diseases are linked to the accumulation of a misfolded isoform (PrPSc) of prion protein (PrP). Evidence suggests that lysosomes are degradation endpoints and sites of the accumulation of PrPSc. We questioned whether lysosomes participate in the early quality control of newly generated misfolded PrP. We found PrP carrying the disease-associated T182A mutation (Mut-PrP) was delivered to lysosomes in a Golgi-independent manner. Time-lapse live cell imaging revealed early formation and uptake of GFP-tagged Mut-PrP aggregates into LysoTracker labeled vesicles. Compared with Wt-PrP, Mut-PrP expression was associated with an elevation in several markers of the autophagy-lysosomal pathway, and it extensively colocalized with the autophagosome-specific marker, LC3B. In autophagy deficient (ATG5−/−) mouse embryonic fibroblasts, or in normal cells treated with the autophagy-inhibitor 3-MA, Mut-PrP colocalization with lysosomes was reduced to a similar extent. Additionally, 3-MA selectively impaired the degradation of insoluble Mut-PrP, resulting in an increase in protease-resistant PrP, whereas the induction of autophagy by rapamycin reduced it. These findings suggest that autophagy might function as a quality control mechanism to limit the accumulation of misfolded PrP that normally leads to the generation of PrPSc. PMID:24454378

Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study.

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Tuakli-Wosornu, Yetsa A; Terry, Alon; Boachie-Adjei, Kwadwo; Harrison, Julian R; Gribbin, Caitlin K; LaSalle, Elizabeth E; Nguyen, Joseph T; Solomon, Jennifer L; Lutz, Gregory E

2016-01-01

To determine whether single injections of autologous platelet-rich plasma (PRP) into symptomatic degenerative intervertebral disks will improve participant-reported pain and function. Prospective, double-blind, randomized controlled study. Outpatient physiatric spine practice. Adults with chronic (≥6 months), moderate-to-severe lumbar diskogenic pain that was unresponsive to conservative treatment. Participants were randomized to receive intradiskal PRP or contrast agent after provocative diskography. Data on pain, physical function, and participant satisfaction were collected at 1 week, 4 weeks, 8 weeks, 6 months, and 1 year. Participants in the control group who did not improve at 8 weeks were offered the option to receive PRP and subsequently followed. Functional Rating Index (FRI), Numeric Rating Scale (NRS) for pain, the pain and physical function domains of the 36-item Short Form Health Survey, and the modified North American Spine Society (NASS) Outcome Questionnaire were used. Forty-seven participants (29 in the treatment group, 18 in the control group) were analyzed by an independent observer with a 92% follow-up rate. Over 8 weeks of follow-up, there were statistically significant improvements in participants who received intradiskal PRP with regards to pain (NRS Best Pain) (P = .02), function (FRI) (P = .03), and patient satisfaction (NASS Outcome Questionnaire) (P = .01) compared with controls. No adverse events of disk space infection, neurologic injury, or progressive herniation were reported following the injection of PRP. Participants who received intradiskal PRP showed significant improvements in FRI, NRS Best Pain, and NASS patient satisfaction scores over 8 weeks compared with controls. Those who received PRP maintained significant improvements in FRI scores through at least 1 year of follow-up. Although these results are promising, further studies are needed to define the subset of participants most likely to respond to biologic intradiskal

Effect of intralesional platelet-rich plasma (PRP) treatment on clinical and ultrasonographic parameters in equine naturally occurring superficial digital flexor tendinopathies - a randomized prospective controlled clinical trial.

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Geburek, Florian; Gaus, Moritz; van Schie, Hans T M; Rohn, Karl; Stadler, Peter M

2016-09-07

Regenerative and anti-inflammatory effects on tendinopathies have been attributed to blood-derived biologicals. To date the evidence for the efficacy of autologous platelet-rich plasma (PRP) treatment of naturally occurring equine tendinopathies is limited. The purpose of this placebo-controlled clinical trial was to describe the effect of a single treatment of equine superficial digital flexor tendon (SDFT) disease with PRP on clinical and ultrasonographic parameters. Twenty horses with naturally occurring tendinopathies of forelimb SDFTs were randomly assigned to the PRP-treated group (n = 10) or control group (n = 10) after clinical and ultrasonographic examination. The SDFTs received an intralesional treatment with autologous PRP or were injected with saline, respectively (day 0). All horses participated in a standardized exercise programme and were re-examined clinically, with B-mode ultrasonography (5 times at regular intervals) and ultrasound tissue characterization (week 12 and 24 after treatment) until week 24. Long-term performance was estimated via telephone inquiry. Compared to day 0, lameness decreased significantly by week 8 after treatment with PRP and by week 12 in the control group. Ultrasonographically there was no difference in the summarized cross sectional area between the groups at any time point. Ultrasound tissue characterization showed that echo types representing disorganized matrix decreased significantly throughout the observation period in the PRP-treated group. Echo type II, representing discontinuous fascicles, not yet aligned into lines of stress was significantly higher 24 weeks after PRP treatment. Eighty percent of the PRP treated horses reached their previous or a higher level of performance after 12 months compared to 50 % in the CG. After 24 months these proportions were 60 % and 50 %, respectively. A single intralesional treatment with PRP up to 8 weeks after onset of clinical signs of tendinopathy contributes

The role of PRP and adipose tissue-derived keratinocytes on burn wound healing in diabetic rats.

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Hosseini Mansoub, Navid; Gürdal, Mehmet; Karadadaş, Elif; Kabadayi, Hilal; Vatansever, Seda; Ercan, Gulinnaz

2018-01-01

Introduction: Diabetic burn wounds and ulcers are significant complications of diabetic patients. The aim of this study is to investigate the use of platelet rich-plasma (PRP) and/or keratinocyte-like cells (KLCs) in diabetic thermal wound rat model and to evaluate EGF, FGF-2, TGF-β1, COL1α2, MCP-1 and VEGF-α as wound healing markers at gene expression level. Method: In this study, we used adipose tissue as the source of mesenchymal stem cells (MSCs) and differentiated MSCs into KLCs. KLCs were characterized and transferred to the burn areas on the dorsum of streptozotocine (STZ)-induced diabetic rats. We prepared PRP from rat blood and evaluated its effect alone or in combination with KLCs. On 3 rd , 7 th , 10 th and 14 th days after treatment, wound areas were measured and biopsy samples were excised from the wound areas of the KLCs and/or PRP-treated and untreated diabetic rats to analyze gene expression levels of wound healing markers by qPCR. Results: We observed that, wound contraction started earlier in the PRP and/or KLCs-treated groups in comparison to the control group. However, PRP and KLCs when applied in combination showed additive affect in wound healing. In all groups treated with KLCs and/or PRP, the gene expression levels of evaluated growth factors and COL1α2 increased, while MCP-1 levels decreased when compared to the untreated diabetic rats. In addition, the most prominent difference in qPCR results belongs to combined PRP and KLCs-treated group. Conclusion: We demonstrated that applying PRP and KLCs in combination has a greater potential for treatment of diabetic burn wounds.

Effectiveness of PRP Injection in Reducing Recovery Time of Acute Hamstring Injury: A Critically Appraised Topic.

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Manduca, Mary Lynn; Straub, Stephen J

2017-07-17

Clinical Scenario Hamstring strains are common athletic injuries, with a high recurrence rate (34%). 2 Recently, platelet-rich-plasma (PRP) injections have gained popularity as a potential treatment option to accelerate healing of hamstring injury. 3 Focused Clinical Question Does the combination of PRP injection and rehabilitation decrease recovery time of acute hamstring injury as compared to rehabilitation alone in collegiate athletes? Summary of Key Findings A literature search resulted in three randomized controlled trials (RCT). One study showed benefits in various outcome measures with PRP, compared to rehabilitation alone, while two showed no benefits. One study reported improved pain, ultrasonography regenerative indications, and recovery time with PRP injection following acute hamstring injury 1 , however, larger studies have shown no benefits. 7-9 The literature demonstrates conflicting evidence regarding benefits of PRP injections in hamstring injuries. Clinical Bottom Line At this time, PRP injections cannot be recommended as having value for hamstring injuries, compared to rehabilitation alone. Strength of Recommendation Due to inconsistent or limited quality patient-oriented evidence in existing literature, the strength of this recommendation is grade B, based on the Strength of Recommendation Taxonomy (SORT). 7 .

Interaction between Shadoo and PrP Affects the PrP-Folding Pathway.

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Ciric, Danica; Richard, Charles-Adrien; Moudjou, Mohammed; Chapuis, Jérôme; Sibille, Pierre; Daude, Nathalie; Westaway, David; Adrover, Miguel; Béringue, Vincent; Martin, Davy; Rezaei, Human

2015-06-01

Prion diseases are characterized by conformational changes of a cellular prion protein (PrP(C)) into a β-sheet-enriched and aggregated conformer (PrP(Sc)). Shadoo (Sho), a member of the prion protein family, is expressed in the central nervous system (CNS) and is highly conserved among vertebrates. On the basis of histoanatomical colocalization and sequence similarities, it is suspected that Sho and PrP may be functionally related. The downregulation of Sho expression during prion pathology and the direct interaction between Sho and PrP, as revealed by two-hybrid analysis, suggest a relationship between Sho and prion replication. Using biochemical and biophysical approaches, we demonstrate that Sho forms a 1:1 complex with full-length PrP with a dissociation constant in the micromolar range, and this interaction consequently modifies the PrP-folding pathway. Using a truncated PrP that mimics the C-terminal C1 fragment, an allosteric binding behavior with a Hill number of 4 was observed, suggesting that at least a tetramerization state occurs. A cell-based prion titration assay performed with different concentrations of Sho revealed an increase in the PrP(Sc) conversion rate in the presence of Sho. Collectively, our observations suggest that Sho can affect the prion replication process by (i) acting as a holdase and (ii) interfering with the dominant-negative inhibitor effect of the C1 fragment. Since the inception of the prion theory, the search for a cofactor involved in the conversion process has been an active field of research. Although the PrP interactome presents a broad landscape, candidates corresponding to specific criteria for cofactors are currently missing. Here, we describe for the first time that Sho can affect PrP structural dynamics and therefore increase the prion conversion rate. A biochemical characterization of Sho-PrP indicates that Sho acts as an ATP-independent holdase. Copyright © 2015, American Society for Microbiology. All Rights

Polymorphisms at Amino Acid Residues 141 and 154 Influence Conformational Variation in Ovine PrP

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Yang, Sujeong; Thackray, Alana M.; Hopkins, Lee; Monie, Tom P.; Burke, David F.; Bujdoso, Raymond

2014-01-01

Polymorphisms in ovine PrP at amino acid residues 141 and 154 are associated with susceptibility to ovine prion disease: Leu141Arg154 with classical scrapie and Phe141Arg154 and Leu141His154 with atypical scrapie. Classical scrapie is naturally transmissible between sheep, whereas this may not be the case with atypical scrapie. Critical amino acid residues will determine the range or stability of structural changes within the ovine prion protein or its functional interaction with potential cofactors, during conversion of PrPC to PrPSc in these different forms of scrapie disease. Here we computationally identified that regions of ovine PrP, including those near amino acid residues 141 and 154, displayed more conservation than expected based on local structural environment. Molecular dynamics simulations showed these conserved regions of ovine PrP displayed genotypic differences in conformational repertoire and amino acid side-chain interactions. Significantly, Leu141Arg154 PrP adopted an extended beta sheet arrangement in the N-terminal palindromic region more frequently than the Phe141Arg154 and Leu141His154 variants. We supported these computational observations experimentally using circular dichroism spectroscopy and immunobiochemical studies on ovine recombinant PrP. Collectively, our observations show amino acid residues 141 and 154 influence secondary structure and conformational change in ovine PrP that may correlate with different forms of scrapie. PMID:25126555

The influence of using anticoagulants (EDTA and citrate acid 3.8% toward the quantity of Platelet Rich Plasma (PRP

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Lilies Anggarwati Astuti

2016-06-01

Full Text Available Platelet Rich Plasma (PRP is a blood concentrate that has a thrombocytes concentration several time higher than normal concentration of thrombocytes in normal human blood. PRP is a promising alternative to surgery with a safe and natural healing. The standard protocol for PRP preparation must be determined to get the right quantity and quality of the matrix of fibrin, leukocytes, platelets and growth factors. It could not be separated from the number of PRP produced. The use of PRP in the success of periodontal treatment would not be separated from methods to obtain it. To detect the influence of using anticoagulants (EDTA and citrate acid 3.8% toward the quantity of PRP. There are 41 subjects studied by taking 21 ml of venous blood in each of the seven tubes. Centrifugation performed twice with different speed, duration, use of anticoagulants then analyzed. This quantity between the two groups differed significantly between the PRP in EDTA group is higher 322.2 ml rather than citrate acid 3.8% group, then control group is higher 329.5 ml rather than citrate acid 3.8% group, while there is no difference between EDTA and control group. There is effect of the use of anticoagulants EDTA compared with citrate acid 3.8% in the quantity of PRP, and there was no effect using citrate acid 3.8% as anticoagulants in quantity of PRP.

Effect of platelet-rich plasma (PRP) concentration on proliferation, neurotrophic function and migration of Schwann cells in vitro.

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Zheng, Canbin; Zhu, Qingtang; Liu, Xiaolin; Huang, Xijun; He, Caifeng; Jiang, Li; Quan, Daping; Zhou, Xiang; Zhu, Zhaowei

2016-05-01

Platelet-rich plasma (PRP) contains various growth factors and appears to have the potential to promote peripheral nerve regeneration, but evidence is lacking regarding its biological effect on Schwann cells (SCs). The present study was designed to investigate the effect of PRP concentration on SCs in order to determine the plausibility of using this plasma-derived therapy for peripheral nerve injury. PRP was obtained from rats by double-step centrifugation and was characterized by determining platelet numbers and growth factor concentrations. Primary cultures of rat SCs were exposed to various concentrations of PRP (40%, 20%, 10%, 5% and 2.5%). Cell proliferation assays and flow cytometry were performed to study to assess SC proliferation. Quantitative real-time PCR and ELISA analysis were performed to determine the ability of PRP to induce SCs to produce nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). Microchemotaxis assay was used to analyse the cell migration capacity. The results obtained indicated that the platelet concentration and growth factors in our PRP preparations were significantly higher than in whole blood. Cell culture experiments showed that 2.5-20% PRP significantly stimulated SC proliferation and migration compared to untreated controls in a dose-dependent manner. In addition, the expression and secretion of NGF and GDNF were significantly increased. However, the above effects of SCs were suppressed by high PRP concentrations (40%). In conclusion, the appropriate concentration of PRP had the potency to stimulate cell proliferation, induced the synthesis of neurotrophic factors and significantly increased migration of SCs dose-dependently. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

Effect of Use of Platelet-Rich Plasma (PRP) in Skin with Intrinsic Aging Process.

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Charles-de-Sá, Luiz; Gontijo-de-Amorim, Natale Ferreira; Takiya, Christina Maeda; Borojevic, Radovan; Benati, Donatella; Bernardi, Paolo; Sbarbati, Andrea; Rigotti, Gino

2018-02-15

In previous papers, we demonstrated that the treatment of human photoaged skin with stromal-vascular fraction-enriched fat or expanded adipose-derived stem cells showed a decrease of elastosis and the appearance of new oxytalan elastic fibers in dermis and an increase in the vascular network. The utilization of fat plus platelet-rich plasma (PRP) led to an increase in the vascular permeability and reactivity of the nervous component. The purpose of this study was to analyze the histologic and ultrastructural changes of human skin after the injection of only PRP in the retroauricular area that was not exposed to sun and did not present the photoaging process, in comparison with our previous results. This study was performed in 13 patients who were candidates for facelift and whose ages ranged between 45 and 65 years. The PRP injection was performed in the mastoidea area. Fragments of skin were removed before and 3 months after treatment and analyzed by optical and electron microscopy. After the injection of PRP, we observed an increase of reticular dermis thickness because of the deposition of elastic fibers and collagen, with a fibrotic aspect. A modified pattern of adipose tissue was also found at the dermohypodermal junction. Significative regenerative aspects were not found at histologic and ultrastructural analysis. The presence of foci of moderate inflammation and microangiopathy were observed. Treatment with PRP increased reticular dermis thickness with a fibrotic aspect. In the long term, the presence of inflammation and microangiopathy caused by PRP injection could lead to trophic alteration of the skin and the precocious aging process. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

Distribution, recovery and concentration of platelets and leukocytes in L-PRP prepared by centrifugation.

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de Melo, Bruna Alice Gomes; Martins Shimojo, Andréa Arruda; Marcelino Perez, Amanda Gomes; Duarte Lana, José Fabio Santos; Andrade Santana, Maria Helena

2018-01-01

Platelet-rich plasma (PRP) is an autologous product prepared from whole blood (WB) that is widely used in regenerative medicine. In clinical practice, discontinuous centrifugation is used for both hand- and machine-prepared PRP. However, separation of WB fractions via centrifugation is a complex process, and the lack of clear mechanisms limits the understanding and evaluation of PRP preparation methods This paper focuses on the distribution, recovery and concentration factor of platelets and leukocytes in L-PRP (leukocyte and platelet-rich plasma) to define a concentration pattern for these blood components due to centrifugation conditions. WB collected from three healthy donors was centrifuged for 10min at 50-800 xg in a first step and then at 400 xg in a second step. The results from the first centrifugation step showed most platelets to be distributed in the upper layer (UL) and the buffy coat (BC), with approximately 14.5±5.2% retained in the bottom layer (BL). Most leukocytes were present in the BL. The greatest platelet recoveries from L-PRP were obtained at up to 150 xg (88.5±16.9%). The cumulative concentration factors with respect to the WB from the second centrifugation step were 6 and 1.2 for platelets and leukocytes, respectively. Thus, the concentration patterns delineated three centrifugation ranges with platelet/leukocyte ratios of 205±18, 325±15 and 107±4 and lymphocyte/granulocyte ratios of 1.54±0.74, 0.90±0.08 and 0.42±0.07. These findings contribute to a scientifically based standardization of L-PRP preparations. Copyright © 2017 Elsevier B.V. All rights reserved.

PrP P102L and Nearby Lysine Mutations Promote Spontaneous In Vitro Formation of Transmissible Prions.

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Kraus, Allison; Raymond, Gregory J; Race, Brent; Campbell, Katrina J; Hughson, Andrew G; Anson, Kelsie J; Raymond, Lynne D; Caughey, Byron

2017-11-01

Accumulation of fibrillar protein aggregates is a hallmark of many diseases. While numerous proteins form fibrils by prion-like seeded polymerization in vitro , only some are transmissible and pathogenic in vivo To probe the structural features that confer transmissibility to prion protein (PrP) fibrils, we have analyzed synthetic PrP amyloids with or without the human prion disease-associated P102L mutation. The formation of infectious prions from PrP molecules in vitro has required cofactors and/or unphysiological denaturing conditions. Here, we demonstrate that, under physiologically compatible conditions without cofactors, the P102L mutation in recombinant hamster PrP promoted prion formation when seeded by minute amounts of scrapie prions in vitro Surprisingly, combination of the P102L mutation with charge-neutralizing substitutions of four nearby lysines promoted spontaneous prion formation. When inoculated into hamsters, both of these types of synthetic prions initiated substantial accumulation of prion seeding activity and protease-resistant PrP without transmissible spongiform encephalopathy (TSE) clinical signs or notable glial activation. Our evidence suggests that PrP's centrally located proline and lysine residues act as conformational switches in the in vitro formation of transmissible PrP amyloids. IMPORTANCE Many diseases involve the damaging accumulation of specific misfolded proteins in thread-like aggregates. These threads (fibrils) are capable of growing on the ends by seeding the refolding and incorporation of the normal form of the given protein. In many cases such aggregates can be infectious and propagate like prions when transmitted from one individual host to another. Some transmitted aggregates can cause fatal disease, as with human iatrogenic prion diseases, while other aggregates appear to be relatively innocuous. The factors that distinguish infectious and pathogenic protein aggregates from more innocuous ones are poorly understood

Na+/K+-ATPase is present in scrapie-associated fibrils, modulates PrP misfolding in vitro and links PrP function and dysfunction.

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James F Graham

Full Text Available Transmissible spongiform encephalopathies are characterised by widespread deposition of fibrillar and/or plaque-like forms of the prion protein. These aggregated forms are produced by misfolding of the normal prion protein, PrP(C, to the disease-associated form, PrP(Sc, through mechanisms that remain elusive but which require either direct or indirect interaction between PrP(C and PrP(Sc isoforms. A wealth of evidence implicates other non-PrP molecules as active participants in the misfolding process, to catalyse and direct the conformational conversion of PrP(C or to provide a scaffold ensuring correct alignment of PrP(C and PrP(Sc during conversion. Such molecules may be specific to different scrapie strains to facilitate differential prion protein misfolding. Since molecular cofactors may become integrated into the growing protein fibril during prion conversion, we have investigated the proteins contained in prion disease-specific deposits by shotgun proteomics of scrapie-associated fibrils (SAF from mice infected with 3 different strains of mouse-passaged scrapie. Concomitant use of negative control preparations allowed us to identify and discount proteins that are enriched non-specifically by the SAF isolation protocol. We found several proteins that co-purified specifically with SAF from infected brains but none of these were reproducibly and demonstrably specific for particular scrapie strains. The α-chain of Na(+/K(+-ATPase was common to SAF from all 3 strains and we tested the ability of this protein to modulate in vitro misfolding of recombinant PrP. Na(+/K(+-ATPase enhanced the efficiency of disease-specific conversion of recombinant PrP suggesting that it may act as a molecular cofactor. Consistent with previous results, the same protein inhibited fibrillisation kinetics of recombinant PrP. Since functional interactions between PrP(C and Na(+/K(+-ATPase have previously been reported in astrocytes, our data highlight this molecule as

Tratamiento de quemaduras mediante plasma rico en plaquetas (PRP: parte I

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G. Rossani

2014-06-01

Full Text Available El objetivo del presente trabajo es determinar la eficacia clínica del plasma rico en plaquetas (PRP en las quemaduras de segundo grado. Estudiamos el tiempo requerido en la reepitelización del tejido dañado, la estancia hospitalaria asociada a la curación de las lesiones y la satisfacción del paciente. Realizamos un estudio prospectivo, observacional y longitudinal, en una muestra de 115 pacientes con quemaduras de segundo grado según la clasificación de Converse-Smith. Las lesiones fueron de menos de 48 horas de evolución, en diferentes zonas de cara y cuerpo. A todos los pacientes se les aplicó de forma ambulatoria PRP por goteo, completándose el tratamiento con la aplicación de gasas parafinadas. El estudio se realizó entre marzo de 2011 y agosto de 2013. Las quemaduras que evolucionaron mejor y de forma más rápida fueron las de cara, seguidas por las de abdomen y, por último, las de extremidades inferiores. En todas, el tiempo de epitelización fue un 30 % inferior que en quemaduras de similar extensión, profundidad y localización, en pacientes anteriormente tratados sin PRP. Los pacientes fueron atendidos ambulatoriamente cuando las lesiones lo permitieron, y si presentaban lesiones más extensas fueron hospitalizados. El tiempo de internamiento en estos casos se redujo como promedio 18 días con respecto al grupo no tratado con PRP. El tiempo de reepitelización, estancia hospitalaria y la satisfacción de los pacientes, alcanzaron significación estadística p< 0,05. En conclusión, creemos que el uso de PRP acorta el tiempo de recuperación en quemaduras de segundo grado, reduce el tiempo de hospitalización y conlleva un alto grado de satisfacción de los pacientes por los resultados obtenidos.

Protein misfolding cyclic amplification induces the conversion of recombinant prion protein to PrP oligomers causing neuronal apoptosis.

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Yuan, Zhen; Yang, Lifeng; Chen, Baian; Zhu, Ting; Hassan, Mohammad Farooque; Yin, Xiaomin; Zhou, Xiangmei; Zhao, Deming

2015-06-01

The formation of neurotoxic prion protein (PrP) oligomers is thought to be a key step in the development of prion diseases. Recently, it was determined that the sonication and shaking of recombinant PrP can convert PrP monomers into β-state oligomers. Herein, we demonstrate that β-state oligomeric PrP can be generated through protein misfolding cyclic amplification from recombinant full-length hamster, human, rabbit, and mutated rabbit PrP, and that these oligomers can be used for subsequent research into the mechanisms of PrP-induced neurotoxicity. We have characterized protein misfolding cyclic amplification-induced monomer-to-oligomer conversion of PrP from three species using western blotting, circular dichroism, size-exclusion chromatography, and resistance to proteinase K (PK) digestion. We have further shown that all of the resulting β-oligomers are toxic to primary mouse cortical neurons independent of the presence of PrP(C) in the neurons, whereas the corresponding monomeric PrP were not toxic. In addition, we found that this toxicity is the result of oligomer-induced apoptosis via regulation of Bcl-2, Bax, and caspase-3 in both wild-type and PrP(-/-) cortical neurons. It is our hope that these results may contribute to our understanding of prion transformation within the brain. We found that β-state oligomeric PrPs can be generated through protein misfolding cyclic amplification (PMCA) from recombinant full-length hamster, human, rabbit, and mutated rabbit PrP. β-oligomers are toxic to primary mouse cortical neurons independent of the presence of PrP(C) in the neurons, while the corresponding monomeric PrPs were not toxic. This toxicity is the result of oligomers-induced apoptosis via regulation of Bcl-2, Bax, and caspase-3. These results may contribute to our understanding of prion transformation within the brain. © 2015 International Society for Neurochemistry.

In vitro study of the role of thrombin in platelet rich plasma (PRP) preparation: utility for gel formation and impact in growth factors release.

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Huber, Stephany Cares; Cunha Júnior, José Luiz Rosenberis; Montalvão, Silmara; da Silva, Letícia Queiroz; Paffaro, Aline Urban; da Silva, Francesca Aparecida Ramos; Rodrigues, Bruno Lima; Lana, José Fabio Santos Duarte; Annichino-Bizzacchi, Joyce Maria

2016-01-01

The use of PRP has been studied for different fields, with promising results in regenerative medicine. Until now, there is no study in the literature evaluating thrombin levels in serum, used as autologous thrombin preparation. Therefore, in the present study we evaluated the role played by different thrombin concentrations in PRP and the impact in the release of growth factors. Also, different activators for PRP gel formation were evaluated. Thrombin levels were measured in different autologous preparations: serum, L-PRP (PRP rich in leukocytes) and T-PRP (thrombin produced through PRP added calcium gluconate). L-PRP was prepared according to the literature, with platelets and leukocytes being quantified. The effect of autologous thrombin associated or not with calcium in PRP gel was determined by measuring the time of gel formation. The relationship between thrombin concentration and release of growth factors was determined by growth factors (PDGF-AA, VEGF and EGF) multiplex analysis. A similar concentration of thrombin was observed in serum, L-PRP and T-PRP (8.13 nM, 8.63 nM and 7.56 nM, respectively) with a high variation between individuals (CV%: 35.07, 43 and 58.42, respectively). T-PRP and serum with calcium chloride showed similar results in time to promote gel formation. The increase of thrombin concentrations (2.66, 8 and 24 nM) did not promote an increase in growth factor release. The technique of using serum as a thrombin source proved to be the most efficient and reproducible for promoting PRP gel formation, with some advantages when compared to other activation methods, as this technique is easier and quicker with no need of consuming part of PRP. Noteworthy, PRP activation using different thrombin concentrations did not promote a higher release of growth factors, appearing not to be necessary when PRP is used as a suspension.

Truncated forms of the prion protein PrP demonstrate the need for complexity in prion structure

Energy Technology Data Exchange (ETDEWEB)

Wan, William; Stöhr, Jan; Kendall, Amy; Stubbs, Gerald

2015-09-01

Self-propagation of aberrant protein folds is the defining characteristic of prions. Knowing the structural basis of self-propagation is essential to understanding prions and their related diseases. Prion rods are amyloid fibrils, but not all amyloids are prions. Prions have been remarkably intractable to structural studies, so many investigators have preferred to work with peptide fragments, particularly in the case of the mammalian prion protein PrP. We compared the structures of a number of fragments of PrP by X-ray fiber diffraction, and found that although all of the peptides adopted amyloid conformations, only the larger fragments adopted conformations that modeled the complexity of self-propagating prions, and even these fragments did not always adopt the PrP structure. It appears that the relatively complex structure of the prion form of PrP is not accessible to short model peptides, and that self-propagation may be tied to a level of structural complexity unobtainable in simple model systems. The larger fragments of PrP, however, are useful to illustrate the phenomenon of deformed templating (heterogeneous seeding), which has important biological consequences.

Truncated forms of the prion protein PrP demonstrate the need for complexity in prion structure.

Science.gov (United States)

Wan, William; Stöhr, Jan; Kendall, Amy; Stubbs, Gerald

2015-01-01

Self-propagation of aberrant protein folds is the defining characteristic of prions. Knowing the structural basis of self-propagation is essential to understanding prions and their related diseases. Prion rods are amyloid fibrils, but not all amyloids are prions. Prions have been remarkably intractable to structural studies, so many investigators have preferred to work with peptide fragments, particularly in the case of the mammalian prion protein PrP. We compared the structures of a number of fragments of PrP by X-ray fiber diffraction, and found that although all of the peptides adopted amyloid conformations, only the larger fragments adopted conformations that modeled the complexity of self-propagating prions, and even these fragments did not always adopt the PrP structure. It appears that the relatively complex structure of the prion form of PrP is not accessible to short model peptides, and that self-propagation may be tied to a level of structural complexity unobtainable in simple model systems. The larger fragments of PrP, however, are useful to illustrate the phenomenon of deformed templating (heterogeneous seeding), which has important biological consequences.

PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry.

Science.gov (United States)

Maréchal, Alexandre; Li, Ju-Mei; Ji, Xiao Ye; Wu, Ching-Shyi; Yazinski, Stephanie A; Nguyen, Hai Dang; Liu, Shizhou; Jiménez, Amanda E; Jin, Jianping; Zou, Lee

2014-01-23

PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). Although the role for PRP19 in splicing is well characterized, its role in the DDR remains elusive. Through a proteomic screen for proteins that interact with RPA-coated single-stranded DNA (RPA-ssDNA), we identified PRP19 as a sensor of DNA damage. PRP19 directly binds RPA and localizes to DNA damage sites via RPA, promoting RPA ubiquitylation in a DNA-damage-induced manner. PRP19 facilitates the accumulation of ATRIP, the regulatory partner of the ataxia telangiectasia mutated and Rad3-related (ATR) kinase, at DNA damage sites. Depletion of PRP19 compromised the phosphorylation of ATR substrates, recovery of stalled replication forks, and progression of replication forks on damaged DNA. Importantly, PRP19 mutants that cannot bind RPA or function as an E3 ligase failed to support the ATR response, revealing that PRP19 drives ATR activation by acting as an RPA-ssDNA-sensing ubiquitin ligase during the DDR. Copyright © 2014 Elsevier Inc. All rights reserved.

Site enforcement tracking system (SETS): PRP listing by site for region 9

International Nuclear Information System (INIS)

1993-04-01

When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

Site enforcement tracking system (SETS): PRP listing by site for region 8

International Nuclear Information System (INIS)

1993-04-01

When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

Site enforcement tracking system (SETS): PRP listing by site for region 10

International Nuclear Information System (INIS)

1993-04-01

When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

Site enforcement tracking system (SETS): PRP listing by site for region 3

International Nuclear Information System (INIS)

1993-04-01

When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

Site enforcement tracking system (SETS): PRP listing by site for region 2

International Nuclear Information System (INIS)

1993-04-01

When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

Site enforcement tracking system (SETS): PRP listing by site for region 5

International Nuclear Information System (INIS)

1993-04-01

When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

Site enforcement tracking system (SETS): PRP listing by site for region 6

International Nuclear Information System (INIS)

1993-04-01

When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

Small kinetochore associated protein (SKAP promotes UV-induced cell apoptosis through negatively regulating pre-mRNA processing factor 19 (Prp19.

Directory of Open Access Journals (Sweden)

Shan Lu

Full Text Available Apoptosis is a regulated cellular suicide program that is critical for the development and maintenance of healthy tissues. Previous studies have shown that small kinetochore associated protein (SKAP cooperates with kinetochore and mitotic spindle proteins to regulate mitosis. However, the role of SKAP in apoptosis has not been investigated. We have identified a new interaction involving SKAP, and we propose a mechanism through which SKAP regulates cell apoptosis. Our experiments demonstrate that both overexpression and knockdown of SKAP sensitize cells to UV-induced apoptosis. Further study has revealed that SKAP interacts with Pre-mRNA processing Factor 19 (Prp19. We find that UV-induced apoptosis can be inhibited by ectopic expression of Prp19, whereas silencing Prp19 has the opposite effect. Additionally, SKAP negatively regulates the protein levels of Prp19, whereas Prp19 does not alter SKAP expression. Finally, rescue experiments demonstrate that the pro-apoptotic role of SKAP is executed through Prp19. Taken together, these findings suggest that SKAP promotes UV-induced cell apoptosis by negatively regulating the anti-apoptotic protein Prp19.

Prion disease susceptibility is affected by β-structure folding propensity and local side-chain interactions in PrP

Science.gov (United States)

Khan, M. Qasim; Sweeting, Braden; Mulligan, Vikram Khipple; Arslan, Pharhad Eli; Cashman, Neil R.; Pai, Emil F.; Chakrabartty, Avijit

2010-01-01

Prion diseases occur when the normally α-helical prion protein (PrP) converts to a pathological β-structured state with prion infectivity (PrPSc). Exposure to PrPSc from other mammals can catalyze this conversion. Evidence from experimental and accidental transmission of prions suggests that mammals vary in their prion disease susceptibility: Hamsters and mice show relatively high susceptibility, whereas rabbits, horses, and dogs show low susceptibility. Using a novel approach to quantify conformational states of PrP by circular dichroism (CD), we find that prion susceptibility tracks with the intrinsic propensity of mammalian PrP to convert from the native, α-helical state to a cytotoxic β-structured state, which exists in a monomer–octamer equilibrium. It has been controversial whether β-structured monomers exist at acidic pH; sedimentation equilibrium and dual-wavelength CD evidence is presented for an equilibrium between a β-structured monomer and octamer in some acidic pH conditions. Our X-ray crystallographic structure of rabbit PrP has identified a key helix-capping motif implicated in the low prion disease susceptibility of rabbits. Removal of this capping motif increases the β-structure folding propensity of rabbit PrP to match that of PrP from mouse, a species more susceptible to prion disease. PMID:21041683

Prion disease susceptibility is affected by beta-structure folding propensity and local side-chain interactions in PrP.

Science.gov (United States)

Khan, M Qasim; Sweeting, Braden; Mulligan, Vikram Khipple; Arslan, Pharhad Eli; Cashman, Neil R; Pai, Emil F; Chakrabartty, Avijit

2010-11-16

Prion diseases occur when the normally α-helical prion protein (PrP) converts to a pathological β-structured state with prion infectivity (PrP(Sc)). Exposure to PrP(Sc) from other mammals can catalyze this conversion. Evidence from experimental and accidental transmission of prions suggests that mammals vary in their prion disease susceptibility: Hamsters and mice show relatively high susceptibility, whereas rabbits, horses, and dogs show low susceptibility. Using a novel approach to quantify conformational states of PrP by circular dichroism (CD), we find that prion susceptibility tracks with the intrinsic propensity of mammalian PrP to convert from the native, α-helical state to a cytotoxic β-structured state, which exists in a monomer-octamer equilibrium. It has been controversial whether β-structured monomers exist at acidic pH; sedimentation equilibrium and dual-wavelength CD evidence is presented for an equilibrium between a β-structured monomer and octamer in some acidic pH conditions. Our X-ray crystallographic structure of rabbit PrP has identified a key helix-capping motif implicated in the low prion disease susceptibility of rabbits. Removal of this capping motif increases the β-structure folding propensity of rabbit PrP to match that of PrP from mouse, a species more susceptible to prion disease.

Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage.

Science.gov (United States)

Moussa, Mayssam; Lajeunesse, Daniel; Hilal, George; El Atat, Oula; Haykal, Gaby; Serhal, Rim; Chalhoub, Antonio; Khalil, Charbel; Alaaeddine, Nada

2017-03-01

Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration. Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1-2-3, aggregan, Collagen type 2, TGF-β, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media. PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-β, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13. These results suggest that PRP could be a potential therapeutic tool for the treatment of OA. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The application of PRP combined with TCP in repairing avascular necrosis of the femoral head after femoral neck fracture in rabbit.

Science.gov (United States)

Zhang, X-L; Wang, Y-M; Chu, K; Wang, Z-H; Liu, Y-H; Jiang, L-H; Chen, X; Zhou, Z-Y; Yin, G

2018-02-01

In view of the high occurrence of avascular necrosis of the femoral head (ANFH) after femoral neck fracture and the difficulties in the treatment, our work aimed to explore the effects of platelet-rich plasma (PRP) combined with tri-calcium phosphate (TCP) on the repair of ANFH after femoral neck fracture and to provide reference for clinical treatment. Thirty New Zealand white rabbits were randomly divided into control group, TCP group, and PRP+TCP group. The rabbit ANFH model was established and femoral head tissues were collected. HE staining was used for histological observation. Image analysis and statistical analysis were used to calculate the New Bone Area fraction (NBA %). The levels of bone morphogenetic protein (BMP)-7, transforming growth factor (TGF)-β1, basic fibroblast growth factor (bFGF), interleukin (IL)-6 and tumor necrosis factor (TNF)-a in serum were detected by Enzyme-Linked ImmunoSorbent Assay (ELISA). The new bone area of TCP group was significantly lower than that of PRP+TCP group (pPRP+TCP groups (pPRP+TCP group was higher than that in TCP group. TCP and PRP+TCP can both significantly reduce the content of IL-6 and TNF-a (pPRP+TCP group compared with the TCP group at 8 weeks after injection. PRP combined with TCP, which can promote new bone formation and inhibit inflammatory response, showed higher efficiency in repairing ANFH than internal fixation alone.

Platelet-Rich Plasma (PRP Rinses for the Treatment of Non-Responding Oral Lichen Planus: A Case Report

Directory of Open Access Journals (Sweden)

Elisabetta Merigo

2018-02-01

Full Text Available Platelet-rich plasma (PRP has been proposed for different applications in the medical field and in maxillofacial surgery thanks to its many growth factors, such as epidermal growth factor (EGF, fibroblast growth factor (FGF, and keratinocyte growth factor (KGF. Oral lichen planus (OLP is a disease that affects the oral mucosa in a chronic way. This disease frequently worsens the quality of life of patients, particularly when clinical manifestations are of the erythematous or erosive/ulcerative type. The properties of PRP that are supported by scientific literature in both oral medicine and other medical fields have suggested the introduction of PRP in clinical practice for the medical treatment of different soft tissues diseases, such as when OLP patients do not respond to conventional therapies, or when conventional treatments have some contraindications or side effects. The aim of this work is to describe the use of PRP used as an oral rinse for the treatment of a patient diagnosed as affected by OLP at the Dentistry, Special Needs and Maxillo-Facial Surgery Unit of the Hospital of Piacenza. PRP protocol was started after the failure of conventional therapies based on the use of topical and systemic corticosteroids, hydroxychloroquine, and low-level laser therapy applications.

Platelet-Rich Plasma (PRP) Rinses for the Treatment of Non-Responding Oral Lichen Planus: A Case Report.

Science.gov (United States)

Merigo, Elisabetta; Oppici, Aldo; Parlatore, Anna; Cella, Luigi; Clini, Fabio; Fontana, Matteo; Fornaini, Carlo

2018-02-06

Platelet-rich plasma (PRP) has been proposed for different applications in the medical field and in maxillofacial surgery thanks to its many growth factors, such as epidermal growth factor (EGF), fibroblast growth factor (FGF), and keratinocyte growth factor (KGF). Oral lichen planus (OLP) is a disease that affects the oral mucosa in a chronic way. This disease frequently worsens the quality of life of patients, particularly when clinical manifestations are of the erythematous or erosive/ulcerative type. The properties of PRP that are supported by scientific literature in both oral medicine and other medical fields have suggested the introduction of PRP in clinical practice for the medical treatment of different soft tissues diseases, such as when OLP patients do not respond to conventional therapies, or when conventional treatments have some contraindications or side effects. The aim of this work is to describe the use of PRP used as an oral rinse for the treatment of a patient diagnosed as affected by OLP at the Dentistry, Special Needs and Maxillo-Facial Surgery Unit of the Hospital of Piacenza. PRP protocol was started after the failure of conventional therapies based on the use of topical and systemic corticosteroids, hydroxychloroquine, and low-level laser therapy applications.

Dynamics of the central bottleneck: dual-task and task uncertainty.

Directory of Open Access Journals (Sweden)

Mariano Sigman

2006-07-01

Full Text Available Why is the human brain fundamentally limited when attempting to execute two tasks at the same time or in close succession? Two classical paradigms, psychological refractory period (PRP and task switching, have independently approached this issue, making significant advances in our understanding of the architecture of cognition. Yet, there is an apparent contradiction between the conclusions derived from these two paradigms. The PRP paradigm, on the one hand, suggests that the simultaneous execution of two tasks is limited solely by a passive structural bottleneck in which the tasks are executed on a first-come, first-served basis. The task-switching paradigm, on the other hand, argues that switching back and forth between task configurations must be actively controlled by a central executive system (the system controlling voluntary, planned, and flexible action. Here we have explicitly designed an experiment mixing the essential ingredients of both paradigms: task uncertainty and task simultaneity. In addition to a central bottleneck, we obtain evidence for active processes of task setting (planning of the appropriate sequence of actions and task disengaging (suppression of the plan set for the first task in order to proceed with the next one. Our results clarify the chronometric relations between these central components of dual-task processing, and in particular whether they operate serially or in parallel. On this basis, we propose a hierarchical model of cognitive architecture that provides a synthesis of task-switching and PRP paradigms.

Study of PrP - I heterogeneous equilibrium

International Nuclear Information System (INIS)

Vasil'eva, I.G.; Mironov, K.E.; Tarasenko, A.D.

1976-01-01

Using static methods the authors have measured the equilibrium vapor pressure in the system PrP+I 2 at different temperatures and different initial iodine concentrations. The equilibrium reactions in the system have been determined. The reaction of PrP with iodine is irreversible. The content of PrI 3 and I 2 in the gas phase is negligible. The pressure in the system is determined by the partial pressure of phosphorus

Investigation of modified platelet-rich plasma (mPRP in promoting the proliferation and differentiation of dental pulp stem cells from deciduous teeth

Directory of Open Access Journals (Sweden)

J. Wen

2016-01-01

Full Text Available Stem cells from human exfoliated deciduous teeth (SHEDs have great potential to treat various dental-related diseases in regenerative medicine. They are usually maintained with 10% fetal bovine serum (FBS in vitro. Modified platelet-rich plasma (mPRP would be a safe alternative to 10% FBS during SHEDs culture. Therefore, our study aimed to compare the proliferation and differentiation of SHEDs cultured in mPRP and FBS medium to explore an optimal concentration of mPRP for SHEDs maintenance. Platelets were harvested by automatic blood cell analyzer and activated by repeated liquid nitrogen freezing and thawing. The platelet-related cytokines were examined and analyzed by ELISA. SHEDs were extracted and cultured with different concentrations of mPRP or 10% FBS medium. Alkaline phosphatase (ALP activity was measured. Mineralization factors, RUNX2 and OCN, were measured by real-time PCR. SHEDs were characterized with mesenchymal stem cells (MSCs markers including vimentin, CD44, and CD105. mPRP at different concentrations (2, 5, 10, and 20% enhanced the growth of SHEDs. Moreover, mPRP significantly stimulated ALP activity and promoted expression of RUNX2 and OCN compared with 10% FBS. mPRP could efficiently facilitate proliferation and differentiation of SHEDs, and 2% mPRP would be an optimal substitute for 10% FBS during SHEDs expansion and differentiation in clinical scale manufacturing.

Successful treatment of radiation retinopathy with panretinal photocoagulation (PRP) in a patient of orbital MALT lymphoma

International Nuclear Information System (INIS)

Okamoto, Hiroyuki; Chikuda, Makoto; Kadoya, Kouji

2012-01-01

Report a case of satisfactory progress radiation retinopathy after radiation for mucosa-associated lymphoid tissue (MALT) lymphoma. A 26-year-old male patient, referred to our department for lacrimal sac tumor. Biopsy was done by otolaryngology and radiation therapy was performed (total irradiation of 41.4 Gy) as pathological examination revealed MALT lymphoma. Soft exudates and macula edema appeared in posterior pole of the right fundus after radiotherapy. Right vision became 0.5 because of macula edema, and panretinal photocoagulation (PRP) was performed. After PRP, macula edema withdrew and right vision improved to 1.2. It is suggested that the fundus must be monitored after radiation therapy, and early treatment, such as PRP is effective in radiation retinopathy. (author)

Characterization of PhPRP1, a histidine domain arabinogalactan protein from Petunia hybrida pistils.

Science.gov (United States)

Twomey, Megan C; Brooks, Jenna K; Corey, Jillaine M; Singh-Cundy, Anu

2013-10-15

An arabinogalactan protein, PhPRP1, was purified from Petunia hybrida pistils and shown to be orthologous to TTS-1 and TTS-2 from Nicotiana tabacum and NaTTS from Nicotiana alata. Sequence comparisons among these proteins, and CaPRP1 from Capsicum annuum, reveal a conserved histidine-rich domain and two hypervariable domains. Immunoblots show that TTS-1 and PhPRP1 are also expressed in vegetative tissues of tobacco and petunia respectively. In contrast to the molecular mass heterogeneity displayed by the pistil proteins, the different isoforms found in seedlings, roots, and leaves each has a discrete size (37, 80, 160, and 200 kDa) on SDS-PAGE gels. On the basis of their chemistry, distinctive domain architecture, and the unique pattern of expression, we have named this group of proteins HD-AGPs (histidine domain-arabinogalactan proteins). Copyright © 2013 Elsevier GmbH. All rights reserved.

Mutant PrP Suppresses Glutamatergic Neurotransmission in Cerebellar Granule Neurons by Impairing Membrane Delivery of VGCC α2δ-1 Subunit

Science.gov (United States)

Senatore, Assunta; Colleoni, Simona; Verderio, Claudia; Restelli, Elena; Morini, Raffaella; Condliffe, Steven B.; Bertani, Ilaria; Mantovani, Susanna; Canovi, Mara; Micotti, Edoardo; Forloni, Gianluigi; Dolphin, Annette C.; Matteoli, Michela; Gobbi, Marco; Chiesa, Roberto

2012-01-01

Summary How mutant prion protein (PrP) leads to neurological dysfunction in genetic prion diseases is unknown. Tg(PG14) mice synthesize a misfolded mutant PrP which is partially retained in the neuronal endoplasmic reticulum (ER). As these mice age, they develop ataxia and massive degeneration of cerebellar granule neurons (CGNs). Here, we report that motor behavioral deficits in Tg(PG14) mice emerge before neurodegeneration and are associated with defective glutamate exocytosis from granule neurons due to impaired calcium dynamics. We found that mutant PrP interacts with the voltage-gated calcium channel α2δ-1 subunit, which promotes the anterograde trafficking of the channel. Owing to ER retention of mutant PrP, α2δ-1 accumulates intracellularly, impairing delivery of the channel complex to the cell surface. Thus, mutant PrP disrupts cerebellar glutamatergic neurotransmission by reducing the number of functional channels in CGNs. These results link intracellular PrP retention to synaptic dysfunction, indicating new modalities of neurotoxicity and potential therapeutic strategies. PMID:22542184

Prion propagation in cells expressing PrP glycosylation mutants.

Science.gov (United States)

Salamat, Muhammad K; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

2011-04-01

Infection by prions involves conversion of a host-encoded cell surface protein (PrP(C)) to a disease-related isoform (PrP(Sc)). PrP(C) carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrP(C) glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrP(Sc) and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrP(Sc), while PrP(C) with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrP(C), were able to form infectious PrP(Sc). Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection.

Platelet-rich plasma (PRP for the treatment of vulvar lichen sclerosus in a premenopausal woman: A case report

Directory of Open Access Journals (Sweden)

D. Franic

2018-04-01

Full Text Available The use of platelet-rich plasma (PRP for the treatment of lichen sclerosus (LS in a 38-year-old premenopausal woman is reported. The diagnosis was confirmed histologically and the symptoms documented using the ICIQ Vaginal Symptoms Questionnaire (ICIQ-VS and the Female Sexual Function Index (FSFI questionnaire. PRP was prepared from autologous blood using the Regen Cellular Matrix Kit. PRP was administered twice over two months. Histology at follow-up one month after the second administration showed the epidermis was nearly normal and upper dermal cellularity had been restored. The patient was symptom-free and both her ICIQ-VS and her FSFI scores had improved significantly. PRP is a potential new treatment option for LS which needs further assessment in randomized controlled trials. Keywords: Platelet-rich plasma, Vulvar lichen sclerosus, Premenopause, Treatment

Evaluation of Not-Activated and Activated PRP in Hair Loss Treatment: Role of Growth Factor and Cytokine Concentrations Obtained by Different Collection Systems

Directory of Open Access Journals (Sweden)

Pietro Gentile

2017-02-01

Full Text Available Platelet rich plasma (PRP was tested as a potential therapy for androgenetic alopecia (AGA through two different clinical protocols in which one population (18 participants received half-head treatment with autologous non-activated PRP (A-PRP produced by CPunT Preparation System (Biomed Device, Modena, Italy and the other half-head with placebo, and a second separated population in which all participants (n = 6, 3 participants per group received treatment with calcium-activated PRP (AA-PRP produced from one of two different PRP collection devices (Regen Blood Cell Therapy or Arthrex Angel System. For the A-PRP study, three treatments were administered over 30-day intervals. Trichoscan analysis of patients, three months post-treatment, showed a clinical improvement in the number of hairs in the target area (36 ± 3 hairs and in total hair density (65±  5 hair cm2, whereas negligible improvements in hair count (1.1±  1.4 hairs and density (1.9 ± 10.2 hair cm2 were seen in the region of the scalp that received placebo. Microscopic evaluation conducted two weeks after treatment showed also an increase in epidermal thickness, Ki67+ keratinocytes, and in the number of follicles. The AA-PRP treatment groups received a singular set of injections, and six months after the treatments were administered, notable differences in clinical outcomes were obtained from the two PRP collection devices (+90 ± 6 hair cm2 versus -73 ± 30 hair cm2 hair densities, Regen versus Arthrex. Growth factor concentrations in AA-PRP prepared from the two collection devices did not differ significantly upon calcium activation.

Evaluation of Not-Activated and Activated PRP in Hair Loss Treatment: Role of Growth Factor and Cytokine Concentrations Obtained by Different Collection Systems.

Science.gov (United States)

Gentile, Pietro; Cole, John P; Cole, Megan A; Garcovich, Simone; Bielli, Alessandra; Scioli, Maria Giovanna; Orlandi, Augusto; Insalaco, Chiara; Cervelli, Valerio

2017-02-14

Platelet rich plasma (PRP) was tested as a potential therapy for androgenetic alopecia (AGA) through two different clinical protocols in which one population (18 participants) received half-head treatment with autologous non-activated PRP (A-PRP) produced by CPunT Preparation System (Biomed Device, Modena, Italy) and the other half-head with placebo, and a second separated population in which all participants (n = 6, 3 participants per group) received treatment with calcium-activated PRP (AA-PRP) produced from one of two different PRP collection devices (Regen Blood Cell Therapy or Arthrex Angel System). For the A-PRP study, three treatments were administered over 30-day intervals. Trichoscan analysis of patients, three months post-treatment, showed a clinical improvement in the number of hairs in the target area (36 ± 3 hairs) and in total hair density (65±  5 hair cm2), whereas negligible improvements in hair count (1.1±  1.4 hairs) and density (1.9 ± 10.2 hair cm2) were seen in the region of the scalp that received placebo. Microscopic evaluation conducted two weeks after treatment showed also an increase in epidermal thickness, Ki67+ keratinocytes, and in the number of follicles. The AA-PRP treatment groups received a singular set of injections, and six months after the treatments were administered, notable differences in clinical outcomes were obtained from the two PRP collection devices (+90 ± 6 hair cm2 versus -73 ± 30 hair cm2 hair densities, Regen versus Arthrex). Growth factor concentrations in AA-PRP prepared from the two collection devices did not differ significantly upon calcium activation.

Autologous platelet-rich plasma (PRP) in chronic penile lichen sclerosus: the impact on tissue repair and patient quality of life.

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Casabona, Francesco; Gambelli, Ilaria; Casabona, Federica; Santi, Pierluigi; Santori, Gregorio; Baldelli, Ilaria

2017-04-01

Lichen sclerosus (LS) is a chronic inflammatory skin condition that frequently involves the anogenital region. Ongoing research is focused on finding more effective treatments for tissue repair and reducing symptoms. The aim of this study is to evaluate the effectiveness of platelet-rich plasma (PRP) local injections in penile LS. Forty-five male patients affected by penile LS underwent injections of autologous PRP in the affected skin areas. Age at diagnosis and at first treatment, number of treatments, clinical conditions (phimosis, splitting, inflammation, synechiae, meatus stenosis), symptoms (pain, burning, itching), and functional impairment were considered. Treatment efficacy was also evaluated through the Investigator's Global Assessment (IGA) on a six-point Likert scale and the Dermatology Life Quality Index (DLQI). The patient age at LS diagnosis was 36.20 ± 9.19 years, while the mean age at the first PRP treatment was 42.96 ± 11.32 years (p PRP injections, it was observed in all patients a significant improvement in clinical conditions, with reduction/disappearance of symptoms. Topical steroid therapy, interrupted before PRP treatment, was not restarted by any patient. Only one patient underwent a later circumcision procedure. Both IGA scale and DLQI score showed a significant difference (p PRP treatment. PRP treatment in penile LS seems to be helpful to regenerate scarring, reduce symptoms, and improve patient quality of life. Further studies are necessary to evaluate long-term results.

A Comparison of Platelet Count and Enrichment Percentages in the Platelet Rich Plasma (PRP) Obtained Following Preparation by Three Different Methods.

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Sabarish, Ram; Lavu, Vamsi; Rao, Suresh Ranga

2015-02-01

Platelet rich plasma (PRP) represents an easily accessible and rich source of autologous growth factors. Different manual methods for the preparation of PRP have been suggested. Lacuna in knowledge exists about the efficacy of PRP preparation by these different manual methods. This study was performed to determine the effects of centrifugation rate revolutions per minute (RPM) and time on the platelet count and enrichment percentages in the concentrates obtained following the three different manual methods of PRP preparation. In vitro experimental study. This was an experimental study in which platelet concentration was assessed in the PRP prepared by three different protocols as suggested by Marx R (method 1), Okuda K (method 2) and Landesberg R (method 3). A total of 60 peripheral blood samples, (n=20 per method) were obtained from healthy volunteers. Baseline platelet count was assessed for all the subjects following which PRP was prepared. The platelet count in the PRP was determined using coulter counter (Sysmex XT 2000i). The mean of the platelet count obtained and their enrichment percentage were calculated and intergroup comparison was done (Tukey's HSD test). The number of platelets and enrichment percentage in PRP prepared by method 1 was higher compared to method 2 and method 3; this difference in platelet concentrates was found to be statistically significant (p < 0.05). The centrifugation rate and time appear to be important parameters, which influence the platelet yield. Method 1 which had lower centrifugation rate and time yielded a greater platelet count and enrichment percentage.

In Vitro Studies on the Degradability, Bioactivity, and Cell Differentiation of PRP/AZ31B Mg Alloys Composite Scaffold

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Jian Zou

2017-01-01

Full Text Available In recent years, more and more methods have been developed to improve the bioactivity of the biodegradable materials in bone tissue regeneration. In present study, we used rat mesenchymal stem cells (rMSCs to evaluate the outcomes of Mg alloys (AZ31B, Magnesium, and Aluminum and Platelet-rich plasma (PRP/Mg alloys on rMSCs biocompatibility and osteogenic differentiation. Water absorption experiments indicated that both bare AZ31B and PRP/AZ31B were capable of absorbing large amounts of water. But the water absorption ratio for PRP/AZ31B was significantly higher than that for bare AZ31B. The degradability experiments implied that both samples degraded at same speed. rMSCs on the surface of AZ31B distributed more and better than those on the AZ31B scaffold. In ALP activity experiment, the activity of rMSCs on the PRP/AZ31B was markedly higher than that on the AZ31B scaffolds on the 7th day and 14th day. qRT-PCR also showed that OPN and OCN were expressed in both samples. OPN and OCN expression in PRP/AZ31B sample were higher than those in bare AZ31B samples. In summary, the in vitro study implied that AZ31B combined with PRP could remarkably improve cell seeding, attachment, proliferation, and differentiation.

A fully liquid DTaP-IPV-HB-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Turkish infants and toddlers

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Ceyhan, Mehmet; Yıldırım, İnci; Tezer, Hasan; Devrim, İlker; Feroldi, Emmanuel

2017-08-23

Background/aim: Immunogenicity and safety of a primary series of a fully liquid, hexavalent DTaP-IPV-HB-PRP-T vaccine given at 2, 3, and 4 months of age compared to licensed comparators and a DTaP-IPV-HB-PRP-T booster at 15?18 months were evaluated. Materials and methods: This was a Phase III, randomized, open-label trial. Primary series (no hepatitis B [HB] at birth) of DTaP-IPV-HB-PRP-T (N = 155) (group 1) or licensed control vaccines (DTaP-IPV//PRP-T and standalone HB: N = 155) (group 2) and DTaP-IPV-HB-PRP-T booster were administered. Noninferiority was evaluated 1 month postprimary series for anti-HB seroprotection (SP). All other analyses were descriptive. Safety was assessed from parental reports. Results: Postprimary series noninferiority of anti-HB ≥ 10 mIU/mL was demonstrated for the DTaP-IPV-HB-PRP-T vaccine (94.0%) compared to the licensed control (96.1%). Postprimary series primary SP and seroconversion (SC) rates were high and similar for both groups. Antibody persistence (prebooster) was high for each antigen and similar between groups except for HB, which was lower for DTaP-IPV-HB-PRP-T than for standalone HB. For each antigen except HB, DTaP-IPV-HB-PRP-T booster responses were high and similar in each group. Safety was good for primary and booster series and similar between groups. Conclusion: The DTaP-IPV-HB-PRP-T vaccine is immunogenic and safe when administered in a challenging primary series schedule without HB vaccination at birth.

Platelet-rich plasma: why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration.

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Filardo, G; Kon, E; Roffi, A; Di Matteo, B; Merli, M L; Marcacci, M

2015-09-01

The aim of this review was to analyze the available evidence on the clinical application of this biological approach for the injective treatment of cartilage lesions and joint degeneration, together with preclinical studies to support the rationale for the use of platelet concentrates, to shed some light and give indications on what to treat and what to expect from intra-articular injections of platelet-rich plasma (PRP). All in vitro, in vivo preclinical and clinical studies on PRP injective treatment in the English language concerning the effect of PRP on cartilage, synovial tissue, menisci, and mesenchymal stem cells were considered. A systematic review on the PubMed database was performed using the following words: (platelet-rich plasma or PRP or platelet concentrate or platelet lysate or platelet supernatant) and (cartilage or chondrocytes or synoviocytes or menisci or mesenchymal stem cells). Fifty-nine articles met the inclusion criteria: 26 were in vitro, 9 were in vivo, 2 were both in vivo and in vitro, and 22 were clinical studies. The analysis showed an increasing number of published studies over time. Preclinical evidence supports the use of PRP injections that might promote a favourable environment for joint tissues healing. Only a few high-quality clinical trials have been published, which showed a clinical improvement limited over time and mainly documented in younger patients not affected by advanced knee degeneration. Besides the limits and sometimes controversial findings, the preclinical literature shows an overall support toward this PRP application. An intra-articular injection does not just target cartilage; instead, PRP might influence the entire joint environment, leading to a short-term clinical improvement. Many biological variables might influence the clinical outcome and have to be studied to optimize PRP injective treatment of cartilage degeneration and osteoarthritis.

Two New PRP Conjugate Gradient Algorithms for Minimization Optimization Models.

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Yuan, Gonglin; Duan, Xiabin; Liu, Wenjie; Wang, Xiaoliang; Cui, Zengru; Sheng, Zhou

2015-01-01

Two new PRP conjugate Algorithms are proposed in this paper based on two modified PRP conjugate gradient methods: the first algorithm is proposed for solving unconstrained optimization problems, and the second algorithm is proposed for solving nonlinear equations. The first method contains two aspects of information: function value and gradient value. The two methods both possess some good properties, as follows: 1) βk ≥ 0 2) the search direction has the trust region property without the use of any line search method 3) the search direction has sufficient descent property without the use of any line search method. Under some suitable conditions, we establish the global convergence of the two algorithms. We conduct numerical experiments to evaluate our algorithms. The numerical results indicate that the first algorithm is effective and competitive for solving unconstrained optimization problems and that the second algorithm is effective for solving large-scale nonlinear equations.

Clinical-grade quality platelet-rich plasma releasate (PRP-R/SRGF) from CaCl2 -activated platelet concentrates promoted expansion of mesenchymal stromal cells.

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Borghese, C; Agostini, F; Durante, C; Colombatti, A; Mazzucato, M; Aldinucci, D

2016-08-01

The aim of our study was to test a platelet-rich plasma releasate (PRP-R/SRGF) from CaCl2 -activated platelets as a source of growth factors for the expansion of mesenchymal stromal cells (MSCs). PRP-R/SRGF, obtained with a low-cost procedure, is characterized by a reduced variability of growth factor release. PRP-R/SRGF is a clinical-grade quality solution obtained from CaCl2 -activated platelets. Its activity was evaluated by measuring the proliferation, the phenotype, the differentiation potential and the immunosuppressive properties of MSCs derived from bone marrow (BM) and adipose tissue (AT). PRP-R/SRGF was more active than FBS to expand BM- and AT-derived MSCs. PRP-R/SRGF treatment did not affect the expression of typical MSCs surface markers, neither MSCs differentiation potential nor their capability to inhibit activated T-cell proliferation. The clinical-grade PRP-R/SRGF may be used in the clinical setting for the expansion of MSCs. © 2016 International Society of Blood Transfusion.

PRP: a FORTRAN IV interactive plotting program

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Andrew, A. S.; Linde, J.

A computer program, PRP, has been designed to plot any arithmetic combination selected from a set of major and trace element data on a y- x graph. y and x are defined and entered as a program string (y, x) which is interpreted sequentially. Operators ( +, -, ∗, /, ( unary) , square root, log 10, In c, antilog 10, exponential, integer, absolute value, (,),,) and integer or real numbers may be included. Axis lengths and scales are determined by the user. Five different plotting symbols are available.

Use of autologous platelet rich plasma (PRP) in stopping massive hemoptysis at the Lung Center of the Philippines: a pilot study.

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Sarmiento, Armand Gregorio C; Danguilan, Jose Luis J; Mariano, Zenaida M; Barzaga, Maria Teresa A

2017-01-01

The purpose of this study is to determine the effect of using autologous platelet rich plasma (PRP) in patients having massive hemoptysis within a period of one week. This is a prospective cohort study involving 20 consecutive patients admitted who met the criteria for massive hemoptysis from July to October 2011. After stabilizing the patient, fiberoptic bronchoscopy (FOB) was performed for localization of bleeding within 6 hours from diagnosis. A 50mL of blood was extracted from the patient whom was to be used for autologous PRP concentrate. After identifying the anatomic site of bleeding, autologous PRP concentrate was instilled on the affected bronchus and was allowed to stay for 5 minutes after instillation. Patients were then monitored from the time the bleeding stopped in the first 24 hours, 2 days and 7 days respectively. Mean age of the study population with massive hemoptysis was 47 years old (SD 17.3). Majority of cases were male 18 out of 20 (90%) and smokers 14 (70%) with a normal BMI (75%). Identification of bleeding site was more commonly seen on the right upper lobe 9 out of 20 (45%). Overall, 14 out of 20 patients (70%) were reported to have stopped bleeding immediately. Subsequent hospital days showed that 8 out of 20 patients (40%) had no hemoptysis. However, one [1] post-tuberculosis (TB) bronchiectatic patient had recurrence of massive hemoptysis, approximately 250 mL per expectorate, expired within the 7 days observation and one patient had lobectomy on the 2nd day. The rest had non-massive hemoptysis wherein their expectorations were only streaks of blood. Moreover, there was one [1] patient who had recurrence of massive hemoptysis 1 week after autologous PRP infusion and was eventually intubated. Majority of the subjects, eleven [11] were diagnosed to have post-TB bronchiectasis. The rest of the patients were worked-up prior to operation. Overall, it was observed that the use of autologous PRP was able to stop bleeding in 40% of the study

A fully liquid DTaP-IPV-Hep B-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Mexican children.

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Aquino, Amalia Guadalupe Becerra; Brito, Maricruz Gutiérrez; Doniz, Carlos E Aranza; Herrera, Juan Francisco Galán; Macias, Mercedes; Zambrano, Betzana; Plennevaux, Eric; Santos-Lima, Eduardo

2012-10-05

To evaluate an investigational, fully liquid hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-Hep B-PRP-T: Hexaxim™) vaccine for primary and booster vaccination of healthy children in Mexico. Infants (N=1189) were randomized to receive one of three lots of the DTaP-IPV-Hep B-PRP-T vaccine or a licensed hexavalent control vaccine (Infanrix™ hexa) for primary vaccination at 2, 4 and 6 months. All participants who completed the primary series and agreed to participate in the booster part of the study received a dose of the investigational vaccine at 15-18 months of age. Validated serological assays and parental reports were used to assess immunogenicity and safety, respectively. Post-primary vaccination, ≥95.8% of participants in both the DTaP-IPV-Hep B-PRP-T and control groups were seroprotected (SP) against diphtheria, tetanus, poliovirus, hepatitis B and PRP, or had seroconverted (SC) to the pertussis toxin (PT) and filamentous hemagglutinin (FHA) pertussis antigens. The SP/SC rates induced by the three DTaP-IPV-Hep B-PRP-T lots were equivalent. No differences in SP/SC rates were observed between the pooled lots of investigational vaccine and the control vaccine. Antibody persistence at 15-18 months was comparable between groups, with strong increases in all antibody concentrations post-DTaP-IPV-Hep B-PRP-T booster. Both vaccines were well tolerated for primary vaccination, as was the booster dose of DTaP-IPV-Hep B-PRP-T. These study findings confirm the suitability of the combined, fully liquid DTaP-IPV-Hep B-PRP-T vaccine for inclusion in routine childhood vaccination schedules. Copyright © 2012 Elsevier Ltd. All rights reserved.

Oxidation of Helix-3 methionines precedes the formation of PK resistant PrP.

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Tamar Canello

2010-07-01

Full Text Available While elucidating the peculiar epitope of the alpha-PrP mAb IPC2, we found that PrPSc exhibits the sulfoxidation of residue M213 as a covalent signature. Subsequent computational analysis predicted that the presence of sulfoxide groups at both Met residues 206 and 213 destabilize the alpha-fold, suggesting oxidation may facilitate the conversion of PrPC into PrPSc. To further study the effect of oxidation on prion formation, we generated pAbs to linear PrP peptides encompassing the Helix-3 region, as opposed to the non-linear complexed epitope of IPC2. We now show that pAbs, whose epitopes comprise Met residues, readily detected PrPC, but could not recognize most PrPSc bands unless they were vigorously reduced. Next, we showed that the alpha-Met pAbs did not recognize newly formed PrPSc, as is the case for the PK resistant PrP present in lines of prion infected cells. In addition, these reagents did not detect intermediate forms such as PK sensitive and partially aggregated PrPs present in infected brains. Finally, we show that PrP molecules harboring the pathogenic mutation E200K, which is linked to the most common form of familial CJD, may be spontaneously oxidized. We conclude that the oxidation of methionine residues in Helix-3 represents an early and important event in the conversion of PrPC to PrPSc. We believe that further investigation into the mechanism and role of PrP oxidation will be central in finally elucidating the mechanism by which a normal cell protein converts into a pathogenic entity that causes fatal brain degeneration.

Two New PRP Conjugate Gradient Algorithms for Minimization Optimization Models.

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Gonglin Yuan

Full Text Available Two new PRP conjugate Algorithms are proposed in this paper based on two modified PRP conjugate gradient methods: the first algorithm is proposed for solving unconstrained optimization problems, and the second algorithm is proposed for solving nonlinear equations. The first method contains two aspects of information: function value and gradient value. The two methods both possess some good properties, as follows: 1 βk ≥ 0 2 the search direction has the trust region property without the use of any line search method 3 the search direction has sufficient descent property without the use of any line search method. Under some suitable conditions, we establish the global convergence of the two algorithms. We conduct numerical experiments to evaluate our algorithms. The numerical results indicate that the first algorithm is effective and competitive for solving unconstrained optimization problems and that the second algorithm is effective for solving large-scale nonlinear equations.

Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage

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Moussa, Mayssam, E-mail: Moussa-mayssam@hotmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Lajeunesse, Daniel, E-mail: daniel.lajeunesse@umontreal.ca [Research Centre in Osteoarthritis, Research Centre in Monteral University (Canada); Hilal, George, E-mail: George2266@gmail.com [Cancer and metabolism Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); El Atat, Oula, E-mail: oulaatat@hotmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Haykal, Gaby, E-mail: Gaby.haykal@hdf.usj.edu.lb [Hotel Dieu de France, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Serhal, Rim, E-mail: rim.basbous@gmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Chalhoub, Antonio, E-mail: Mava.o@hotmail.com [Carantina Hospital, Beirut (Lebanon); Khalil, Charbel, E-mail: charbelk3@hotmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Alaaeddine, Nada, E-mail: Nada.aladdin@gmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon)

2017-03-01

Objectives: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration. Methods: Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1–2–3, aggregan, Collagen type 2, TGF-β, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media. Results: PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-β, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13. Conclusion: These results suggest that PRP could be a potential therapeutic tool for the treatment of OA. - Highlights: • Platelet Rich Plasma is suggested as a new treatment for osteoarthritis. • The proposed therapeutic effect is

Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage

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Moussa, Mayssam; Lajeunesse, Daniel; Hilal, George; El Atat, Oula; Haykal, Gaby; Serhal, Rim; Chalhoub, Antonio; Khalil, Charbel; Alaaeddine, Nada

2017-01-01

Objectives: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration. Methods: Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1–2–3, aggregan, Collagen type 2, TGF-β, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media. Results: PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-β, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13. Conclusion: These results suggest that PRP could be a potential therapeutic tool for the treatment of OA. - Highlights: • Platelet Rich Plasma is suggested as a new treatment for osteoarthritis. • The proposed therapeutic effect is

Platelet-rich plasma (PRP for acute muscle injury: a systematic review.

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Mohamad Shariff A Hamid

Full Text Available INTRODUCTION: Acute muscle injury is one of the commonest injuries that often result in loss of training and competition time. The best management for muscle injury has not been identified. Sports medicine practitioners used several approaches in attempt to accelerate time to recovery from muscle injury. More recently growing interest focussed on autologous blood product injection. METHODS: A literature search was conducted systematically using OvidMEDLINE, PubMed, EMBASE, SPORTDiscus and CINAHL databases to retrieve articles published until December 2012. Controlled trials and controlled laboratory studies comparing different strategies to promote early recovery of muscle injury were included. The methodological quality of studies was assessed. RESULTS: There are limited studies on the effects of PRP therapy for muscle injury. Three in vivo laboratory studies and one pilot human study were reviewed. The laboratory studies reported histological evidence on significant acceleration of muscle healing in animals treated with autologous conditioned serum (ACS, platelet-rich plasma (PRP and platelet rich fibrin matrix (PRFM. A pilot human study found athletes treated with repeated ACS injection recovers significantly faster than retrospective controls. CONCLUSION: Several in vivo laboratory studies suggest beneficial effects of ACS, PRP and PRFM in accelerating muscle recovery. Evidence to suggest similar effects on humans is however limited, as valuable information from robust human controlled trials is still not available at this moment. Hence, more studies of satisfactory methodological quality with platelet-rich plasma interventions on muscle injury are justified.

Comparison between Conventional Mechanical Fixation and Use of Autologous Platelet Rich Plasma (PRP) in Wound Beds Prior to Resurfacing with Split Thickness Skin Graft.

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P Waiker, Veena; Shivalingappa, Shanthakumar

2015-01-01

Platelet rich plasma is known for its hemostatic, adhesive and healing properties in view of the multiple growth factors released from the platelets to the site of wound. The primary objective of this study was to use autologous platelet rich plasma (PRP) in wound beds for anchorage of skin grafts instead of conventional methods like sutures, staplers or glue. In a single center based randomized controlled prospective study of nine months duration, 200 patients with wounds were divided into two equal groups. Autologous PRP was applied on wound beds in PRP group and conventional methods like staples/sutures used to anchor the skin grafts in a control group. Instant graft adherence to wound bed was statistically significant in the PRP group. Time of first post-graft inspection was delayed, and hematoma, graft edema, discharge from graft site, frequency of dressings and duration of stay in plastic surgery unit were significantly less in the PRP group. Autologous PRP ensured instant skin graft adherence to wound bed in comparison to conventional methods of anchorage. Hence, we recommend the use of autologous PRP routinely on wounds prior to resurfacing to ensure the benefits of early healing.

Prion Propagation in Cells Expressing PrP Glycosylation Mutants ▿

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Salamat, Muhammad K.; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

2011-01-01

Infection by prions involves conversion of a host-encoded cell surface protein (PrPC) to a disease-related isoform (PrPSc). PrPC carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrPC glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrPSc and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrPSc, while PrPC with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrPC, were able to form infectious PrPSc. Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection. PMID:21248032

Comparison between PRP, PRGF and PRF: lights and shadows in three similar but different protocols.

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Giannini, S; Cielo, A; Bonanome, L; Rastelli, C; Derla, C; Corpaci, F; Falisi, G

2015-01-01

The main goal of the modern surgery is to get a low invasiveness and a high rate of clinical healing: in the last years, it has been introduced the concept of a "regenerative surgery", and many techniques has been widely described in the literature. The most used are PRP, PRGF and PRF techniques. Aim of this research is to compare the three protocol of PRP, PRF and PRGF in their essential features, so to suggest to the practitioners the best blood product to use in the regenerative surgery. Among the advantages that shows the PRF, compared to PRP and PRGF, we can cite a greater simplicity of production for the absence of manipulation that leads to a reduced possibility of alteration of the protocol due to an error of the operator. The special texture of the PRF and its biological features shows clearly an interesting surgical versatility and all the characteristics that can support a faster tissues regeneration and high-quality clinical outcomes.

PrPST, a Soluble, Protease Resistant and Truncated PrP Form Features in the Pathogenesis of a Genetic Prion Disease

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Frid, Kati; Binyamin, Orli; Gabizon, Ruth

2013-01-01

While the conversion of PrPC into PrPSc in the transmissible form of prion disease requires a preexisting PrPSc seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrPST), a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrPST as in TgMHu2ME199K mice, and “classical” PrPSc as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition. PMID:23922744

PLATELET-RICH PLASMA (PRP AND ITS APPLICATION IN THE TREATMENT OF CHRONIC AND HARD-TO-HEAL SKIN WOUNDS. A Review.

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Tsvetan Sokolov

2015-12-01

Full Text Available In the last few years various methods are being applied in the use of platelet-rich plasma (PRP during treatment in different orthopedic disease. They allow improvement of local biological condition and regeneration of different types of tissues. PRP is a modern treatment strategy with worldwide recognition. There is a high concentration of platelet growth factors in small amounts of plasma. PRP and its various forms have become one of the best methods to support the healing process of various tissues. PRP is used in regenerative medicine, because it provides two of three components (growth factors and scaffolds necessary for complete tissue regeneration. The particular reason for the appearance of lesions is important in order to select an appropriate treatment method and technical application. PRP may be used for treatment of various chronic and hard-to-heal cutaneous wounds, especially when standard conventional therapy is not good enough and surgical treatment is not possible. It reduces the duration, cost of treatment and the hospital stay. There is reduction of wound pain after starting the treatment, reduced risk of blood-borne disease transmission, wound healing is restored, and local immunity is activated.

Exercise and the platelet activator calcium chloride both influence the growth factor content of platelet-rich plasma (PRP): overlooked biochemical factors that could influence PRP treatment

NARCIS (Netherlands)

Hamilton, Bruce; Tol, Johannes L.; Knez, Wade; Chalabi, Hakim

2015-01-01

There is strong evidence that exercise affects platelet haemostasis factors, but this potential effect on growth factor concentrations in platelet-rich plasma (PRP) has never been studied. In addition, there is a paucity of studies focusing on the effects of activating agents used in conjunction

Using PRP and human amniotic fluid combination for osteogenesis in rabbit socket preservation

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Amir Hossein Moradi

2015-01-01

Full Text Available Introduction: Platelet-rich plasma (PRP is used as an adjunct treatment during periodontal grafting surgery because of its capability of enhancing healing process. Amniotic fluid is a rich source of growth factors and hyaluronic acid (HA and a good point to study its properties of wound healing and bone formation. The aim of this study was to evaluate the osteogenic properties of a combination of amniotic fluid and PRP in rabbit′s dental socket preservation. Materials and Methods: The study population consisted of 24 healthy male laboratory rabbits (average weight 3,125 ± 185 gr that were randomly allocated into four groups. PRP for the first group, human amniotic fluid (HAF for the second group, a combination of PRP and HAF (PRHA for the third group was used. In the fourth (control group, no biomaterial was used. In each group, half of the rabbits were sacrificed at 4 weeks following surgery and the rest were sacrificed after 8 weeks. Histological analysis of biopsies of the sockets was performed using hematoxylin and eosin (H&E staining. Data were analyzed using Statistical Package for the Social Sciences (SPSS software (version 16 and P-value <0.05 was considered significance. Results: All three experimental groups showed positive effect on bone formation in terms of area of trabecular bone and number of osteocytes and also vessel formation. Socket preservation using HAF and PRHA showed the highest impact on bone formation. Socket preservation using HAF also had the highest impact on vessel formation. Conclusion: PRHA and HAF appear to be useful for enhancing bone formation. Since there was no difference between HAF and PRHA, it seems beneficial to use HAF due to its simplicity of application.

Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP versus Hyaluronic Acid (A one-year randomized clinical trial

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Seyed Ahmad Raeissadat

2015-01-01

Full Text Available Introduction Knee osteoarthritis (OA is the most common articular disease. Different methods are used to alleviate the symptoms of patients with knee OA, including analgesics, physical therapy, exercise prescription, and intra-articular injections (glucocorticoids, hyaluronic acid [HA], etc. New studies have focused on modern therapeutic methods that stimulate cartilage healing process and improve the damage, including the use of platelet-rich plasma (PRP as a complex of growth factors. Due to the high incidence of OA and its consequences, we decided to study the long-term effect of intraarticular injection of PRP and HA on clinical outcome and quality of life of patients with knee OA. Method This non-placebo-controlled randomized clinical trial involved 160 patients affected by knee OA, grade 1–4 of Kellgren–Lawrence scale. In the PRP group ( n = 87, two intra-articular injections at 4-week interval were applied, and in the HA group ( n = 73, three doses of intra-articular injection at 1-week interval were applied. All patients were prospectively evaluated before and at 12 months after the treatment by Western Ontario and McMaster Universities Arthritis Index (WOMAC and SF-36 questionnaires. The results were analyzed using SPSS 16.1 software (RCT code: IRCT2014012113442N5. Results At the 12-month follow-up, WOMAC pain score and bodily pain significantly improved in both groups; however, better results were determined in the PRP group compared to the HA group ( P < 0.001. Other WOMAC and SF-36 parameters improved only in the PRP group. More improvement (but not statistically significant was achieved in patients with grade 2 OA in both the groups. Conclusion This study suggests that PRP injection is more efficacious than HA injection in reducing symptoms and improving quality of life and is a therapeutic option in select patients with knee OA who have not responded to conventional treatment.

Microbicidal properties of Leukocyte- and Platelet-Rich Plasma/Fibrin (L-PRP/L-PRF): new perspectives.

Science.gov (United States)

Cieslik-Bielecka, A; Dohan Ehrenfest, D M; Lubkowska, A; Bielecki, T

2012-01-01

Platelets, as main actors of the first stage of the healing process, play an important role in tissue repair. Their granules contain many active substances, particularly over 30 growth factors with significant effects on the resident cells at the site of injury, such as mesenchymal stem cells, chondrocytes, fibroblasts, osteoblasts. This potential may be increased by the concentration of the platelets, using platelet-rich plasma/fibrin products. In the four families of platelet concentrates, 2 families contain also significant concentrations of leukocytes: L-PRP (Leukocyte- and Platelet-Rich Plasma) and L-PRF (Leukocyte- and Platelet-Rich Fibrin). Inductive properties of platelet concentrates were widely described. However, they present also antimicrobial effects. The antibacterial effects of L-PRP were highlighted in only a few in vitro studies. Strong activity comparable to gentamicin and oxacillin for L-PRP against methicillin susceptible Staphylococcus aureus (MSSA) was already demonstrated. L-PRP also inhibited the growth of methicillin resistant Staphylococcus aureus (MRSA) and Escherichia coli. Some authors also reported clinical observations about the reduction of infections and the induction of healing processes after the use of platelet concentrates in cardiac, orthopaedic, oral and maxillofacial surgery. However, very little is yet known about the antibacterial effects of these concentrates. In this manuscript, the current data about the antimicrobial agents and cells present in the platelet-rich plasma/fibrin are highlighted and discussed, in order to introduce this new key chapter of the platelet concentrate technology history.

Dynamic Contacts of U2, RES, Cwc25, Prp8 and Prp45 Proteins with the Pre-mRNA Branch-Site and 3' Splice Site during Catalytic Activation and Step 1 Catalysis in Yeast Spliceosomes.

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Cornelius Schneider

Full Text Available Little is known about contacts in the spliceosome between proteins and intron nucleotides surrounding the pre-mRNA branch-site and their dynamics during splicing. We investigated protein-pre-mRNA interactions by UV-induced crosslinking of purified yeast B(act spliceosomes formed on site-specifically labeled pre-mRNA, and analyzed their changes after conversion to catalytically-activated B* and step 1 C complexes, using a purified splicing system. Contacts between nucleotides upstream and downstream of the branch-site and the U2 SF3a/b proteins Prp9, Prp11, Hsh49, Cus1 and Hsh155 were detected, demonstrating that these interactions are evolutionarily conserved. The RES proteins Pml1 and Bud13 were shown to contact the intron downstream of the branch-site. A comparison of the B(act crosslinking pattern versus that of B* and C complexes revealed that U2 and RES protein interactions with the intron are dynamic. Upon step 1 catalysis, Cwc25 contacts with the branch-site region, and enhanced crosslinks of Prp8 and Prp45 with nucleotides surrounding the branch-site were observed. Cwc25's step 1 promoting activity was not dependent on its interaction with pre-mRNA, indicating it acts via protein-protein interactions. These studies provide important insights into the spliceosome's protein-pre-mRNA network and reveal novel RNP remodeling events during the catalytic activation of the spliceosome and step 1 of splicing.

On the extent of homogeneity region of PrP phase in the system praseodymium-phosphorus

International Nuclear Information System (INIS)

Mironov, K.E.

1984-01-01

For constructed by ion type compounds in the metal or metalloid systems homogeneity region boundary position can be observed at different compositions depending on which side the approximation to it occurs: on the metal or compound side. As an example the PrP homogeneity region in the praseodymium-phosphorus system is considered. An assumption is made on the prevalence of this phenomenon among rare earth monopnictides and monochalcogenides. For the PrP phase it is indicated that the monophopshide cell parameter depends on content of impurities in the initial metal, oxygen, in particular

Recent Advances in Fractional Laser Resurfacing: New Paradigm in Optimal Parameters and Post-Treatment Wound Care

Science.gov (United States)

Hsiao, Francis C.; Bock, Gerald N.; Eisen, Daniel B.

2012-01-01

Background Laser plays an increasingly prominent role in skin rejuvenation. The advent of fractional photothermolysis revolutionizes its application. Microcolumns of skin are focally injured, leaving intervening normal skin to facilitate rapid wound healing and orderly tissue remodeling. The Problem Even with the popularity of fractional laser devices, we still have limited knowledge about the ideal treatment parameters and postlaser wound care. Basic/Clinical Science Advances Many clinicians believe that higher microbream energy in fractional laser devices results in better clinical outcome. Two recent studies argue against this assumption. One article demonstrates that lower fluence can induce comparable molecular changes with fewer side effects. Another study corroborates this by showing that lower-density settings produce similar clinical outcome in scar remodeling as higher-density ones, but with fewer side effects. To shed light on the optimal post-treatment wound care regimen from fractional ablative resurfacing, another paper shows that platelet-rich plasma (PRP) can reduce transepidermal water loss and skin color changes within 1 month after treatment. Clinical Care Relevance For fractional nonablative resurfacing, lower settings in fluence or density may produce similar dermal remodeling as higher settings and with a better side-effect profile. Moreover, autologous PRP appears to expedite wound healing after fractional ablative resurfacing. Conclusion Lower microbeam energy in fractional laser resurfacing produces similar molecular changes and clinical outcome with fewer side effects. The findings might portend a shift in the paradigm of treatment parameters. Autologous PRP can facilitate better wound healing, albeit modestly. Long-term follow-ups and larger studies are necessary to confirm these findings. PMID:24527307

The Locus of Tool-Transformation Costs

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Kunde, Wilfried; Pfister, Roland; Janczyk, Markus

2012-01-01

Transformations of hand movements by tools such as levers or electronic input devices can invoke performance costs compared to untransformed movements. This study investigated by means of the Psychological Refractory Period (PRP) paradigm at which stage of information processing such tool-transformation costs arise. We used an inversion…

Platelet-rich plasma (PRP) and adipose-derived mesenchymal stem cells: stimulatory effects on proliferation and migration of fibroblasts and keratinocytes in vitro.

Science.gov (United States)

Stessuk, Talita; Puzzi, Maria Beatriz; Chaim, Elinton Adami; Alves, Paulo César Martins; de Paula, Erich Vinicius; Forte, Andresa; Izumizawa, Juliana Massae; Oliveira, Carolina Caliári; Frei, Fernando; Ribeiro-Paes, João Tadeu

2016-09-01

The clinical use of tissue engineering associated with cell therapy is considered a new alternative therapy for the repair of chronic lesions with potential application in different medical areas, mostly in orthopedic and dermatological diseases. Platelet-rich plasma (PRP) is a rich source of growth factors and cytokines important for wound healing. Adipose-derived mesenchymal stem cells (ADSCs) have shown potential to accelerate the resolution of ulcers, to stimulate cell proliferation, and to benefit the quality of skin repair. This study aims to determine the effect of PRP and conditioned medium (CM) from ADSC on fibroblast and keratinocyte proliferation in vitro. Migration and proliferation assays were performed to evaluate the growth of fibroblasts and keratinocytes in the presence of PRP, CM, and CM + PRP. Significant proliferative stimulation was observed after 48 h of culture (p PRP, 100 % CM, and 25 % PRP + 25 % CM, if compared with control. Keratinocyte proliferation was stimulated after 48 h in cultures with 25, 50, and 100 % CM, and growth was compared with controls. The migration assay detected a significant migratory stimulus in fibroblasts cultured with 10 % PRP + 10 % CM after 48 h. These in vitro results suggest that PRP and ADSC have therapeutic potential for healing and re-epithelialization of chronic wounds in vivo.

Effect of Platelet-Rich Plasma (PRP versus Autologous Whole Blood on Pain and Function Improvement in Tennis Elbow: A Randomized Clinical Trial

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Seyed Ahmad Raeissadat

2014-01-01

Full Text Available Background. Autologous whole blood and platelet-rich plasma (PRP have been both suggested to treat chronic tennis elbow. The aim of the present study was to compare the effects of PRP versus autologous whole blood local injection in chronic tennis elbow. Methods. Forty patients with tennis elbow were randomly divided into 2 groups. Group 1 was treated with a single injection of 2 mL of autologous PRP and group 2 with 2 mL of autologous blood. Tennis elbow strap, stretching, and strengthening exercises were administered for both groups during a 2-month followup. Pain and functional improvements were assessed using visual analog scale (VAS, modified Mayo Clinic performance index for the elbow, and pressure pain threshold (PPT at 0, 4, and 8 weeks. Results. All pain and functional variables including VAS, PPT, and Mayo scores improved significantly in both groups 4 weeks after injection. No statistically significant difference was noted between groups regarding pain scores in 4-week follow-up examination (P>0.05. At 8-week reevaluations, VAS and Mayo scores improved only in PRP group (P<0.05. Conclusion. PRP and autologous whole blood injections are both effective to treat chronic lateral epicondylitis. PRP might be slightly superior in 8-week followup. However, further studies are suggested to get definite conclusion.

Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study.

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Togashi, Takehiro; Mitsuya, Nodoka; Kogawara, Osamu; Sumino, Shuji; Takanami, Yohei; Sugizaki, Kayoko

2016-08-31

Broad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013. We compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria-tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the "long-term seroprotection rate", defined as the group proportion with anti-PRP antibody titers ⩾1.0μg/mL, after the primary series. Long-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group - PRP-T group) was 3.7% (95% confidence interval: 0.099-7.336), demonstrating that PRP-CRM197 vaccine was non-inferior to PRP-T vaccine (pvaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles. The immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns. Registered on ClinicalTrials.gov: NCT01379846. Copyright © 2016 The Authors

The relative kicking frequency of infants born full-term and preterm during learning and short-term and long-term memory periods of the mobile paradigm.

Science.gov (United States)

Heathcock, Jill C; Bhat, Anjana N; Lobo, Michele A; Galloway, James C

2005-01-01

Infants born preterm differ in their spontaneous kicking, as well as their learning and memory abilities in the mobile paradigm, compared with infants born full-term. In the mobile paradigm, a supine infant's ankle is tethered to a mobile so that leg kicks cause a proportional amount of mobile movement. The purpose of this study was to investigate the relative kicking frequency of the tethered (right) and nontethered (left) legs in these 2 groups of infants. Ten infants born full-term and 10 infants born preterm (infants participated in the study. The relative kicking frequencies of the tethered and nontethered legs were analyzed during learning and short-term and long-term memory periods of the mobile paradigm. Infants born full-term showed an increase in the relative kicking frequency of the tethered leg during the learning period and the short-term memory period but not for the long-term memory period. Infants born preterm did not show a change in kicking pattern for learning or memory periods, and consistently kicked both legs in relatively equal amounts. Infants born full-term adapted their baseline kicking frequencies in a task-specific manner to move the mobile and then retained this adaptation for the short-term memory period. In contrast, infants born preterm showed no adaptation, suggesting a lack of purposeful leg control. This lack of control may reflect a general decrease in the ability of infants born preterm to use their limb movements to interact with their environment. As such, the mobile paradigm may be clinically useful in the early assessment and intervention of infants born preterm and at risk for future impairment.

Oxidation reduces the fibrillation but not the neurotoxicity of the prion peptide PrP106-126

DEFF Research Database (Denmark)

Bergstrøm, Linda Alice; Chabry, J.; Bastholm, L.

2007-01-01

There is increasing evidence that soluble oligomers of misfolded protein may play a role in the pathogenesis of protein misfolding diseases including the transmissible spongiform encephalopathies (TSE) where the protein involved is the prion protein, PrP. The effect of oxidation on fibrillation...... tendency and neurotoxicity of different molecular variants of the prion peptide PrP106-126 was investigated. It was found that methionine oxidation significantly reduced amyloid fibril formation and proteinase K resistance, but it did not reduce (but rather increase slightly) the neurotoxicity...

PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice

NARCIS (Netherlands)

McBride, P. A.; Eikelenboom, P.; Kraal, G.; Fraser, H.; Bruce, M. E.

1992-01-01

Abnormal forms of a host protein, PrP, accumulate in the central nervous system in scrapie-affected animals. Here, PrP protein was detected immunocytochemically in tissue sections of spleen, lymph node, Peyer's patches, thymus, and pancreas from uninfected mice and from mice infected with a range of

In search of a consensus terminology in the field of platelet concentrates for surgical use: platelet-rich plasma (PRP), platelet-rich fibrin (PRF), fibrin gel polymerization and leukocytes.

Science.gov (United States)

Dohan Ehrenfest, David M; Bielecki, Tomasz; Mishra, Allan; Borzini, Piero; Inchingolo, Francesco; Sammartino, Gilberto; Rasmusson, Lars; Everts, Peter A

2012-06-01

In the field of platelet concentrates for surgical use, most products are termed Platelet-Rich Plasma (PRP). Unfortunately, this term is very general and incomplete, leading to many confusions in the scientific database. In this article, a panel of experts discusses this issue and proposes an accurate and simple terminology system for platelet concentrates for surgical use. Four main categories of products can be easily defined, depending on their leukocyte content and fibrin architecture: Pure Platelet-Rich Plasma (P-PRP), such as cell separator PRP, Vivostat PRF or Anitua's PRGF; Leukocyteand Platelet-Rich Plasma (L-PRP), such as Curasan, Regen, Plateltex, SmartPReP, PCCS, Magellan, Angel or GPS PRP; Pure Plaletet-Rich Fibrin (P-PRF), such as Fibrinet; and Leukocyte- and Platelet-Rich Fibrin (L-PRF), such as Choukroun's PRF. P-PRP and L-PRP refer to the unactivated liquid form of these products, their activated versions being respectively named P-PRP gels and L-PRP gels. The purpose of this search for a terminology consensus is to plead for a more serious characterization of these products. Researchers have to be aware of the complex nature of these living biomaterials, in order to avoid misunderstandings and erroneous conclusions. Understanding the biomaterials or believing in the magic of growth factors ? From this choice depends the future of the field.

Superfund TIO videos. Set B. Basics of administrative law, and prp search process: PRP search, information exchange and access. Part 3. Audio-Visual

International Nuclear Information System (INIS)

1990-01-01

The videotape is divided into two sections. Section 1 identifies the various types of administrative hearings, including quasi-legislative, quasi-judicial, and hybrid types. Section 2 provides an overview of the PRP search process; explains how and when to issue Section 104(e) letters and administrative subpoenas; outlines the enforcement authorities available in cases of non-compliance; and describes the types of information that can be released to PRPs

Adjunctive Platelet-Rich Plasma (PRP in Infrabony Regenerative Treatment: A Systematic Review and RCT’s Meta-Analysis

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Mubashir Saleem

2018-01-01

Full Text Available Background and Objective. The purpose of this study was to highlight the clinical performance of platelet-rich plasma (PRP used as an adjunctive tool for regeneration in infrabony periodontal defects using different biomaterials or performing different surgical flap approaches. Comparative evaluation of main clinical outcomes as probing pocket depth reduction, clinical attachment gain, and recession reduction with and without the use of PRP has been analysed. Materials and Methods. According to the focused question, an electronic and hand searching has been performed up to December 2016. From a batch of 73 articles, the selection strategy and Jadad quality assessment led us to include 15 studies for the meta-analysis. Results. Despite the high heterogeneity found and the lack of complete data regarding the selected clinical outcomes, a comparative analysis has been possible by the categorization of used biomaterials and surgical flap approaches. This method led us to observe the best performance of grafts with the use of adjunctive PRP in CAL gain and PPD reduction. No difference has been outlined with a specific surgical flap. Conclusions. Although PRP is considered a cheap and patient’s derived growth factor, the not conclusive data reported would suggest that its use in addition to bone substitutes could be of some clinical benefit in the regenerative treatment of infrabony defects. Clinical Relevance. This systematic review was intended to sort out the huge controversial debate in the field about the possible use of PRP in regenerative surgery in infrabony defect. The clinical relevance of using blood-borne growth factors to conventional procedures is effective as these could determine a better performance and outcomes despite the surgical approach adopted and limit the use of additional biomaterials for the blood clot stabilization.

PrP(ST), a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease.

Science.gov (United States)

Friedman-Levi, Yael; Mizrahi, Michal; Frid, Kati; Binyamin, Orli; Gabizon, Ruth

2013-01-01

While the conversion of PrP(C) into PrP(Sc) in the transmissible form of prion disease requires a preexisting PrP(Sc) seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrP(ST)), a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrP(ST) as in TgMHu2ME199K mice, and "classical" PrP(Sc) as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition.

PrP(ST, a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease.

Directory of Open Access Journals (Sweden)

Yael Friedman-Levi

Full Text Available While the conversion of PrP(C into PrP(Sc in the transmissible form of prion disease requires a preexisting PrP(Sc seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrP(ST, a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrP(ST as in TgMHu2ME199K mice, and "classical" PrP(Sc as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition.

A Randomized, Controlled Study of DTaP-IPV-HB-PRP-T, a Fully Liquid Hexavalent Vaccine, Administered in a 3-, 5- and 11- to 12-month Schedule.

Science.gov (United States)

Vesikari, Timo; Silfverdal, Sven-Arne; Jordanov, Emilia; Feroldi, Emmanuel

2017-01-01

To assess the immunogenicity and safety of a fully liquid, ready-to-use hexavalent DTaP-IPV-HB-PRP-T vaccine when administered in a 2 + 1 schedule at 3, 5 and 11-12 months of age. Phase III, randomized, active-controlled, observer-blind, multicenter study. Infants were randomized to receive DTaP-IPV-HB-PRP-T (N = 275) or a licensed control hexavalent vaccine (DTaP-IPV-HB//PRP~T: N = 275), both given in coadministration with Prevenar 13. Serum was analyzed for immune responses to all vaccine antigens. Noninferiority of DTaP-IPV-HB-PRP-T to the control vaccine was tested at completion of the primary series using predefined seroprotection (SP) rate and vaccine response (VR) rates. Safety was assessed using parental reports. Noninferiority of DTaP-IPV-HB-PRP-T to the control vaccine was demonstrated postdose 3 for each antigen, and the SP (for D, T, poliovirus 1, 2 and 3, hepatitis B and polyribosylribitol phosphate) and VR rates (for pertussis toxin and filamentous hemagglutinin) were high in each group. SP rates for D, T, polio 1, 2, 3 and VR rates for pertussis toxin and filamentous hemagglutinin were similar in each group. For hepatitis B, SP rate was slightly higher for DTaP-IPV-HB//PRP~T (99.6%) than DTaP-IPV-HB-PRP-T (96.4%), and for PRP, SP rate was higher for DTaP-IPV-HB-PRP-T (93.5%) than DTaP-IPV-HB//PRP~T (85.2%). For Prevenar 13, the SP rate was high for each serotype and similar for both groups. All vaccines were well tolerated. These study findings confirm the safety and immunogenicity and thus the suitability of this fully liquid hexavalent vaccine for administration in a 2 + 1 schedule.

Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial.

Science.gov (United States)

Görmeli, Gökay; Görmeli, Cemile Ayşe; Ataoglu, Baybars; Çolak, Cemil; Aslantürk, Okan; Ertem, Kadir

2017-03-01

To compare the effectiveness of intraarticular (IA) multiple and single platelet-rich plasma (PRP) injections as well as hyaluronic acid (HA) injections in different stages of osteoarthritis (OA) of the knee. A total of 162 patients with different stages of knee OA were randomly divided into four groups receiving 3 IA doses of PRP, one dose of PRP, one dose of HA or a saline injection (control). Then, each group was subdivided into two groups: early OA (Kellgren-Lawrence grade 0 with cartilage degeneration or grade I-III) and advanced OA (Kellgren-Lawrence grade IV). The patients were evaluated before the injection and at the 6-month follow-ups using the EuroQol visual analogue scale (EQ-VAS) and International Knee Documentation Committee (IKDC) subjective scores. Adverse events and patient satisfaction were recorded. There was a statistically significant improvement in the IKDC and EQ-VAS scores in all the treatment groups compared with the control group. The knee scores of patients treated with three PRP injections were significantly better than those patients of the other groups. There was no significant difference in the scores of patients injected with one dose of PRP or HA. In the early OA subgroups, significantly better clinical results were achieved in the patients treated with three PRP injections, but there was no significant difference in the clinical results of patients with advanced OA among the treatment groups. The clinical results of this study suggest IA PRP and HA treatment for all stages of knee OA. For patients with early OA, multiple (3) PRP injections are useful in achieving better clinical results. For patients with advanced OA, multiple injections do not significantly improve the results of patients in any group. I.

The Effect of Platelet-Rich Plasma (PRP on Improvement in Pain and Symptoms of Shoulder Subacromial Impingement Syndrome

Directory of Open Access Journals (Sweden)

Parisa Nejati

2015-08-01

Full Text Available Abstract Background: Subacromial impingement is one of the most common complaints of shoulder. Treatments include avoiding of painful activities, oral anti-pain drugs, physical therapy modalities, corticosteroid injection and exercise therapy. Some studies have shown that platelet- rich plasma(PRP is effective on tendinitis and tearing of tendons, ligaments and muscles, but evidence that has proved PRP as a conservative treatment in shoulder pathologies is very limited. This study aims to investigate the effect of PRP injection on relieving pain and improving daily function of patients with shoulder impingement syndrome. Materials and Methods: In this clinical trial study, patients older than 40 with pain more than three months were included. If they had three of four positive diagnostic clinical tests of shoulder impingement that were confirmed by shoulder MRI, could be injected PRP twice. The time between injections was 1 month. Pain was measured by visual analog scale (VAS and function was measured by two questionnaires named disabilities of the arm, shoulder and hand (DASH and western Ontario rotator cuff index (WORC. Range of motion (ROM of shoulder was measured in five directions by goniometry . All of these parameters were evaluated before intervention and in 1, 3, 6 months later. Results: with due attention to a six-month folloe-up, PRR injection was effective in pain reduction and improvement of patient's function (p<0.05. Shoulder Rom increased in all directions except external rotation and the power of shoulder muscles was evidently improved statistically in flexion, abduction and internal toration. Conclusion: PRP injection could effectively reduce pain and improve daily activities in patients with shoulder impingement syndrome.

Evidence for a central role of PrP helix 2 in the nucleation of amyloid fibrils.

Science.gov (United States)

Honda, Ryo; Kuwata, Kazuo

2018-02-01

Amyloid fibrils are filamentous protein aggregates associated with the pathogenesis of a wide variety of human diseases. The formation of such aggregates typically follows nucleation-dependent kinetics, wherein the assembly and structural conversion of amyloidogenic proteins into oligomeric aggregates (nuclei) is the rate-limiting step of the overall reaction. In this study, we sought to gain structural insights into the oligomeric nuclei of the human prion protein (PrP) by preparing a series of deletion mutants lacking 14-44 of the C-terminal 107 residues of PrP and examined the kinetics and thermodynamics of these mutants in amyloid formation. An analysis of the experimental data using the concepts of the Φ-value analysis indicated that the helix 2 region (residues 168-196) acquires an amyloid-like β-sheet during nucleation, whereas the other regions preserves a relatively disordered structure in the nuclei. This finding suggests that the helix 2 region serves as the nucleation site for the assembly of amyloid fibrils.-Honda, R., Kuwata, K. Evidence for a central role of PrP helix 2 in the nucleation of amyloid fibrils.

Familial CJD Associated PrP Mutants within Transmembrane Region Induced Ctm-PrP Retention in ER and Triggered Apoptosis by ER Stress in SH-SY5Y Cells

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Wang, Xin; Shi, Qi; Xu, Kun; Gao, Chen; Chen, Cao; Li, Xiao-Li; Wang, Gui-Rong; Tian, Chan; Han, Jun; Dong, Xiao-Ping

2011-01-01

Background Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP) gene that are presumed to favor conversion of the cellular isoform of PrP (PrPC) to the pathogenic one (PrPSc). The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K) into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. Methodology/Principal Findings To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER), the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL) and PrP with three amino acids exchange in transmembrane region (PrP-3AV) were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP) were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and capase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V) induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K) failed. Conclusions/Significance The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them the mutants

Familial CJD associated PrP mutants within transmembrane region induced Ctm-PrP retention in ER and triggered apoptosis by ER stress in SH-SY5Y cells.

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Xin Wang

Full Text Available BACKGROUND: Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP gene that are presumed to favor conversion of the cellular isoform of PrP (PrP(C to the pathogenic one (PrP(Sc. The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. METHODOLOGY/PRINCIPAL FINDINGS: To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER, the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL and PrP with three amino acids exchange in transmembrane region (PrP-3AV were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and caspase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K failed. CONCLUSIONS/SIGNIFICANCE: The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them

A modified three-term PRP conjugate gradient algorithm for optimization models.

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Wu, Yanlin

2017-01-01

The nonlinear conjugate gradient (CG) algorithm is a very effective method for optimization, especially for large-scale problems, because of its low memory requirement and simplicity. Zhang et al. (IMA J. Numer. Anal. 26:629-649, 2006) firstly propose a three-term CG algorithm based on the well known Polak-Ribière-Polyak (PRP) formula for unconstrained optimization, where their method has the sufficient descent property without any line search technique. They proved the global convergence of the Armijo line search but this fails for the Wolfe line search technique. Inspired by their method, we will make a further study and give a modified three-term PRP CG algorithm. The presented method possesses the following features: (1) The sufficient descent property also holds without any line search technique; (2) the trust region property of the search direction is automatically satisfied; (3) the steplengh is bounded from below; (4) the global convergence will be established under the Wolfe line search. Numerical results show that the new algorithm is more effective than that of the normal method.

Is Platelet-Rich Plasma (PRP) Effective in the Treatment of Acute Muscle Injuries? A Systematic Review and Meta-Analysis.

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Grassi, Alberto; Napoli, Francesca; Romandini, Iacopo; Samuelsson, Kristian; Zaffagnini, Stefano; Candrian, Christian; Filardo, Giuseppe

2018-04-01

Muscle lesions account for one-third of sport-related injuries, thus representing a substantial problem for both players and their teams. The use of platelet-rich plasma (PRP) injections is rapidly growing in clinical practice, prompted by an unmet clinical need with a large commercial market. However, after early reports of positive preliminary experience, higher quality studies recently questioned the real benefit provided by PRP injections to promote muscle healing and return to sport. To evaluate the effect of platelet-rich plasma (PRP) injections on outcomes following acute muscle injuries. Meta-analysis of randomized, controlled trials (RCTs), Level I. PubMed (MEDLINE), Cochrane (CENTRAL), Web of Science, clinicaltrials.gov, who.int, isrctn.com, greylit.org, opengrey.eu. RCTs investigating the effect of PRP for the treatment of acute muscle injuries against at least one control group including patients treated with placebo injection or physical therapy. The outcomes evaluated were time to return to sport, re-injuries, complications, pain, muscle strength, range of motion (ROM)/flexibility, muscle function, and imaging. Six studies, involving 374 patients, were included in the meta-analysis. The time to return to sport evaluated in all six studies was significantly shorter in patients treated with PRP (mean difference = - 7.17 days). However, if only the double-blind studies (n = 2) or studies including only hamstring injuries (n = 3) were considered, non-significant differences were found. Re-injuries (relative risk = - 0.03) and complications (relative risk = 0.01) were also similar between the two groups (p > 0.05), nor were any substantial differences found regarding pain, muscle strength, ROM/flexibility, muscle function, and imaging. The performance bias was high risk due to the lack of patient blinding in four studies. The quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was

Comparative assessment of prophylactic transfusions of platelet concentrates obtained by the PRP or buffy-coat methods, in patients undergoing allogeneic hematopoietic stem cell transplantation.

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Fernández-Muñoz, Hermógenes; Plaza, Eva M; Rivera-Caravaca, José Miguel; Candela, María José; Romera, Marta; De Arriba, Felipe; Lozano, María L; Vicente, Vicente; Heras, Inmaculada; Castilla-Llorente, Cristina; Rivera, José

2018-03-27

Whole blood-derived platelet concentrates can be obtained by the platelet-rich plasma (PRP-PCs) or the buffy-coat (BC-PCs) method. Few studies have shown that BC-PCs display lower in vitro platelet activation, but scarce information exists regarding transfusion efficacy. We have performed a retrospective study assessing platelet transfusion in patients undergoing allogeneic hematopoietic cell transplantation (AHCT) in our clinic, before and after the implementation of BC-PCs. We reviewed clinical records corresponding to 70 PRP-PCs and 86 BC-PCs prophylactic transfusions, which were performed to 55 AHCT patients. Transfusion efficacy was assessed by the 24-h post-transfusion corrected count increment (24-h CCI) and bleeding events. Clinical factors affecting transfusion outcome were also investigated. Clinical characteristics and the total number of platelet transfusions were similar among groups. Mean donor exposure was 5.8 and 5.0 in each single PRP-PCs and BC-PCs transfusion, respectively (p PRP-PCs (8.3[2.7-13.4] vs. 4.7[1.3-8.1]; p PRP-PCs transfusion (HR 4.54; 95% CI 1.72-12.01; p = 0.002). There were no differences between both groups regarding the bleeding events. In the AHCT setting, we hypothesize that BC-PCs transfusion, when compared to PRP-PCs, results in higher CCI and reduced donor exposure, but provides no significant benefit regarding bleeding outcome.

The folding mechanism and key metastable state identification of the PrP127-147 monomer studied by molecular dynamics simulations and Markov state model analysis.

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Zhou, Shuangyan; Wang, Qianqian; Wang, Yuwei; Yao, Xiaojun; Han, Wei; Liu, Huanxiang

2017-05-10

The structural transition of prion proteins from a native α-helix (PrP C ) to a misfolded β-sheet-rich conformation (PrP Sc ) is believed to be the main cause of a number of prion diseases in humans and animals. Understanding the molecular basis of misfolding and aggregation of prion proteins will be valuable for unveiling the etiology of prion diseases. However, due to the limitation of conventional experimental techniques and the heterogeneous property of oligomers, little is known about the molecular architecture of misfolded PrP Sc and the mechanism of structural transition from PrP C to PrP Sc . The prion fragment 127-147 (PrP127-147) has been reported to be a critical region for PrP Sc formation in Gerstmann-Straussler-Scheinker (GSS) syndrome and thus has been used as a model for the study of prion aggregation. In the present study, we employ molecular dynamics (MD) simulation techniques to study the conformational change of this fragment that could be relevant to the PrP C -PrP Sc transition. Employing extensive replica exchange molecular dynamics (REMD) and conventional MD simulations, we sample a huge number of conformations of PrP127-147. Using the Markov state model (MSM), we identify the metastable conformational states of this fragment and the kinetic network of transitions between the states. The resulting MSM reveals that disordered random-coiled conformations are the dominant structures. A key metastable folded state with typical extended β-sheet structures is identified with Pro137 being located in a turn region, consistent with a previous experimental report. Conformational analysis reveals that intrapeptide hydrophobic interaction and two key residue interactions, including Arg136-His140 and Pro137-His140, contribute a lot to the formation of ordered extended β-sheet states. However, network pathway analysis from the most populated disordered state indicates that the formation of extended β-sheet states is quite slow (at the millisecond

A Randomized Controlled Study of a Fully Liquid DTaP-IPV-HB-PRP-T Hexavalent Vaccine for Primary and Booster Vaccinations of Healthy Infants and Toddlers in Latin America.

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López, Pío; Arguedas Mohs, Adriano; Abdelnour Vásquez, Arturo; Consuelo-Miranda, Maria; Feroldi, Emmanuel; Noriega, Fernando; Jordanov, Emilia; B Chir, Siham; Zambrano, Betzana

2017-11-01

Hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-HB-PRP-T)-containing vaccines are increasingly the standard of care. This study evaluated the primary series (NCT01177722) and booster (NCT01444781) of a fully liquid DTaP-IPV-HB-PRP-T vaccine in Latin America. Infants (N = 1375) received hepatitis B vaccine at birth and were randomized to one of 3 batches of the investigational DTaP-IPV-HB-PRP-T or licensed control vaccine (DTaP-HB-IPV//PRP-T) at 2-4 to 6 months of age, coadministered with 7-valent pneumococcal conjugate vaccine (PCV7) (2-4-6 months) and rotavirus vaccine (2-4 months). A booster of either DTaP-IPV-HB-PRP-T or control was given at 12-24 months, coadministered with PCV7. Immunogenicity was assessed by validated assays and safety from parental reports. Primary series seroprotection and vaccine response rates were equivalent for DTaP-IPV-HB-PRP-T batches. For pooled batches, noninferiority to the control vaccine was demonstrated for each antigen. There were no descriptive differences in antibody persistence or booster response between DTaP-IPV-HB-PRP-T and the control. The booster responses to either vaccine following DTaP-IPV-HB-PRP-T primary series or to DTaP-IPV-HB-PRP-T following a control vaccine primary series were similar. The anti-aP component (filamentous hemagglutinin [FHA] and pertussis toxin [PT]) vaccine response and anti-Haemophilus influenzae type b (PRP) series seroprotection (≥0.15 µg/mL) rates were ≥73.0% after 2 primary series doses. Antipyretics had no effect on the immune response, and an extra (oral) polio vaccination had no effect on the antipolio booster response. Responses to PCV7 and rotavirus vaccine were similar for each coadministration. There were no safety concerns observed with any vaccine. These results confirm the suitability of the fully liquid DTaP-IPV-HB-PRP-T vaccine for primary and booster vaccination of infants.

Tendinopathies and platelet-rich plasma (PRP: from pre-clinical experiments to therapeutic use

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Kaux JF

2015-05-01

Full Text Available Objectives: The restorative properties of platelets, through the local release of growth factors, are used in various medical areas. This article reviews fundamental and clinical research relating to platelet-rich plasma applied to tendinous lesions. Materials and method: Articles in French and English, published between 1 January 2012 and 31 December 2014. dealing with PRP and tendons were searched for using the Medline and Scopus data bases. Results: Forty-seven articles were identified which addressed pre-clinical and clinical studies: 27 relating to in vitro and in vivo animal studies and 20 relating to human studies. Of these, five addressed lateral epicondylitis, two addressed rotator cuff tendinopathies, ten dealt with patellar tendinopathies and three looked at Achilles tendinopathies. Conclusions: The majority of pre-clinical studies show that PRP stimulates the tendon's healing process. However, clinical series remain more controversial and level 1, controlled, randomised studies are still needed.

The α-helical C-terminal domain of full-length recombinant PrP converts to an in-register parallel β-sheet structure in PrP fibrils: evidence from solid state nuclear magnetic resonance.

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Tycko, Robert; Savtchenko, Regina; Ostapchenko, Valeriy G; Makarava, Natallia; Baskakov, Ilia V

2010-11-09

We report the results of solid state nuclear magnetic resonance (NMR) measurements on amyloid fibrils formed by the full-length prion protein PrP (residues 23−231, Syrian hamster sequence). Measurements of intermolecular 13C−13C dipole−dipole couplings in selectively carbonyl-labeled samples indicate that β-sheets in these fibrils have an in-register parallel structure, as previously observed in amyloid fibrils associated with Alzheimer’s disease and type 2 diabetes and in yeast prion fibrils. Two-dimensional 13C−13C and 15N−13C solid state NMR spectra of a uniformly 15N- and 13C-labeled sample indicate that a relatively small fraction of the full sequence, localized to the C-terminal end, forms the structurally ordered, immobilized core. Although unique site-specific assignments of the solid state NMR signals cannot be obtained from these spectra, analysis with a Monte Carlo/simulated annealing algorithm suggests that the core is comprised primarily of residues in the 173−224 range. These results are consistent with earlier electron paramagnetic resonance studies of fibrils formed by residues 90−231 of the human PrP sequence, formed under somewhat different conditions [Cobb, N. J., Sonnichsen, F. D., McHaourab, H., and Surewicz, W. K. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 18946−18951], suggesting that an in-register parallel β-sheet structure formed by the C-terminal end may be a general feature of PrP fibrils prepared in vitro.

Role of Ultrasound Guided Platelet-Rich Plasma (PRP Injection in Treatment of Lateral Epicondylitis

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Enass M. Khattab

2017-06-01

Conclusion: We concluded that US-guided platelet-rich plasma (PRP injection for treatment of lateral epicondylitis was a safe, minimally invasive and effective procedure in improving the sonographic and pathological changes of common extensor tendon (CET.

Winnicott's paradigm outlined

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Zeljko Loparic

Full Text Available The main objective of this paper is to present a unified view of Winnicott’s contribution to psychoanalysis. Part I (Sections 1-4 starts off by recalling that, according to some important commentators, Winnicott introduced a change in paradigms in psychoanalysis. In order to show that this change can be viewed as an overall “switch in paradigms”, in the sense given by T. S. Kuhn, this paper presents an account of the Kuhn’s view of science and offers a reconstruction of Freud’s Oedipal, Triangular or “Toddler-in-the-Mother’s-Bed” Paradigm. Part II (Sections 5-13 shows that as early as the 1920’s Winnicott encountered insurmountable anomalies in the Oedipal paradigm and, for that reason, started what can be called revolutionary research for a new framework of psychoanalysis. This research led Winnicott, especially during the last period of his life, to produce an alternative dual or “Baby-on-the-Mother’s-Lap” Paradigm. This new paradigm is described in some detail, especially the paradigmatic dual mother-baby relation and Winnicott’s dominant theory of maturation. Final remarks are made regarding Winnicott’s heritage and the future of psychoanalysis.

Evaluation of the effect of platelet rich plasma (PRP) on enhancement of bone healing in diaphyseal bone defects by radiography and computed tomography

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Özak, Ahmet; Yardimci, Cenk; Nİsbet, Özlem H.; Bayrak, İlkay Koray; Nİsbet, Cevat

2010-01-01

The effect of platelet-rich plasma (PRP) with autogenous cancellous bone graft on enhancement of bone healing in diaphyseal bone defects was evaluated. A 4-mm defect was created in the middiaphysis of the tibias of 20 rabbits. Rabbits were divided into two groups of ten animals each: only autogenous cancellous graft, PRP and autogenous cancellous graft. In animals of group 1, only autogenous cancellous grafts, and to those in group 2, PRP and autogenous cancellous grafts, were applied to the defect. Radiographical and computed tomography (CT) views were taken and evaluated on postoperative days 0, 15, 30, 60, and 90. According to the bone formation, union, and remodeling scores, group 1 had better scores than group 2 on days 30, 60, and 90. The density was significantly increased on day 60 than on days 0, 15, and 30 in group 1. In conclusion, it was evaluated that PRP could not enhance the bone regeneration in diaphyseal defects when used with autogenous cancellous bone graft

Autologous US-guided PRP injection versus US-guided focal extracorporeal shock wave therapy for chronic lateral epicondylitis: A minimum of 2-year follow-up retrospective comparative study.

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Alessio-Mazzola, Mattia; Repetto, Ilaria; Biti, Besmir; Trentini, Roberto; Formica, Matteo; Felli, Lamberto

2018-01-01

To compare the efficacy of two independent groups of patients treated with ultrasound (US)-guided extracorporeal shock wave (ESW) therapy and with US-guided injection of platelet-rich plasma (PRP) for chronic lateral epicondylitis (LE) with a minimum of 2-year follow-up. We retrospectively evaluated 63 patients treated for chronic LE (31 patients with autologous US-guided PRP injection and 32 patients with US-guided focal ESW therapy) from 2009 to 2014. All the patients were evaluated by means of Roles-Maudsley (RM) score, quick Disabilities of Arm, Shoulder, and Hand (QuickDASH) score, visual analogic scale (VAS) and patient-rated tennis elbow evaluation (PRTEE) to retrospectively assess the pain relief, level of activity, the self-reported function and subjective satisfaction at minimum of 2-year follow-up. Both US-guided autologous PRP injection and US-guided focal ESW administration proved effective in chronic LE with significant improvement in the QuickDASH, VAS, RM and PRTEE scores ( p 0.05). The mean time between treatment and symptom resolution was significantly shorter for the PRP treatment ( p = 0.0212); furthermore, the mean time to return to the normal activities was quicker for PRP group ( p = 0.0119). Both PRP injection and ESW therapy are feasible and safe options for the treatment of chronic LE with low risk of complications and with good long-term follow-up results. US-guided PRP injection has quick efficacy when compared with US-guided focal ESW therapy.

A DTAP–IPV//PRP~T VACCINE: A REVIEW OF 16 YEARS’ CLINICAL EXPERIENCE

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Stanley A. Plotkin

2012-01-01

Full Text Available Owing to their low reactogenicity, confirmed efficacy and availability in combination vaccines, acellular pertussis (aP-inactivated poliovirus (IPV combined vaccines are now included in various national immunization programs worldwide. We provide an overview of 16 years of clinical experience with a diphtheria (D, tetanus (T, aP, IPV and Haemophilus influenzae type b (Hib polysaccharide conjugated to tetanus protein (PRP~T combined vaccine (DTaP–IPV//PRP~T — Pentaxim, Sanofi Pasteur, France. Good immunogenicity has been demonstrated after primary vaccination with Pentaxim, regardless of the population ethnicity and primary vaccination schedule. A booster vaccination in the second year of life also resulted in a high immune response for each antigen. Furthermore, 10 years of national surveillance in Sweden has demonstrated the effectiveness of Pentaxim in controlling pertussis. As is the case for other aP-containing combined vaccines, Pentaxim is well tolerated, with the safety profile being better than for whole-cell pertussiscontaining combination vaccines for primary and booster vaccinations.

Functional assessment of autologous platelet-rich plasma (PRP) after long-term storage at -20 °C without any preservation agent.

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Hosnuter, Mubin; Aslan, Cem; Isik, Daghan; Caliskan, Gorkem; Arslan, Banu; Durgun, Mustafa

2017-08-01

Platelet-rich plasma (PRP) is increasingly being used in the treatment of chronic wounds, pathologies of the musculoskeletal system, and in cosmetic medicine; however, the preparation of platelet-rich plasma is both time-consuming and requires invasive intervention. Additional costs are introduced if special equipment is used during preparation. The aim of the present study is to test whether autologous platelet-rich plasma (PRP) preserves the feature of growth factor release when stored at -20 °C after preparation. Autologous PRP concentrates were prepared using whole blood samples obtained from 20 healthy subjects and divided into three parts to form three groups. Epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet derived growth factor-AB (PDGF-AB), insulin-like growth factor 1 (IGF-1), transforming growth factor-beta (TGF-β), and P-Selectin levels were immediately analysed in the control group. The other groups were defined as the experimental groups and were stored at -20 °C and analysed on the 7th and the 14th days. The same growth factors were tested in the experimental groups. The growth factors (EGF, VEGF, PDGF-AB, IGF-1, TGF-β) and P-selectin levels were significantly decreased in the autologous PRP samples stored at -20 °C compared to the control group. The growth factor levels on days 7 and 14 suggest that autologous PRP can be stored at -20 °C without preservative agents, although in vivo studies are required in order to evaluate the clinical efficacy of the detected growth factor levels.

Glycosylphosphatidylinositol Anchor Modification Machinery Deficiency Is Responsible for the Formation of Pro-Prion Protein (PrP) in BxPC-3 Protein and Increases Cancer Cell Motility*

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Yang, Liheng; Gao, Zhenxing; Hu, Lipeng; Wu, Guiru; Yang, Xiaowen; Zhang, Lihua; Zhu, Ying; Wong, Boon-Seng; Xin, Wei; Sy, Man-Sun; Li, Chaoyang

2016-01-01

The normal cellular prion protein (PrP) is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein. However, in pancreatic ductal adenocarcinoma cell lines, such as BxPC-3, PrP exists as a pro-PrP retaining its glycosylphosphatidylinositol (GPI) peptide signaling sequence. Here, we report the identification of another pancreatic ductal adenocarcinoma cell line, AsPC-1, which expresses a mature GPI-anchored PrP. Comparison of the 24 genes involved in the GPI anchor modification pathway between AsPC-1 and BxPC-3 revealed 15 of the 24 genes, including PGAP1 and PIG-F, were down-regulated in the latter cells. We also identified six missense mutations in DPM2, PIG-C, PIG-N, and PIG-P alongside eight silent mutations. When BxPC-3 cells were fused with Chinese hamster ovary (CHO) cells, which lack endogenous PrP, pro-PrP was successfully converted into mature GPI-anchored PrP. Expression of the individual gene, such as PGAP1, PIG-F, or PIG-C, into BxPC-3 cells does not result in phosphoinositide-specific phospholipase C sensitivity of PrP. However, when PIG-F but not PIG-P is expressed in PGAP1-expressing BxPC-3 cells, PrP on the surface of the cells becomes phosphoinositide-specific phospholipase C-sensitive. Thus, low expression of PIG-F and PGAP1 is the major factor contributing to the accumulation of pro-PrP. More importantly, BxPC-3 cells expressing GPI-anchored PrP migrate much slower than BxPC-3 cells bearing pro-PrP. In addition, GPI-anchored PrP-bearing AsPC-1 cells also migrate slower than pro-PrP bearing BxPC-3 cells, although both cells express filamin A. “Knocking out” PRNP in BxPC-3 cell drastically reduces its migration. Collectively, these results show that multiple gene irregularity in BxPC-3 cells is responsible for the formation of pro-PrP, and binding of pro-PrP to filamin A contributes to enhanced tumor cell motility. PMID:26683373

Superior integrin activating capacity and higher adhesion to fibrinogen matrix in buffy coat-derived platelet concentrates (PCs) compared to PRP-PCs.

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Beshkar, Pezhman; Hosseini, Ehteramolsadat; Ghasemzadeh, Mehran

2018-02-01

Regardless of different sources, methods or devices which are applied for preparation of therapeutic platelets, these products are generally isolated from whole blood by the sedimentation techniques which are based on PRP or buffy coat (BC) separation. As a general fact, platelet preparation and storage are also associated with some deleterious changes that known as platelet storage lesion (PSL). Although these alternations in platelet functional activity are aggravated during storage, whether technical issues within preparation can affect integrin activation and platelet adhesion to fibrinogen were investigated in this study. PRP- and BC-platelet concentrates (PCs) were subjected to flowcytometry analysis to examine the expression of platelet activation marker, P-selectin as well as active confirmation of the GPIIb/IIIa (α IIb β 3 ) on day 0, 1, 3 and 5 post-storage. Platelet adhesion to fibrinogen matrix was evaluated by fluorescence microscopy. Glucose concentration and LDH activity were also measured by colorimetric methods. The increasing P-selectin expression during storage was in a reverse correlation with PAC-1 binding (r = -0.67; p = .001). PRP-PCs showed the higher level of P-selectin expression than BC-PCs, whereas the levels of PAC-1 binding and platelet adhesion to fibrinogen matrix were significantly lower in PRP-PCs. Higher levels of active confirmation of the GPIIb/IIIa in BC-PCs were also associated with greater concentration of glucose in these products. We demonstrated the superior capacities of integrin activation and adhesion to fibrinogen for BC-PCs compared to those of PRP-PCs. These findings may provide more advantages for BC method of platelet preparation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of strong selection for the PrP major gene on genetic variability of four French sheep breeds (Open Access publication

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Pantano Thais

2008-11-01

Full Text Available Abstract Effective selection on the PrP gene has been implemented since October 2001 in all French sheep breeds. After four years, the ARR "resistant" allele frequency increased by about 35% in young males. The aim of this study was to evaluate the impact of this strong selection on genetic variability. It is focussed on four French sheep breeds and based on the comparison of two groups of 94 animals within each breed: the first group of animals was born before the selection began, and the second, 3–4 years later. Genetic variability was assessed using genealogical and molecular data (29 microsatellite markers. The expected loss of genetic variability on the PrP gene was confirmed. Moreover, among the five markers located in the PrP region, only the three closest ones were affected. The evolution of the number of alleles, heterozygote deficiency within population, expected heterozygosity and the Reynolds distances agreed with the criteria from pedigree and pointed out that neutral genetic variability was not much affected. This trend depended on breed, i.e. on their initial states (population size, PrP frequencies and on the selection strategies for improving scrapie resistance while carrying out selection for production traits.

Semisynthetic prion protein (PrP) variants carrying glycan mimics at position 181 and 197 do not form fibrils† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc02719b Click here for additional data file.

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Araman, Can; Thompson, Robert E.; Wang, Siyao; Hackl, Stefanie; Payne, Richard J.

2017-01-01

The prion protein (PrP) is an N-glycosylated protein attached to the outer leaflet of eukaryotic cell membranes via a glycosylphosphatidylinositol (GPI) anchor. Different prion strains have distinct glycosylation patterns and the extent of glycosylation of potentially pathogenic misfolded prion protein (PrPSc) has a major impact on several prion-related diseases (transmissible spongiform encephalopathies, TSEs). Based on these findings it is hypothesized that posttranslational modifications (PTMs) of PrP influence conversion of cellular prion protein (PrPC) into PrPSc and, as such, modified PrP variants are critical tools needed to investigate the impact of PTMs on the pathogenesis of TSEs. Here we report a semisynthetic approach to generate PrP variants modified with monodisperse polyethyleneglycol (PEG) units as mimics of N-glycans. Incorporating PEG at glycosylation sites 181 and 197 in PrP induced only small changes to the secondary structure when compared to unmodified, wildtype PrP. More importantly, in vitro aggregation was abrogated for all PEGylated PrP variants under conditions at which wildtype PrP aggregated. Furthermore, the addition of PEGylated PrP as low as 10 mol% to wildtype PrP completely blocked aggregation. A similar effect was observed for synthetic PEGylated PrP segments comprising amino acids 179–231 alone if these were added to wildtype PrP in aggregation assays. This behavior raises the question if large N-glycans interfere with aggregation in vivo and if PEGylated PrP peptides could serve as potential therapeutics. PMID:28989689

No effects of PRP on ultrasonographic tendon structure and neovascularisation in chronic midportion Achilles tendinopathy

NARCIS (Netherlands)

de Vos, R. J.; Weir, A.; Tol, J. L.; Verhaar, J. A. N.; Weinans, H.; van Schie, H. T. M.

2011-01-01

To assess whether a platelet-rich plasma (PRP) injection leads to an enhanced tendon structure and neovascularisation, measured with ultrasonographic techniques, in chronic midportion Achilles tendinopathy. Double-blind, randomised, placebo-controlled clinical trial. Sports medical department of The

Behavior of Gingival Fibroblasts on Titanium Implant Surfaces in Combination with either Injectable-PRF or PRP

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Xuzhu Wang

2017-02-01

Full Text Available Various strategies have been employed to speed tissue regeneration using bioactive molecules. Interestingly, platelet concentrates derived from a patient’s own blood have been utilized as a regenerative strategy in recent years. In the present study, a novel liquid platelet formulation prepared without the use of anti-coagulants (injectable-platelet-rich fibrin, i-PRF was compared to standard platelet-rich plasma (PRP with gingival fibroblasts cultured on smooth and roughened titanium implant surfaces. Standard PRP and i-PRF (centrifuged at 700 rpm (60× g for 3 min were compared by assays for fibroblast biocompatibility, migration, adhesion, proliferation, as well as expression of platelet-derived growth factor (PDGF, transforming growth factor-β (TGF-β, collagen1 (COL1 and fibronectin (FN. The results demonstrate that i-PRF induced significantly higher cell migration, as well as higher messenger RNA (mRNA levels of PDGF, TGF-β, collagen1 and fibronectin when compared to PRP. Furthermore, collagen1 synthesis was highest in the i-PRF group. These findings demonstrate that liquid platelet concentrates can be formulated without the use of anticoagulants and present much translational potential for future research. Future animal and clinical trials are now necessary to further investigate the potential of utilizing i-PRF for soft tissue regenerative protocols in combination with various biomaterials.

Combined use of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and platelet rich plasma (PRP) stimulates proliferation and differentiation of myoblasts in vitro: new therapeutic perspectives for skeletal muscle repair/regeneration.

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Sassoli, Chiara; Vallone, Larissa; Tani, Alessia; Chellini, Flaminia; Nosi, Daniele; Zecchi-Orlandini, Sandra

2018-02-05

Satellite cell-mediated skeletal muscle repair/regeneration is compromised in cases of extended damage. Bone marrow mesenchymal stromal cells (BM-MSCs) hold promise for muscle healing but some criticisms hamper their clinical application, including the need to avoid animal serum contamination for expansion and the scarce survival after transplant. In this context, platelet-rich plasma (PRP) could offer advantages. Here, we compare the effects of PRP or standard culture media on C2C12 myoblast, satellite cell and BM-MSC viability, survival, proliferation and myogenic differentiation and evaluate PRP/BM-MSC combination effects in promoting myogenic differentiation. PRP induced an increase of mitochondrial activity and Ki67 expression comparable or even greater than that elicited by standard media and promoted AKT signaling activation in myoblasts and BM-MSCs and Notch-1 pathway activation in BM-MSCs. It stimulated MyoD, myogenin, α-sarcomeric actin and MMP-2 expression in myoblasts and satellite cell activation. Notably, PRP/BM-MSC combination was more effective than PRP alone. We found that BM-MSCs influenced myoblast responses through a paracrine activation of AKT signaling, contributing to shed light on BM-MSC action mechanisms. Our results suggest that PRP represents a good serum substitute for BM-MSC manipulation in vitro and could be beneficial towards transplanted cells in vivo. Moreover, it might influence muscle resident progenitors' fate, thus favoring the endogenous repair/regeneration mechanisms. Finally, within the limitations of an in vitro experimentation, this study provides an experimental background for considering the PRP/BM-MSC combination as a potential therapeutic tool for skeletal muscle damage, combining the beneficial effects of BM-MSCs and PRP on muscle tissue, while potentiating BM-MSC functionality.

Glycosylphosphatidylinositol Anchor Modification Machinery Deficiency Is Responsible for the Formation of Pro-Prion Protein (PrP) in BxPC-3 Protein and Increases Cancer Cell Motility.

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Yang, Liheng; Gao, Zhenxing; Hu, Lipeng; Wu, Guiru; Yang, Xiaowen; Zhang, Lihua; Zhu, Ying; Wong, Boon-Seng; Xin, Wei; Sy, Man-Sun; Li, Chaoyang

2016-02-19

The normal cellular prion protein (PrP) is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein. However, in pancreatic ductal adenocarcinoma cell lines, such as BxPC-3, PrP exists as a pro-PrP retaining its glycosylphosphatidylinositol (GPI) peptide signaling sequence. Here, we report the identification of another pancreatic ductal adenocarcinoma cell line, AsPC-1, which expresses a mature GPI-anchored PrP. Comparison of the 24 genes involved in the GPI anchor modification pathway between AsPC-1 and BxPC-3 revealed 15 of the 24 genes, including PGAP1 and PIG-F, were down-regulated in the latter cells. We also identified six missense mutations in DPM2, PIG-C, PIG-N, and PIG-P alongside eight silent mutations. When BxPC-3 cells were fused with Chinese hamster ovary (CHO) cells, which lack endogenous PrP, pro-PrP was successfully converted into mature GPI-anchored PrP. Expression of the individual gene, such as PGAP1, PIG-F, or PIG-C, into BxPC-3 cells does not result in phosphoinositide-specific phospholipase C sensitivity of PrP. However, when PIG-F but not PIG-P is expressed in PGAP1-expressing BxPC-3 cells, PrP on the surface of the cells becomes phosphoinositide-specific phospholipase C-sensitive. Thus, low expression of PIG-F and PGAP1 is the major factor contributing to the accumulation of pro-PrP. More importantly, BxPC-3 cells expressing GPI-anchored PrP migrate much slower than BxPC-3 cells bearing pro-PrP. In addition, GPI-anchored PrP-bearing AsPC-1 cells also migrate slower than pro-PrP bearing BxPC-3 cells, although both cells express filamin A. "Knocking out" PRNP in BxPC-3 cell drastically reduces its migration. Collectively, these results show that multiple gene irregularity in BxPC-3 cells is responsible for the formation of pro-PrP, and binding of pro-PrP to filamin A contributes to enhanced tumor cell motility. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Quantification of platelets and platelet derived growth factors from platelet-rich-plasma (PRP) prepared at different centrifugal force (g) and time.

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Arora, Satyam; Doda, Veena; Kotwal, Urvershi; Dogra, Mitu

2016-02-01

Platelet derived biomaterials represent a key source of cytokines and growth factors extensively used for tissue regeneration; wound healing and tissue repair. Our study was to quantify platelets and growth factors released by PRP when prepared at different centrifugal force (g) and time. Our study was approved by the institutional ethical committee. One hundred millilitres of whole blood (WB) was collected in bag with CPDA as the anticoagulant(AC); (14 mL for 100 mL WB ratio). Nine aliquots of 10 mL each were made from the bag and set of three aliquots were made a group. PRP was prepared at varying centrifugal force (group A: -110 g, group B: -208 g & group C: -440 g) & time (1: -5 min, 2: -10 min & 3: -20 min). Contents of each PRP prepared were analysed. Commercial sandwich ELISA kits were used to quantify the concentrations of CD62P (Diaclone SAS; France), Platelet derived growth factors-AB (Qayee-Bio; China), transforming growth factor-β1 (DRG; Germany) and vascular endothelial growth factor (Boster Immuno Leader; USA) released in each PRP prepared. Eight volunteers were enrolled in the study (24-30 years). The baseline blood counts of all the volunteers were comparable (p ≥ 0.05). Mean ± SD of platelet yield of all nine groups ranged from 17.2 ± 4.2% to 78.7 ± 5.7%. Each PRP was activated with calcified thromboplastin to quantify the growth factors released by them. Significantly higher (p < 0.05) transforming growth factor-β1 and vascular endothelial growth factor were released compared to the baseline. Our study highlights the variation in both force (g) and time results in changes at cellular level and growth factor concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intra-articular platelet-rich plasma (PRP) injections for treating knee pain associated with osteoarthritis of the knee in the Japanese population: a phase I and IIa clinical trial.

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Taniguchi, Yu; Yoshioka, Tomokazu; Kanamori, Akihiro; Aoto, Katsuya; Sugaya, Hisashi; Yamazaki, Masashi

2018-02-01

Intra-articular platelet-rich plasma (PRP) injection has been found to be effective for treating osteoarthritis in patients from Western countries; however, the safety and efficacy of PRP have not been sufficiently investigated in Japanese patients. The present study aimed to evaluate the safety and feasibility of intra-articular PRP injection in Japanese patients with knee osteoarthritis. PRP without white blood cells was prepared using a single-spin centrifuge (PRGF-Endoret; BTI Biotechnology Institute, Vitoria, Spain). A 6-mL PRP volume was injected in the knee joint three times at 1 week intervals. All patients were prospectively evaluated before intervention and at 1, 3, and 6 months after the treatment. Adverse events, the Visual Analog Scale (VAS) pain score, Japanese Knee Osteoarthritis Measure (JKOM) score and Japanese Orthopedic Association score were evaluated. Ten patients (all women; average age, 60.6 years) were treated. Only minor adverse events after injection were noted, and symptoms resolved within 48 hours after the injection. The average VAS pain scores were 71.6 mm and 18.4 mm at baseline and the 6-month follow-up, respectively (P PRP injection likely represents a safe treatment option for Japanese patients with mild-to-moderate knee osteoarthritis, and has the potential to relieve pain for up to 6 months, but further study is needed to verify the efficacy.

Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome.

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Saturveithan, C; Premganesh, G; Fakhrizzaki, S; Mahathir, M; Karuna, K; Rauf, K; William, H; Akmal, H; Sivapathasundaram, N; Jaspreet, K

2016-07-01

Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option.

Intra-articular Hyaluronic Acid (HA and Platelet Rich Plasma (PRP injection versus Hyaluronic acid (HA injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA: A Retrospective Study on Functional Outcome

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Saturveithan C

2016-07-01

Full Text Available Introduction: Intra-articular hyaluronic acid (HA is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option.

Substitutions of PrP N-terminal histidine residues modulate scrapie disease pathogenesis and incubation time in transgenic mice.

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Eigenbrod, Sabina; Frick, Petra; Bertsch, Uwe; Mitteregger-Kretzschmar, Gerda; Mielke, Janina; Maringer, Marko; Piening, Niklas; Hepp, Alexander; Daude, Nathalie; Windl, Otto; Levin, Johannes; Giese, Armin; Sakthivelu, Vignesh; Tatzelt, Jörg; Kretzschmar, Hans; Westaway, David

2017-01-01

Prion diseases have been linked to impaired copper homeostasis and copper induced-oxidative damage to the brain. Divalent metal ions, such as Cu2+ and Zn2+, bind to cellular prion protein (PrPC) at octapeptide repeat (OR) and non-OR sites within the N-terminal half of the protein but information on the impact of such binding on conversion to the misfolded isoform often derives from studies using either OR and non-OR peptides or bacterially-expressed recombinant PrP. Here we created new transgenic mouse lines expressing PrP with disrupted copper binding sites within all four histidine-containing OR's (sites 1-4, H60G, H68G, H76G, H84G, "TetraH>G" allele) or at site 5 (composed of residues His-95 and His-110; "H95G" allele) and monitored the formation of misfolded PrP in vivo. Novel transgenic mice expressing PrP(TetraH>G) at levels comparable to wild-type (wt) controls were susceptible to mouse-adapted scrapie strain RML but showed significantly prolonged incubation times. In contrast, amino acid replacement at residue 95 accelerated disease progression in corresponding PrP(H95G) mice. Neuropathological lesions in terminally ill transgenic mice were similar to scrapie-infected wt controls, but less severe. The pattern of PrPSc deposition, however, was not synaptic as seen in wt animals, but instead dense globular plaque-like accumulations of PrPSc in TgPrP(TetraH>G) mice and diffuse PrPSc deposition in (TgPrP(H95G) mice), were observed throughout all brain sections. We conclude that OR and site 5 histidine substitutions have divergent phenotypic impacts and that cis interactions between the OR region and the site 5 region modulate pathogenic outcomes by affecting the PrP globular domain.

Effects of Frequency and Motion Paradigm on Perception of Tilt and Translation During Periodic Linear Acceleration

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Beaton, K. H.; Holly, J. E.; Clement, G. R.; Wood, Scott J.

2009-01-01

Previous studies have demonstrated an effect of frequency on the gain of tilt and translation perception. Results from different motion paradigms are often combined to extend the stimulus frequency range. For example, Off-Vertical Axis Rotation (OVAR) and Variable Radius Centrifugation (VRC) are useful to test low frequencies of linear acceleration at amplitudes that would require impractical sled lengths. The purpose of this study was to compare roll-tilt and lateral translation motion perception in 12 healthy subjects across four paradigms: OVAR, VRC, sled translation and rotation about an earth-horizontal axis. Subjects were oscillated in darkness at six frequencies from 0.01875 to 0.6 Hz (peak acceleration equivalent to 10 deg, less for sled motion below 0.15 Hz). Subjects verbally described the amplitude of perceived tilt and translation, and used a joystick to indicate the direction of motion. Consistent with previous reports, tilt perception gain decreased as a function of stimulus frequency in the motion paradigms without concordant canal tilt cues (OVAR, VRC and Sled). Translation perception gain was negligible at low stimulus frequencies and increased at higher frequencies. There were no significant differences between the phase of tilt and translation, nor did the phase significantly vary across stimulus frequency. There were differences in perception gain across the different paradigms. Paradigms that included actual tilt stimuli had the larger tilt gains, and paradigms that included actual translation stimuli had larger translation gains. In addition, the frequency at which there was a crossover of tilt and translation gains appeared to vary across motion paradigm between 0.15 and 0.3 Hz. Since the linear acceleration in the head lateral plane was equivalent across paradigms, differences in gain may be attributable to the presence of linear accelerations in orthogonal directions and/or cognitive aspects based on the expected motion paths.

Protecting effect of PrP codons M142 and K222 in goats orally challenged with bovine spongiform encephalopathy prions.

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Fast, C; Goldmann, W; Berthon, P; Tauscher, K; Andréoletti, O; Lantier, I; Rossignol, C; Bossers, A; Jacobs, J G; Hunter, N; Groschup, M H; Lantier, F; Langeveld, J P M

2017-09-19

Breeding towards genetic resistance to prion disease is effective in eliminating scrapie. In sheep, classical forms of scrapie have been eradicated almost completely in several countries by breeding programs using a prion protein (PrP) gene (PRNP) amino acid polymorphism. For goats, field and experimental studies have provided evidence for several amino acid polymorphisms that are associated with resistance to scrapie, but only limited data are available concerning the susceptibility of caprine PRNP genotypes to BSE. In this study, goat kids representing five PRNP genotypes based on three polymorphisms (M142, Q211 and K222 and the wild type I142, R211 and Q222) were orally challenged with bovine or goat BSE. Wild type goats were killed with clinical signs between 24-28 months post inoculation (mpi) to both challenges, and goats with genotype R/Q211 succumbed between 29-36 mpi. I/M142 goats developed clinical signs at 44-45 mpi and M/M142 goats remained healthy until euthanasia at 48 mpi. None of the Q/K222 goats showed definite clinical signs. Taken together the highest attack ratios were seen in wild type and R/Q211 goats, and the lowest in I/M142, M/M142 and Q/K222. In all genotype groups, one or more goats remained healthy within the incubation period in both challenges and without detectable PrP deposition in the tissues. Our data show that both the K222 and M142 polymorphisms lengthen the incubation period significantly compared to wild type animals, but only K222 was associated with a significant increase in resistance to BSE infection after oral exposure to both BSE sources.

Crystallization and preliminary X-ray diffraction analysis of the C-terminal domain of the human spliceosomal DExD/H-box protein hPrp22

International Nuclear Information System (INIS)

Kudlinzki, Denis; Nagel, Christian; Ficner, Ralf

2009-01-01

The cloning, purification and crystallization of the C-terminal domain of human hPrp22 are reported. This communication also contains data for the preliminary X-ray diffraction analysis. The Homo sapiens DExD/H-box protein hPrp22 is a crucial component of the eukaryotic pre-mRNA splicing machinery. Within the splicing cycle, it is involved in the ligation of exons and generation of the lariat and it additionally catalyzes the release of mature mRNA from the spliceosomal U5 snRNP. The yeast homologue of this protein, yPrp22, shows ATP-dependent RNA-helicase activity and is capable of unwinding RNA/RNA duplex molecules. A truncated construct coding for residues 950–1183 of human Prp22, comprising the structurally and functionally uncharacterized C-terminal domain, was cloned into an Escherichia coli expression vector. The protein was subsequently overproduced, purified and crystallized. The crystals obtained diffracted to 2.1 Å resolution, belonged to the tetragonal space group P4 1 2 1 2 or P4 3 2 1 2, with unit-cell parameters a = b = 78.2, c = 88.4 Å, and contained one molecule in the asymmetric unit

Tratamiento de quemaduras mediante plasma rico en plaquetas (PRP): parte I

OpenAIRE

G. Rossani; I. Hernández; J.M. Alcolea; R. Castro-Sierra; W. Pérez-Soto; M.A. Trelles

2014-01-01

El objetivo del presente trabajo es determinar la eficacia clínica del plasma rico en plaquetas (PRP) en las quemaduras de segundo grado. Estudiamos el tiempo requerido en la reepitelización del tejido dañado, la estancia hospitalaria asociada a la curación de las lesiones y la satisfacción del paciente. Realizamos un estudio prospectivo, observacional y longitudinal, en una muestra de 115 pacientes con quemaduras de segundo grado según la clasificación de Converse-Smith. Las lesiones fueron ...

Cytoplasmic viral RNA-dependent RNA polymerase disrupts the intracellular splicing machinery by entering the nucleus and interfering with Prp8.

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Yen-Chin Liu

2014-06-01

Full Text Available The primary role of cytoplasmic viral RNA-dependent RNA polymerase (RdRp is viral genome replication in the cellular cytoplasm. However, picornaviral RdRp denoted 3D polymerase (3D(pol also enters the host nucleus, where its function remains unclear. In this study, we describe a novel mechanism of viral attack in which 3D(pol enters the nucleus through the nuclear localization signal (NLS and targets the pre-mRNA processing factor 8 (Prp8 to block pre-mRNA splicing and mRNA synthesis. The fingers domain of 3D(pol associates with the C-terminal region of Prp8, which contains the Jab1/MPN domain, and interferes in the second catalytic step, resulting in the accumulation of the lariat form of the splicing intermediate. Endogenous pre-mRNAs trapped by the Prp8-3D(pol complex in enterovirus-infected cells were identified and classed into groups associated with cell growth, proliferation, and differentiation. Our results suggest that picornaviral RdRp disrupts pre-mRNA splicing processes, that differs from viral protease shutting off cellular transcription and translation which contributes to the pathogenesis of viral infection.

The Effect of Autologous Activated Platelet Rich Plasma (AA-PRP Injection on Pattern Hair Loss: Clinical and Histomorphometric Evaluation

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V. Cervelli

2014-01-01

Full Text Available To investigate the safety and clinical efficacy of AA-PRP injections for pattern hair loss. AA-PRP, prepared from a small volume of blood, was injected on half of the selected patients’ scalps with pattern hair loss. The other half was treated with placebo. Three treatments were given for each patient, with intervals of 1 month. The endpoints were hair re-growth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki-67 evaluation. At the end of the 3 cycles of treatment, the patients presented clinical improvement in the mean number of hairs, with a mean increase of 18.0 hairs in the target area, and a mean increase in total hair density of 27.7 ( number of hairs/cm2 compared with baseline values. Microscopic evaluation showed the increase of epidermis thickness and of the number of hair follicles two weeks after the last AA-PRP treatment compared to baseline value (P<0.05. We also observed an increase of Ki67+ keratinocytes of epidermis and of hair follicular bulge cells and a slight increase of small blood vessels around hair follicles in the treated skin compared to baseline (P<0.05.

Emergence of two prion subtypes in ovine PrP transgenic mice infected with human MM2-cortical Creutzfeldt-Jakob disease prions.

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Chapuis, Jérôme; Moudjou, Mohammed; Reine, Fabienne; Herzog, Laetitia; Jaumain, Emilie; Chapuis, Céline; Quadrio, Isabelle; Boulliat, Jacques; Perret-Liaudet, Armand; Dron, Michel; Laude, Hubert; Rezaei, Human; Béringue, Vincent

2016-02-05

Mammalian prions are proteinaceous pathogens responsible for a broad range of fatal neurodegenerative diseases in humans and animals. These diseases can occur spontaneously, such as Creutzfeldt-Jakob disease (CJD) in humans, or be acquired or inherited. Prions are primarily formed of macromolecular assemblies of the disease-associated prion protein PrP(Sc), a misfolded isoform of the host-encoded prion protein PrP(C). Within defined host-species, prions can exist as conformational variants or strains. Based on both the M/V polymorphism at codon 129 of PrP and the electrophoretic signature of PrP(Sc) in the brain, sporadic CJD is classified in different subtypes, which may encode different strains. A transmission barrier, the mechanism of which remains unknown, limits prion cross-species propagation. To adapt to the new host, prions have the capacity to 'mutate' conformationally, leading to the emergence of a variant with new biological properties. Here, we transmitted experimentally one rare subtype of human CJD, designated cortical MM2 (129 MM with type 2 PrP(Sc)), to transgenic mice overexpressing either human or the VRQ allele of ovine PrP(C). In marked contrast with the reported absence of transmission to knock-in mice expressing physiological levels of human PrP, this subtype transmitted faithfully to mice overexpressing human PrP, and exhibited unique strain features. Onto the ovine PrP sequence, the cortical MM2 subtype abruptly evolved on second passage, thereby allowing emergence of a pair of strain variants with distinct PrP(Sc) biochemical characteristics and differing tropism for the central and lymphoid tissues. These two strain components exhibited remarkably distinct replicative properties in cell-free amplification assay, allowing the 'physical' cloning of the minor, lymphotropic component, and subsequent isolation in ovine PrP mice and RK13 cells. Here, we provide in-depth assessment of the transmissibility and evolution of one rare subtype of

Brain regional networks active during the mismatch negativity vary with paradigm.

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MacLean, Shannon E; Blundon, Elizabeth G; Ward, Lawrence M

2015-08-01

We used independent component analysis (ICA) of high-density EEG recordings coupled with single dipole fitting to identify the dominant brain regions active during the MMN in two different versions of a passive oddball paradigm: a simple, monotic, frequency-deviant paradigm and a more complex, dichotic, frequency-deviant paradigm with deviants occurring in either ear alone or in both ears at the same time. In both paradigms we found brain regional sources in the temporal and frontal cortices active during the MMN period, consistent with some previous studies. In the simpler paradigm, the scalp-potential variance during the earlier (70-120 ms) MMN was mostly accounted for by a wide array of temporal, frontal, and parietal sources. In the more complex paradigm, however, a generator in the prefrontal cortex accounted for a substantial amount of the variance of the scalp potential during the somewhat later MMN period (120-200 ms). These findings are consistent with a more nuanced view of the MMN and its generators than has been held in the past. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prion Protein Does Not Confer Resistance to Hippocampus-Derived Zpl Cells against the Toxic Effects of Cu2+, Mn2+, Zn2+ and Co2+ Not Supporting a General Protective Role for PrP in Transition Metal Induced Toxicity.

Science.gov (United States)

Cingaram, Pradeep Kumar Reddy; Nyeste, Antal; Dondapati, Divya Teja; Fodor, Elfrieda; Welker, Ervin

2015-01-01

The interactions of transition metals with the prion protein (PrP) are well-documented and characterized, however, there is no consensus on their role in either the physiology of PrP or PrP-related neurodegenerative disorders. PrP has been reported to protect cells from the toxic stimuli of metals. By employing a cell viability assay, we examined the effects of various concentrations of Cu2+, Zn2+, Mn2+, and Co2+ on Zpl (Prnp-/-) and ZW (Prnp+/+) hippocampus-derived mouse neuronal cells. Prnp-/- Zpl cells were more sensitive to all four metals than PrP-expressing Zw cells. However, when we introduced PrP or only the empty vector into Zpl cells, we could not discern any protective effect associated with the presence of PrP. This observation was further corroborated when assessing the toxic effect of metals by propidium-iodide staining and fluorescence activated cell sorting analysis. Thus, our results on this mouse cell culture model do not seem to support a strong protective role for PrP against transition metal toxicity and also emphasize the necessity of extreme care when comparing cells derived from PrP knock-out and wild type mice.

Absence of Evidence for a Causal Link between Bovine Spongiform Encephalopathy Strain Variant L-BSE and Known Forms of Sporadic Creutzfeldt-Jakob Disease in Human PrP Transgenic Mice.

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Jaumain, Emilie; Quadrio, Isabelle; Herzog, Laetitia; Reine, Fabienne; Rezaei, Human; Andréoletti, Olivier; Laude, Hubert; Perret-Liaudet, Armand; Haïk, Stéphane; Béringue, Vincent

2016-12-01

Prions are proteinaceous pathogens responsible for subacute spongiform encephalopathies in animals and humans. The prions responsible for bovine spongiform encephalopathy (BSE) are zoonotic agents, causing variant Creutzfeldt-Jakob disease (CJD) in humans. The transfer of prions between species is limited by a species barrier, which is thought to reflect structural incompatibilities between the host cellular prion protein (PrP C ) and the infecting pathological PrP assemblies (PrP Sc ) constituting the prion. A BSE strain variant, designated L-BSE and responsible for atypical, supposedly spontaneous forms of prion diseases in aged cattle, demonstrates zoonotic potential, as evidenced by its capacity to propagate more easily than classical BSE in transgenic mice expressing human PrP C and in nonhuman primates. In humanized mice, L-BSE propagates without any apparent species barrier and shares similar biochemical PrP Sc signatures with the CJD subtype designated MM2-cortical, thus opening the possibility that certain CJD cases classified as sporadic may actually originate from L-type BSE cross-transmission. To address this issue, we compared the biological properties of L-BSE and those of a panel of CJD subtypes representative of the human prion strain diversity using standard strain-typing criteria in human PrP transgenic mice. We found no evidence that L-BSE causes a known form of sporadic CJD. Since the quasi-extinction of classical BSE, atypical BSE forms are the sole BSE variants circulating in cattle worldwide. They are observed in rare cases of old cattle, making them difficult to detect. Extrapolation of our results suggests that L-BSE may propagate in humans as an unrecognized form of CJD, and we urge both the continued utilization of precautionary measures to eliminate these agents from the human food chain and active surveillance for CJD phenotypes in the general population. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Paradigms and pragmatism: approaches to medical statistics.

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Healy, M J

2000-01-01

Until recently, the dominant philosophy of science was that due to Karl Popper, with its doctrine that the proper task of science was the formulation of hypotheses followed by attempts at refuting them. In spite of the close analogy with significance testing, these ideas do not fit well with the practice of medical statistics. The same can be said of the later philosophy of Thomas Kuhn, who maintains that science proceeds by way of revolutionary upheavals separated by periods of relatively pedestrian research which are governed by what Kuhn refers to as paradigms. Through there have been paradigm shifts in the history of statistics, a degree of continuity can also be discerned. A current paradigm shift is embodied in the spread of Bayesian ideas. It may be that a future paradigm will emphasise the pragmatic approach to statistics that is associated with the name of Daniel Schwartz.

Effects of the Pathogenic Mutation A117V and the Protective Mutation H111S on the Folding and Aggregation of PrP106-126: Insights from Replica Exchange Molecular Dynamics Simulations.

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Lulu Ning

Full Text Available The fragment 106-126 of prion protein exhibits similar properties to full-length prion. Experiments have shown that the A117V mutation enhances the aggregation of PrP106-126, while the H111S mutation abolishes the assembly. However, the mechanism of the change in the aggregation behavior of PrP106-126 upon the two mutations is not fully understood. In this study, replica exchange molecular dynamics simulations were performed to investigate the conformational ensemble of the WT PrP106-126 and its two mutants A117V and H111S. The obtained results indicate that the three species are all intrinsically disordered but they have distinct morphological differences. The A117V mutant has a higher propensity to form β-hairpin structures than the WT, while the H111S mutant has a higher population of helical structures. Furthermore, the A117V mutation increases the hydrophobic solvent accessible surface areas of PrP106-126 and the H111S mutation reduces the exposure of hydrophobic residues. It can be concluded that the difference in populations of β-hairpin structures and the change of hydrophobic solvent accessible areas may induce the different aggregation behaviors of the A117V and the H111S mutated PrP106-126. Understanding why the two mutations have contrary effects on the aggregation of PrP106-126 is very meaningful for further elucidation of the mechanism underlying aggregation and design of inhibitor against aggregation process.

Platelet rich Plasma in Achilles Tendon Healing 2 (PATH-2) trial: protocol for a multicentre, participant and assessor-blinded, parallel-group randomised clinical trial comparing platelet-rich plasma (PRP) injection versus placebo injection for Achilles tendon rupture.

Science.gov (United States)

Alsousou, Joseph; Keene, David J; Hulley, Philippa A; Harrison, Paul; Wagland, Susan; Byrne, Christopher; Schlüssel, Michael Maia; Dutton, Susan J; Lamb, Sarah E; Willett, Keith

2017-11-16

Achilles tendon injuries give rise to substantial long-lasting morbidity and pose considerable challenges for clinicians and patients during the lengthy healing period. Current treatment strategies struggle to curb the burden of this injury on health systems and society due to lengthy rehabilitation, work absence and reinjury risk. Platelet-rich plasma (PRP) is an autologous preparation that has been shown to improve the mechanobiological properties of tendons in laboratory and animal studies. The use of PRP in musculoskeletal injuries is on the increase despite the lack of adequately powered clinical studies. This is a multicentre randomised controlled trial to evaluate the efficacy and mechanism of PRP in patients with acute Achilles tendon rupture (ATR). All adults with acute ATR presenting within 12 days of the injury who are to be treated non-operatively are eligible. A total of 230 consenting patients will be randomly allocated via a remote web-based service to receive PRP injection or placebo injection to the site of the injury. All participants will be blinded to the intervention and will receive standardised rehabilitation to reduce efficacy interference.Participants will be followed up with blinded assessments of muscle-tendon function, quality of life, pain and overall patient's functional goals at 4, 7, 13, 24 weeks and 24 months post-treatment. The primary outcome is the heel-rise endurance test (HRET), which will be supervised by a blinded assessor at 24 weeks. A subgroup of 16 participants in one centre will have needle biopsy under ultrasound guidance at 6 weeks. Blood and PRP will be analysed for cell count, platelet activation and growth factor concentrations. The protocol has been approved by the Oxfordshire Research Ethics Committee (Oxfordshire Research Ethics Committee A, reference no 14/SC/1333). The trial will be reported in accordance with the CONSORT statement and published in peer-reviewed scientific journals. ISRCTN: 54992179, assigned

Efectividad del PRP en el tratamiento de la artrosis de rodilla: Estudio de casos

OpenAIRE

Fernández Valverde, Noelia; Fidalgo González, Verónica

2016-01-01

La artrosis es una enfermedad degenerativa de elevada prevalencia para la cual, en la actualidad, no hay tratamiento curativo. Una de las localizaciones más frecuentes es la rodilla. La utilización de infiltraciones de plasma rico en plaquetas constituye una alternativa en el tratamiento de esta patología. Objetivo: demostrar la efectividad y la seguridad de las infiltraciones con PRP en el tratamiento de pacientes con artrosis de rodilla. Resultado: este trabajo muestra una...

Functions for fission yeast splicing factors SpSlu7 and SpPrp18 in alternative splice-site choice and stress-specific regulated splicing.

Directory of Open Access Journals (Sweden)

Geetha Melangath

Full Text Available Budding yeast spliceosomal factors ScSlu7 and ScPrp18 interact and mediate intron 3'ss choice during second step pre-mRNA splicing. The fission yeast genome with abundant multi-intronic transcripts, degenerate splice signals and SR proteins is an apt unicellular fungal model to deduce roles for core spliceosomal factors in alternative splice-site choice, intron retention and to study the cellular implications of regulated splicing. From our custom microarray data we deduce a stringent reproducible subset of S. pombe alternative events. We examined the role of factors SpSlu7 or SpPrp18 for these splice events and investigated the relationship to growth phase and stress. Wild-type log and stationary phase cells showed ats1+ exon 3 skipped and intron 3 retained transcripts. Interestingly the non-consensus 5'ss in ats1+ intron 3 caused SpSlu7 and SpPrp18 dependent intron retention. We validated the use of an alternative 5'ss in dtd1+ intron 1 and of an upstream alternative 3'ss in DUF3074 intron 1. The dtd1+ intron 1 non-canonical 5'ss yielded an alternative mRNA whose levels increased in stationary phase. Utilization of dtd1+ intron 1 sub-optimal 5' ss required functional SpPrp18 and SpSlu7 while compromise in SpSlu7 function alone hampered the selection of the DUF3074 intron 1 non canonical 3'ss. We analysed the relative abundance of these splice isoforms during mild thermal, oxidative and heavy metal stress and found stress-specific splice patterns for ats1+ and DUF3074 intron 1 some of which were SpSlu7 and SpPrp18 dependent. By studying ats1+ splice isoforms during compromised transcription elongation rates in wild-type, spslu7-2 and spprp18-5 mutant cells we found dynamic and intron context-specific effects in splice-site choice. Our work thus shows the combinatorial effects of splice site strength, core splicing factor functions and transcription elongation kinetics to dictate alternative splice patterns which in turn serve as an additional

PrP mRNA and protein expression in brain and PrP(c) in CSF in Creutzfeldt-Jakob disease MM1 and VV2.

Science.gov (United States)

Llorens, Franc; Ansoleaga, Belén; Garcia-Esparcia, Paula; Zafar, Saima; Grau-Rivera, Oriol; López-González, Irene; Blanco, Rosi; Carmona, Margarita; Yagüe, Jordi; Nos, Carlos; Del Río, José Antonio; Gelpí, Ellen; Zerr, Inga; Ferrer, Isidre

2013-01-01

Creutzfeldt-Jakob disease (CJD) is a heterogenic neurodegenerative disorder associated with abnormal post-translational processing of cellular prion protein (PrP(c)). CJD displays distinctive clinical and pathological features which correlate with the genotype at the codon 129 (methionine or valine: M or V respectively) in the prion protein gene and with size of the protease-resistant core of the abnormal prion protein PrP(sc) (type 1: 20/21 kDa and type 2: 19 kDa). MM1 and VV2 are the most common sporadic CJD (sCJD) subtypes. PrP mRNA expression levels in the frontal cortex and cerebellum are reduced in sCJD in a form subtype-dependent. Total PrP protein levels and PrP(sc) levels in the frontal cortex and cerebellum accumulate differentially in sCJD MM1 and sCJD VV2 with no relation between PrP(sc) deposition and spongiform degeneration and neuron loss, but with microgliosis, and IL6 and TNF-α response. In the CSF, reduced PrP(c), the only form present in this compartment, occurs in sCJD MM1 and VV2. PrP mRNA expression is also reduced in the frontal cortex in advanced stages of Alzheimer disease, Lewy body disease, progressive supranuclear palsy, and frontotemporal lobe degeneration, but PrP(c) levels in brain varies from one disease to another. Reduced PrP(c) levels in CSF correlate with PrP mRNA expression in brain, which in turn reflects severity of degeneration in sCJD.

PRP Comments for ICF Q1/Q2 FY17 Experiments 3/10/16

Energy Technology Data Exchange (ETDEWEB)

Kauffman, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2016-04-14

The PRP generally endorsed the Program plan during the short time for discussions. We agree that the strategy to develop a hohlraum that is symmetric and has low laser-plasma instabilities and to develop an alternative method for supporting the capsule is the best path forward for making progress in understanding ignition performance. The Program is oriented toward a milestone in 2020 for “determining the efficacy of NIF for ignition and credible physics-scaling to multi-megajoule yields for all ICF approaches.” We are concerned that the time and resources are not sufficient to vet all of the various approaches that are being pursued to make an informed decision by this date. For NIF to meet this goal, a process will be needed to to select the most promising paths forward. We recommend that the Program develop this process for selecting the path forward to optimize resources. We were glad to see that the direct drive program took our comments under consideration. We think that the proposed experiments have the program headed in a better direction. The PRP had only a short time to discuss the detailed experimental proposals. The following are comments on the detailed proposals. We did not have time to discuss them as a group. They represent individual opinions and provided to you as feedback to your proposals.

Integrity of Helix 2-Helix 3 Domain of the PrP Protein Is Not Mandatory for Prion Replication*

Science.gov (United States)

Salamat, Khalid; Moudjou, Mohammed; Chapuis, Jérôme; Herzog, Laetitia; Jaumain, Emilie; Béringue, Vincent; Rezaei, Human; Pastore, Annalisa; Laude, Hubert; Dron, Michel

2012-01-01

The process of prion conversion is not yet well understood at the molecular level. The regions critical for the conformational change of PrP remain mostly debated and the extent of sequence change acceptable for prion conversion is poorly documented. To achieve progress on these issues, we applied a reverse genetic approach using the Rov cell system. This allowed us to test the susceptibility of a number of insertion mutants to conversion into prion in the absence of wild-type PrP molecules. We were able to propagate several prions with 8 to 16 extra amino acids, including a polyglycine stretch and His or FLAG tags, inserted in the middle of the protease-resistant fragment. These results demonstrate the possibility to increase the length of the loop between helices H2 and H3 up to 4-fold, without preventing prion replication. They also indicate that this loop probably remains unstructured in PrPSc. We also showed that bona fide prions can be produced following insertion of octapeptides in the two C-terminal turns of H2. These insertions do not interfere with the overall fold of the H2-H3 domain indicating that the highly conserved sequence of the terminal part of H2 is not critical for the conversion. Altogether these data showed that the amplitude of modifications acceptable for prion conversion in the core of the globular domain of PrP is much greater than one might have assumed. These observations should help to refine structural models of PrPSc and elucidate the conformational changes underlying prions generation. PMID:22511770

Integrity of helix 2-helix 3 domain of the PrP protein is not mandatory for prion replication.

Science.gov (United States)

Salamat, Khalid; Moudjou, Mohammed; Chapuis, Jérôme; Herzog, Laetitia; Jaumain, Emilie; Béringue, Vincent; Rezaei, Human; Pastore, Annalisa; Laude, Hubert; Dron, Michel

2012-06-01

The process of prion conversion is not yet well understood at the molecular level. The regions critical for the conformational change of PrP remain mostly debated and the extent of sequence change acceptable for prion conversion is poorly documented. To achieve progress on these issues, we applied a reverse genetic approach using the Rov cell system. This allowed us to test the susceptibility of a number of insertion mutants to conversion into prion in the absence of wild-type PrP molecules. We were able to propagate several prions with 8 to 16 extra amino acids, including a polyglycine stretch and His or FLAG tags, inserted in the middle of the protease-resistant fragment. These results demonstrate the possibility to increase the length of the loop between helices H2 and H3 up to 4-fold, without preventing prion replication. They also indicate that this loop probably remains unstructured in PrP(Sc). We also showed that bona fide prions can be produced following insertion of octapeptides in the two C-terminal turns of H2. These insertions do not interfere with the overall fold of the H2-H3 domain indicating that the highly conserved sequence of the terminal part of H2 is not critical for the conversion. Altogether these data showed that the amplitude of modifications acceptable for prion conversion in the core of the globular domain of PrP is much greater than one might have assumed. These observations should help to refine structural models of PrP(Sc) and elucidate the conformational changes underlying prions generation.

Prediction and optimization of the recovery rate in centrifugal separation of platelet-rich plasma (PRP)

Science.gov (United States)

Piao, Linfeng; Park, Hyungmin; Jo, Chris

2016-11-01

We present a theoretical model of the recovery rate of platelet and white blood cell in the process of centrifugal separation of platelet-rich plasma (PRP). For the practically used conditions in the field, the separation process is modeled as a one-dimensional particle sedimentation; a quasi-linear partial differential equation is derived based on the kinematic-wave theory. This is solved to determine the interface positions between supernatant-suspension and suspension-sediment, used to estimate the recovery rate of the plasma. While correcting the Brown's hypothesis (1989) claiming that the platelet recovery is linearly proportional to that of plasma, we propose a new correlation model for prediction of the platelet recovery, which is a function of the volume of whole blood, centrifugal acceleration and time. For a range of practical parameters, such as hematocrit, volume of whole blood and centrifugation (time and acceleration), the predicted recovery rate shows a good agreement with available clinical data. We propose that this model is further used to optimize the preparation method of PRP that satisfies the customized case. Supported by a Grant (MPSS-CG-2016-02) through the Disaster and Safety Management Institute funded by Ministry of Public Safety and Security of Korean government.

Is the psychological refractory period effect for ideomotor compatible tasks eliminated by speed-stress instructions?

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Shin, Yun Kyoung; Cho, Yang Seok; Lien, Mei-Ching; Proctor, Robert W

2007-09-01

It has been argued that the psychological refractory period (PRP) effect is eliminated with two ideomotor compatible tasks when instructions stress fast and simultaneous responding. Three experiments were conducted to test this hypothesis. In all experiments, Task 1 required spatially compatible manual responses (left or right) to the direction of an arrow, and Task 2 required saying the name of the auditory letter A or B. In Experiments 1 and 3, the manual responses were keypresses made with the left and right hands, whereas in Experiment 2 they were left-right toggle-switch movements made with the dominant hand. Instructions that stressed response speed reduced reaction time and increased error rate compared to standard instructions to respond fast and accurately, but did not eliminate the PRP effect on Task 2 reaction time. These results imply that, even when response speed is emphasized, ideomotor compatible tasks do not bypass response selection.

The Underlying Social Dynamics of Paradigm Shifts.

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Rodriguez-Sickert, Carlos; Cosmelli, Diego; Claro, Francisco; Fuentes, Miguel Angel

2015-01-01

We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution) within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i) marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm); and ii) radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology) that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm.

The Underlying Social Dynamics of Paradigm Shifts.

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Carlos Rodriguez-Sickert

Full Text Available We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm; and ii radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm.

A novel Gerstmann-Sträussler-Scheinker disease mutation defines a precursor for amyloidogenic 8 kDa PrP fragments and reveals N-terminal structural changes shared by other GSS alleles

Science.gov (United States)

Mercer, Robert C. C.; Fu, Ze-Lin; Mays, Charles E.; Gapeshina, Hristina; Wohlgemuth, Serene L.; Acevedo-Morantes, Claudia Y.; Cashman, Neil R.; Coulthart, Michael B.; Jansen, Gerard H.; Stepanova, Maria

2018-01-01

To explore pathogenesis in a young Gerstmann-Sträussler-Scheinker Disease (GSS) patient, the corresponding mutation, an eight-residue duplication in the hydrophobic region (HR), was inserted into the wild type mouse PrP gene. Transgenic (Tg) mouse lines expressing this mutation (Tg.HRdup) developed spontaneous neurologic syndromes and brain extracts hastened disease in low-expressor Tg.HRdup mice, suggesting de novo formation of prions. While Tg.HRdup mice exhibited spongiform change, PrP aggregates and the anticipated GSS hallmark of a proteinase K (PK)-resistant 8 kDa fragment deriving from the center of PrP, the LGGLGGYV insertion also imparted alterations in PrP's unstructured N-terminus, resulting in a 16 kDa species following thermolysin exposure. This species comprises a plausible precursor to the 8 kDa PK-resistant fragment and its detection in adolescent Tg.HRdup mice suggests that an early start to accumulation could account for early disease of the index case. A 16 kDa thermolysin-resistant signature was also found in GSS patients with P102L, A117V, H187R and F198S alleles and has coordinates similar to GSS stop codon mutations. Our data suggest a novel shared pathway of GSS pathogenesis that is fundamentally distinct from that producing structural alterations in the C-terminus of PrP, as observed in other prion diseases such as Creutzfeldt-Jakob Disease and scrapie. PMID:29338055

Ideomotor compatibility in the psychological refractory period effect: 29 years of oversimplification.

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Lien, Mei-Ching; Proctor, Robert W; Allen, Philip A

2002-04-01

Four experiments examined whether the psychological refractory period (PRP) effect can be eliminated with ideomotor compatible (IM) but not stimulus-response compatible (SR) tasks, as reported by A. G. Greenwald and H. G. Shulman (1973). Their tasks were used: a left or right movement to a left- or right-pointing arrow (IM) or to the word left or right (SR) for Task 1; saying "A" or "B" (IM) or "1" or "2" (SR) to an auditory A or B for Task 2. The stimulus onset asynchronies were 0, 100, 200, 300, 500, and 1,000 ms in Experiment 1, and only 0, 100, 200, and 1,000 ms in Experiments 2-4. The arrow was in the center of the screen in Experiments 1-3 and to the left or right in Experiment 4. As in Greenwald and Shulman's Experiment 2, the instructions stated that most often the 2 stimuli would be presented simultaneously. A PRP effect was obtained in all conditions, most likely because response-selection decisions are required even for IM tasks.

Concomitant administration of a fully liquid, ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal serogroup C conjugate vaccine in infants.

Science.gov (United States)

Vesikari, Timo; Borrow, Ray; Da Costa, Xavier; Richard, Patrick; Eymin, Cécile; Boisnard, Florence; Lockhart, Stephen

2017-01-11

DTaP-IPV-HB-PRP-T or hexavalent vaccines are indicated for primary and booster vaccination of infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib). The present study evaluates the safety and immunogenicity of a ready-to-use hexavalent vaccine when co-administered with a meningococcal serogroup C conjugate (MenC) vaccine in infants. This was a phase III, open-label, randomised, multicentre study conducted in Finland. Healthy infants, aged 46-74days (n=350), were randomised in a ratio of 1:1 to receive DTaP-IPV-HB-PRP-T vaccine at two, three and four months, either with a MenC vaccine co-administered at two and four months (Group 1; n=175) or without MenC vaccine (Group 2; n=175). All infants also received routine rotavirus and 13-valent pneumococcal conjugate vaccines. The proportion of participants with an anti-HBs concentration ⩾10mIU/mL assessed one month after the third dose of DTaP-IPV-HB-PRP-T vaccine was 97.5% [95%CI: 93.1-99.3] in the coadministration group and 96.1% [95%CI: 91.8-98.6] in the group without MenC vaccine. The proportion of participants with an anti-MenC SBA titre ⩾8 assessed one month after the second dose of MenC vaccine was 100% in the coadministration group. Both primary objectives were achieved. Secondary immunogenicity and safety analyses showed that co-administration of DTaP-IPV-HB-PRP-T and MenC vaccines did not impact the immune response to the antigens of each of the two vaccines. All vaccines were well tolerated and the safety profile of DTaP-IPV-HB-PRP-T vaccine was similar in both groups. ClinicalTrials.gov identifier: NCT01839175; EudraCT number: 2012-005547-24. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Vascular access surveillance: case study of a false paradigm.

Science.gov (United States)

Paulson, William D; Moist, Louise; Lok, Charmaine E

2013-01-01

The hemodialysis vascular access surveillance controversy provides a case study of how enthusiasm for a new test or treatment can lead to adoption of a false paradigm. Paradigms are the beliefs and assumptions shared by those in a field of knowledge, and are commonly included in clinical practice guidelines. The guidelines of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommend that arteriovenous vascular accesses undergo routine surveillance for detection and correction of stenosis. This recommendation is based on the paradigm that surveillance of access blood flow or dialysis venous pressure combined with correction of stenosis improves access outcomes. However, the quality of evidence that supports this paradigm has been widely criticized. We tested the validity of the surveillance paradigm by applying World Health Organization (WHO) criteria for evaluating screening tests to a literature review of published vascular access studies. These criteria include four components: undesired condition, screening test, intervention, and desired outcome. The WHO criteria show that surveillance as currently practiced fails all four components and provides little or no significant benefit, suggesting that surveillance is a false paradigm. Once a paradigm is established, however, challenges to its validity are usually resisted even as new evidence indicates the paradigm is not valid. Thus, it is paramount to apply rigorous criteria when developing guidelines. Regulators may help promote needed changes in paradigms when cost and safety considerations coincide. © 2013 Wiley Periodicals, Inc.

Trace elements as paradigms of developmental neurotoxicants

DEFF Research Database (Denmark)

Grandjean, Philippe; Herz, Katherine T

2015-01-01

Trace elements have contributed unique insights into developmental neurotoxicity and serve as paradigms for such adverse effects. Many trace elements are retained in the body for long periods and can be easily measured to assess exposure by inexpensive analytical methods that became available...

Amidation and structure relaxation abolish the neurotoxicity of the prion peptide PrP106-126 in vivo and in vitro

DEFF Research Database (Denmark)

Bergstrøm, Linda Alice; Hvass, Henriette Cordes; Zsurger, N.

2005-01-01

One of the major pathological hallmarks of transmissible spongiform encephalopathies (TSEs) is the accumulation of a pathogenic (scrapie) isoform (PrPSc) of the cellular prion protein (PrPC) primarily in the central nervous system. The synthetic prion peptide PrP106-126 shares many characteristics...

PrP0\\0 mice show behavioral abnormalities that suggest PrPC has a role in maintaining the cytoskeleton.

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Background/Introduction. PrPC is highly conserved among mammals, but its natural function is unclear. Prnp ablated mice (PrP0/0) appear to develop normally and are able to reproduce. These observations seem to indicate that the gene is not essential for viability, in spite of it being highly conse...

PARADIGMS IN CONSUMER BEHAVIOR

Directory of Open Access Journals (Sweden)

Sabrina Oktoria Sihombing

2011-05-01

Full Text Available A paradigm influences what we see and conceive about certain facts. Paradigm can also influence what we accept as a truth. Yet, the debate over which paradigm and methodology is best suit for marketing and consumer behavior has begun since 1980s. Many researchers criticized the domination of logical empiricism paradigm and offered alternative paradigm to understand marketing and consumer behavior. This article discusses several paradigms and methodology, which are part of qualitative paradigm, and compares them with positivism paradigm. This article will also point to the importance of reconciliation between qualitative and quantitative paradigm in order to improve marketing and consumer behavior studies.

PARADIGMS IN CONSUMER BEHAVIOR

OpenAIRE

Sabrina Oktoria Sihombing

2011-01-01

A paradigm influences what we see and conceive about certain facts. Paradigm can also influence what we accept as a truth. Yet, the debate over which paradigm and methodology is best suit for marketing and consumer behavior has begun since 1980s. Many researchers criticized the domination of logical empiricism paradigm and offered alternative paradigm to understand marketing and consumer behavior. This article discusses several paradigms and methodology, which are part of qualitative paradigm...

Radiation a new paradigm... Societal impacts

International Nuclear Information System (INIS)

Sutcliffe, Jill

2010-01-01

Latency is associated with the time lag it takes for the health effects resulting from exposure to ionising radiation to show up. However, the term latency can also be applied to the time it takes for a policy to be implemented. This length of time has been suggested as broadly 40-year process. Given that radioactivity was identified and named in 1896, three paradigms are identified and examined from 1896 to 2016 and the criteria for a 4th paradigm suggested for the period 2017-2056. The review examines the changes that have taken place in scientific understanding and in public trust, a few key developments and the associated establishment of the related organisational infrastructure designed to collate and assess the evidence.

Low fraction of the 222K PrP variant in the protease-resistant moiety of PrPres in heterozygous scrapie positive goats.

Science.gov (United States)

Mazza, Maria; Guglielmetti, Chiara; Ingravalle, Francesco; Brusadore, Sonia; Langeveld, Jan P M; Ekateriniadou, Loukia V; Andréoletti, Olivier; Casalone, Cristina; Acutis, Pier Luigi

2017-07-01

The presence of lysine (K) at codon 222 has been associated with resistance to classical scrapie in goats, but few scrapie cases have been identified in 222Q/K animals. To investigate the contribution of the 222K variant to PrPres formation in natural and experimental Q/K scrapie cases, we applied an immunoblotting method based on the use of two different monoclonal antibodies, F99/97.6.1 and SAF84, chosen for their different affinities to 222K and 222Q PrP variants. Our finding that PrPres seems to be formed nearly totally by the 222Q variant provides evidence that the 222K PrP variant confers resistance to conversion to PrPres formation and reinforces the view that this mutation has a protective role against classical scrapie in goats.

Nuestra experiencia en el tratamiento de úlceras crónicas mediante PRF-Vivostat®: Serie de 10 casos Our experience in the treatment of chronic ulcers by PRP-Vivostat®: Series of 10 cases

Directory of Open Access Journals (Sweden)

E. Monclús Fuertes

2009-06-01

Full Text Available Pretendemos mostrar nuestra experiencia clínica en el manejo de úlceras crónicas de distinta etiología, mediante tratamiento conservador con gel rico en fibrina autóloga más factores de crecimiento plaquetarios o PRP, experiencia que reafirma los buenos resultados obtenidos en estudios anteriores referentes a Cirugía Plástica, Estética y Reparadora El hecho diferencial de nuestro estudio es el trato de las lesiones única y exclusivamente con PRP, sin otros tratamientos adyuvantes como es habitual en otros estudios acerca de este tema Entre los años 2002 y 2007 tratamos con PRP 10 pacientes con historia de fallo en los tratamientos convencionales, con una edad media de 65.6 años. Se realizaron entre 3 y 5 sesiones por paciente, espaciadas por una semana. El método de obtención elegido fue el sistema VIVOSTAT® (MBA Group. Se realizó un control fotográfico en cada sesión. Realizamos un seguimiento visual de las lesiones (pretratamiento- postratamiento, valorándolas según una modificación de la escala de Valbonesi et al a la que llamamos "Escala de Zaragoza", siendo el resultado pobre en 1 paciente, regular en 2, bueno en 5 y excelente en 2. El uso de PRP para úlceras crónicas en pacientes refractarios a otro tipo de tratamientos, tanto conservadores como quirúrgicos, es actualmente una alternativa real para conseguir una mejoría evidente e incluso la curación completa de las lesiones.The aim of this study is to evaluate our clinical experience in the management of chronic ulcers by conservative treatment with autologous fibrin-rich gel further platelet growth factors or PRP. This experience reaffirms the good results obtained in earlier studies relating to Plastic, Reconstructive and Aesthetic Surgery; moreover, the strength of our study is the use of PRP as the only treatment of such injuries, without other adjuvant treatments as usual in other works on this topic. From 2002 to 2007, we treated with PRP 10 patients with a

The Next Paradigm

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Bernardo Kastrup

2018-04-01

Full Text Available In order to perceive the world, we need more than just raw sensory input: a subliminal paradigm of thought is required to interpret raw sensory data and, thereby, create the objects and events we perceive around ourselves. As such, the world we see reflects our own unexamined, culture-bound assumptions and expectations, which explains why every generation in history has believed that it more or less understood the world. Today, we perceive a world of objects and events outside and independent of mind, which merely reflects our current paradigm of thought. Anomalies that contradict this paradigm have been accumulated by physicists over the past couple of decades, which will eventually force our culture to move to a new paradigm. Under this new paradigm, a form of universal mind will be viewed as nature’s sole fundamental entity. In this paper, I offer a sketch of what the new paradigm may look like.

Platelet-Rich Plasma (PRP) Rinses for the Treatment of Non-Responding Oral Lichen Planus: A Case Report

OpenAIRE

Elisabetta Merigo; Aldo Oppici; Anna Parlatore; Luigi Cella; Fabio Clini; Matteo Fontana; Carlo Fornaini

2018-01-01

Platelet-rich plasma (PRP) has been proposed for different applications in the medical field and in maxillofacial surgery thanks to its many growth factors, such as epidermal growth factor (EGF), fibroblast growth factor (FGF), and keratinocyte growth factor (KGF). Oral lichen planus (OLP) is a disease that affects the oral mucosa in a chronic way. This disease frequently worsens the quality of life of patients, particularly when clinical manifestations are of the erythematous or erosive/ulce...

The Risk-Benefit Paradigm vs the Causal Exposure Paradigm: LDL as a primary cause of vascular disease.

Science.gov (United States)

Toth, Peter P; Thanassoulis, George; Williams, Ken; Furberg, Curt D; Sniderman, Allan

2014-01-01

All current guidelines use the 10-year risk of a cardiovascular event to select subjects for statin primary preventive therapy. Benefit from therapy is stated to be determined by risk with the result that statin primary preventive therapy is initiated only when the risk of a cardiovascular event over the next decade exceeds a specified level. Thus all current guidelines are based primarily on the Risk-Benefit paradigm of primary prevention. The recent American Heart Association/American College of Cardiology guidelines differ from others in basing selection for statin therapy virtually exclusively on risk except for those few subjects with markedly elevated levels of low-density lipoprotein cholesterol (LDL-C). The Causal Exposure paradigm differs from the Risk-Benefit paradigm in that the objective of therapy is to prevent the anatomic disease within arterial walls that produces cardiovascular risk. Moreover, the anatomic disease and, therefore, the cardiovascular risk, is a function of the injurious action of the causal factors of vascular disease, such as blood pressure and LDL, on the arterial wall over long periods. In this article, we explain the strengths and weaknesses of both paradigms to provide a more secure framework to compare the strengths and weaknesses in the different cholesterol guidelines with particular emphasis on the evidence that the cardiovascular risk and the benefit from statin therapy is related to the level of LDL. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Effects of in vivo applications of peripheral blood-derived mesenchymal stromal cells (PB-MSCs) and platlet-rich plasma (PRP) on experimentally injured deep digital flexor tendons of sheep.

Science.gov (United States)

Martinello, Tiziana; Bronzini, Ilaria; Perazzi, Anna; Testoni, Stefania; De Benedictis, Gulia Maria; Negro, Alessandro; Caporale, Giovanni; Mascarello, Francesco; Iacopetti, Ilaria; Patruno, Marco

2013-02-01

Tendon injuries, degenerative tendinopathies, and overuse tendinitis are common in races horses. Novel therapies aim to restore tendon functionality by means of cell-based therapy, growth factor delivery, and tissue engineering approaches. This study examined the use of autologous mesenchymal stromal cells derived from peripheral blood (PB-MSCs), platelet-rich plasma (PRP) and a combination of both for ameliorating experimental lesions on deep digital flexor tendons (DDFT) of Bergamasca sheep. In particular, testing the combination of blood-derived MSCs and PRP in an experimental animal model represents one of the few studies exploring a putative synergistic action of these treatments. Effectiveness of treatments was evaluated at 30 and 120 days comparing clinical, ultrasonographic, and histological features together with immunohistochemical expression of collagen types 1 and 3, and cartilage oligomeric matrix protein (COMP). Significant differences were found between treated groups and their corresponding controls (placebo) regarding tendon morphology and extracellular matrix (ECM) composition. However, our results indicate that the combined use of PRP and MSCs did not produce an additive or synergistic regenerative response and highlighted the predominant effect of MSCs on tendon healing, enhanced tissue remodeling and improved structural organization. Copyright © 2012 Orthopaedic Research Society.

New energy paradigm?

International Nuclear Information System (INIS)

Goldoni, Giovanni

2007-01-01

The rise of oil prices, the difficulties in markets liberalization, and the poor results of competition have convinced many that a new energy paradigm is necessary. Taking the original definition of scientific paradigm, it doesn't seem that a practical solution could be found outside the present paradigm of energy policy, made of privatisation, liberalisation and competition [it

A general method for the purification of synthetic oligodeoxyribonucleotides containing strong secondary structure by reversed-phase high-performance liquid chromatography on PRP-1 resin.

Science.gov (United States)

Germann, M W; Pon, R T; van de Sande, J H

1987-09-01

Synthetic 5'-dimethoxytritylated oligodeoxyribonucleotides, which contained strong secondary structure, were satisfactorily denatured and purified by reversed-phase HPLC on PRP-1 columns when strongly alkaline conditions (0.05 M NaOH) were employed. This procedure was suitable for the purification of hairpin structures, e.g., d(CG)nT4(CG)n (n = 4, 5, 6), and oligo(dG) sequences, e.g., d(G)24, as well as oligodeoxyribonucleotide probes which contained degenerate base sites. Oligodeoxyribonucleotides as long as 50 bases in length were purified. Recovery of injected oligonucleotides was typically 90% or better. The high capacity of the PRP-1 resin also allowed purification to be performed on a preparative scale (2-8 mg per injection). Enzymatic degradation and HPLC analysis indicated that no modification of the heterocyclic bases occurred under the alkaline conditions described.

Reduced response of splenocytes after mitogen-stimulation in the prion protein (PrP) gene-deficient mouse: PrPLP/Doppel production and cerebral degeneration

International Nuclear Information System (INIS)

Kim, Chi-Kyeong; Hirose, Yuko; Sakudo, Akikazu; Takeyama, Natsumi; Kang, Chung-Boo; Taniuchi, Yojiro; Matsumoto, Yoshitsugu; Itohara, Shigeyoshi; Sakaguchi, Suehiro; Onodera, Takashi

2007-01-01

Splenocytes of wild-type (Prnp +/+ ) and prion protein gene-deficient (Prnp -/- ) mice were treated with various activation stimuli such as T cell mitogen concanavalin A (ConA), phorbol 12-myristate 13-acetate (PMA) + ionomycin (Io), or B cell mitogen lipopolysaccharide (LPS). Cellular prion protein (PrP C ) expression was enhanced following ConA stimulation, but not PMA + Io or LPS in Prnp +/+ splenocytes. Rikn Prnp -/- splenocytes elicited lower cell proliferations than Prnp +/+ or Zrch I Prnp -/- splenocytes after LPS stimulation and showed sporadic nerve cells in the cerebral cortex and deeper structure. Around the degenerated nerve cells, mild vacuolation in the neuropil was observed. This neural alteration correlated well to the suppressed response of B cells in the spleen. The finding that discrete lesions within the central nervous systems induced marked modulation of immune function probably indicates the existence of a delicately balanced neural-endocrine network by PrP C and PrPLP/Doppel

Identification of seven haplotypes of the caprine PrP gene at codons 127, 142, 154, 211, 222 and 240 in French Alpine and Saanen breeds and their association with classical scrapie.

Science.gov (United States)

Barillet, F; Mariat, D; Amigues, Y; Faugeras, R; Caillat, H; Moazami-Goudarzi, K; Rupp, R; Babilliot, J M; Lacroux, C; Lugan, S; Schelcher, F; Chartier, C; Corbière, F; Andréoletti, O; Perrin-Chauvineau, C

2009-03-01

In sheep, susceptibility to scrapie is mainly influenced by polymorphisms of the PrP gene. In goats, there are to date few data related to scrapie susceptibility association with PrP gene polymorphisms. In this study, we first investigated PrP gene polymorphisms of the French Alpine and Saanen breeds. Based on PrP gene open reading frame sequencing of artificial insemination bucks (n=404), six encoding mutations were identified at codons 127, 142, 154, 211, 222 and 240. However, only seven haplotypes could be detected: four (GIH(154)RQS, GIRQ(211)QS, GIRRK(222)S and GIRRQP(240)) derived from the wild-type allele (G(127)I(142)R(154)R(211)Q(222)S(240)) by a single-codon mutation, and two (S(127)IRRQP(240) and GM(142)RRQP(240)) by a double-codon mutation. A case-control study was then implemented in a highly affected Alpine and Saanen breed herd (90 cases/164 controls). Mutations at codon 142 (I/M), 154 (R/H), 211 (R/Q) and 222 (Q/K) were found to induce a significant degree of protection towards natural scrapie infection. Compared with the baseline homozygote wild-type genotype I(142)R(154)R(211)Q(222)/IRRQ goats, the odds of scrapie cases in IRQ(211)Q/IRRQ and IRRK(222)/IRRQ heterozygous animals were significantly lower [odds ratio (OR)=0.133, PFrench Alpine and Saanen breeds were low (0.5-18.5 %), which prevent us from assessing the influence of all the possible genotypes in natural exposure conditions.

Efficacy of Platelet-Rich-Plasma (PRP and Highly Purified Bovine Xenograft (Laddec® Combination in Bone Regeneration after Cyst Enucleation: Radiological and Histological Evaluation

Directory of Open Access Journals (Sweden)

Sabrina Pappalardo

2013-10-01

Full Text Available Objectives: The purpose of the present study was to evaluate the efficacy of adding platelet-rich plasma (PRP to a new highly purified bovine allograft (Laddec® in the bone regeneration of cystic bony defects augmented following cystectomy.Material and Methods: Study sample included 20 patients undergoing cystectomy in which the bone defect was filled with PRP and Laddec®. All patients were examined with periapical radiographs before operation and at follow-up. After 3 months, at re-entry surgery for implant placement, bone core was taken for histological and histomorphometric analysis.Results: The postoperative successive radiographs showed a good regeneration of bone in the height of bony defects with application of PRP to bone graft. By the first postoperative month, about 48% of the defect was filled, which gradually increased in each month and showed about 90% of defect-fill by 6 months. Histological and histomorphometric analysis, showed a significant presence of bone tissue and vessels, with newly formed bone in contact with anorganic bone particles. The mean volume of vital bone was 68 ± 1.6% and the mean percentage of vital bone was 48 ± 2.4%. The mean percentage of inorganic particles in tissues was 20 ± 1.2% of the total volume. All the samples analyzed did not evidence the presence of inflammatory cells.Conclusions: The results of this study showed how the use of Laddec® in association with platelet-rich plasma allows bone regeneration and has a potential for routine clinical use for regeneration of cystic bony defects.

Ovine recombinant PrP as an inhibitor of ruminant prion propagation in vitro.

Science.gov (United States)

Workman, Rob G; Maddison, Ben C; Gough, Kevin C

2017-07-04

Prion diseases are fatal and incurable neurodegenerative diseases of humans and animals. Despite years of research, no therapeutic agents have been developed that can effectively manage or reverse disease progression. Recently it has been identified that recombinant prion proteins (rPrP) expressed in bacteria can act as inhibitors of prion replication within the in vitro prion replication system protein misfolding cyclic amplification (PMCA). Here, within PMCA reactions amplifying a range of ruminant prions including distinct Prnp genotypes/host species and distinct prion strains, recombinant ovine VRQ PrP displayed consistent inhibition of prion replication and produced IC50 values of 122 and 171 nM for ovine scrapie and bovine BSE replication, respectively. These findings illustrate the therapeutic potential of rPrPs with distinct TSE diseases.

Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (A-PRF), and concentrated growth factors (CGF).

Science.gov (United States)

Masuki, Hideo; Okudera, Toshimitsu; Watanebe, Taisuke; Suzuki, Masashi; Nishiyama, Kazuhiko; Okudera, Hajime; Nakata, Koh; Uematsu, Kohya; Su, Chen-Yao; Kawase, Tomoyuki

2016-12-01

The development of platelet-rich fibrin (PRF) drastically simplified the preparation procedure of platelet-concentrated biomaterials, such as platelet-rich plasma (PRP), and facilitated their clinical application. PRF's clinical effectiveness has often been demonstrated in pre-clinical and clinical studies; however, it is still controversial whether growth factors are significantly concentrated in PRF preparations to facilitate wound healing and tissue regeneration. To address this matter, we performed a comparative study of growth factor contents in PRP and its derivatives, such as advanced PRF (A-PRF) and concentrated growth factors (CGF). PRP and its derivatives were prepared from the same peripheral blood samples collected from healthy donors. A-PRF and CGF preparations were homogenized and centrifuged to produce extracts. Platelet and white blood cell counts in A-PRF and CGF preparations were determined by subtracting those counts in red blood cell fractions, supernatant acellular serum fractions, and A-PRF/CGF exudate fractions from those counts of whole blood samples. Concentrations of growth factors (TGF-β1, PDGF-BB, VEGF) and pro-inflammatory cytokines (IL-1β, IL-6) were determined using ELISA kits. Compared to PRP preparations, both A-PRF and CGF extracts contained compatible or higher levels of platelets and platelet-derived growth factors. In a cell proliferation assay, both A-PRF and CGF extracts significantly stimulated the proliferation of human periosteal cells without significant reduction at higher doses. These data clearly demonstrate that both A-PRF and CGF preparations contain significant amounts of growth factors capable of stimulating periosteal cell proliferation, suggesting that A-PRF and CGF preparations function not only as a scaffolding material but also as a reservoir to deliver certain growth factors at the site of application.

Changing environments or shifting paradigms? Strategic decision making toward water protection in Helsinki, 1850-2000.

Science.gov (United States)

Laakkonen, Simo; Laurila, Sari

2007-04-01

The study examines the history of strategic decision-making concerning water protection in Helsinki, 1850-2000. We identified five major strategic decisions that occurred during the study period. The results indicate that strategic decision-making evolves in long-term policy cycles that last on average 20-30 years. New policy cycles are caused by paradigm shifts. Paradigms are shared and predominant ways of understanding reality that help when groups must act to solve common and complex environmental problems. However the internal structure and external dynamics of paradigms are contradictory. Although paradigms serve initially as means to redefine problems and find creative solutions, as time goes by each paradigm seems to become also a barrier that restricts the introduction of new ways of thinking and acting. The power of paradigms lies in the fact that they can be defined as scientific but also social, political, or cultural agreements depending on the context.

Didaktiske paradigmer og refleksion

DEFF Research Database (Denmark)

Christensen, Torben Spanget

2014-01-01

analysis of subject didactics by Sigmund Ongstad. The two positions offer fundamentally different insights into didactics. Nielsen’s position establishes didactics as a knowledge domain and Ongstad’s position points to the dynamics of subject didactics by analyzing communication as a basic aspect. Krogh...... this article. A possible utilitarian didactical paradigm, already indicated by Krogh as a historical paradigm prominent in our time, is also discussed. It is suggested that reflection could be seen as a normative response to the utilitarian paradigm, and not as a paradigm in its own right. It is concluded...

Golkar Party's Political Communications the New Paradigm Bakrie Leadership 2009-2013

Directory of Open Access Journals (Sweden)

Khoiruddin Muchtar

2013-11-01

Full Text Available This study base on the efforts of the Golkar Party's to the process of interpretation, socialization, and implementation of the new paradigm, the paradigm guide to reformations Golkar Party's become to democratic, independent, solid, strong, foundamental, and responsive. How Golkar party's political communication about socialization and implementation of a new paradigm of Golkar Party's leadership Aburizal Bakrie-year period from 2009 to 2012.The aim of this research is to study and overview of the process of socialization and implementation new paradigm Golkar Party's of the Aburizal Bakrie’s leadership. This contect described to using constructivist paradigm through the theory of Performance of Communication and Structuration. Research using the case study method. Data obtained by participation observer, unstructured interviews, and documentary study. The data also collected from informants. The results of this research show: 1 The Golkar Party's has a very significant infrastructure, so the making easier to socialization new paradigm to internal party, but Golkar Party's can not erase stigma society as the New Order party. Socializing new paradigm Golkar Party's to be done in integrated, systematic and continuous addressed to all cadres of various levels from the center to the village. 2 the new paradigm Golkar Party's ideals as the basis and foundation values stand for the Golkar Party's, the implementation is faced with the reality of the condition of the various political considerations and the interests of power, so it can not shown the Golkar Party's political communication with the direction of the reality, Golkar Party's must be have to political communication with the role of multi faces.

SLAVIC LITERATURES IN DALMATIAN PERIODICALS IN THE PERIOD OF CROATIAN MODERNISM

Directory of Open Access Journals (Sweden)

Robert Bacalja

2010-01-01

Full Text Available The paper analyzes translations and mediatorial articles from the Slavic literature published in Dalmatian newspapers and periodicals which contribute most to mediation during the period of Croatian Modernism. While periodicals in Dalmatia traditionally mediates from the Roman literature, especially from the Italian, in the examined corpus can be seen the remarkable reception of Slavic literature, particularly Russian.. The paradigm of the most recognized culture and literature in non Slavic world is desirable identity basis of the Croatian literature as a part of a large Slavic stem from romanticism to modernism. Mediation of Slavic literatures is examined on the corpus of newspapers and periodicals published in Dubrovnik, Split and Zadar (Crvena Hrvatska, Srđ, Sloboda, Jedinstvo/Novo jedinstvo, Novi vijek, Narodni list, Smotra dalmatinska, Iskra, Glasnik Matice dalmatinske, Lovor, etc..

An Integrative Paradigm

Science.gov (United States)

Hammack, Phillip L.

2005-01-01

Through the application of life course theory to the study of sexual orientation, this paper specifies a new paradigm for research on human sexual orientation that seeks to reconcile divisions among biological, social science, and humanistic paradigms. Recognizing the historical, social, and cultural relativity of human development, this paradigm…

The resilience of paradigm mixes

DEFF Research Database (Denmark)

Daugbjerg, Carsten; Farsund, Arild Aurvåg; Langhelle, Oluf

2017-01-01

This paper argues that a policy regime based on a paradigm mix may be resilient when challenged by changing power balances and new agendas. Controversies between the actors can be contained within the paradigm mix as it enables them to legitimize different ideational positions. Rather than engaging...... context changed. The paradigm mix proved sufficiently flexible to accommodate food security concerns and at the same time continue to take steps toward further liberalization. Indeed, the main players have not challenged the paradigm mix....

Lab-oriented radical innovations as drivers of paradigm shifts in science

NARCIS (Netherlands)

Coccia, M.

2014-01-01

An interesting problem in the economics of innovation and strategic management of labs is to explain the drivers of breakthroughs and paradigm shifts in science. This study confronts the issue by analysing a main case study: the technological determinant of the discovery of quasi-periodic materials

Shifting the Climate Finance Paradigm: Nine Key Challenges for Developed Countries

Energy Technology Data Exchange (ETDEWEB)

Curtin, Joseph

2013-03-13

In 2009, developed countries committed to part-funding the cost of adapting to the impacts of climate change and of low carbon development in developing countries. From 2010 to 2012, fast start finance began to flow from developed country exchequers. However, the climate finance paradigm is now shifting. A transition from loans and grants provided from scarce exchequer resources to innovative instruments for leveraging private capital and mitigating investment risk is required in the coming period. But what are the implications for developed countries? This policy brief explores the policy context defining the current climate finance debate; examines the extent to which commitments have been met; and identifies nine key challenges for developed countries as they enter the new climate finance paradigm, drawing on the lessons of the fast start finance period. This is the second in a series of Environment Nexus policy briefs by leading experts in the fields of agriculture, energy, climate change and water.

The influence of environmental variables on platelet concentration in horse platelet-rich plasma.

Science.gov (United States)

Rinnovati, Riccardo; Romagnoli, Noemi; Gentilini, Fabio; Lambertini, Carlotta; Spadari, Alessandro

2016-07-04

Platelet-rich plasma (PRP) commonly refers to blood products which contain a higher platelet (PLT) concentration as compared to normal plasma. Autologous PRP has been shown to be safe and effective in promoting the natural processes of soft tissue healing or reconstruction in humans and horses. Variability in PLT concentration has been observed in practice between PRP preparations from different patients or from the same individual under different conditions. A change in PLT concentration could modify PRP efficacy in routine applications. The aim of this study was to test the influence of environmental, individual and agonistic variables on the PLT concentration of PRP in horses. Six healthy Standardbred mares were exposed to six different variables with a one-week washout period between variables, and PRP was subsequently obtained from each horse. The variables were time of withdrawal during the day (morning/evening), hydration status (overhydration/dehydration) treatment with anti-inflammatory drugs and training periods on a treadmill. The platelet concentration was significantly higher in horses treated with a non-steroidal anti-inflammatory drug (P = 0.03). The leukocyte concentration increased 2-9 fold with respect to whole blood in the PRP which was obtained after exposure to all the variable considered. Environmental variation in platelet concentration should be taken into consideration during PRP preparation.

Polo-like kinase 3 (PLK3) mediates the clearance of the accumulated PrP mutants transiently expressed in cultured cells and pathogenic PrP(Sc) in prion infected cell line via protein interaction.

Science.gov (United States)

Wang, Hui; Tian, Chan; Fan, Xue-Yu; Chen, Li-Na; Lv, Yan; Sun, Jing; Zhao, Yang-Jing; Zhang, Lu-bin; Wang, Jing; Shi, Qi; Gao, Chen; Chen, Cao; Shao, Qi-Xiang; Dong, Xiao-Ping

2015-05-01

Polo-like kinases (PLKs) family has long been known to be critical for cell cycle and recent studies have pointed to new dimensions of PLKs function in the nervous system. Our previous study has verified that the levels of PLK3 in the brain are severely downregulated in prion-related diseases. However, the associations of PLKs with prion protein remain unclear. In the present study, we confirmed that PrP protein constitutively interacts with PLK3 as determined by both in vitro and in vivo assays. Both the kinase domain and polo-box domain of PLK3 were proved to bind PrP proteins expressed in mammalian cell lines. Overexpression of PLK3 did not affect the level of wild-type PrP, but significantly decreased the levels of the mutated PrPs in cultured cells. The kinase domain appeared to be responsible for the clearance of abnormally aggregated PrPs, but this function seemed to be independent of its kinase activity. RNA-mediated knockdown of PLK3 obviously aggravated the accumulation of cytosolic PrPs. Moreover, PLK3 overexpression in a scrapie infected cell line caused notable reduce of PrP(Sc) level in a dose-dependent manner, but had minimal effect on the expression of PrP(C) in its normal partner cell line. Our findings here confirmed the molecular interaction between PLK3 and PrP and outlined the regulatory activity of PLK3 on the degradation of abnormal PrPs, even its pathogenic isoform PrP(Sc). We, therefore, assume that the recovery of PLK3 in the early stage of prion infection may be helpful to prevent the toxic accumulation of PrP(Sc) in the brain tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

An adaptive semantic matching paradigm for reliable and valid language mapping in individuals with aphasia.

Science.gov (United States)

Wilson, Stephen M; Yen, Melodie; Eriksson, Dana K

2018-04-17

Research on neuroplasticity in recovery from aphasia depends on the ability to identify language areas of the brain in individuals with aphasia. However, tasks commonly used to engage language processing in people with aphasia, such as narrative comprehension and picture naming, are limited in terms of reliability (test-retest reproducibility) and validity (identification of language regions, and not other regions). On the other hand, paradigms such as semantic decision that are effective in identifying language regions in people without aphasia can be prohibitively challenging for people with aphasia. This paper describes a new semantic matching paradigm that uses an adaptive staircase procedure to present individuals with stimuli that are challenging yet within their competence, so that language processing can be fully engaged in people with and without language impairments. The feasibility, reliability and validity of the adaptive semantic matching paradigm were investigated in sixteen individuals with chronic post-stroke aphasia and fourteen neurologically normal participants, in comparison to narrative comprehension and picture naming paradigms. All participants succeeded in learning and performing the semantic paradigm. Test-retest reproducibility of the semantic paradigm in people with aphasia was good (Dice coefficient = 0.66), and was superior to the other two paradigms. The semantic paradigm revealed known features of typical language organization (lateralization; frontal and temporal regions) more consistently in neurologically normal individuals than the other two paradigms, constituting evidence for validity. In sum, the adaptive semantic matching paradigm is a feasible, reliable and valid method for mapping language regions in people with aphasia. © 2018 Wiley Periodicals, Inc.

Of Paradigms and Power

DEFF Research Database (Denmark)

Carstensen, Martin B.; Matthijs, Matthias

in the study of policy paradigms. To demonstrate the general applicability of our framework, the paper examines the evolution of British macroeconomic policy making since 1990. We show that various Prime Ministers and their Chancellors were able to reinterpret and redefine the dominant neoliberal understanding......? Despite the profound impact of Peter Hall’s approach to policy paradigms and social learning, there is a burgeoning consensus that transposing a rudimentary ‘Kuhnian’ understanding of paradigms into the context of public policy making leads to a notion of punctuated equilibrium style shifts as the only...

PrP expression, PrPSc accumulation and innervation of splenic compartments in sheep experimentally infected with scrapie.

Directory of Open Access Journals (Sweden)

Randi Sørby

Full Text Available BACKGROUND: In prion disease, the peripheral expression of PrP(C is necessary for the transfer of infectivity to the central nervous system. The spleen is involved in neuroinvasion and neural dissemination in prion diseases but the nature of this involvement is not known. The present study undertook the investigation of the spatial relationship between sites of PrP(Sc accumulation, localisation of nerve fibres and PrP(C expression in the tissue compartments of the spleen of scrapie-inoculated and control sheep. METHODOLOGY/PRINCIPAL FINDINGS: Laser microdissection and quantitative PCR were used to determine PrP mRNA levels and results were compared with immunohistochemical protocols to distinguish PrP(C and PrP(Sc in tissue compartments of the spleen. In sheep experimentally infected with scrapie, the major sites of accumulation of PrP(Sc in the spleen, namely the lymphoid nodules and the marginal zone, expressed low levels of PrP mRNA. Double immunohistochemical labelling for PrP(Sc and the pan-nerve fibre marker, PGP, was used to evaluate the density of innervation of splenic tissue compartments and the intimacy of association between PrP(Sc and nerves. Some nerve fibres were observed to accompany blood vessels into the PrP(Sc-laden germinal centres. However, the close association between nerves and PrP(Sc was most apparent in the marginal zone. Other sites of close association were adjacent to the wall of the central artery of PALS and the outer rim of germinal centres. CONCLUSIONS/SIGNIFICANCE: The findings suggest that the degree of PrP(Sc accumulation does not depend on the expression level of PrP(C. Though several splenic compartments may contribute to neuroinvasion, the marginal zone may play a central role in being the compartment with most apparent association between nerves and PrP(Sc.

Understanding paradigms used for nursing research.

Science.gov (United States)

Weaver, Kathryn; Olson, Joanne K

2006-02-01

The aims of this paper are to add clarity to the discussion about paradigms for nursing research and to consider integrative strategies for the development of nursing knowledge. Paradigms are sets of beliefs and practices, shared by communities of researchers, which regulate inquiry within disciplines. The various paradigms are characterized by ontological, epistemological and methodological differences in their approaches to conceptualizing and conducting research, and in their contribution towards disciplinary knowledge construction. Researchers may consider these differences so vast that one paradigm is incommensurable with another. Alternatively, researchers may ignore these differences and either unknowingly combine paradigms inappropriately or neglect to conduct needed research. To accomplish the task of developing nursing knowledge for use in practice, there is a need for a critical, integrated understanding of the paradigms used for nursing inquiry. We describe the evolution and influence of positivist, postpositivist, interpretive and critical theory research paradigms. Using integrative review, we compare and contrast the paradigms in terms of their philosophical underpinnings and scientific contribution. A pragmatic approach to theory development through synthesis of cumulative knowledge relevant to nursing practice is suggested. This requires that inquiry start with assessment of existing knowledge from disparate studies to identify key substantive content and gaps. Knowledge development in under-researched areas could be accomplished through integrative strategies that preserve theoretical integrity and strengthen research approaches associated with various philosophical perspectives. These strategies may include parallel studies within the same substantive domain using different paradigms; theoretical triangulation to combine findings from paradigmatically diverse studies; integrative reviews; and mixed method studies. Nurse scholars are urged to

A ZIP6-ZIP10 heteromer controls NCAM1 phosphorylation and integration into focal adhesion complexes during epithelial-to-mesenchymal transition.

Science.gov (United States)

Brethour, Dylan; Mehrabian, Mohadeseh; Williams, Declan; Wang, Xinzhu; Ghodrati, Farinaz; Ehsani, Sepehr; Rubie, Elizabeth A; Woodgett, James R; Sevalle, Jean; Xi, Zhengrui; Rogaeva, Ekaterina; Schmitt-Ulms, Gerold

2017-01-18

The prion protein (PrP) evolved from the subbranch of ZIP metal ion transporters comprising ZIPs 5, 6 and 10, raising the prospect that the study of these ZIPs may reveal insights relevant for understanding the function of PrP. Building on data which suggested PrP and ZIP6 are critical during epithelial-to-mesenchymal transition (EMT), we investigated ZIP6 in an EMT paradigm using ZIP6 knockout cells, mass spectrometry and bioinformatic methods. Reminiscent of PrP, ZIP6 levels are five-fold upregulated during EMT and the protein forms a complex with NCAM1. ZIP6 also interacts with ZIP10 and the two ZIP transporters exhibit interdependency during their expression. ZIP6 contributes to the integration of NCAM1 in focal adhesion complexes but, unlike cells lacking PrP, ZIP6 deficiency does not abolish polysialylation of NCAM1. Instead, ZIP6 mediates phosphorylation of NCAM1 on a cluster of cytosolic acceptor sites. Substrate consensus motif features and in vitro phosphorylation data point toward GSK3 as the kinase responsible, and interface mapping experiments identified histidine-rich cytoplasmic loops within the ZIP6/ZIP10 heteromer as a novel scaffold for GSK3 binding. Our data suggests that PrP and ZIP6 inherited the ability to interact with NCAM1 from their common ZIP ancestors but have since diverged to control distinct posttranslational modifications of NCAM1.

Dynamic paradigm of turbulence

International Nuclear Information System (INIS)

Mukhamedov, Alfred M.

2006-01-01

In this paper a dynamic paradigm of turbulence is proposed. The basic idea consists in the novel definition of chaotic structure given with the help of Pfaff system of PDE associated with the turbulent dynamics. A methodological analysis of the new and the former paradigm is produced

Robust nonlinear PID-like fuzzy logic control of a planar parallel (2PRP-PPR) manipulator.

Science.gov (United States)

Londhe, P S; Singh, Yogesh; Santhakumar, M; Patre, B M; Waghmare, L M

2016-07-01

In this paper, a robust nonlinear proportional-integral-derivative (PID)-like fuzzy control scheme is presented and applied to complex trajectory tracking control of a 2PRP-PPR (P-prismatic, R-revolute) planar parallel manipulator (motion platform) with three degrees-of-freedom (DOF) in the presence of parameter uncertainties and external disturbances. The proposed control law consists of mainly two parts: first part uses a feed forward term to enhance the control activity and estimated perturbed term to compensate for the unknown effects namely external disturbances and unmodeled dynamics, and the second part uses a PID-like fuzzy logic control as a feedback portion to enhance the overall closed-loop stability of the system. Experimental results are presented to show the effectiveness of the proposed control scheme. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

The detour paradigm in animal cognition.

Science.gov (United States)

Kabadayi, Can; Bobrowicz, Katarzyna; Osvath, Mathias

2018-01-01

In this paper, we review one of the oldest paradigms used in animal cognition: the detour paradigm. The paradigm presents the subject with a situation where a direct route to the goal is blocked and a detour must be made to reach it. Often being an ecologically valid and a versatile tool, the detour paradigm has been used to study diverse cognitive skills like insight, social learning, inhibitory control and route planning. Due to the relative ease of administrating detour tasks, the paradigm has lately been used in large-scale comparative studies in order to investigate the evolution of inhibitory control. Here we review the detour paradigm and some of its cognitive requirements, we identify various ecological and contextual factors that might affect detour performance, we also discuss developmental and neurological underpinnings of detour behaviors, and we suggest some methodological approaches to make species comparisons more robust.

The WIMP Paradigm: Current Status

International Nuclear Information System (INIS)

Feng, Jonathan

2011-01-01

The WIMP paradigm is the glue that joins together much of the high energy and cosmic frontiers. It postulates that most of the matter in the Universe is made of weakly-interacting massive particles, with implications for a broad range of experiments and observations. I will review the WIMP paradigm's underlying motivations, its current status in view of rapid experimental progress on several fronts, and recent theoretical variations on the WIMP paradigm theme.

Linking aims, paradigm and method in nursing research.

Science.gov (United States)

Houghton, Catherine; Hunter, Andrew; Meskell, Pauline

2012-01-01

To explore the use of paradigms as ontological and philosophical guides for conducting PhD research. A paradigm can help to bridge the aims of a study and the methods to achieve them. However, choosing a paradigm can be challenging for doctoral researchers: there can be ambiguity about which paradigm is suitable for a particular research question and there is a lack of guidance on how to shape the research process for a chosen paradigm. The authors discuss three paradigms used in PhD nursing research: post-positivism, interpretivism and pragmatism. They compare each paradigm in relation to its ontology, epistemology and methodology, and present three examples of PhD nursing research studies to illustrate how research can be conducted using these paradigms in the context of the research aims and methods. The commonalities and differences between the paradigms and their uses are highlighted. Creativity and flexibility are important when deciding on a paradigm. However, consistency and transparency are also needed to ensure the quality and rigour necessary for conducting nursing research. When choosing a suitable paradigm, the researcher should ensure that the ontology, epistemology and methodology of the paradigm are manifest in the methods and research strategies employed.

Study of platelet-rich plasma injections in the treatment of androgenetic alopecia through an one-year period

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Maria-Angeliki Gkini

2014-01-01

Full Text Available Background: Platelet-rich plasma (PRP is defined as an autologous concentration of plasma with a greater count of platelets than that of whole blood. Its action depends on the released growth factors from platelets. It has been investigated and used in numerous fields of medicine. Recently, PRP has received growing attention as a potential therapeutic tool for hair loss. Aims: To evaluate the efficacy and safety of PRP injections in the scalp of patients with androgenetic alopecia. Settings and Design: Prospective cohort study. Materials and Methods: 20 patients, 18 males and 2 females, with androgenetic alopecia were enrolled in the study. PRP was prepared using a single spin method (Regenlab SA. Upon activation, it was injected in the androgen-related areas of scalp. Three treatment sessions were performed with an interval of 21 days and a booster session at 6 months following the onset of therapy. Statistical Analysis: Statistical analysis of the data was performed using the Statistical Package for the Social Sciences (SPSS, version 19.0 (IBM, NY, USA. Results: Hair loss reduced and at 3 months it reached normal levels. Hair density reached a peak at 3 months (170.70 ± 37.81, P < 0.001. At 6 months and at 1 year, it was significantly increased, 156.25 ± 37.75 (P < 0.001 and 153.70 ± 39.92 (P < 0.001 respectively, comparing to baseline. Patients were satisfied with a mean result rating of 7.1 on a scale of 1-10. No remarkable adverse effects were noted. Conclusions: Our data suggest that PRP injections may have a positive therapeutic effect on male and female pattern hair loss without remarkable major side effects. Further studies are needed to confirm its efficacy.

Dissonance: scientific paradigms underpinning the study of sound in geography

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Daniel Paiva

2018-05-01

Full Text Available The objective of this article is to approach the different conceptions of sound – and its relations to the underlying scientific paradigms – that emerged throughout the history of geography. There has been a growing interest among geographers in understanding the spatialities of sound, and geographies of sound have become an emerging subfield of the discipline. For this reason, it is the right time to address how the discipline has approached sound throughout its history. Several theoretical perspectives influenced geography in the twentieth century, changing its methodologies and how its subjects were conceived. Sound, like other subjects, has been conceived very differently by geographers of competing paradigms. Concepts such as noise, soundscape, or sound as affect, among others, have dominated geographies of sound at specific periods. Due to the marginality of the subject in the discipline, assessments of these conceptual shifts are rare. I tackle this issue in this article as I provide a first attempt of writing a history of sound in geography. The article reviews debates regarding the name of the subfield, and the conceptions of sound in the successive and competing scientific paradigms in geography.

Clinical fMRI of language function in aphasic patients: Reading paradigm successful, while word generation paradigm fails

International Nuclear Information System (INIS)

Engstroem, Maria; Landtblom, Anne-Marie; Ragnehed, Mattias; Lundberg, Peter; Karlsson, Marie; Crone, Marie; Antepohl, Wolfram

2010-01-01

Background: In fMRI examinations, it is very important to select appropriate paradigms assessing the brain function of interest. In addition, the patients' ability to perform the required cognitive tasks during fMRI must be taken into account. Purpose: To evaluate two language paradigms, word generation and sentence reading for their usefulness in examinations of aphasic patients and to make suggestions for improvements of clinical fMRI. Material and Methods: Five patients with aphasia after stroke or trauma sequelae were examined by fMRI. The patients' language ability was screened by neurolinguistic tests and elementary pre-fMRI language tests. Results: The sentence-reading paradigm succeeded to elicit adequate language-related activation in perilesional areas whereas the word generation paradigm failed. These findings were consistent with results on the behavioral tests in that all patients showed very poor performance in phonemic fluency, but scored well above mean at a reading comprehension task. Conclusion: The sentence-reading paradigm is appropriate to assess language function in this patient group, while the word-generation paradigm seems to be inadequate. In addition, it is crucial to use elementary pre-fMRI language tests to guide the fMRI paradigm decision.

Clinical fMRI of language function in aphasic patients: Reading paradigm successful, while word generation paradigm fails

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Engstroem, Maria; Landtblom, Anne-Marie; Ragnehed, Mattias; Lundberg, Peter (Center for Medical Image Science and Visualization (CMIV), Linkoeping Univ., Linkoeping (Sweden)), e-mail: maria.engstrom@liu.se; Karlsson, Marie; Crone, Marie (Dept. of Clinical and Experimental Medicine/Logopedics, Linkoeping Univ., Linkoeping (Sweden)); Antepohl, Wolfram (Dept. of Clinical and Experimental Medicine/Rehabilitation, Linkoeping Univ., Linkoeping (Sweden))

2010-07-15

Background: In fMRI examinations, it is very important to select appropriate paradigms assessing the brain function of interest. In addition, the patients' ability to perform the required cognitive tasks during fMRI must be taken into account. Purpose: To evaluate two language paradigms, word generation and sentence reading for their usefulness in examinations of aphasic patients and to make suggestions for improvements of clinical fMRI. Material and Methods: Five patients with aphasia after stroke or trauma sequelae were examined by fMRI. The patients' language ability was screened by neurolinguistic tests and elementary pre-fMRI language tests. Results: The sentence-reading paradigm succeeded to elicit adequate language-related activation in perilesional areas whereas the word generation paradigm failed. These findings were consistent with results on the behavioral tests in that all patients showed very poor performance in phonemic fluency, but scored well above mean at a reading comprehension task. Conclusion: The sentence-reading paradigm is appropriate to assess language function in this patient group, while the word-generation paradigm seems to be inadequate. In addition, it is crucial to use elementary pre-fMRI language tests to guide the fMRI paradigm decision.

A modified parallel paradigm for clinical evaluation of auditory echoic memory.

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Karino, Shotaro; Yumoto, Masato; Itoh, Kenji; Yamakawa, Keiko; Mizuochi, Tomomi; Kaga, Kimitaka

2005-05-12

We established a new parallel paradigm for mismatch negativity by presenting repetitive trains of three consonant-vowel syllables and those of three sinusoidal tones alternately. Magnetoencephalography was performed to test the new method, and mismatch negativities in six study participants with normal hearing were compared with the results of the conventional oddball paradigm. Peak amplitude and latencies of mismatch negativity showed no significant difference between the methods. The maximum amplitude in short memory probe interval of 1.0 s was significantly larger than in long memory probe interval of 3.0 s, demonstrating decay in auditory echoic memory caused by a prolonged memory probe interval. The new method facilitated simultaneous evaluation of mismatch negativity with various stimuli in a shorter period.

Pityriasis Rubra Pilaris In The Indian Scenario

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Sarkar Rashmi

2002-01-01

Full Text Available Pityriasis rubra pilaris (PRP is an uncommon idiopathic papulosqamous disorder characterized by circumscribed follicular keratosis, palmoplantar keratoderma and frequently erythroderma. Seven patients of PRP (five females and two males in the age range of 2 to 50 years seen over a 2-year period are presented with their clinical features, triggering factors, associations and laboratory investigations. The clinical type of PRP was adult onset classical variety in three, juvenile circumscribed variety in two and adult onset atypical variety and juvenile classical variety in one each. The triggering factors were upper respiratory tract infection with nutritional deficiencies in two and folliculitis in one. The histopathology was consistent with PRP in all. Four patients were managed with oral vitamin A while one each was put on methotrexate, etretinate and topical steroids and they showed a good response. More number of cases should be studied over a longer period to substantiate the suggested immunologic mechanism of PRP.

[Meta-legal paradigms of nanomedicine].

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Pérez Alvarez, Salvador

2012-01-01

Nanomedicine is the Nanotechnology applied in the field of Medicine. Nanomedicine includes a wide range of technologies applied to devices, materials, medical procedures and treatment modalities are being developed, in some cases, through the convergence of living and nonliving materials. The developments in this scientific field are the prelude of a new era in health where Nanotechnology will provide, in a short period of time, substantial benefits for the general welfare and health of people with serious and incurable diseases using other more traditional medical treatments. This is, in brief, the object of this research that has been focused in the study of the ethical-legal paradigms that should inform the developments and expectations generated by medical applications of Nanotechnology.

Evolution of the radiological protection paradigms

International Nuclear Information System (INIS)

Sordi, Gian Maria A.A.

2009-01-01

We consider as initial radiological protection paradigms those in vigour after the release of the atomic energy for pacific usages in 1955. In that occasion, only one paradigm was introduced, presently named dose limitation system. After arguing about the basis that raised the paradigm, we introduced the guidance, that is, the measurements to be implemented to comply with the paradigm. In that occasion, they were two, i.e., the radiation dose monitoring and the workplace classification. Afterwards, the reasons that caused the radiological protection paradigms changes in force until 1995 are discussed. The initial paradigm was modified introducing the justification and the optimization principles, adding that the radiological protection should be economical and effective. The guidance also increased to four: personal monitoring, workplace classification, reference level and workers classification. Afterwards, we give the main justifications for the present paradigms that besides the formers were added the dose constraints, the potential exposure and the annual risk limits. Due to these modifications, the workers classifications were eliminated from the guidance, but the potential exposure and the search for the dose constraints were added. Eventually, we discuss the tendencies for the next future and the main changes introduced by the ICRP in the Publication 103, 2007. (author)

Platelet rich plasma promotes skeletal muscle cell migration in association with up-regulation of FAK, paxillin, and F-Actin formation.

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Tsai, Wen-Chung; Yu, Tung-Yang; Lin, Li-Ping; Lin, Mioa-Sui; Tsai, Ting-Ta; Pang, Jong-Hwei S

2017-11-01

Platelet rich plasma (PRP) contains various cytokines and growth factors which may be beneficial to the healing process of injured muscle. The aim of this study was to investigate the effect and molecular mechanism of PRP on migration of skeletal muscle cells. Skeletal muscle cells intrinsic to Sprague-Dawley rats were treated with PRP. The cell migration was evaluated by transwell filter migration assay and electric cell-substrate impedance sensing. The spreading of cells was evaluated microscopically. The formation of filamentous actin (F-actin) cytoskeleton was assessed by immunofluorescence staining. The protein expressions of paxillin and focal adhesion kinase (FAK) were assessed by Western blot analysis. Transfection of paxillin small-interfering RNA (siRNAs) to muscle cells was performed to validate the role of paxillin in PRP-mediated promotion of cell migration. Dose-dependently PRP promotes migration of and spreading and muscle cells. Protein expressions of paxillin and FAK were up-regulated dose-dependently. F-actin formation was also enhanced by PRP treatment. Furthermore, the knockdown of paxillin expression impaired the effect of PRP to promote cell migration. It was concluded that PRP promoting migration of muscle cells is associated with up-regulation of proteins expression of paxillin and FAK as well as increasing F-actin formation. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2506-2512, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Multiple bottlenecks in hierarchical control of action sequences: what does "response selection" select in skilled typewriting?

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Yamaguchi, Motonori; Logan, Gordon D; Li, Vanessa

2013-08-01

Does response selection select words or letters in skilled typewriting? Typing performance involves hierarchically organized control processes: an outer loop that controls word level processing, and an inner loop that controls letter (or keystroke) level processing. The present study addressed whether response selection occurs in the outer loop or the inner loop by using the psychological refractory period (PRP) paradigm in which Task1 required typing single words and Task2 required vocal responses to tones. The number of letters (string length) in the words was manipulated to discriminate selection of words from selection of keystrokes. In Experiment 1, the PRP effect depended on string length of words in Task1, suggesting that response selection occurs in the inner loop. To assess contributions of the outer loop, the influence of string length was examined in a lexical-decision task that also involves word encoding and lexical access (Experiment 2), or to-be-typed words were preexposed so outer-loop processing could finish before typing started (Experiment 3). Response time for Task2 (RT2) did not depend on string length with lexical decision, and RT2 still depended on string length with typing preexposed strings. These results support the inner-loop locus of the PRP effect. In Experiment 4, typing was performed as Task2, and the effect of string length on typing RT interacted with stimulus onset asynchrony superadditively, implying that another bottleneck also exists in the outer loop. We conclude that there are at least two bottleneck processes in skilled typewriting. 2013 APA, all rights reserved

Three paradigms of horror

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Dejan Ognjanović

2016-07-01

Full Text Available Starting with the definition of horror as a literary genre the core story of which is based on a meeting with threatening Otherness whose influx into consensual reality and it’s tacit normality creates unrest and awakens fear in the protagonists and the audience, this paper defines the three key paradigms of the horror genre, based on the causes of fear, or rather the “monstrous” Otherness in them. Paradigm 1 concerns the “fear of one’s own self”: the root of the fear is inside, in the individual psyche, in the split, deceived, or in some other way unreliable self which is, consciously or unconsciously, harmful to others, and ultimately to itself. Paradigm 2 deals with the “Fear of others”: the root of fear is outside and is concerned with other people and other creatures which have an urge to occupy a certain human microcosm. Paradigm 3 is concerned with the “Fear of the numinous”: the root of the fear is mostly situated on the outside; however its shape is amorphous, ambivalent and unknowable. The “monster” is faceless; it touches on primary forces of the divine/demonic, and as such is situated on the very border between inside/outside. All three paradigms, with their main approaches and constitutive elements, are modulated through two basic possible treatments: the conservative and the progressive (liberal, which affords a total of six basic variations of horror. Starting from definitions given by John Carpenter, Robin Wood and his own, the author analyzes representative examples from horror literature and film for each paradigm and its variation, with a special accent on the image of Otherness and its connection to the norm, its intrusion into the status quo, anthropocentrism and the presence or absence of a happy ending. The paper demonstrates the richness of connotative potential within the horror genre and provides a basis for its taxonomy.

Intraarticular injection autologous platelet-rich plasma and bone marrow concentrate in a goat osteoarthritis model.

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Wang, Zhen; Zhai, Chenjun; Fei, Hao; Hu, Junzheng; Cui, Weiding; Wang, Zhen; Li, Zeng; Fan, Weimin

2018-02-21

To evaluate the effects of intraarticular injections of autologous platelet-rich plasma (PRP) or bone marrow concentrate (BMC) on osteoarthritis (OA), 24 adult goats were equally divided into control (Ctrl), saline (NS), PRP, and BMC groups, and OA was induced by surgery in NS, PRP, and BMC groups. Autologous PRP and BMC were obtained from whole blood and bone marrow aspirates, respectively. The data revealed, platelets were increased in BMC by 1.8-fold, monocytes by 5.6-fold, TGF-β1 by 7.7-fold, and IGF-1 by 3.6-fold (p BMC were administered by intraarticular injection once every 4 weeks, three consecutive times. After the animals were sacrificed, inflammatory cytokines in the synovial fluid was measured, and bone and cartilage degeneration progression was observed by macroscopy, histology, and immunohistochemistry. Compared with the NS group, the level of inflammatory cytokines was reduced in the PRP and BMC groups (p BMC treated groups (p BMC group showed greater cartilage protection and less ECM loss than the PRP group (p BMC has therapeutic efficacy in a goat osteoarthritis model, with the greater benefit in terms of cartilage protection being observed in the BMC-treated group than PRP. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Combination of platelet rich plasma in fractional carbon dioxide laser treatment increased clinical efficacy of for acne scar by enhancement of collagen production and modulation of laser-induced inflammation.

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Min, Seonguk; Yoon, Ji Young; Park, Seon Yong; Moon, Jungyoon; Kwon, Hyuck Hoon; Suh, Dae Hun

2018-04-01

Platelet-rich plasma (PRP) which contains large amounts of growth factors has been tried to enhance therapeutic efficacy of laser treatment for acne scar with unknown underlying mechanism. The present study was conducted to investigate the molecular mechanism of increased clinical efficacy of PRP when combined with fractional laser treatment for treating acne scars. Subjects with mild to moderate acne scars were treated with two sessions of fractional CO 2 laser therapy given with and without co-administration of PRP. Skin biopsy specimens were obtained at baseline, 1, 3, 7, and 28 days for investigation of molecular profiles associated with skin changes produced by laser plus PRP treatment. The PRP treatment increased clinical efficacy with decreased severity of adverse effects such as erythema, swelling and oozing. Productions of TGFβ1 and TGFβ3 proteins were more highly elevated on the PRP-treated side of the face compared to the control side at day 28. Furthermore, PRP-treated side showed significant increase of c-myc, TIMP, and HGF expression. Experimental fibroblast culture model was also used. PRP administration after laser irradiation increased expressions of p-Akt, TGFβ1, TGFβ3, β-catenin, collagen 1, and collagen 3 in both dose-dependent and time dependent manners in fibroblast. Moreover, we acquired clinical and histological data through randomized control clinical trial. Taken together with human study results combined with the data from cell experiments we suggest that PRP treatment increased fibrogenetic molecules induced by fractional CO 2 laser, which have association with clinical effect. Lasers Surg. Med. 50:302-310, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The Cognitive Paradigm Ontology: Design and Application

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Laird, Angela R.

2013-01-01

We present the basic structure of the Cognitive Paradigm Ontology (CogPO) for human behavioral experiments. While the experimental psychology and cognitive neuroscience literature may refer to certain behavioral tasks by name (e.g., the Stroop paradigm or the Sternberg paradigm) or by function (a working memory task, a visual attention task), these paradigms can vary tremendously in the stimuli that are presented to the subject, the response expected from the subject, and the instructions given to the subject. Drawing from the taxonomy developed and used by the BrainMap project (www.brainmap.org) for almost two decades to describe key components of published functional imaging results, we have developed an ontology capable of representing certain characteristics of the cognitive paradigms used in the fMRI and PET literature. The Cognitive Paradigm Ontology is being developed to be compliant with the Basic Formal Ontology (BFO), and to harmonize where possible with larger ontologies such as RadLex, NeuroLex, or the Ontology of Biomedical Investigations (OBI). The key components of CogPO include the representation of experimental conditions focused on the stimuli presented, the instructions given, and the responses requested. The use of alternate and even competitive terminologies can often impede scientific discoveries. Categorization of paradigms according to stimulus, response, and instruction has been shown to allow advanced data retrieval techniques by searching for similarities and contrasts across multiple paradigm levels. The goal of CogPO is to develop, evaluate, and distribute a domain ontology of cognitive paradigms for application and use in the functional neuroimaging community. PMID:21643732

Effects of FlAsH/Tetracysteine (TC) tag on PrP proteolysis and PrPres formation by TC-scanning

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Taguchi, Yuzuru; Hohsfield, Lindsay A.; Hollister, Jason R.

2014-01-01

The FlAsH/tetracysteine (FlAsH/TC) tag is a powerful tool for fluorescent labeling of proteins. However, even small tags such as FlAsH/TC could alter the behavior of the tagged proteins, especially if the insertion occurs at internal sites. Defining the influence of FlAsH/TC on nearby protein-protein interactions might aid in selecting appropriate positions for internal TC insertions and allow the exploitation of serial FlAsH/TC insertions (TC-scanning) as a probe to characterize sites of protein-protein interaction. To explore this application in the context of substrate-protease interactions, we analyzed the effect of FlAsH/TC insertions on proteolysis of cellular prion protein (PrPsen) in in vitro reactions and generation of the C1 metabolic fragment of PrPsen in live neuroblastoma cells. The influence of FlAsH/TC insertion was evaluated by TC-scanning across the cleavage sites of each protease. The results showed that FlAsH/TC inhibited protease cleavage only within limited ranges of the cleavage sites that varied from about 1 to 6 residues-wide depending on the protease, providing an estimate of the PrP residues interacting with each protease. TC-scanning was also used to probe a different type of protein-protein interaction, the conformational conversion of FlAsH-PrPsen to the prion disease-associated isoform, PrPres. PrP constructs with FlAsH/TC insertions at residues 90–96 but not 97–101 were converted to FlAsH-PrPres, identifying a boundary separating loosely versus compactly folded regions of PrPres. Our observations demonstrate that TC-scanning with the FlAsH/TC tag can be a versatile method for probing protein-protein interactions and folding processes. PMID:23943295

Low fraction of the 222K PrP variant in the protease-resistant moiety of PrPres in heterozygous scrapie positive goats

OpenAIRE

Mazza, Maria; Guglielmetti, Chiara; Ingravalle, Francesco; Brusadore, Sonia; Langeveld, Jan P. M.; Ekateriniadou, Loukia V.; Andréoletti, Olivier; Casalone, Cristina; Acutis, Pier Luigi

2017-01-01

The presence of lysine (K) at codon 222 has been associated with resistance to classical scrapie in goats, but few scrapie cases have been identified in 222Q/K animals. To investigate the contribution of the 222K variant to PrPres formation in natural and experimental Q/K scrapie cases, we applied an immunoblotting method based on the use of two different monoclonal antibodies, F99/97.6.1 and SAF84, chosen for their different affinities to 222K and 222Q PrP variants. Our finding that PrPres s...

Shifting Paradigms in Music Education Research (1953-1978): A Theoretical and Quantitative Reassessment

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Jorgensen, Estelle R.; Ward-Steinman, Patrice Madura

2015-01-01

The purpose of this study was to examine evidence of a hypothesized shift in the operative research paradigms in music education during the first quarter century of the publication of the "Journal of Research in Music Education," during the period 1953 to 1978. This shift was from humanities-oriented historical and philosophical studies…

Does Flywheel Paradigm Training Improve Muscle Volume and Force? A Meta-Analysis.

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Nuñez Sanchez, Francisco J; Sáez de Villarreal, Eduardo

2017-11-01

Núñez Sanchez, FJ and Sáez de Villarreal, E. Does flywheel paradigm training improve muscle volume and force? A meta-analysis. J Strength Cond Res 31(11): 3177-3186, 2017-Several studies have confirmed the efficacy of flywheel paradigm training for improving or benefiting muscle volume and force. A meta-analysis of 13 studies with a total of 18 effect sizes was performed to analyse the role of various factors on the effectiveness of flywheel paradigm training. The following inclusion criteria were employed for the analysis: (a) randomized studies; (b) high validity and reliability instruments; (c) published in a high quality peer-reviewed journal; (d) healthy participants; (e) studies where the eccentric programme were described; and (f) studies where increases in muscle volume and force were measured before and after training. Increases in muscle volume and force were noted through the use of flywheel systems during short periods of training. The increase in muscle mass appears was not influenced by the existence of eccentric overload during the exercise. The increase in force was significantly higher with the existence of eccentric overload during the exercise. The responses identified in this analysis are essential and should be considered by strength and conditioning professionals regarding the most appropriate dose response trends for flywheel paradigm systems to optimize the increase in muscle volume and force.

A new learning paradigm: learning using privileged information.

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Vapnik, Vladimir; Vashist, Akshay

2009-01-01

In the Afterword to the second edition of the book "Estimation of Dependences Based on Empirical Data" by V. Vapnik, an advanced learning paradigm called Learning Using Hidden Information (LUHI) was introduced. This Afterword also suggested an extension of the SVM method (the so called SVM(gamma)+ method) to implement algorithms which address the LUHI paradigm (Vapnik, 1982-2006, Sections 2.4.2 and 2.5.3 of the Afterword). See also (Vapnik, Vashist, & Pavlovitch, 2008, 2009) for further development of the algorithms. In contrast to the existing machine learning paradigm where a teacher does not play an important role, the advanced learning paradigm considers some elements of human teaching. In the new paradigm along with examples, a teacher can provide students with hidden information that exists in explanations, comments, comparisons, and so on. This paper discusses details of the new paradigm and corresponding algorithms, introduces some new algorithms, considers several specific forms of privileged information, demonstrates superiority of the new learning paradigm over the classical learning paradigm when solving practical problems, and discusses general questions related to the new ideas.

Platelet rich plasma versus laser therapy in lateral epicondylitis of elbow.

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Tonk, Gyaneshwar; Kumar, Anish; Gupta, Amit

2014-07-01

Platelet rich plasma (PRP) extract has shown to be a general stimulation for repair and currently used widely in various sports injury. A prospective observational study was done to assess the efficacy of autologous PRP injection in lateral epicondylitis of elbow, and compare the result with low level laser therapy. The trial was conducted at a tertiary care center for a period of 2 years. Eighty-one patients with chronic lateral epicondylitis were divided into two groups. PRP group (n = 39) and laser therapy group (n = 42). The primary analysis included Nirschl pain score, local tenderness, pain on wrist extension, grip strength, elbow swelling were clinically assessed at different interval of followup (minimum followup: 52 weeks) and; clinical and functional outcome evaluated at final followup. The statistical analysis were done. The mean Nirschl pain score decreased significantly from baseline in PRP when compared with low level laser therapy (P ≤ 0.05). Treatment of patients with chronic lateral epicondylitis with PRP extract reduced pain and significantly increased function, exceeding the effect of low level laser therapy on long term followup. Low-level laser therapy is better in the short term period, but on long term followup injection PRP therapy is better than laser therapy in lateral epicondylitis.

The search for understanding: the role of paradigms.

Science.gov (United States)

Kelly, Marcella; Dowling, Maura; Millar, Michelle

2018-03-16

Kuhn's ( 1962 ) acknowledgement of a paradigm as a way that scientists make sense of their world and its reality gave recognition to the idea of 'paradigm shift'. This shift exposes the transience of paradigm development shaped by societal and scientific evolution. This ongoing evolutionary development provides the researcher with many paradigms to consider regarding how research is undertaken and the search for understanding achieved. An understanding of paradigm development is necessary when planning a study and can shape the search for understanding. It is hoped that the discussion presented here will assist novice and experienced researchers in articulating the rationales for their paradigm choices. An overview of the dominant paradigms is presented, reflecting ongoing paradigm development shaped by ontological, epistemological and methodological perspectives. Potential paradigm choices that shape research aims, objectives and focus in the search for understanding are considered. The inherent debates about paradigm shift, division, war and synthesis leave the researcher many perspectives to consider. Articulating the world views underpinning constructivism, interpretivism and pragmatism is particularly challenging because of the blurring of boundaries between them. The evolutionary nature of paradigmatic development has provided nurse researchers with the opportunity for methodological openness to the myriad research approaches, methods and designs that they may choose to answer their research question. However, it is imperative that researchers consider their ontological stances and the nature of their research questions. This is challenging in constructivism, interpretivism and pragmatism, where there is often an overlap of paradigm world views. ©2018 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

A Brief History of Biomedical Research Ethics in Iran: Conflict of Paradigms.

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Aramesh, Kiarash

2015-08-01

During the past two decades, Iran has experienced a noteworthy growth in its biomedical research sector. At the same time, ethical concerns and debates resulting from this burgeoning enterprise has led to increasing attention paid to biomedical ethics. In Iran, Biomedical research ethics and research oversight passed through major periods during the past decades, separated by a paradigm shift. Period 1, starting from the early 1970s, is characterized by research paternalism and complete reliance on researchers as virtuous and caring physicians. This approach was in concordance with the paternalistic clinical practice of physicians outside of research settings during the same period. Period 2, starting from the late 1990s, was partly due to revealing of ethical flaws that occurred in biomedical research in Iran. The regulatory and funding bodies concluded that it was not sufficient to rely solely on the personal and professional virtues of researchers to safeguard human subjects' rights and welfare. The necessity for independent oversight, emphasized by international declarations, became obvious and undeniable. This paradigm shift led to the establishment of research ethics committees throughout the country, the establishment of academic research centers focusing on medical ethics (MEHR) and the compilation of the first set of national ethical guidelines on biomedical research-one of the first and most important projects conducted by and in the MEHR. Although not yet arrived, 'period 3' is on its way. It is predictable from the obvious trends toward performance of high-quality clinical research and the appearance of a highly educated new generation, especially among women. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Ostracism Online: A social media ostracism paradigm.

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Wolf, Wouter; Levordashka, Ana; Ruff, Johanna R; Kraaijeveld, Steven; Lueckmann, Jan-Matthis; Williams, Kipling D

2015-06-01

We describe Ostracism Online, a novel, social media-based ostracism paradigm designed to (1) keep social interaction experimentally controlled, (2) provide researchers with the flexibility to manipulate the properties of the social situation to fit their research purposes, (3) be suitable for online data collection, (4) be convenient for studying subsequent within-group behavior, and (5) be ecologically valid. After collecting data online, we compared the Ostracism Online paradigm with the Cyberball paradigm (Williams & Jarvis Behavior Research Methods, 38, 174-180, 2006) on need-threat and mood questionnaire scores (van Beest & Williams Journal of Personality and Social Psychology 91, 918-928, 2006). We also examined whether ostracized targets of either paradigm would be more likely to conform to their group members than if they had been included. Using a Bayesian analysis of variance to examine the individual effects of the different paradigms and to compare these effects across paradigms, we found analogous effects on need-threat and mood. Perhaps because we examined conformity to the ostracizers (rather than neutral sources), neither paradigm showed effects of ostracism on conformity. We conclude that Ostracism Online is a cost-effective, easy to use, and ecologically valid research tool for studying the psychological and behavioral effects of ostracism.

Biogeochemical processes on tree islands in the greater everglades: Initiating a new paradigm

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Wetzel, P.R.; Sklar, Fred H.; Coronado, C.A.; Troxler, T.G.; Krupa, S.L.; Sullivan, P.L.; Ewe, S.; Price, R.M.; Newman, S.; Orem, W.H.

2011-01-01

Scientists' understanding of the role of tree islands in the Everglades has evolved from a plant community of minor biogeochemical importance to a plant community recognized as the driving force for localized phosphorus accumulation within the landscape. Results from this review suggest that tree transpiration, nutrient infiltration from the soil surface, and groundwater flow create a soil zone of confluence where nutrients and salts accumulate under the head of a tree island during dry periods. Results also suggest accumulated salts and nutrients are flushed downstream by regional water flows during wet periods. That trees modulate their environment to create biogeochemical hot spots and strong nutrient gradients is a significant ecological paradigm shift in the understanding of the biogeochemical processes in the Everglades. In terms of island sustainability, this new paradigm suggests the need for distinct dry-wet cycles as well as a hydrologic regime that supports tree survival. Restoration of historic tree islands needs further investigation but the creation of functional tree islands is promising. Copyright ?? 2011 Taylor & Francis Group, LLC.

RENEGOTIATION MINING CONTRACT: LEGAL PARADIGM RECONSTRUCTION EFFORTS

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Marilang -

2014-07-01

Full Text Available Renegotiation contract mining is not a priori notion that was born but is driven by the fact that empirical Work Contract (KK and coal mining concessions of the Works Agreement (Cca that are valid for this resulted in profits which are not comparable between countries with investors (domestic and foreign. In addition, Law No. 4 of 2009 about Mineral and Coal Mining (minerba through article 169 have been injected that though the mining contracts during the validity of this, still respected until the end, however, if the implementation of these contracts give rise to distortions for the national interest, then the Government must encourage the investors to do Renegotiation against existing contracts to comply with legislation minerba forever within a period of one year since the enactment of the legislation this minerba. Renegotiation mining contracts that have been approved on the fact of the matter is simply an attempt to reconstruct the ruling paradigm, so with that paradigm shift, both parties can reach the intersection for the benefit of both parties, i.e. the parties proportionately Indonesia suffered no losses on the one hand, and the benefit of the domestic and foreign investors remain in reasonable limits on the other. 

A radical paradigm shift for a new definition of architecture

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Alessio Erioli

2015-11-01

Full Text Available Architecture is facing a period of great challenges and possibilities, typical of all crises. In such periods, the paradigms we have taken for granted so far are the same ones that generated the crisis, therefore they should undergo a critical revision and new modes of thought and operation (driven by computation can be actively explored and pursued. Instead of retreating to intellectual “safe houses”, architecture should open itself up to and be restructured by the accelerated pace of change imposed by reality, renouncing obsolete methods of anticipating and exerting control and welcoming a more proactive behaviour. It is therefore of primary importance to promote the exercise of projective imagination.

Policy paradigms, transnationalism, and domestic politics

National Research Council Canada - National Science Library

Skogstad, Grace Darlene

2011-01-01

Policy Paradigms, Transnationalism, and Domestic Politics offers a variety of perspectives on the development of policy paradigms -- the ideas that structure thinking about what can and should be done in a policy domain...

Paradigm Shifts in Ophthalmic Diagnostics.

Science.gov (United States)

Sebag, J; Sadun, Alfredo A; Pierce, Eric A

2016-08-01

Future advances in ophthalmology will see a paradigm shift in diagnostics from a focus on dysfunction and disease to better measures of psychophysical function and health. Practical methods to define genotypes will be increasingly important and non-invasive nanotechnologies are needed to detect molecular changes that predate histopathology. This is not a review nor meant to be comprehensive. Specific topics have been selected to illustrate the principles of important paradigm shifts that will influence the future of ophthalmic diagnostics. It is our impression that future evaluation of vision will go beyond visual acuity to assess ocular health in terms of psychophysical function. The definition of disease will incorporate genotype into what has historically been a phenotype-centric discipline. Non-invasive nanotechnologies will enable a paradigm shift from disease detection on a cellular level to a sub-cellular molecular level. Vision can be evaluated beyond visual acuity by measuring contrast sensitivity, color vision, and macular function, as these provide better insights into the impact of aging and disease. Distortions can be quantified and the psychophysical basis of vision can be better evaluated than in the past by designing tests that assess particular macular cell function(s). Advances in our understanding of the genetic basis of eye diseases will enable better characterization of ocular health and disease. Non-invasive nanotechnologies can assess molecular changes in the lens, vitreous, and macula that predate visible pathology. Oxygen metabolism and circulatory physiology are measurable indices of ocular health that can detect variations of physiology and early disease. This overview of paradigm shifts in ophthalmology suggests that the future will see significant improvements in ophthalmic diagnostics. The selected topics illustrate the principles of these paradigm shifts and should serve as a guide to further research and development. Indeed

[New paradigm for soil and water conservation: a method based on watershed process modeling and scenario analysis].

Science.gov (United States)

Zhu, A-Xing; Chen, La-Jiao; Qin, Cheng-Zhi; Wang, Ping; Liu, Jun-Zhi; Li, Run-Kui; Cai, Qiang-Guo

2012-07-01

With the increase of severe soil erosion problem, soil and water conservation has become an urgent concern for sustainable development. Small watershed experimental observation is the traditional paradigm for soil and water control. However, the establishment of experimental watershed usually takes long time, and has the limitations of poor repeatability and high cost. Moreover, the popularization of the results from the experimental watershed is limited for other areas due to the differences in watershed conditions. Therefore, it is not sufficient to completely rely on this old paradigm for soil and water loss control. Recently, scenario analysis based on watershed modeling has been introduced into watershed management, which can provide information about the effectiveness of different management practices based on the quantitative simulation of watershed processes. Because of its merits such as low cost, short period, and high repeatability, scenario analysis shows great potential in aiding the development of watershed management strategy. This paper elaborated a new paradigm using watershed modeling and scenario analysis for soil and water conservation, illustrated this new paradigm through two cases for practical watershed management, and explored the future development of this new soil and water conservation paradigm.

Unconscious intuition or conscious analysis? Critical questions for the Deliberation-Without-Attention paradigm

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Balazs Aczel

2011-06-01

Full Text Available The Deliberation without Attention (DWA effect refers to apparent improvements in decision-making following a period of distraction. It has been presented as evidence for beneficial unconscious cognitive processes. We identify two major concerns with this claim: first, as these demonstrations typically involve subjective preferences, the effects of distraction cannot be objectively assessed as beneficial; second, there is no direct evidence that the DWA manipulation promotes unconscious decision processes. We describe two tasks based on the DWA paradigm in which we found no evidence that the distraction manipulation led to decision processes that are subjectively unconscious, nor that it reduced the influence of presentation order upon performance. Crucially, we found that a lack of awareness of decision process was associated with poorer performance, both in terms of subjective preference measures used in traditional DWA paradigm and in an equivalent task where performance can be objectively assessed. Therefore, we argue that reliance on conscious memory itself can explain the data. Thus the DWA paradigm is not an adequate method of assessing beneficial unconscious thought.

Membrane paradigm

International Nuclear Information System (INIS)

Price, R.H.; Thorne, K.S.

1986-01-01

The membrane paradigm is a modified frozen star approach to modeling black holes, with particles and fields assuming a complex, static, boundary-layer type structure (membrane) near the event horizon. The membrane has no effects on the present or future evolution of particles and fields above itself. The mathematical representation is a combination of a formalism containing terms for the shear and bulk viscosity, surface pressure, momentum, temperature, entropy, etc., of the horizon and the 3+1 formalism. The latter model considers a family of three-dimensional spacelike hypersurfaces in one-dimensional time. The membrane model considers a magnetic field threading the hole and undergoing torque from the hole rotation. The field is cleaned by the horizon and distributed over the horizon so that ohmic dissipation is minimized. The membrane paradigm is invalid inside the horizon, but is useful for theoretically probing the properties of slowly evolving black holes

Information processing as a paradigm for decision making.

Science.gov (United States)

Oppenheimer, Daniel M; Kelso, Evan

2015-01-03

For decades, the dominant paradigm for studying decision making--the expected utility framework--has been burdened by an increasing number of empirical findings that question its validity as a model of human cognition and behavior. However, as Kuhn (1962) argued in his seminal discussion of paradigm shifts, an old paradigm cannot be abandoned until a new paradigm emerges to replace it. In this article, we argue that the recent shift in researcher attention toward basic cognitive processes that give rise to decision phenomena constitutes the beginning of that replacement paradigm. Models grounded in basic perceptual, attentional, memory, and aggregation processes have begun to proliferate. The development of this new approach closely aligns with Kuhn's notion of paradigm shift, suggesting that this is a particularly generative and revolutionary time to be studying decision science.

Bion and the sublime: the origins of an aesthetic paradigm.

Science.gov (United States)

Civitarese, Giuseppe

2014-12-01

In constructing his theory Bion drew on a number of symbolic matrices: psychoanalysis, philosophy, mathematics, literature, aesthetics. The least investigated of these is the last. True, we know that Bion cites many authors of the Romantic period, such as Coleridge, Keats, Blake and Wordsworth, as well as others who were held in high esteem in the Romantic period, such as Milton. However, less is known about the influence exerted on him by the aesthetics of the sublime, which while chronologically preceding Romanticism is in fact one of its components. My working hypothesis is that tracing a number of Bion's concepts back to this secret model can serve several purposes: firstly, it contributes to the study of the sources, and, secondly, it makes these concepts appear much less occasional and idiosyncratic than we might believe, being as they are mostly those less immediately understandable but not less important (O, negative capability, nameless dread, the infinite, the language of achievement, unison etc.). Finally, connecting these notions to a matrix, that is, disclosing the meaning of elements that are not simply juxtaposed but dynamically interrelated, in my view significantly increases not only their theoretical intelligibility but also their usefulness in clinical practice. In conclusion, one could legitimately argue that Bion gradually subsumed all the other paradigms he drew on within the aesthetic paradigm. Copyright © 2014 Institute of Psychoanalysis.

Dodecylphosphocholine Micelles Induce Amyloid Formation of the PrP(110-136 Peptide via an α-Helical Metastable Conformation.

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Simon Sauvé

Full Text Available A peptide encompassing the conserved hydrophobic region and the first β-strand of the prion protein (PrP(110-136 shown to interact with the surface of dodecylphosphocholine micelles adopts an α-helical conformation that is localized below the head-group layer. This surface-bound peptide has a half-life of one day, and readily initiates the formation of amyloid fibrils. The presence of the latter was confirmed using birefringence microscopy upon Congo red binding and thioflavin T-binding induced fluorescence. The observation of this metastable α-helical conformer provides a unique snapshot of the early steps of the inter-conversion pathway. These findings together with the body of evidence from the prion literature allowed us to propose a mechanism for the conversion of PrPC to amyloid material.

An ancient conserved role for prion protein in learning and memory

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Patricia L. A. Leighton

2018-01-01

Full Text Available The misfolding of cellular prion protein (PrPC to form PrP Scrapie (PrPSc is an exemplar of toxic gain-of-function mechanisms inducing propagated protein misfolding and progressive devastating neurodegeneration. Despite this, PrPC function in the brain is also reduced and subverted during prion disease progression; thus understanding the normal function of PrPC in healthy brains is key. Disrupting PrPC in mice has led to a myriad of controversial functions that sometimes map onto disease symptoms, including a proposed role in memory or learning. Intriguingly, PrPC interaction with amyloid beta (Aβ oligomers at synapses has also linked its function to Alzheimer's disease and dementia in recent years. We set out to test the involvement of PrPC in memory using a disparate animal model, the zebrafish. Here we document an age-dependent memory decline in prp2−/− zebrafish, pointing to a conserved and ancient role of PrPC in memory. Specifically, we found that aged (3-year-old prp2−/− fish performed poorly in an object recognition task relative to age-matched prp2+/+ fish or 1-year-old prp2−/− fish. Further, using a novel object approach (NOA test, we found that aged (3-year-old prp2−/− fish approached the novel object more than either age-matched prp2+/+ fish or 1-year-old prp2−/− fish, but did not have decreased anxiety when we tested them in a novel tank diving test. Taken together, the results of the NOA and novel tank diving tests suggest an altered cognitive appraisal of the novel object in the 3-year-old prp2−/− fish. The learning paradigm established here enables a path forward to study PrPC interactions of relevance to Alzheimer's disease and prion diseases, and to screen for candidate therapeutics for these diseases. The findings underpin a need to consider the relative contributions of loss- versus gain-of-function of PrPC during Alzheimer's and prion diseases, and have implications upon the prospects of several

Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 1—Psychometric Characteristics of 5 Paradigms.

Science.gov (United States)

Reddy, L Felice; Horan, William P; Barch, Deanna M; Buchanan, Robert W; Dunayevich, Eduardo; Gold, James M; Lyons, Naomi; Marder, Stephen R; Treadway, Michael T; Wynn, Jonathan K; Young, Jared W; Green, Michael F

2015-09-01

Impairments in willingness to exert effort contribute to the motivational deficits characteristic of the negative symptoms of schizophrenia. The current study evaluated the psychometric properties of 5 new or adapted paradigms to determine their suitability for use in clinical trials of schizophrenia. This study included 94 clinically stable participants with schizophrenia and 40 healthy controls. The effort-based decision-making battery was administered twice to the schizophrenia group (baseline, 4-week retest) and once to the control group. The 5 paradigms included 1 that assesses cognitive effort, 1 perceptual effort, and 3 that assess physical effort. Each paradigm was evaluated on (1) patient vs healthy control group differences, (2) test-retest reliability, (3) utility as a repeated measure (ie, practice effects), and (4) tolerability. The 5 paradigms showed varying psychometric strengths and weaknesses. The Effort Expenditure for Rewards Task showed the best reliability and utility as a repeated measure, while the Grip Effort Task had significant patient-control group differences, and superior tolerability and administration duration. The other paradigms showed weaker psychometric characteristics in their current forms. These findings highlight challenges in adapting effort and motivation paradigms for use in clinical trials. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2015.

Analysis of the Paradigm Evolution of Digital Libraries in China

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Tan Sun

2007-10-01

Full Text Available The authors analyze the developmental framework of digital libraries in China and point out their current demand characteristics, development requirements, and developmental period. They then conclude that it is necessary to start up a new paradigm evolution of a digital library, from a traditional digital library to a virtual digital library. On that basis, they describe in detail several problems and developmental approaches that developing a virtual digital library must deal with, drawing lessons from the prototype DILIGENT.

Thought Suppression Research Methods: Paradigms, Theories, Methodological Concerns

Directory of Open Access Journals (Sweden)

Niczyporuk Aneta

2016-12-01

Full Text Available It is hard to provide an unequivocal answer to the question of whether or not thought suppression is effective. Two thought suppression paradigms - the “white bear” paradigm and the think/no-think paradigm - give mixed results. Generally, “white bear” experiments indicate that thought suppression is counterproductive, while experiments in the think/no-think paradigm suggest that it is possible to effectively suppress a thought. There are also alternative methods used to study thought suppression, for instance the directed forgetting paradigm or the Stroop task. In the article, I describe the research methods used to explore thought suppression efficacy. I focus on the “white bear” and the think/no-think paradigms and discuss theories proposed to explain the results obtained. I also consider the internal and external validity of the methods used.

Central as well as peripheral attentional bottlenecks in dual-task performance activate lateral prefrontal cortices

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Andre J Szameitat

2016-03-01

Full Text Available Human information processing suffers from severe limitations in parallel processing. In particular, when required to respond to two stimuli in rapid succession, processing bottlenecks may appear at central and peripheral stages of task processing. Importantly, it has been suggested that executive functions are needed to resolve the interference arising at such bottlenecks. The aims of the present study were to test whether central attentional limitations (i.e., bottleneck at the decisional response selection stage as well as peripheral limitations (i.e., bottleneck at response initiation both demand executive functions located in the lateral prefrontal cortex. For this, we re-analysed two previous studies, in which a total of 33 participants performed a dual-task according to the paradigm of the psychological refractory period (PRP during fMRI. In one study (N=17, the PRP task consisted of two two-choice response tasks known to suffer from a central bottleneck (CB group. In the other study (N=16, the PRP task consisted of two simple-response tasks known to suffer from a peripheral bottleneck (PB group. Both groups showed considerable dual-task costs in form of slowing of the second response in the dual-task (PRP effect. Imaging results are based on the subtraction of both single-tasks from the dual-task within each group. In the CB group, the bilateral middle frontal gyri and inferior frontal gyri were activated. Higher activation in these areas was associated with lower dual-task costs. In the PB group, the right middle frontal and inferior frontal gyrus were activated. Here, higher activation was associated with higher dual-task costs. In conclusion we suggest that central and peripheral bottlenecks both demand executive functions located in lateral prefrontal cortices. Differences between the CB and PB groups with respect to the exact prefrontal areas activated and the correlational patterns suggest that the executive functions resolving

Three paradigms of horror

OpenAIRE

Dejan Ognjanović

2016-01-01

Starting with the definition of horror as a literary genre the core story of which is based on a meeting with threatening Otherness whose influx into consensual reality and it’s tacit normality creates unrest and awakens fear in the protagonists and the audience, this paper defines the three key paradigms of the horror genre, based on the causes of fear, or rather the “monstrous” Otherness in them. Paradigm 1 concerns the “fear of one’s own self”: the root of the fear is inside, in the indivi...

ENVIRONMENTALISM AND CLASSIC PARADIGMS OF INTERNATIONAL RELATIONS

OpenAIRE

D. D. Miniaeva

2014-01-01

This article examines an environmentalism integration process into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism) into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism). The main purpose of this study is to reveal the result of this integration. Methods used in this article include analysis and comparison of "ecological" paradigms on selected parameters (the nature of international relations, actors, ta...

The safety implications of emerging software paradigms

International Nuclear Information System (INIS)

Suski, G.J.; Persons, W.L.; Johnson, G.L.

1994-10-01

This paper addresses some of the emerging software paradigms that may be used in developing safety-critical software applications. Paradigms considered in this paper include knowledge-based systems, neural networks, genetic algorithms, and fuzzy systems. It presents one view of the software verification and validation activities that should be associated with each paradigm. The paper begins with a discussion of the historical evolution of software verification and validation. Next, a comparison is made between the verification and validation processes used for conventional and emerging software systems. Several verification and validation issues for the emerging paradigms are discussed and some specific research topics are identified. This work is relevant for monitoring and control at nuclear power plants

Morally-Relevant Similarities and Differences Between Assisted Dying Practices in Paradigm and Non-Paradigm Circumstances: Could They Inform Regulatory Decisions?

Science.gov (United States)

Kirby, Jeffrey

2017-12-01

There has been contentious debate over the years about whether there are morally relevant similarities and differences between the three practices of continuous deep sedation until death, physician-assisted suicide, and voluntary euthanasia. Surprisingly little academic attention has been paid to a comparison of the uses of these practices in the two types of circumstances in which they are typically performed. A comparative domains of ethics analysis methodological approach is used in the paper to compare 1) the use of the three practices in paradigm circumstances, and 2) the use of the practices in paradigm circumstances to their use in non-paradigm circumstances. The analytical outcomes suggest that a bright moral line cannot be demonstrated between any two of the practices in paradigm circumstances, and that there are significant, morally-relevant distinctions between their use in paradigm and non-paradigm circumstances. A thought experiment is employed to illustrate how these outcomes could possibly inform the decisions of hypothetical deliberators who are engaged in the collaborative development of assisted dying regulatory frameworks.

Assessment of the efficacy and safety of single platelet-rich plasma injection on different types and grades of facial wrinkles.

Science.gov (United States)

Elnehrawy, Naema Y; Ibrahim, Zeinab A; Eltoukhy, Azza M; Nagy, Hala M

2017-03-01

Platelet-rich plasma (PRP) is considered as a growing modality for tissue regeneration and a developing research area for clinicians and researchers. PRP injection treatment provides supraphysiological concentrations of growth factors that may help in accelerated tissue remodeling and regeneration. To evaluate the efficacy and safety of single autologous PRP intradermal injection for treatment of facial wrinkles and for facial rejuvenation. A total of 20 subjects with different types of facial wrinkles were included in this study. All subjects received single PRP intradermal injection and were clinically assessed before and after treatment for a period of 8 weeks using Wrinkle Severity Rating Scale (WSRS), Skin Homogeneity and Texture (SHnT) Scale, Physician Assessment Scale, and Subject Satisfaction Scale. The mean value of WSRS reduced from 2.90 ± 0.91 before treatment to 2.10 ± 0.79 after 8 weeks of treatment. The most significant results were with younger subjects that have mild and moderate wrinkles of the nasolabial folds (NLFs). Fourteen of seventeen subjects with NLFs showed more than 25% improvement in their appearance. Side effects of PRP treatment were minimal to mild and with excellent tolerability. Single PRP intradermal injection is well tolerated and capable of rejuvenating the face and producing a significant correction of wrinkles especially the NLFs. © 2016 Wiley Periodicals, Inc.

Project management: a new service delivery paradigm

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G. van der Walt

2007-07-01

Full Text Available In line with international trends in governance, the South African Government’s initial focus on the development of policy frameworks, structures and systems in order to give effect to the values and principles of the Constitution, shifted to the most critical issue, namely service delivery. The Government became increasingly aware that a significant expansion in the scope and quality of service provision was not possible with traditional delivery settings and approaches. There is growing evidence that there is a need for a significant departure from conventional approaches and that a leap into a new service delivery paradigm is necessary. Increasingly this new paradigm highlights the need to further develop the government’s project management skills and applications with a view to achieving improved delivery capability. In this article the focus will be placed on the changing service delivery paradigm – from an “old” traditional model through the transition to a “new” paradigm. This paradigm is shaped by international and national trends and events in government. The contribution and advantages of project management applications for effective governance are highlighted and the article concludes with an explanation of project management organisational arrangements necessary to support the new paradigm.

Testing the membrane paradigm with holography

NARCIS (Netherlands)

de Boer, J.; Heller, M.P.; Pinzani-Fokeeva, N.

2015-01-01

One version of the membrane paradigm states that, as far as outside observers are concerned, black holes can be replaced by a dissipative membrane with simple physical properties located at the stretched horizon. We demonstrate that such a membrane paradigm is incomplete in several aspects. We argue

Paradigm Shift or Business as Usual? Dynamic Complementarities in Innovation Strategies

OpenAIRE

James Love; Stephen Roper; Priit Vahter

2013-01-01

We investigate claims of a ‘paradigm shift’ towards firms using open innovation as a conscious strategic choice. Such a claim implicitly involves two elements: first, there should be some evidence that firms are increasingly likely to use a combination of internal and external knowledge in their innovation activity, and second, there should evidence that firms derive a systematic advantage from so doing. Using a panel of Irish manufacturing plants over the period 1991-2008 we develop four arc...

Romanian spa tourism: a communist paradigm in a post communist era

OpenAIRE

George Erdeli; Ana Irina Dincă; Aurel Gheorghilas; Camelia Surugiu

2011-01-01

Spa tourism is one of the oldest forms of tourism which continuously evolved in time as the leisure industry paradigm and the consumers’ behavior changed. Similar to other countries in Central and Eastern Europe, spa tourism is an old phenomenon in Romania which expanded to the dimensions of a well defined tourism industry during the mass tourism period which also corresponded to the communism epoch. Although severely affected by the major political and socio-economic changes which occurred a...

The Digital Twin Paradigm for Future NASA and U.S. Air Force Vehicles

Science.gov (United States)

Glaessgen, Edward H.; Stargel, D. S.

2012-01-01

Future generations of NASA and U.S. Air Force vehicles will require lighter mass while being subjected to higher loads and more extreme service conditions over longer time periods than the present generation. Current approaches for certification, fleet management and sustainment are largely based on statistical distributions of material properties, heuristic design philosophies, physical testing and assumed similitude between testing and operational conditions and will likely be unable to address these extreme requirements. To address the shortcomings of conventional approaches, a fundamental paradigm shift is needed. This paradigm shift, the Digital Twin, integrates ultra-high fidelity simulation with the vehicle s on-board integrated vehicle health management system, maintenance history and all available historical and fleet data to mirror the life of its flying twin and enable unprecedented levels of safety and reliability.

The Consumption Paradigm in Marketing

Directory of Open Access Journals (Sweden)

Eka Ardianto

2003-08-01

Full Text Available This article elaborates consumption paradigm in marketing. In background, this paper reviews different perspectives of consumption: economic perspective and marketing perspective. In ontology, this work describes various issues regarding consumption view. In epistemology, this article demonstrates how marketers especially researches explore the consumption phenomena. In methodology, the article describes experiential marketing –one of applied consumption paradigm in marketing, which could be an alternative choice of marketing practices.

Epidemiology, Treatment Efficacy, and Anxiety Aspects of Music Students Affected by Playing-Related Pain: A Retrospective Evaluation with Follow-up.

Science.gov (United States)

Ioannou, Christos I; Hafer, Julia; Lee, André; Altenmüller, Eckart

2018-03-01

Playing-related pain (PRP) is a common problem among music students. We retrospectively assessed epidemiological factors that contributed to the manifestation of PRP and evaluated the efficacy of treatment methods used by affected music students. The long-term course of PRP symptoms was also examined, along with current (today) levels of trait anxieties. Demographic and epidemiological data of 186 music students who visited the musicians' outpatient clinic over a 5-year period were retrieved. Of these students, 122 had been diagnosed with PRP and were invited to participate (response rate 61.5%) in a follow-up online survey to: a) estimate the long-term course of their PRP symptoms, b) assess the efficacy of treatment methods they used, and c) assess their current trait anxiety (general and performance-related) using two standardized psychodiagnostic questionnaires. Two-thirds of music students who sought medical care were affected by PRP, with most being affected during their first year of studies, and with 69% having acute rather than chronic pain. The sudden increase in practice time was the main triggering factor for PRP (but not for non-PRP-related problems). Concerning the course of PRP, almost all students recovered or improved significantly. Students reported that "active" treatment methods (e.g., physical activities) were more effective than "passive" methods (e.g., oral medications). Psychodiagnostic questionnaires indicated that about 40% of PRP-affected students currently had increased levels of trait anxieties (music and non-music related), possibly warranting further medical assistance. PRP in music students occurs mainly at the beginning of their studies and has a good prognosis, although recovery may be lengthy. It is necessary to provide students with early information about PRP and about the multidimensional treatment framework that allows for individualized care of PRP in affected music students.

Composite paradigms in medicine: analysing Gillies' claim of reclassification of disease without paradigm shift in the case of Helicobacter pylori.

Science.gov (United States)

Hutton, Joseph

2012-09-01

Since the publication of Kuhn's The Structure of Scientific Revolutions in 1962, the notion of paradigms has shaped the way that philosophy views scientific discovery and how changes in what is regarded as empirical fact occur. This drew heavily on examples from the history of the natural sciences to support Kuhn's hypothesis. However, some argue that medicine is different from the natural sciences. Gillies has proposed another theory of how paradigms apply to medicine; that of composite paradigms. In doing so, Gillies uses the example of Helicobacter pylori and the shift from the excess-acid theory to the current bacterial-infection theory of gastric ulcers to illustrate these fundamental differences between medicine and the natural sciences. Upon analysis of Gillies' claim, it is evident that traditional Kuhnian paradigms are also composite and that the manner in which Gillies proposes disease is classified is insufficient in describing medicine. Furthermore, new local paradigms are demonstrably introduced and the change was accompanied by many of the markers of paradigmatic change including changes in worldview, resistance, incommensurability and the introduction of new questions that could not have existed under the previous paradigm. Whilst this change may not be on the scale of the Chemical revolution, it can still be considered paradigm shift. Thagard also proposes an alternate view of discovery using the case of H. pylori. This has much in common with Kuhnian paradigms but Thagard's theory offers further elucidation and refinement. This allows it to better characterise all of the associated features of discovery relevant in the case of H. pylori, thus provides a preferable tool for examination of this important recent discovery. Copyright © 2012 Elsevier Ltd. All rights reserved.

Innovative technological paradigm-based approach towards biofuel feedstock

International Nuclear Information System (INIS)

Xu, Jiuping; Li, Meihui

2017-01-01

Highlights: • DAS was developed through an innovative approach towards literature mining and technological paradigm theory. • A novel concept of biofuel feedstock development paradigm (BFDP) is proposed. • The biofuel production diffusion velocity model gives predictions for the future. • Soft path appears to be the driving force for the new paradigm shift. • An integrated biofuel production feedstock system is expected to play a significant role in a low-carbon sustainable future. - Abstract: Biofuels produced from renewable energy biomass are playing a more significant role because of the environmental problems resulting from the use of fossil fuels. However, a major problem with biofuel production is that despite the range of feedstock that can be used, raw material availability varies considerably. By combining a series of theories and methods, the research objective of this study is to determine the current developments and the future trends in biofuel feedstock. By combining technological paradigm theory with literature mining, it was found that biofuel feedstock production development followed a three-stage trajectory, which was in accordance with the traditional technological paradigm – the S-curve. This new curve can be divided into BFDP (biofuel feedstock development paradigm) competition, BFDP diffusion, and BFDP shift. The biofuel production diffusion velocity model showed that there has been constant growth from 2000, with the growth rate reaching a peak in 2008, after which time it began to drop. Biofuel production worldwide is expected to remain unchanged until 2030 when a paradigm shift is expected. This study also illustrates the results of our innovative procedure – a combination of the data analysis system and the technological paradigm theory – for the present biofuel feedstock soft path that will lead to this paradigm shift, with integrated biofuel production feedstock systems expected to be a significant new trend.

The string-pulling paradigm in comparative psychology.

Science.gov (United States)

Jacobs, Ivo F; Osvath, Mathias

2015-05-01

String pulling is one of the most widely used paradigms in comparative psychology. First documented 2 millennia ago, it has been a well-established scientific paradigm for a century. More than 160 bird and mammal species have been tested in over 200 studies with countless methodological variations. The paradigm can be used to address a wide variety of issues on animal cognition; for example, what animals understand about contact and connection as well as whether they rely on perceptual feedback, grasp the functionality of strings, generalize across conditions, apply their knowledge flexibly, and possess insight. Mammals are typically tested on a horizontal configuration, birds on a vertical one, making the studies difficult to compare; in particular, pulling a string vertically requires better coordination and attention. A species' performance on the paradigm is often influenced by its ecology, especially concerning whether limbs are used for foraging. Many other factors can be of importance and should be considered. The string-pulling paradigm is easy to administer, vary, and apply to investigate a wide array of cognitive abilities. Although it can be and has been used to compare species, divergent methods and unclear reporting have limited its comparative utility. With increasing research standards, the paradigm is expected to become an even more fundamental tool in comparative psychology. (c) 2015 APA, all rights reserved).

A knowledge-centered paradigm for operations and design

International Nuclear Information System (INIS)

Perin, C.

2005-01-01

A paradigm premised on the reactor design basis and on its systems, structures, and components also governs nuclear power plant operations. This machine-centered paradigm emphasizes a functional and discipline-based division of responsibilities, which can create hierarchical 'silos' and 'stovepipes' inhibiting the development and lateral exchange of knowledge about safety-critical system interactions. A knowledge-centered paradigm instead encourages the timely development, analysis, and exchange of information about system conditions and their likely consequences. This new paradigm puts operational focus on the importance of operating experience, informative root cause analyses, effective corrective actions, and cross-discipline exchange and cooperation. Although the knowledge-centered paradigm is already central to three main strategies of risk reduction, it is less likely to be recognized as such in terms of priorities, resources, and training: configuration control, control room operations, and root cause analysis. To maintain the capacity for safe shutdown and to preserve public trust, the knowledge-centered paradigm places as high a priority on interactions of safety-critical knowledge as it does on interactions of safety-critical systems, structures, and components. (author)

Therapeutic Effect of Platelet-Rich Plasma in Rat Spinal Cord Injuries

Directory of Open Access Journals (Sweden)

Nan-Fu Chen

2018-04-01

Full Text Available Platelet-rich plasma (PRP is prepared by centrifuging fresh blood in an anticoagulant state, and harvesting the platelet-rich portion or condensing platelets. Studies have consistently demonstrated that PRP concentrates are an abundant source of growth factors, such as platelet-derived growth factor (PDGF, transforming growth factor β (TGF-β, insulin-like growth factor 1 (IGF-1, and epithelial growth factor (EGF. The complex mechanisms underlying spinal cord injury (SCI diminish intrinsic repair and neuronal regeneration. Several studies have suggested that growth factor-promoted axonal regeneration can occur for an extended period after injury. More importantly, the delivery of exogenous growth factors contained in PRP, such as EGF, IGF-1, and TGF-β, has neurotrophic effects on central nervous system (CNS injuries and neurodegenerative diseases. However, only a few studies have investigated the effects of PRP on CNS injuries or neurodegenerative diseases. According to our review of relevant literature, no study has investigated the effect of intrathecal (i.t. PRP injection into the injured spinal cord and activation of intrinsic mechanisms. In the present study, we directly injected i.t. PRP into rat spinal cords and examined the effects of PRP on normal and injured spinal cords. In rats with normal spinal cords, PRP induced microglia and astrocyte activation and PDGF-B and ICAM-1 expression. In rats with SCIs, i.t. PRP enhanced the locomotor recovery and spared white matter, promoted angiogenesis and neuronal regeneration, and modulated blood vessel size. Furthermore, a sustained treatment (a bolus of PRP followed by a 1/3 dose of initial PRP concentration exerted more favorable therapeutic effects than a single dose of PRP. Our findings suggest by i.t. PRP stimulate angiogenesis, enhancing neuronal regeneration after SCI in rats. Although PRP induces minor inflammation in normal and injured spinal cords, it has many advantages. It is an

Active training paradigm for motor imagery BCI.

Science.gov (United States)

Li, Junhua; Zhang, Liqing

2012-06-01

Brain-computer interface (BCI) allows the use of brain activities for people to directly communicate with the external world or to control external devices without participation of any peripheral nerves and muscles. Motor imagery is one of the most popular modes in the research field of brain-computer interface. Although motor imagery BCI has some advantages compared with other modes of BCI, such as asynchronization, it is necessary to require training sessions before using it. The performance of trained BCI system depends on the quality of training samples or the subject engagement. In order to improve training effect and decrease training time, we proposed a new paradigm where subjects participated in training more actively than in the traditional paradigm. In the traditional paradigm, a cue (to indicate what kind of motor imagery should be imagined during the current trial) is given to the subject at the beginning of a trial or during a trial, and this cue is also used as a label for this trial. It is usually assumed that labels for trials are accurate in the traditional paradigm, although subjects may not have performed the required or correct kind of motor imagery, and trials may thus be mislabeled. And then those mislabeled trials give rise to interference during model training. In our proposed paradigm, the subject is required to reconfirm the label and can correct the label when necessary. This active training paradigm may generate better training samples with fewer inconsistent labels because it overcomes mistakes when subject's motor imagination does not match the given cues. The experiments confirm that our proposed paradigm achieves better performance; the improvement is significant according to statistical analysis.

Paradigm Shift in Language Teaching and Language Teacher Education

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Elaine Ferreira do Vale Borges

2014-11-01

Full Text Available In this article, I intend to conduct a short literature review and discussion about paradigm shift in language teaching and language teacher education from Cartesian to the complexity paradigm. For that, I use the Kuhnian notion of scientific revolution to present a short compilation of works related to paradigm shift in different sciences, including psychology, linguistics and, more emphatically, applied linguistics. The main proposal is to show the evolutions of paradigm shift in language and social sciences and its impact on the emergence of the complexity paradigm in language teaching and language teacher education fields.

Quantitative analysis of distributed control paradigms of robot swarms

DEFF Research Database (Denmark)

Ngo, Trung Dung

2010-01-01

describe the physical and simulated robots, experiment scenario, and experiment setup. Third, we present our robot controllers based on behaviour based and neural network based paradigms. Fourth, we graphically show their experiment results and quantitatively analyse the results in comparison of the two......Given a task of designing controller for mobile robots in swarms, one might wonder which distributed control paradigms should be selected. Until now, paradigms of robot controllers have been within either behaviour based control or neural network based control, which have been recognized as two...... mainstreams of controller design for mobile robots. However, in swarm robotics, it is not clear how to determine control paradigms. In this paper we study the two control paradigms with various experiments of swarm aggregation. First, we introduce the two control paradigms for mobile robots. Second, we...

About hypotheses and paradigms: exploring the Discreetness-Chance Paradigm.

Science.gov (United States)

Kaellis, Eugene

2006-01-01

Hypotheses generally conform to paradigms which, over time, change, usually tardily, after they have become increasingly difficult to sustain under the impact of non-conforming evidence and alternative hypotheses, but more important, when they no longer are comfortably ensconced in the surrounding social-economic-political-cultural milieu. It is asserted that this milieu is the most important factor in shaping scientific theorizing. Some examples are cited: the rejection of the evidence that the world orbits around the sun (suspected by Pythagoras) in favor of centuries-long firm adherence to the Ptolemaic geocentric system; the early acceptance of Natural Selection in spite of its tautological essence and only conjectural supporting evidence, because it justified contemporaneous social-political ideologies as typified by, e.g., Spencer and Malthus. Economic, social, and cultural factors are cited as providing the ground, i.e., ideational substrate, for what is cited as the Discreetness-Chance Paradigm (DCP), that has increasingly dominated physics, biology, and medicine for over a century and which invokes small, discrete packets of energy/matter (quanta, genes, microorganisms, aberrant cells) functioning within an environment of statistical, not determined, causality. There is speculation on a possible paradigmatic shift from the DCP, which has fostered the proliferation, parallel with ("splitting") taxonomy, of alleged individual disease entities, their diagnoses, and, when available, their specific remedies, something particularly prominent in, e.g., psychiatry's Diagnostic and Statistical Manual, a codified compendium of alleged mental and behavioral disorders, but evident in any textbook of diagnosis and treatment of physical ailments. This presumed paradigm shift may be reflected in Western medicine, presently increasingly empirical and atomized, towards a growing acceptance of a more generalized, subject-oriented, approach to health and disease, a non

Revisiting System Paradigms from the Viewpoint of Manufacturing Sustainability

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Zhuming Bi

2011-08-01

Full Text Available A system paradigm is an abstract representation of system; it includes system architecture used to determine the types and numbers of components and their relations in the system. The design of system paradigm relies on customers’ requirements and the characteristics of the manufacturing environment. Many system paradigms and design guidelines have been proposed for a variety of customers’ needs including functions, cost, quality, personalization, and lead time of products. However, the consideration of sustainability becomes essential to today’s manufacturing systems; a new challenge is how to evolve existing paradigms to accommodate the requirements of sustainability. In contrast to ample research activities on system paradigms in past decades, recent studies on system paradigms have been restricted, partially due to unclear research directions. Limited works can be found on conceiving new manufacturing system paradigms from the perspective of sustainability; most of the related literature concerns the new requirements of sustainability. The objectives of this work are (i to examine the requirements of manufacturing systems in a wider scope; (ii to revisit existing paradigms to clarify their limitations and bottlenecks; and eventually (iii to identify some research directions, which will lead to a solution of sustainable manufacturing. To achieve these objectives, firstly, a brief description of today’s manufacturing environment is provided. Secondly, the requirements of sustainability are discussed, and the relevant researches on system sustainability are surveyed. Thirdly, the reconfigurable system paradigm is focused, and the gaps between a reconfigurable manufacturing system and a sustainable manufacturing system are discussed. Finally, the future endeavors towards to the next-generation manufacturing system paradigms are discussed.

Systematic review of the use of platelet-rich plasma in aesthetic dermatology.

Science.gov (United States)

Leo, Michael S; Kumar, Alur S; Kirit, Raj; Konathan, Rajyalaxmi; Sivamani, Raja K

2015-12-01

Platelet-rich plasma (PRP) is a highly concentrated autologous solution of plasma prepared from a patient's own blood. PRP contains platelets that are purported to release numerous growth factors that may be valuable in numerous dermatologic applications. Here, we review systematically the clinical cosmetic applications of PRP including: androgenetic alopecia, scar revision, acne scars, skin rejuvenation, dermal augmentation, and striae distensae to understand the potential and best practices for PRP use. A systematic search was conducted on three databases: Pubmed, Embase, and Web of Science. Publications were included if they were in English, investigated the clinical applications of PRP in aesthetic dermatology and reported clinical results either as case reports or clinical studies. There were a total of 22 manuscripts that fulfilled these criteria. Four evaluated hair-related applications, eight evaluated the treatment of scars and postprocedure recovery, eight evaluated skin rejuvenation and dermal augmentation, and two evaluated treatment of striae distensae. PRP is a relatively new treatment modality with studies suggesting its utility in aesthetic dermatology. The combination of PRP with other therapies is particularly interesting. Future studies should include controls, including incorporation of split-face comparisons, to reduce intersubject variability. © 2015 Wiley Periodicals, Inc.

A flow paradigm in heavy-ion collisions

Science.gov (United States)

Yan, Li

2018-04-01

The success of hydrodynamics in high energy heavy-ion collisions leads to a flow paradigm, to understand the observed features of harmonic flow in terms of the medium collective expansion with respect to initial state geometrical properties. In this review, we present some essential ingredients in the flow paradigm, including the hydrodynamic modeling, the characterization of initial state geometry and the medium response relations. The extension of the flow paradigm to small colliding systems is also discussed. Supported by Natural Sciences and Engineering Research Council of Canada

PARADIGM OF EDUCATION FOR THE INFORMATION SOCIETY

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Yuriy M. Bogachkov

2015-10-01

Full Text Available Considering total crisis in education in Informational Age, we suggest that to overcome the crisis, it is necessary to promote pedagogical science up from "pre-paradigm stage” to the "paradigm stage". For this purpose it is necessary to separate the "educational science" from "education." “Educational paradigm” in such study will be the subject of the science. The key concepts for the "pedagogical paradigm" should be the concepts of "educational practice", "class of problems" and "educational text". We offer some axioms around these concepts.

The Prerequisites for a Degrowth Paradigm Shift

DEFF Research Database (Denmark)

Buch-Hansen, Hubert

2018-01-01

What would it take for a degrowth paradigm shift to take place? Drawing on contemporary critical political economy scholarship, this article identifies four prerequisites for socio-economic paradigm shifts: deep crisis, an alternative political project, a comprehensive coalition of social forces...... currently facing humanity. On the other hand, the prospects for a degrowth paradigm shift remain bleak: unlike political projects that became hegemonic in the past, degrowth has neither support from a comprehensive coalition of social forces nor any consent to its agenda among the broader population....

Programming Language Paradigms

OpenAIRE

Felician ALECU

2013-01-01

This paper's goal is to briefly explain the basic theory behind programming languages and their history while taking a close look at different programming paradigms that are used today as well as describing their differences, benefits, and drawbacks

Programming Paradigms in Computer Science Education

OpenAIRE

Bolshakova, Elena

2005-01-01

Main styles, or paradigms of programming – imperative, functional, logic, and object-oriented – are shortly described and compared, and corresponding programming techniques are outlined. Programming languages are classified in accordance with the main style and techniques supported. It is argued that profound education in computer science should include learning base programming techniques of all main programming paradigms.

ENVIRONMENTALISM AND CLASSIC PARADIGMS OF INTERNATIONAL RELATIONS

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D. D. Miniaeva

2014-06-01

Full Text Available This article examines an environmentalism integration process into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism. The main purpose of this study is to reveal the result of this integration. Methods used in this article include analysis and comparison of "ecological" paradigms on selected parameters (the nature of international relations, actors, targets, tools, processes. Results of research show that the beginning of the XXI century is distinguished by the development of new types of political concepts that explain interaction of elements in modern international relations in the area of environmental protection. The reason of these changes lies in the phenomena of environmentalism integration into Three paradigms of international relations. However, we cannot say that any of the examined paradigms accumulated all features of environmentalism without their modification. Better to say, it's rather similar to adaptation of environmental ideas. Therefore, to understand modern international relations processes, it is necessary to take into account their environmental element. Purchase on Elibrary.ru > Buy nowDOI: http://dx.doi.org/10.12731/2070-7568-2014-3-4

Preoperative autologous plateletpheresis in patients undergoing open heart surgery.

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Tomar Akhlesh

2003-01-01

Full Text Available Blood conservation is an important aspect of care provided to the patients undergoing cardiac operations with cardiopulmonary bypass (CPB. It is even more important in patients with anticipated prolonged CPB, redo cardiac surgery, patients having negative blood group and in patients undergoing emergency cardiac surgery. In prolonged CPB the blood is subjected to more destruction of important coagulation factors, in redo surgery the separation of adhesions leads to increased bleeding and difficulty in achieving the haemostasis and in patients with negative blood group and emergency operations, the availability of sufficient blood can be a problem. Harvesting the autologous platelet rich plasma (PRP can be a useful method of blood conservation in these patients. The above four categories of patients were prospectively studied, using either autologous whole blood donation or autologous platelet rich plasma (PRP harvest in the immediate pre-bypass period. Forty two patients were included in the study and randomly divided into two equal groups of 21 each, control group (Group I in which one unit of whole blood was withdrawn, and PRP group (Group II where autologous plateletpheresis was utilised. After reversal of heparin, autologous whole blood was transfused in the control group and autologous PRP was transfused in the PRP group. The chest tube drainage and the requirement of homologous blood and blood products were recorded. Average PRP harvest was 643.33 +/- 133.51 mL in PRP group and the mean whole blood donation was 333.75 +/- 79.58 mL in the control group. Demographic, preoperative and intra operative data showed no statistically significant differences between the two groups. The PRP group patients drained 26.44% less (p<0.001 and required 38.5% less homologous blood and blood products (p<0.05, in the postoperative period. Haemoglobin levels on day zero (day of operation and day three were statistically not different between the two groups. We

Programming Language Paradigms

Directory of Open Access Journals (Sweden)

Bartoníček Jan

2014-01-01

Full Text Available This paper's goal is to briefly explain the basic theory behind programming languages and their history while taking a close look at different programming paradigms that are used today as well as describing their differences, benefits, and drawbacks

A nomenclature paradigm for benign midmembranous vocal fold lesions.

Science.gov (United States)

Rosen, Clark A; Gartner-Schmidt, Jackie; Hathaway, Bridget; Simpson, C Blake; Postma, Gregory N; Courey, Mark; Sataloff, Robert T

2012-06-01

There is a significant lack of uniform agreement regarding nomenclature for benign vocal fold lesions (BVFLs). This confusion results in difficulty for clinicians communicating with their patients and with each other. In addition, BVFL research and comparison of treatment methods are hampered by the lack of a detailed and uniform BVFL nomenclature. Clinical consensus conferences were held to develop an initial BVFL nomenclature paradigm. Perceptual video analysis was performed to validate the stroboscopy component of the paradigm. The culmination of the consensus conferences and the video-perceptual analysis was used to evaluate the BVFL nomenclature paradigm using a retrospective review of patients with BVFL. An initial BVFL nomenclature paradigm was proposed utilizing detailed definitions relating to vocal fold lesion morphology, stroboscopy, response to voice therapy and intraoperative findings. Video-perceptual analysis of stroboscopy demonstrated that the proposed binary stroboscopy system used in the BVFL nomenclature paradigm was valid and widely applicable. Retrospective review of 45 patients with BVFL followed to the conclusion of treatment demonstrated that slight modifications of the initial BVFL nomenclature paradigm were required. With the modified BVFL nomenclature paradigm, 96% of the patients fit into the predicted pattern and definitions of the BVFL nomenclature system. This study has validated a multidimensional BVFL nomenclature paradigm. This vocal fold nomenclature paradigm includes nine distinct vocal fold lesions: vocal fold nodules, vocal fold polyp, pseudocyst, vocal fold cyst (subepithelial or ligament), nonspecific vocal fold lesion, vocal fold fibrous mass (subepithelial or ligament), and reactive lesion. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Cancer research in need of a scientific revolution: Using `paradigm ...

Indian Academy of Sciences (India)

It has been proposed that science proceeds not only by accumulating data but also through paradigm shifts. Here, we propose to use the concept of `paradigm shift' as a method of investigation when dominant paradigms fail to achieve their promises. The first step in using the `paradigm shift' method in cancer research ...

Transmission pricing: paradigms and methodologies

Energy Technology Data Exchange (ETDEWEB)

Shirmohammadi, Dariush [Pacific Gas and Electric Co., San Francisco, CA (United States); Vieira Filho, Xisto; Gorenstin, Boris [Centro de Pesquisas de Energia Eletrica (CEPEL), Rio de Janeiro, RJ (Brazil); Pereira, Mario V.P. [Power System Research, Rio de Janeiro, RJ (Brazil)

1994-12-31

In this paper we describe the principles of several paradigms and methodologies for pricing transmission services. The paper outlines some of the main characteristics of these paradigms and methodologies such as where they may be used for best results. Due to their popularity, power flow based MW-mile and short run marginal cost pricing methodologies will be covered in some detail. We conclude the paper with examples of the application of these two pricing methodologies for pricing transmission services in Brazil. (author) 25 refs., 2 tabs.

Paradigm for new scientific technology; Shinkagaku gijutsu paradigm

Energy Technology Data Exchange (ETDEWEB)

Shindo, Y [National Chemical Lab. for Industry, Tokyo (Japan)

1995-01-05

This paper reviews the current status from the standpoint of chemical engineers facing the coming of the 21st century, and surveys the paradigm for new scientific technologies. The criticism is mixed with unique opinions everywhere, such as `departure of students from scientific and engineering faculties is none other than the result of a market principle`, `national burden of trillions of yens should not be spent only under a justice of advancement of the science`, and `the global civilization itself has no other way but to change from the conventional expansive development type of the western country style to the internal development type of the oriental country style`. Values that define the paradigm for new scientific technologies may include such keywords as saturation in technology, baseless expansion of research projects, criticism on science, market principle, and centering human being. It should be looked at seriously that profit from research and development should exceed the cast invested therein in the future, and scientific technologies that serve truly the society should be aimed at. These efforts will result in one of the large pillars that support the future in which creation of new functions is aimed at as a result of structuring the new systems. Trying to overcome the environmental problems is one of them.

Reexamining unconscious response priming: A liminal-prime paradigm.

Science.gov (United States)

Avneon, Maayan; Lamy, Dominique

2018-03-01

Research on the limits of unconscious processing typically relies on the subliminal-prime paradigm. However, this paradigm is limited in the issues it can address. Here, we examined the implications of using the liminal-prime paradigm, which allows comparing unconscious and conscious priming with constant stimulation. We adapted an iconic demonstration of unconscious response priming to the liminal-prime paradigm. On the one hand, temporal attention allocated to the prime and its relevance to the task increased the magnitude of response priming. On the other hand, the longer RTs associated with the dual task inherent to the paradigm resulted in response priming being underestimated, because unconscious priming effects were shorter-lived than conscious-priming effects. Nevertheless, when the impact of long RTs was alleviated by considering the fastest trials or by imposing a response deadline, conscious response priming remained considerably larger than unconscious response priming. These findings suggest that conscious perception strongly modulates response priming. Copyright © 2017 Elsevier Inc. All rights reserved.

Introduction: Science, Sexuality, and Psychotherapy: Shifting Paradigms.

Science.gov (United States)

Cerbone, Armand R

2017-08-01

This introduction presents an overview of the current issue (73, 8) of Journal of Clinical Psychology: In Session. This issue features a series of articles, with clinical cases, each presented to illustrate the challenges faced by individuals and couples whose sexual and gender identities and expressions do not comport with traditional and cultural norms. These articles also document the challenges to the therapists who treat them. Considered individually, each article underscores the need to recognize the importance of evidence in guiding psychotherapy in cases involving sexuality. The discussions in each article offer recommendations meant to help and guide psychotherapists. Considered collectively, they raise important questions and considerations about shifting paradigms of human sexuality. Implications for assessment and treatment of cases involving sexuality and gender identity are discussed and recommended. © 2017 Wiley Periodicals, Inc.

Paradigm shift in psychiatry: what may it involve?

Science.gov (United States)

Valent, Paul

2018-02-01

This study aims to examine the potential nature of an ongoing paradigm shift in psychiatry that has been suggested to be occurring. New findings in traumatology and neuroscience do form a potential platform for a paradigm shift. Prior conflicting paradigms are suggested to be due to biases arising from mental structures themselves. A new wholist perspective is proposed, which makes sense of and incorporates previous paradigms, and coheres recent understanding of right- and left-brain functioning and biopsychosocial traumatic processes and their ramifications. The perspective makes sense of the great variety of post-traumatic manifestations ranging from somatic to meaning-making dysfunctions. The wholist perspective may well be an important step in solidifying a fresh paradigmatic perspective in psychiatry.

Cryptic species as a window into the paradigm shift of the species concept.

Science.gov (United States)

Fišer, Cene; Robinson, Christopher T; Malard, Florian

2018-02-01

The species concept is the cornerstone of biodiversity science, and any paradigm shift in the delimitation of species affects many research fields. Many biologists now are embracing a new "species" paradigm as separately evolving populations using different delimitation criteria. Individual criteria can emerge during different periods of speciation; some may never evolve. As such, a paradigm shift in the species concept relates to this inherent heterogeneity in the speciation process and species category-which is fundamentally overlooked in biodiversity research. Cryptic species fall within this paradigm shift: they are continuously being reported from diverse animal phyla but are poorly considered in current tests of ecological and evolutionary theory. The aim of this review is to integrate cryptic species in biodiversity science. In the first section, we address that the absence of morphological diversification is an evolutionary phenomenon, a "process" counterpart to the long-studied mechanisms of morphological diversification. In the next section regarding taxonomy, we show that molecular delimitation of cryptic species is heavily biased towards distance-based methods. We also stress the importance of formally naming of cryptic species for better integration into research fields that use species as units of analysis. Finally, we show that incorporating cryptic species leads to novel insights regarding biodiversity patterns and processes, including large-scale biodiversity assessments, geographic variation in species distribution and species coexistence. It is time for incorporating multicriteria species approaches aiming to understand speciation across space and taxa, thus allowing integration into biodiversity conservation while accommodating for species uncertainty. © 2018 John Wiley & Sons Ltd.

Paradigm Adherence and Personality Correlates across Mental Health Professions

Science.gov (United States)

Rauscher, Laura Anne

2012-01-01

Paradigm adherence has been developed as a meta-theoretical approach to organize and to classify the multitude of different theories of counseling and psychotherapy. Four paradigms have been identified in the literature: The Organic-Medical, The Psychological, The Systemic-Relational, and the Social Constructivist paradigms. Only one other study…

New radiobiological, radiation risk and radiation protection paradigms

International Nuclear Information System (INIS)

Goodhead, Dudley T.

2010-01-01

The long-standing conventional paradigm for radiobiology has formed a logical basis for the standard paradigm for radiation risk of cancer and heritable effects and, from these paradigms, has developed the internationally applied system for radiation protection, but with many simplifications, assumptions and generalizations. A variety of additional radiobiological phenomena that do not conform to the standard paradigm for radiobiology may have potential implications for radiation risk and radiation protection. It is suggested, however, that the current state of knowledge is still insufficient for these phenomena, individually or collectively, to be formulated systematically into a new paradigm for radiobiology. Additionally, there is at present lack of direct evidence of their relevance to risk for human health, despite attractive hypotheses as to how they might be involved. Finally, it remains to be shown how incorporation of such phenomena into the paradigm for radiation protection would provide sufficient added value to offset disruption to the present widely applied system. Further research should aim for better mechanistic understanding of processes such as radiation-induced genomic instability (for all radiation types) and bystander effects (particularly for low-fluence high-LET particles) and also priority should be given to confirmation, or negation, of the relevance of the processes to human health risks from radiation.

A new hybrid BCI paradigm based on P300 and SSVEP.

Science.gov (United States)

Wang, Minjue; Daly, Ian; Allison, Brendan Z; Jin, Jing; Zhang, Yu; Chen, Lanlan; Wang, Xingyu

2015-04-15

P300 and steady-state visual evoked potential (SSVEP) approaches have been widely used for brain-computer interface (BCI) systems. However, neither of these approaches can work for all subjects. Some groups have reported that a hybrid BCI that combines two or more approaches might provide BCI functionality to more users. Hybrid P300/SSVEP BCIs have only recently been developed and validated, and very few avenues to improve performance have been explored. The present study compares an established hybrid P300/SSVEP BCIs paradigm to a new paradigm in which shape changing, instead of color changing, is adopted for P300 evocation to decrease the degradation on SSVEP strength. The result shows that the new hybrid paradigm presented in this paper yields much better performance than the normal hybrid paradigm. A performance increase of nearly 20% in SSVEP classification is achieved using the new hybrid paradigm in comparison with the normal hybrid paradigm. All the paradigms except the normal hybrid paradigm used in this paper obtain 100% accuracy in P300 classification. The new hybrid P300/SSVEP BCIs paradigm in which shape changing, instead of color changing, could obtain as high classification accuracy of SSVEP as the traditional SSVEP paradigm and could obtain as high classification accuracy of P300 as the traditional P300 paradigm. P300 did not interfere with the SSVEP response using the new hybrid paradigm presented in this paper, which was superior to the normal hybrid P300/SSVEP paradigm. Copyright © 2014 Elsevier B.V. All rights reserved.

The synthesis paradigm in genetics.

Science.gov (United States)

Rice, William R

2014-02-01

Experimental genetics with model organisms and mathematically explicit genetic theory are generally considered to be the major paradigms by which progress in genetics is achieved. Here I argue that this view is incomplete and that pivotal advances in genetics--and other fields of biology--are also made by synthesizing disparate threads of extant information rather than generating new information from experiments or formal theory. Because of the explosive expansion of information in numerous "-omics" data banks, and the fragmentation of genetics into numerous subdisciplines, the importance of the synthesis paradigm will likely expand with time.

CNN a paradigm for complexity

CERN Document Server

Chua, Leon O

1998-01-01

Revolutionary and original, this treatise presents a new paradigm of EMERGENCE and COMPLEXITY, with applications drawn from numerous disciplines, including artificial life, biology, chemistry, computation, physics, image processing, information science, etc.CNN is an acronym for Cellular Neural Networks when used in the context of brain science, or Cellular Nonlinear Networks, when used in the context of emergence and complexity. A CNN is modeled by cells and interactions: cells are defined as dynamical systems and interactions are defined via coupling laws. The CNN paradigm is a universal Tur

Understanding Mixed Emotions: Paradigms and Measures

Science.gov (United States)

Kreibig, Sylvia D.; Gross, James J.

2017-01-01

In this review, we examine the paradigms and measures available for experimentally studying mixed emotions in the laboratory. For eliciting mixed emotions, we describe a mixed emotions film library that allows for the repeated elicitation of a specific homogeneous mixed emotional state and appropriately matched pure positive, pure negative, and neutral emotional states. For assessing mixed emotions, we consider subjective and objective measures that fall into univariate, bivariate, and multivariate measurement categories. As paradigms and measures for objectively studying mixed emotions are still in their early stages, we conclude by outlining future directions that focus on the reliability, temporal dynamics, and response coherence of mixed emotions paradigms and measures. This research will build a strong foundation for future studies and significantly advance our understanding of mixed emotions. PMID:28804752

Towards a New Paradigm of Moral Personhood

Science.gov (United States)

Frimer, Jeremy A.; Walker, Lawrence J.

2008-01-01

Moral psychology is between paradigms. Kohlberg's model of moral rationality has proved inadequate in explaining action; yet its augmentation--moral personality--awaits empirical embodiment. This article addresses some critical issues in developing a comprehensive empirical paradigm of moral personhood. Is a first-person or a third-person…

A Cultural Paradigm--Learning by Observing and Pitching In.

Science.gov (United States)

Rogoff, Barbara; Mejía-Arauz, Rebeca; Correa-Chávez, Maricela

2015-01-01

We discuss Learning by Observing and Pitching In (LOPI) as a cultural paradigm that provides an interesting alternative to Assembly-Line Instruction for supporting children's learning. Although LOPI may occur in all communities, it appears to be especially prevalent in many Indigenous and Indigenous-heritage communities of the Americas. We explain key features of this paradigm, previewing the chapters of this volume, which examine LOPI as it occurs in the lives of families and communities. In this introductory chapter, we focus especially on one feature of the paradigm that plays an important role in its uptake and maintenance in families, institutions, and communities-the nature of assessment. We consider the power of the dominant paradigm and the challenges in making paradigm shifts. © 2015 Elsevier Inc. All rights reserved.

An engineering paradigm in the biomedical sciences: Knowledge as epistemic tool.

Science.gov (United States)

Boon, Mieke

2017-10-01

In order to deal with the complexity of biological systems and attempts to generate applicable results, current biomedical sciences are adopting concepts and methods from the engineering sciences. Philosophers of science have interpreted this as the emergence of an engineering paradigm, in particular in systems biology and synthetic biology. This article aims at the articulation of the supposed engineering paradigm by contrast with the physics paradigm that supported the rise of biochemistry and molecular biology. This articulation starts from Kuhn's notion of a disciplinary matrix, which indicates what constitutes a paradigm. It is argued that the core of the physics paradigm is its metaphysical and ontological presuppositions, whereas the core of the engineering paradigm is the epistemic aim of producing useful knowledge for solving problems external to the scientific practice. Therefore, the two paradigms involve distinct notions of knowledge. Whereas the physics paradigm entails a representational notion of knowledge, the engineering paradigm involves the notion of 'knowledge as epistemic tool'. Copyright © 2017 Elsevier Ltd. All rights reserved.

SCIENTIFIC PARADIGM SHIFT AS THE BACKGROUND OF LANGUAGE EDUCATION

Directory of Open Access Journals (Sweden)

V. D. Tabanakova

2017-01-01

Full Text Available Introduction. Recently, there has been a cardinal restructuring of university preparation. Linguistic education takes up nearly the last position in the new model of the higher school dictated by economic interests. Investments in linguistic projects are considered as unprofitable today. The linguistic component in educational programs of a bachelor degree is reduced to a minimum, and focused on language knowledge promoting as communication technologies.The aim of the work purposes to trace how the scientific and the linguistic paradigm shift have an impact on the domestic linguistic education system, and to show the unrealized potential capacity of linguistic knowledge.Methodology and research methods. The methodology of the offered research is based, on the one hand, upon the domestic periodical press review on the linguistic education problems for the last 15 years, on the other – on the philosophical analysis of science historical forms which change has caused the past, the present and the future of linguistics and linguistic education. The inductive methods to integrate different approaches are also used.Theoretical significance. The author emphasizes the need to consider the problems of higher education in philosophical aspect, through the interaction of a scientific and educational paradigm.Results and scientific novelty. At a time of global changes in domestic higher education the linguistic education is considered to be a display of the convergence process of natural sciences, technology and humanities. The philosophical study of the scientific paradigms – classical, non-classical and post-non-classical has revealed the regularities of the linguistic scientific paradigms – structural, communicative and cognitive. Each of the paradigms was traced in the frame of linguistic education functions alternation and constantly changing academic programs.A new take on the U-turn of a centrifugal vector in science has obviously demonstrated

Long-term reliability of the visual EEG Poffenberger paradigm.

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Friedrich, Patrick; Ocklenburg, Sebastian; Mochalski, Lisa; Schlüter, Caroline; Güntürkün, Onur; Genc, Erhan

2017-07-14

The Poffenberger paradigm is a simple perception task that is used to estimate the speed of information transfer between the two hemispheres, the so-called interhemispheric transfer time (IHTT). Although the original paradigm is a behavioral task, it can be combined with electroencephalography (EEG) to assess the underlying neurophysiological processes during task execution. While older studies have supported the validity of both paradigms for investigating interhemispheric interactions, their long-term reliability has not been assessed systematically before. The present study aims to fill this gap by determining both internal consistency and long-term test-retest reliability of IHTTs produced by using the two different versions of the Poffenberger paradigm in a sample of 26 healthy subjects. The results show high reliability for the EEG Poffenberger paradigm. In contrast, reliability measures for the behavioral Poffenberger paradigm were low. Hence, our results indicate that electrophysiological measures of interhemispheric transfer are more reliable than behavioral measures; the later should be used with caution in research investigating inter-individual differences of neurocognitive measures. Copyright © 2017 Elsevier B.V. All rights reserved.

e-Science Paradigm for Astroparticle Physics at KISTI

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Kihyeon Cho

2016-03-01

Full Text Available The Korea Institute of Science and Technology Information (KISTI has been studying the e-Science paradigm. With its successful application to particle physics, we consider the application of the paradigm to astroparticle physics. The Standard Model of particle physics is still not considered perfect even though the Higgs boson has recently been discovered. Astrophysical evidence shows that dark matter exists in the universe, hinting at new physics beyond the Standard Model. Therefore, there are efforts to search for dark matter candidates using direct detection, indirect detection, and collider detection. There are also efforts to build theoretical models for dark matter. Current astroparticle physics involves big investments in theories and computing along with experiments. The complexity of such an area of research is explained within the framework of the e-Science paradigm. The idea of the e-Science paradigm is to unify experiment, theory, and computing. The purpose is to study astroparticle physics anytime and anywhere. In this paper, an example of the application of the paradigm to astrophysics is presented.

Platelet rich plasma versus laser therapy in lateral epicondylitis of elbow

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Gyaneshwar Tonk

2014-01-01

Conclusions: Treatment of patients with chronic lateral epicondylitis with PRP extract reduced pain and significantly increased function, exceeding the effect of low level laser therapy on long term followup. Low-level laser therapy is better in the short term period, but on long term followup injection PRP therapy is better than laser therapy in lateral epicondylitis.

Is This the Paradigm Shift We Need?

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Mirvis, Jonathan

2012-01-01

Dr. Woocher's essay, states Mirvis, is seminal in the field of Jewish education. It proposes a new paradigm for Jewish education in North America. This proposed paradigm is supported by a comprehensive multi-disciplinary research drawing on literature from education, philosophy, history, sociology, psychology, and economics. The essay reflects a…

A New Paradigm for Chemical Engineering?

DEFF Research Database (Denmark)

Gani, Rafiqul

evidence of this change comes from the jobs taken by graduating chemical engineering professionals in North America, Europe, and some of the Asian countries. In terms of where the graduating chemical engineers are going to work, a clear shift from the commodity chemical industry to the product oriented...... businesses has been observed. There is an increasing trend within the chemical industry to focus on products and the sustainable processes that can make them. Do these changes point to a paradigm shift in chemical engineering as a discipline? Historically, two previous paradigm shifts in chemical engineering...... corresponded to major shifts in chemical engineering as a discipline, which affected not only the education of chemical engineers, but also the development of chemical engineering as a discipline. Has the time come for a new paradigm shift that will prepare the current and future chemical engineering graduates...

[Nursing knowledge: the evolution of scientific philosophies and paradigm trends].

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Hung, Hsuan-Man; Wang, Hui-Ling; Chang, Yun-Hsuan; Chen, Chung-Hey

2010-02-01

Different aspects of philosophy are derived from different paradigms that contain various main points, some of which are repeated or overlap. Belief and practice are two components of a paradigm that provide perspective and framework and lead to nursing research. Changes in healthcare have popularized empirical and evidence-based research in the field of nursing research. However, the evidence-base study approach has given rise to a certain level of debate. Until now, no standard paradigm has been established for the nursing field, as different professionals use different paradigms in their studies. Such provides certain limitations as well as advantages. The quantitative aspects of a nursing paradigm were developed by Peplau and Henderson (1950) and Orem (1980). Such remained the standard until 1990, when Guba and Parse proposed qualitative viewpoints in contextual features. Therefore, the nursing paradigm has made great contributions to the development of knowledge in nursing care, although debate continues due to incomplete knowledge attributable to the presentation of knowledge and insight within individually developed paradigms. It is better to apply multiple paradigms to different research questions. It is suggested that better communication amongst experts regarding their individual points of view would help nursing members to integrate findings within the global pool of knowledge and allow replication over multiple studies.

PARADIGM: A BIBLIOMETRIC ANALYSIS OF PAPERS PRESENTED AT THE CONFERENCES OF THE POMS FROM 2000 TO 2010

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João Almeida Santos

2014-01-01

Full Text Available This study presents bibliometrics on Paradigm in papers presented at the Production and Operation Management Society (POMS from 2000 to 2010, and establishes the profile of the authors and the theoretical relationships present in those papers’ content. The portal of the Production and Operation Management Society and the abstracts contained in each of the events of the period were used, seeking to highlight the concept of Paradigm and its approaches. As a result, the articles presented at the POMS from 2000 to 2010, at least three out of the four hundred papers had the concept in its title or abstract, besides being within the central arguments of these same items analyzed by this study.

The visual mismatch negativity (vMMN): toward the optimal paradigm.

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Qian, Xiaosen; Liu, Yi; Xiao, Bing; Gao, Li; Li, Songlin; Dang, Lijie; Si, Cuiping; Zhao, Lun

2014-09-01

In the present article, we tested an optimal vMMN paradigm allowing one to obtain vMMNs for several visual attributes in a short time. vMMN responses to changes in color, duration, orientation, shape, and size were compared between the traditional 'oddball' paradigm (a single type of visual change in each sequence) and the optimal paradigm in which all the 5 types of changes appeared within the same sequence. The vMMNs obtained in the optimal paradigm were equal or larger in amplitude to those in the traditional vMMN paradigm. The optimal paradigm can provide 5 different vMMNs in the same time in which usually only one MMN is obtained. This short objective measure could putatively be used as an index for visual cognition function especially in clinical research. Copyright © 2014 Elsevier B.V. All rights reserved.

Safety and Efficacy of Intra-articular Injection of Platelet-Rich Plasma in Patients With Ankle Osteoarthritis.

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Fukawa, Taisuke; Yamaguchi, Satoshi; Akatsu, Yorikazu; Yamamoto, Yohei; Akagi, Ryuichiro; Sasho, Takahisa

2017-06-01

An intra-articular injection of platelet-rich plasma (PRP) may be an effective treatment for osteoarthritis (OA). However, its efficacy in ankle OA has not been investigated yet. The purpose of this study was to assess the safety and efficacy of an intra-articular injection of PRP in patients with ankle OA during a 24-week period. Twenty ankles of 20 patients with varus-type ankle OA who received intra-articular injections of PRP were evaluated. PRP was extracted from whole blood by using the double-spin technique. Three injections of 2-mL PRP were administered to the ankle at an interval of 2 weeks under ultrasonographic guidance. Adverse events and efficacy were assessed at 4, 12, and 24 weeks after the last injection. Clinical outcomes were assessed by using the visual analog scale (VAS) for pain, the Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot scale, and the Self-Administered Foot Evaluation Questionnaire (SAFE-Q). No serious adverse effects were observed during the follow-up period. The VAS and JSSF scale scores significantly decreased from baseline to 4, 12, and 24 weeks after treatment ( P SAFE-Q significantly improved from baseline to 12 weeks after treatment ( P = .04). Overall, the amount of pain reduction was maximal at 12 weeks after the last injection, and the effect was reduced at 24 weeks. The patients with late-stage OA had worse scores in all outcomes than those with early-stage OA. Intra-articular injections of PRP resulted in no serious adverse effects and significantly reduced pain in the patients with ankle OA. PRP treatment can be safe and effective and may be an option in the treatment of ankle OA. Level IV, case series.

Relationship of cytokine levels and clinical effect on platelet-rich plasma-treated lateral epicondylitis.

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Lim, Wonbong; Park, Sang H; Kim, Bora; Kang, Sin W; Lee, Jung W; Moon, Young L

2018-03-01

Lateral epicondylitis (LE) is difficult to manage and can result in significant patient morbidity. Currently, the clinical use of platelet-rich plasma (PRP) for painful tendons has received attention, but its efficacy remains controversial. This study aimed to investigate the clinical effects of PRP and its biological components. A total of 156 patients with LE were randomly divided into group 1, treated with a single injection of 2-ml autologous PRP, and group 2, treated with a control received only physical therapy without injection. Both groups used a tennis elbow strap and performed stretching and strengthening exercises during 24 weeks' follow-up. Pain and functional improvements were assessed using the visual analog scale (VAS), Modified Mayo Clinic Performance Index for the elbow, and magnetic resonance imaging (MRI). White blood cell count, platelet count, and levels of platelet-derived growth factor-AB (PDGF-AB), PDGF-BB, transforming growth factor-β (TGF-β), vascular endothelial growth factor, epithelial growth factor, and interleukin-1 β in PRP were measured and investigated for statistical correlation with the clinical score. At 24 weeks, all pain and functional variables, including VAS score, Mayo Clinic performance scores, and MRI grade, improved significantly in group 1 (p < 0.05). PDGF-AB, PDGF-BB, and TGF-β levels were more significantly increased in PRP than in whole blood. TGF-β level significantly correlated with Mayo Clinic performance score and MRI grade improvement. Thus, TGF-β level in PRP is considered to play a pivotal role in tendon healing. These results may contribute to identifying the best protocol for PRP application in tendinopathies. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:913-920, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Crustal layering, simplicity, and the oil industry: The alteration of an epistemic paradigm by a commercial environment

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Anduaga, Aitor

This paper proposes that the gradual alteration of the predominant epistemic paradigm in crustal seismology in the interwar period-namely, simplicity-came about because of the strong influence of a particular commercial environment, i.e. the oil industry. I begin by demonstrating the interwar predominance of Jeffreys' 'simplicity postulate' and his probabilistic epistemology, highlighting the espousal by several seismologists (Bullen, Stoneley, Byerly), whose crustal models drew on mathematical idealisations. Next, I demonstrate that the renunciation of simplicity in the 1930s came about too quickly, and, above all, too heterodoxically to have been the result of new geological evidence. Rather, I argue, the paradigm shift among seismologists was a result of the significant rise in seismic exploration generated by the oil industry. Driven by market demands, American petroleum companies pioneered new technologies, organised research initiatives, and trained young geophysicists who, through the fusion of experimentalism and field experience, brought about fundamental progress in earthquake seismology. Remarkably, historians of science have almost entirely failed to recognise the interwar primacy of the simplicity paradigm as well as its subsequent renunciation. More importantly, they have failed to acknowledge the role the oil industry played in contributing to this renunciation and to the development of new paradigms in seismology.

Preoperative autologous plateletpheresis in patients undergoing open heart surgery.

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Tomar, Akhlesh S; Tempe, Deepak K; Banerjee, Amit; Hegde, Radhesh; Cooper, Andrea; Khanna, S K

2003-07-01

Blood conservation is an important aspect of care provided to the patients undergoing cardiac operations with cardiopulmonary bypass (CPB). It is even more important in patients with anticipated prolonged CPB, redo cardiac surgery, patients having negative blood group and in patients undergoing emergency cardiac surgery. In prolonged CPB the blood is subjected to more destruction of important coagulation factors, in redo surgery the separation of adhesions leads to increased bleeding and difficulty in achieving the haemostasis and in patients with negative blood group and emergency operations, the availability of sufficient blood can be a problem. Harvesting the autologous platelet rich plasma (PRP) can be a useful method of blood conservation in these patients. The above four categories of patients were prospectively studied, using either autologous whole blood donation or autologous platelet rich plasma (PRP) harvest in the immediate pre-bypass period. Forty two patients were included in the study and randomly divided into two equal groups of 21 each, control group (Group I) in which one unit of whole blood was withdrawn, and PRP group (Group II) where autologous plateletpheresis was utilised. After reversal of heparin, autologous whole blood was transfused in the control group and autologous PRP was transfused in the PRP group. The chest tube drainage and the requirement of homologous blood and blood products were recorded. Average PRP harvest was 643.33 +/- 133.51 mL in PRP group and the mean whole blood donation was 333.75 +/- 79.58 mL in the control group. Demographic, preoperative and intra operative data showed no statistically significant differences between the two groups. The PRP group patients drained 26.44% less (pblood products (pconservation in terms of better haemostasis, and less requirement of blood and blood products in the postoperative period as compared with the autologous whole blood donation. This technique can be especially useful in the

Peroxiredoxin 6 promotes upregulation of the prion protein (PrP in neuronal cells of prion-infected mice

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Wagner Wibke

2012-12-01

Full Text Available Abstract Background It has been widely established that the conversion of the cellular prion protein (PrPC into its abnormal isoform (PrPSc is responsible for the development of transmissible spongiform encephalopathies (TSEs. However, the knowledge of the detailed molecular mechanisms and direct functional consequences within the cell is rare. In this study, we aimed at the identification of deregulated proteins which might be involved in prion pathogenesis. Findings Apolipoprotein E and peroxiredoxin 6 (PRDX6 were identified as upregulated proteins in brains of scrapie-infected mice and cultured neuronal cell lines. Downregulation of PrP gene expression using specific siRNA did not result in a decrease of PRDX6 amounts. Interestingly, selective siRNA targeting PRDX6 or overexpression of PRDX6 controlled PrPC and PrPSc protein amounts in neuronal cells. Conclusions Besides its possible function as a novel marker protein in the diagnosis of TSEs, PDRX6 represents an attractive target molecule in putative pharmacological intervention strategies in the future.

Multi-level programming paradigm for extreme computing

International Nuclear Information System (INIS)

Petiton, S.; Sato, M.; Emad, N.; Calvin, C.; Tsuji, M.; Dandouna, M.

2013-01-01

In order to propose a framework and programming paradigms for post peta-scale computing, on the road to exa-scale computing and beyond, we introduced new languages, associated with a hierarchical multi-level programming paradigm, allowing scientific end-users and developers to program highly hierarchical architectures designed for extreme computing. In this paper, we explain the interest of such hierarchical multi-level programming paradigm for extreme computing and its well adaptation to several large computational science applications, such as for linear algebra solvers used for reactor core physic. We describe the YML language and framework allowing describing graphs of parallel components, which may be developed using PGAS-like language such as XMP, scheduled and computed on supercomputers. Then, we propose experimentations on supercomputers (such as the 'K' and 'Hooper' ones) of the hybrid method MERAM (Multiple Explicitly Restarted Arnoldi Method) as a case study for iterative methods manipulating sparse matrices, and the block Gauss-Jordan method as a case study for direct method manipulating dense matrices. We conclude proposing evolutions for this programming paradigm. (authors)

Paradigms of Interaction Between Culture and Politics

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Morteza Bahrani

2012-12-01

Full Text Available Political thought as a normative knowledge seeks a good society and the means for its realization. Accordingly, every intellectual paradigm introduces us a social and individual situation which is the best. This model, itself requires a dramatic change in the culture and flourishes it. In another words, there is a necessary relationship between the elements of political thought and the culture in every society. This relationship is twofold, so it is impossible to indicate whether which aspect is the first. So every paradigm feeds some special elements into the current culture of society, while there is it feedback. It is important that political thought goes in search of condition for cultural flourishing which is according whit the criteria of good society. This paper focuses on most important paradigm in political thought history and shows the trend in which indicates the relationships between political thought and culture. This trend looks at human beings as "citizen", then "the individual"; and in the modem era, paradigms of "critical modem", "postmodern", and "communitarian" has a key role in prospering the realm of culture.

A epidemiologia, os valores e o significado de paradigma Epidemiology, values, and the meaning of paradigm

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Djalma Agripino de Melo Filho

1997-10-01

Full Text Available Recentemente, o emprego do termo paradigma chegou ao âmbito epidemiológico. Este texto analisou criticamente uma classificação de 'paradigmas epidemiológicos', proposta por Almeida-Filho. Inicialmente constatou-se que os valores não foram considerados como elementos fundamentais para a construção dos paradigmas, distanciando-se, assim, da matriz kuhniana. Uma vez que a sistematização procurou unir tendências antitéticas, ela pareceu estar mais próxima da epistéme foucaultiana. Finalmente, considerou-se mais apropriada a utilização do termo hegemonia, em vez de paradigma, para sistematizar períodos epidemiológicos, pois os valores das vertentes estão comprometidos com a particularidade (principalmente classe social.Use of the term paradigm has recently reached the epidemiological milieu. This article provides a critical analysis of a classification of "epidemiological paradigms" as proposed by Almeida-Filho. It was initially ascertained that values were not considered fundamental elements for the construction of paradigms, and that they therefore distanced themselves from the Kuhnian matrix. Systematization sought to unite antithetical tendencies and thus seemed closer to the Foucaltian epistéme. Finally, hegemony was considered a more appropriate term than paradigm for systematizing epidemiological periods, since the values of the different watersheds are committed to particularity (principally social class.

The Membrane Paradigm and black-hole thermodynamics

International Nuclear Information System (INIS)

Thorne, K.S.

1986-01-01

A brief overview is given of the theoretical underpinnings of the Membrane Paradigm for black-hole physics. Then those underpinnings are used to elucidate the Paradigm's view that the laws of black-hole thermodynamics (including the statistical origin of black-hole entropy) are just a special case of the laws of thermodynamics for an ordinary, rotating, thermal reservoir

Enhanced Sternal Healing via Platelet-Rich Plasma and Biodegradable Gelatin Hydrogel.

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Shibata, Masafumi; Takagi, Gen; Kudo, Mitsuhiro; Kurita, Jiro; Kawamoto, Yoko; Miyagi, Yasuo; Kanazashi, Mikimoto; Sakatani, Takashi; Naito, Zenya; Tabata, Yasuhiko; Miyamoto, Masaaki; Nitta, Takashi

2018-05-16

Platelet-rich plasma (PRP) contains numerous growth factors and promotes bone fracture healing. The aim of this study was to evaluate the effectiveness of the controlled release of PRP from biodegradable gelatin hydrogel for promoting healing in a rabbit ischemic sternal model. PRP was prepared from the whole blood of a Japanese white rabbit. Sixteen rabbits were randomized into four groups (each n = 4) and all underwent median sternotomy and bilateral internal thoracic artery removal. Before the sternum was closed, the following solutions were applied between the sternum incisions in three of the groups: 30 mg of gelatin hydrogel incorporating 300 μL of phosphate-buffered saline, 300 μL of a solution form of PRP, or 30 mg of gelatin hydrogel incorporating 300 μL of PRP (PRP+Gel). The fourth group acted as a control. Sternal healing was evaluated by histology and micro-computed tomography 7 days after the intervention. The PRP+Gel group showed a significantly higher proportion of fibrosis within the fracture area (an indicator of sternal healing) than the other groups and a significantly higher mean intensity of osteocalcin. These results indicate that the controlled release of PRP from locally applied gelatin hydrogel was markedly effective in enhancing sternal healing in the early postoperative period. This novel therapy could potentially help prevent complications such as deep sternal wound infection and could result in early postoperative ambulation after median sternotomy.

The Imperative Paradigm of Korowai, a language of West Papua

NARCIS (Netherlands)

de Vries, Lourens; Aikhenvald, Alexandra; Dixon, R.M.W

2017-01-01

The imperative paradigm of Korowai, a Papuan language of West Papua, is the richest independent verb paradigm of Korowai: it makes more tense, aspect, mood, person and number distinctions than all other verb paradigms. This formal richness is matched by functional richness: imperatives are used in a

A Viable Paradigm for Quantum Reality

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Srivastava, Jagdish

2010-10-01

After a brief discussion of the EPR paradox, Bell's inequality, and Aspect's experiment, arguments will be presented in favor of the following statements: ``As it stands, Quantum mechanics is incomplete. There is further hidden structure, which would involve variables. No influence can move faster than light. The wave function is one whole thing and any change in its structure instantly influences its outcomes. Bell's theorem has not been applied correctly. There is a better paradigm.'' The said paradigm will be presented.

International business and the eclectic paradigm

DEFF Research Database (Denmark)

The eclectic paradigm has become the dominant theoretical basis in the study of international business, multinational corporations and internationalization since 1980. However, developments such as economic globalization and the subsequent growth of global and alliance capitalism have fundamentally......, finance, evolutionary economics, resource-based theory or strategic management? Can it be utilized to explain new developments in international business and economics? Do these require new ideas and concepts to be integrated within the eclectic paradigm? What are the new challenges to which international...

Affective Computing used in an imaging interaction paradigm

DEFF Research Database (Denmark)

Schultz, Nette

2003-01-01

This paper combines affective computing with an imaging interaction paradigm. An imaging interaction paradigm means that human and computer communicates primarily by images. Images evoke emotions in humans, so the computer must be able to behave emotionally intelligent. An affective image selection...

Formal Epistemology and New Paradigm Psychology of Reasoning

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Pfeifer, Niki; Douven, Igor

This position paper advocates combining formal epistemology and the new paradigm psychology of reasoning in the studies of conditionals and reasoning with uncertainty. The new paradigm psychology of reasoning is characterized by the use of probability theory as a rationality framework instead of

A Practical Examination of Two Diverse Research Paradigms

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Brewer, Robert A.

2007-01-01

This manuscript examines the practical differences between quantitative and qualitative inquiry by comparing the differences between one article from each paradigm. Quantitative research differs greatly from qualitative inquiry in purpose, assumptions, methodology, and representation. While quantitative research has been the dominant paradigm for…

Geographic Object-Based Image Analysis - Towards a new paradigm.

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Blaschke, Thomas; Hay, Geoffrey J; Kelly, Maggi; Lang, Stefan; Hofmann, Peter; Addink, Elisabeth; Queiroz Feitosa, Raul; van der Meer, Freek; van der Werff, Harald; van Coillie, Frieke; Tiede, Dirk

2014-01-01

The amount of scientific literature on (Geographic) Object-based Image Analysis - GEOBIA has been and still is sharply increasing. These approaches to analysing imagery have antecedents in earlier research on image segmentation and use GIS-like spatial analysis within classification and feature extraction approaches. This article investigates these development and its implications and asks whether or not this is a new paradigm in remote sensing and Geographic Information Science (GIScience). We first discuss several limitations of prevailing per-pixel methods when applied to high resolution images. Then we explore the paradigm concept developed by Kuhn (1962) and discuss whether GEOBIA can be regarded as a paradigm according to this definition. We crystallize core concepts of GEOBIA, including the role of objects, of ontologies and the multiplicity of scales and we discuss how these conceptual developments support important methods in remote sensing such as change detection and accuracy assessment. The ramifications of the different theoretical foundations between the ' per-pixel paradigm ' and GEOBIA are analysed, as are some of the challenges along this path from pixels, to objects, to geo-intelligence. Based on several paradigm indications as defined by Kuhn and based on an analysis of peer-reviewed scientific literature we conclude that GEOBIA is a new and evolving paradigm.

Shifting the paradigm

DEFF Research Database (Denmark)

Kiss, Katalin; Brozik, Anna; Kucsma, Nora

2012-01-01

ABCB6, a member of the adenosine triphosphate-binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticuloc...... paradigm linking the expression and function of ABCB6 to mitochondria....

The movement from the paradigm of production to the paradigm of language in Habermas’s critical theory of society. [Spanish

Directory of Open Access Journals (Sweden)

Javier Roberto Suárez González

2010-01-01

Full Text Available My aim in this paper is first to develop the question raised by Habermas concerning the possibilities of a history of philosophy oriented to praxis. This line of analysis will let see the internal connection between theory and praxis within the framework of a materialistic understanding of philosophy. Secondly, I will show how this question becomes a reconstruction of historical materialism in the context of an analysis of the processes which characterise social transformations. With this background Habermas moves from the paradigm of production to that of language seeking a foundation Theory of Communicative Action. Reconstruction, historical materialism,systemic interaction, social interaction, production paradigm, language paradigm.

Magnitude of exercise capacity and quality of life improvement following repeat pulmonary rehabilitation in patients with COPD

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Sandoz JS

2017-04-01

Full Text Available Jacqueline S Sandoz,1,2 Mary M Roberts,1,3,4 Jin-Gun Cho,1,3–5 John R Wheatley1,3–5 1Respiratory Ambulatory Care Service, Western Sydney Local Health District, NSW, Australia; 2Canadian Alternatives in Non-invasive Ventilation (CANVent Program, Ottawa Hospital Rehabilitation Centre, Division of Respiratory Medicine, Ottawa Hospital, Ontario, Canada; 3Department of Respiratory and Sleep Medicine, Westmead Hospital, 4Ludwig Engel Centre for Respiratory Research, Westmead Institute for Medical Research, 5Sydney Medical School, University of Sydney, Westmead, NSW, Australia Background: Maintenance and repeated pulmonary rehabilitation programs (PRPs for patients with COPD have attempted to prolong PRP benefits beyond 12–24 months. However, there is limited evidence as to the magnitude of benefit or the ideal interval between repeating the program under “real-world” conditions in which patients are referred based on clinical necessity. Therefore, we reviewed the effects of repeating PRP in a physician-referred cohort of patients with COPD. Methods: A total of 141 individuals with COPD completed PRP twice and 35 completed PRP three times over a 12-year period. We used linear mixed-effects models to quantify the magnitude and change in 6-minute walk distance (6MWD, St George’s Respiratory Questionnaire (SGRQ, and Hospital Anxiety and Depression Scale (HADS for each PRP. One-way analysis of variance with Tukey’s post hoc analysis compared the effects of different time intervals on 6MWD, SGRQ, and HADS between PRPs. Results: Despite 39 mL/year average decrease in forced expiratory volume in 1 second, overall 6MWD improved following each PRP (PRP1=58 m, P<0.0001; PRP2=42 m, P<0.0001; PRP3=32 m, P<0.003. Mean SGRQ decreased after PRP1 (-7.0 units; P<0.001 and PRP2 (-4.9 units;P<0.0001 but not after PRP3 (-3.2 units; P=0.10. HADS decreased after PRP1 (-1.9 units; P<0.0001 and PRP2 (-1.7 units; P=0.0001 but not after PRP3 (-0.4 units

Increasing platelet concentration in platelet-rich plasma inhibits anterior cruciate ligament cell function in three-dimensional culture.

Science.gov (United States)

Yoshida, Ryu; Cheng, Mingyu; Murray, Martha M

2014-02-01

Tissue engineering is one new strategy being developed to treat ACL ruptures. One such approach is bio-enhanced ACL repair, where a suture repair is supplemented with a bio-active scaffold containing platelets. However, the optimal concentration of platelets to stimulate ACL healing is not known. We hypothesized that increasing platelet concentrations in the scaffold would enhance critical cell behaviors. Porcine ACL fibroblasts were obtained from explant culture and suspended in platelet poor plasma (PPP), 1× platelet-rich plasma (PRP), 3× PRP, 5× PRP, or phosphate buffered saline (PBS). The cell suspensions were cultured in a 3D collagen scaffold. Cellular metabolism (MTT assay), apoptosis (TUNEL assay), and gene expression for type I and type III collagen were measured. 1× PRP significantly outperformed 5× PRP in all parameters studied: Type I and III collagen gene expression, apoptosis prevention, and cell metabolism stimulation. ACL fibroblasts cultured with 1× PRP had the highest type I and type III collagen gene expression. 1× PRP and PPP groups had the highest cell metabolism and lowest apoptosis rates. Concentration of platelets had significant effects on the behavior of ACL fibroblasts; thus, it is an important parameter that should be specified in clinical or basic science studies. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Motor imagery enhancement paradigm using moving rubber hand illusion system.

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Minsu Song; Jonghyun Kim

2017-07-01

Motor imagery (MI) has been widely used in neurorehabilitation and brain computer interface. The size of event-related desynchronization (ERD) is a key parameter for successful motor imaginary rehabilitation and BCI adaptation. Many studies have used visual guidance for enhancement/ amplification of motor imagery ERD amplitude, but their enhancements were not significant. We propose a novel ERD enhancing paradigm using body-ownership illusion, or also known as rubber hand illusion (RHI). The system was made by motorized, moving rubber hand which can simulate wrist extension. The amplifying effects of the proposed RHI paradigm were evaluated by comparing ERD sizes of the proposed paradigm with motor imagery and actual motor execution paradigms. The comparison result shows that the improvement of ERD size due to the proposed paradigm was statistically significant (pparadigms.

Underlying Paradigms in Student Affairs Research and Practice

Science.gov (United States)

Guido, Florence M.; Chavez, Alicia Fedelina; Lincoln, Yvonna S.

2010-01-01

Student affairs professionals benefit from understanding paradigms, worldviews, and ways of being among diverse faculty, staff, and students. It is challenging to understand core differences of paradigms, design student affairs practice and research in congruence with or across specific philosophies, and work effectively with individuals operating…

The prevalence of disability among children: paradigms and estimates.

Science.gov (United States)

Mudrick, Nancy R

2002-11-01

Every examination of disability among children must first grapple with definition of disability. The challenges to identifying disability among children involve not only determining the appropriate paradigm for defining disability, but also applying that paradigm to children in a meaningful way. This discussion of the prevalence of disability among children starts by examining the various paradigms utilized to identify disability and how they are interpreted when applied to children. Estimates of the prevalence of childhood disability, under different definitions of disability are presented. The goal of the discussion is to illustrate the sensitivity of the estimates of disability prevalence to the particular definition and data set used. Finally, the potential influence of the choice of paradigm on further measurement and service delivery is outlined.

Scaling, Similarity, and the Fourth Paradigm for Hydrology

Science.gov (United States)

Peters-Lidard, Christa D.; Clark, Martyn; Samaniego, Luis; Verhoest, Niko E. C.; van Emmerik, Tim; Uijlenhoet, Remko; Achieng, Kevin; Franz, Trenton E.; Woods, Ross

2017-01-01

In this synthesis paper addressing hydrologic scaling and similarity, we posit that roadblocks in the search for universal laws of hydrology are hindered by our focus on computational simulation (the third paradigm), and assert that it is time for hydrology to embrace a fourth paradigm of data-intensive science. Advances in information-based hydrologic science, coupled with an explosion of hydrologic data and advances in parameter estimation and modelling, have laid the foundation for a data-driven framework for scrutinizing hydrological scaling and similarity hypotheses. We summarize important scaling and similarity concepts (hypotheses) that require testing, describe a mutual information framework for testing these hypotheses, describe boundary condition, state flux, and parameter data requirements across scales to support testing these hypotheses, and discuss some challenges to overcome while pursuing the fourth hydrological paradigm. We call upon the hydrologic sciences community to develop a focused effort towards adopting the fourth paradigm and apply this to outstanding challenges in scaling and similarity.

Effects of three blood derived products on equine corneal cells, an in vitro study.

Science.gov (United States)

Rushton, J O; Kammergruber, E; Tichy, A; Egerbacher, M; Nell, B; Gabner, S

2018-05-01

Despite advances in therapy of corneal ulcerative diseases in horses, a vast number of cases require surgical intervention, due to poor response to treatment. Topical application of serum has been used for many years, based on its anticollagenolytic properties and the presence of growth factors promoting corneal wound healing. However, although other blood derived products i.e. platelet rich plasma (PRP), plasma rich in growth factors (PRGF) have been widely used in equine orthopaedics and in human ophthalmology, no reports of the effects of these blood derived products exist in equine ophthalmology. To determine in vitro effects of PRGF and PRP on equine corneal cells compared with serum. Prospective controlled cohort study. Blood from 35 healthy horses was used to produce serum, PRGF (Endoret ® ), and PRP (E-PET™). Limbal- and stromal cells were isolated from healthy corneas of six horses and treated with 20% serum, 20% PRGF or 20% PRP. Proliferation rates and migration capacity were analysed in single cell cultures as well as co-culture systems. Cell proliferation increased with PRP treatment, remained constant in PRGF treated cells, and declined upon serum treatment over a period of 48 h. Migration capacity was significantly enhanced with PRP treatment, compared with PRGF treatment. Intact leucocytes, mainly eosinophils, were only detected in PRP. Due to the study design use of autologous blood products on corneal cells was not possible. The results demonstrate beneficial effects of PRP on proliferation as well as migration capacity of equine corneal cells in vitro. In vivo studies are warranted to determine further beneficial effects of PRP in horses with corneal ulcers. © 2017 EVJ Ltd.

Health Paradigm Shifts in the 20th Century

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Jose Miguel DeAngulo

2015-01-01

Full Text Available The application of systems theory and the study of complexity to medicine and human health allows for a more comprehensive understanding and a more holistic view of what it means to be human. Such application overcomes the limitations of the traditional, fragmented understanding of phenomena and problems based on the mechanistic or Newtonian worldview. It recognizes that phenomena are interrelated, and that individual parts cannot be understood by only focusing on the analysis of their individual qualities. Rather, the individual parts can only be understood in relation to the whole and by being analyzed in the context of their interaction with the whole. The door is opened to previously unimagined models of thinking.In the 20th Century there have been shifts in the paradigms that have governed medicine and human health in the modern western world. There has been a shift from the focus on specific biological analysis and pathological diagnostics to complex human interactions with the environment and with sociopolitical and economic processes. There are complex models of systems in immunology, in neuroscience, and in genetics, as well as complex ways of understanding interactions as in epidemic modeling, in social media technologies, socioeconomic factors, and artificial intelligence.In this paper we describe three paradigms of the health-disease process that in some degree correspond to the historical development of modern medicine and healthcare over the previous century. The oldest paradigm focused on specific disease mechanisms and treatment. This gave way to paradigms that historically were broader and more inclusive, such as “international health”. The international health paradigm focused primarily on the control of epidemics across national borders and considered government as the only health actor. However, this perspective has come to be seen as excessively reductionist and excluded many critical components essential to a robust

YOUTH STUDIES – A SPECIFIC GENRE OF THE EMPIRICAL PARADIGM IN SOCIAL SCIENCES

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Agnė Dorelaitienė

2017-09-01

Full Text Available The article presents the situation of youth in contemporary society. Neoliberal economy, ageing society, rapid globalisation, technological changes, increase of social risk have prompted specific, historically unfamiliar, and fairly difficult to forecast social change. Social adaptation and construction of own identity are becoming challenging to youth as a specific social group in this period of great uncertainty, risk, and opportunities. Youth studies are referred to as one of the means to help understand the youth phenomenon and form the respective policy. Aim of the article is to reveal the role of youth studies as a specific interdisciplinary genre of the empirical-analytic paradigm in social sciences. Research objectives: (1 To identify the traditions of youth studies and differences between them; (2. To reveal the specific character of youth studies as an empirical paradigm in the contemporary context. Analysis of scientific sources and document analysis are used for achievement of the goal and objectives. Since the 20th century, youth studies have been developing as an independent research discipline and tradition. Perception of the notion of a young person has been changing along with development of the paradigmatic and methodological research traditions. Modernity has doubtlessly contributed to a young person finding his/her place in other age groups and putting an emphasis on the importance of youth as a specific social group. Recently, youth has been viewed as both the risk and the opportunity group. Although qualitative research, in particular, where youth emancipation is aspired, prevails in the contemporary research tradition, the empirical-analytic paradigm has not lost its relevance. The research has demonstrated that empirical-analytic paradigm is a specific genre of the youth studies characterised by quantitative approach and strong link to politics and practical situation of the phenomenon.

Black hole evaporation: a paradigm

International Nuclear Information System (INIS)

Ashtekar, Abhay; Bojowald, Martin

2005-01-01

A paradigm describing black hole evaporation in non-perturbative quantum gravity is developed by combining two sets of detailed results: (i) resolution of the Schwarzschild singularity using quantum geometry methods and (ii) time evolution of black holes in the trapping and dynamical horizon frameworks. Quantum geometry effects introduce a major modification in the traditional spacetime diagram of black hole evaporation, providing a possible mechanism for recovery of information that is classically lost in the process of black hole formation. The paradigm is developed directly in the Lorentzian regime and necessary conditions for its viability are discussed. If these conditions are met, much of the tension between expectations based on spacetime geometry and structure of quantum theory would be resolved

Exponential time paradigms through the polynomial time lens

NARCIS (Netherlands)

Drucker, A.; Nederlof, J.; Santhanam, R.; Sankowski, P.; Zaroliagis, C.

2016-01-01

We propose a general approach to modelling algorithmic paradigms for the exact solution of NP-hard problems. Our approach is based on polynomial time reductions to succinct versions of problems solvable in polynomial time. We use this viewpoint to explore and compare the power of paradigms such as

Health impact assessment research and practice: A place for paradigm positioning?

International Nuclear Information System (INIS)

Haigh, Fiona; Harris, Patrick; Haigh, Neil

2012-01-01

In this article, we provide a critical review of the place of paradigm in health impact assessment (HIA) research and practice. We contend that most HIA practitioners have given insufficient attention to paradigm positioning when developing and applying HIA methodologies and that some concerns about current HIA practice can be attributed to this. We review HIA literature to assess the extent and nature of attention given to paradigm positioning and these related concerns. We then respond to our critique by exploring the implications, opportunities and challenges of adopting a critical realist paradigm, which we believe has the potential to help HIA practitioners to develop HIA methodology in a way that addresses these issues. - Highlights: ► We provide a critical review of the place of paradigm in HIA. ► We demonstrate that HIA practitioners give insufficient attention to paradigm. ► The implications, opportunities and challenges of adopting a critical realist paradigm are explored. ► This is the first paper, to our knowledge, that discusses a critical realist approach to HIA.

Bayesian evidence and predictivity of the inflationary paradigm

Energy Technology Data Exchange (ETDEWEB)

Gubitosi, Giulia; Lagos, Macarena; Magueijo, João [Theoretical Physics, Blackett Laboratory, Imperial College, London, SW7 2BZ (United Kingdom); Allison, Rupert, E-mail: g.gubitosi@imperial.ac.uk, E-mail: m.lagos13@imperial.ac.uk, E-mail: j.magueijo@imperial.ac.uk, E-mail: rupert.allison@astro.ox.ac.uk [Astrophysics, University of Oxford, DWB, Keble Road, Oxford OX1 3RH (United Kingdom)

2016-06-01

In this paper we consider the issue of paradigm evaluation by applying Bayes' theorem along the following nested hierarchy of progressively more complex structures: i) parameter estimation (within a model), ii) model selection and comparison (within a paradigm), iii) paradigm evaluation. In such a hierarchy the Bayesian evidence works both as the posterior's normalization at a given level and as the likelihood function at the next level up. Whilst raising no objections to the standard application of the procedure at the two lowest levels, we argue that it should receive a considerable modification when evaluating paradigms, when testability and fitting data are equally important. By considering toy models we illustrate how models and paradigms that are difficult to falsify are always favoured by the Bayes factor. We argue that the evidence for a paradigm should not only be high for a given dataset, but exceptional with respect to what it would have been, had the data been different. With this motivation we propose a measure which we term predictivity , as well as a prior to be incorporated into the Bayesian framework, penalising unpredictivity as much as not fitting data. We apply this measure to inflation seen as a whole, and to a scenario where a specific inflationary model is hypothetically deemed as the only one viable as a result of information alien to cosmology (e.g. Solar System gravity experiments, or particle physics input). We conclude that cosmic inflation is currently hard to falsify, but that this could change were external/additional information to cosmology to select one of its many models. We also compare this state of affairs to bimetric varying speed of light cosmology.

A Case-Conference Exercise to Facilitate Understanding of Paradigms in Abnormal Psychology

Science.gov (United States)

Lafosse, Jose M.; Zinser, Michael C.

2002-01-01

In this article we describe an in-class case-conference exercise designed to enhance the teaching of paradigms in abnormal psychology courses. The primary pedagogical goals are to increase awareness of how paradigms are applied in real-life settings; better distinguish between paradigms; and recognize how paradigms influence understanding of…

Paradigms and nursing management, analysis of the current organizational structure in a large hospital.

Science.gov (United States)

Wilson, D

1992-01-01

Hospitals developed over the period of time when positivism become a predominant world view. Positivism was founded by four Western trends: preponderance of hierarchy and autocracy, popularization of bureaucracy, extensive application of a machine orientation to work and predominance of "scientific" inquiry. Organizational theory developed largely from quantitative research findings arising from a positivistic world view. A case study, analyzing a current nursing organizational structure at one large hospital, is presented. Nursing management was found to be based upon the positivistic paradigm. The predominance of a machine orientation, and an autocratic and bureaucratic structure are evidence of this. A change to shared governance had been attempted, indicating a shift to a more modern organizational structure based on a different paradigm. The article concludes by emphasizing that managers are largely responsible for facilitating change; change that will meet internal human resource needs and the cost-effectiveness crises of hospitals today through more effective use of human resources.

Behavioral Assessment of Listening Effort Using a Dual-Task Paradigm

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Jean-Pierre Gagné

2017-01-01

Full Text Available Published investigations (n = 29 in which a dual-task experimental paradigm was employed to measure listening effort during speech understanding in younger and older adults were reviewed. A summary of the main findings reported in the articles is provided with respect to the participants’ age-group and hearing status. Effects of different signal characteristics, such as the test modality, on dual-task outcomes are evaluated, and associations with cognitive abilities and self-report measures of listening effort are described. Then, several procedural issues associated with the use of dual-task experiment paradigms are discussed. Finally, some issues that warrant future research are addressed. The review revealed large variability in the dual-task experimental paradigms that have been used to measure the listening effort expended during speech understanding. The differences in experimental procedures used across studies make it difficult to draw firm conclusions concerning the optimal choice of dual-task paradigm or the sensitivity of specific paradigms to different types of experimental manipulations. In general, the analysis confirmed that dual-task paradigms have been used successfully to measure differences in effort under different experimental conditions, in both younger and older adults. Several research questions that warrant further investigation in order to better understand and characterize the intricacies of dual-task paradigms were identified.

An autopsied case of MM1 + MM2-cortical with thalamic-type sporadic Creutzfeldt-Jakob disease presenting with hyperintensities on diffusion-weighted MRI before clinical onset.

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Iwasaki, Yasushi; Mori, Keiko; Ito, Masumi; Mimuro, Maya; Kitamoto, Tetsuyuki; Yoshida, Mari

2017-02-01

A 78-year-old Japanese man presented with rapidly progressive dementia and gait disturbances. Eight months before the onset of clinical symptoms, diffusion-weighted magnetic resonance imaging (DWI) demonstrated hyperintensities in the right temporal, right parietal and left medial occipital cortices. Two weeks after symptom onset, DWI showed extensive hyperintensity in the bilateral cerebral cortex, with regions of higher brightness that existed prior to symptom onset still present. Four weeks after clinical onset, periodic sharp wave complexes were identified on an electroencephalogram. Myoclonus was observed 8 weeks after clinical onset. The patient reached an akinetic mutism state and died 5 months after onset. Neuropathological examination showed widespread cerebral neocortical involvement of fine vacuole-type spongiform changes with large confluent vacuole-type spongiform changes. Spongiform degeneration with neuron loss and hypertrophic astrocytosis was also observed in the striatum and medial thalamus. The inferior olivary nucleus showed severe neuron loss with hypertrophic astrocytosis. Prion protein (PrP) immunostaining showed widespread synaptic-type PrP deposition with perivacuolar-type PrP deposition in the cerebral neocortex. Mild to moderate PrP deposition was also observed extensively in the basal ganglia, thalamus, cerebellum and brainstem, but it was not apparent in the inferior olivary nucleus. PrP gene analysis showed no mutations, and polymorphic codon 129 showed methionine homozygosity. Western blot analysis of protease-resistant PrP showed both type 1 scrapie type PrP (PrP Sc ) and type 2 PrP Sc . Based on the relationship between the neuroimaging and pathological findings, we speculated that cerebral cortical lesions with large confluent vacuoles and type 2 PrP Sc would show higher brightness and continuous hyperintensity on DWI than those with fine vacuoles and type 1 PrP Sc . We believe the present patient had a combined form of MM1�

Platelet rich plasma for treatment of nonhealing diabetic foot ulcers: a case report.

Science.gov (United States)

Mehrannia, Masoud; Vaezi, Mitra; Yousefshahi, Fardin; Rouhipour, Nahid

2014-02-01

Diabetic foot ulcers are one of the most important causes of lower limb amputations worldwide. The conventional treatments of diabetic foot ulcers are costly and often require patients to be hospitalized for long periods of time, thus representing a huge burden on any health care system. The use of autologous platelet-rich plasma (PRP), which is rich in multiple growth factors, may bear some similarities to the natural wound healing process. Nonetheless, few studies on human subjects have so far addressed the efficacy of PRP as a novel and minimally invasive treatment. Today, there is only 1 approved and available system to separate PRP from a patient's own blood in order to be used in diabetic ulcers. This system incorporates bovine thrombin for activation of PRP gel and may be applied by many healthcare providers without the need for extensive special training. In this report, a patient with extensive diabetic foot ulcers, non-responsive to other treatment modalities, was successfully treated by PRP. Copyright © 2014 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Cosmological horizons as new examples of the membrane paradigm

International Nuclear Information System (INIS)

Wang, Tower

2015-01-01

In this paper we aim to provide new examples of the application and the generality of the membrane paradigm. The membrane paradigm is a formalism for studying the event horizon of black holes. After analyzing it with some technical details and realizing it in the Reissner–Nordström black hole, we apply the paradigm to cosmological horizons, first to the pure de Sitter horizon, and then to the trapping horizon of the Friedmann–Lemaître–Robertson–Walker Universe. In the latter case, the cosmological stretched horizon is oblique, thus the running of the renormalization parameter is nonzero in the timelike direction and gives a correction to the membrane pressure. In this paradigm, the cosmological equations come from continuity equations of the membrane fluid and the bulk fluid respectively. (paper)

Approaches to and Treatment Strategies for Playing-Related Pain Problems Among Czech Instrumental Music Students: An Epidemiological Study.

Science.gov (United States)

Ioannou, Christos I; Altenmüller, Eckart

2015-09-01

The current study examined the severity of playing-related pain (PRP) problems among music students at the Prague State Conservatoire, as well as the various treatment methods used by these students and how they approach and deal with these phenomena while studying. In total, 180 instrumental students participated and completed a paper questionnaire. Of these, 88.9% reported that they had experienced PRP at least once in their lives, with 12.6% experiencing pain every time they play. The onset of PRP seemed to coincide with the transition period on entry to the conservatoire and was associated with the increase in hours of practice. Specific body regions associated with playing each particular instrument were most frequently affected, with females being more susceptible than males to the development of PRP. An alarming 35% of the affected students tended not to seek help at all, whereas those who did tended to seek advice first from their instrument tutor and second from medical doctors. Most students who visited doctors reported that medical treatments only partially helped them to overcome PRP problems. The most frequent treatment methods used were resting, gel or creams, and physical exercises. Students believed that inappropriate posture played a key role in the development of their PRP problems. Finally, students indicated a willingness to be aware of and educated about PRP issues during their studies. Further exploration of PRP problems among student musicians is warranted. Better understanding of differing attitudes toward, use of, and efficiency of various treatment methods after the occurrence of PRPs will provide additional insight for prevention and treatment.

Negative pressure darwinism: survival of the fittest paradigm.

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Miller, Michael; Bybordi, Farhad

2009-07-01

The use of negative pressure for wound healing has been based on a set of parameters and devices that until recently were combined into a single paradigm. Despite historical and more recent evidence providing viable alternative considerations, it is only recently that this paradigm and its tenets have come into question. As the understanding of the limits of the current paradigm and specific instances of its benefits and drawbacks are identified, shifts in the paradigm must take place if the therapy is to evolve, develop, and continue to be efficacious. The pertinence of the concept of survival of the fittest is used to explore the need for a paradigm shift in negative pressure wound therapy.

Examining Recall Memory in Infancy and Early Childhood Using the Elicited Imitation Paradigm.

Science.gov (United States)

Lukowski, Angela F; Milojevich, Helen M

2016-04-28

The ability to recall the past allows us to report on details of previous experiences, from the everyday to the significant. Because recall memory is commonly assessed using verbal report paradigms in adults, studying the development of this ability in preverbal infants and children proved challenging. Over the past 30 years, researchers have developed a non-verbal means of assessing recall memory known as the elicited or deferred imitation paradigm. In one variant of the procedure, participants are presented with novel three-dimensional stimuli for a brief baseline period before a researcher demonstrates a series of actions that culminate in an end- or goal-state. The participant is allowed to imitate the demonstrated actions immediately, after a delay, or both. Recall performance is then compared to baseline or to performance on novel control sequences presented at the same session; memory can be assessed for the individual target actions and the order in which they were completed. This procedure is an accepted analogue to the verbal report techniques used with adults, and it has served to establish a solid foundation of the nature of recall memory in infancy and early childhood. In addition, the elicited or deferred imitation procedure has been modified and adapted to answer questions relevant to other aspects of cognitive functioning. The broad utility and application of imitation paradigms is discussed, along with limitations of the approach and directions for future research.

The California Central Coast Research Partnership: Building Relationships, Partnerships and Paradigms for University-Industry Research Collaboration

Science.gov (United States)

2007-04-26

thin films. Immobilized MgO nanoparticles in polyelectrolyte thin films of polyethyleneimine and polyacrylic acid have been made and characterized by...and limiting the amount of students in the lab. Potassium Hydroxide (KOH) was studied and characterized for the application of SiO 2 diaphragms due to...Partnerships and Paradigms for University-Industry Research Collaboration. FINAL REPORT ON ONR GRANT NO. N00014-05-1-0855 PERIOD OF PERFORMANCE: June 15

Periodization Theory: Confronting an Inconvenient Truth.

Science.gov (United States)

Kiely, John

2018-04-01

Periodization theory has, over the past seven decades, emerged as the preeminent training planning paradigm. The philosophical underpinnings of periodization theory can be traced back to the integration of diverse shaping influences, whereby coaching beliefs and traditions were blended with historically available scientific insights and contextualized against pervading social planning models. Since then, many dimensions of elite preparation have evolved significantly, as driven by a combination of coaching innovations and science-led advances in training theory, techniques, and technologies. These advances have been incorporated into the fabric of the pre-existing periodization planning framework, yet the philosophical assumptions underpinning periodization remain largely unchallenged and unchanged. One particularly influential academic sphere of study, the science of stress, particularly the work of Hans Selye, is repeatedly cited by theorists as a central pillar upon which periodization theory is founded. A fundamental assumption emanating from the early stress research is that physical stress is primarily a biologically mediated phenomenon: a presumption translated to athletic performance contexts as evidence that mechanical training stress directly regulates the magnitude of subsequent 'fitness' adaptations. Interestingly, however, since periodization theory first emerged, the science of stress has evolved extensively from its historical roots. This raises a fundamental question: if the original scientific platform upon which periodization theory was founded has disintegrated, should we critically re-evaluate conventional perspectives through an updated conceptual lens? Realigning periodization philosophy with contemporary stress theory thus presents us with an opportunity to recalibrate training planning models with both contemporary scientific insight and progressive coaching practice.

The World Religions Paradigm Time for a Change

Science.gov (United States)

Owen, Suzanne

2011-01-01

The teaching of religions has long relied on the World Religions paradigm to guide curricula throughout education, which has led to a widening gap, on the one hand, between what is taught in schools and in universities and, on the other, between research and teaching. While the World Religions paradigm has allowed the inclusion of non-Christian…

Solution Methods for the Periodic Petrol Station Replenishment Problem

OpenAIRE

C Triki

2013-01-01

In this paper we introduce the Periodic Petrol Station Replenishment Problem (PPSRP) over a T-day planning horizon and describe four heuristic methods for its solution. Even though all the proposed heuristics belong to the common partitioning-then-routing paradigm, they differ in assigning the stations to each day of the horizon. The resulting daily routing problems are then solved exactly until achieving optimalization. Moreover, an improvement procedure is also developed with the aim of ens...

Deconstructing Research: Paradigms Lost

Science.gov (United States)

Trifonas, Peter Pericles

2009-01-01

In recent decades, proponents of naturalistic and/or critical modes of inquiry advocating the use of ethnographic techniques for the narrative-based study of phenomena within pedagogical contexts have challenged the central methodological paradigm of educational research: that is, the tendency among its practitioners to adhere to quantitative…

Language-learning disabilities: Paradigms for the nineties.

Science.gov (United States)

Wiig, E H

1991-01-01

We are beginning a decade, during which many traditional paradigms in education, special education, and speech-language pathology will undergo change. Among paradigms considered promising for speech-language pathology in the schools are collaborative language intervention and strategy training for language and communication. This presentation introduces management models for developing a collaborative language intervention process, among them the Deming Management Method for Total Quality (TQ) (Deming 1986). Implementation models for language assessment and IEP planning and multicultural issues are also introduced (Damico and Nye 1990; Secord and Wiig in press). While attention to processes involved in developing and implementing collaborative language intervention is paramount, content should not be neglected. To this end, strategy training for language and communication is introduced as a viable paradigm. Macro- and micro-level process models for strategy training are featured and general issues are discussed (Ellis, Deshler, and Schumaker 1989; Swanson 1989; Wiig 1989).

The effect of platelet-rich plasma on clinical outcomes in lateral epicondylitis.

Science.gov (United States)

Ahmad, Zafar; Brooks, Roger; Kang, Sertaz-Niel; Weaver, Holly; Nunney, Ian; Tytherleigh-Strong, Graham; Rushton, Neil

2013-11-01

To evaluate the evidence for application of platelet-rich plasma (PRP) in lateral epicondylitis. We carried out a systematic review of the current evidence on the effects of PRP in lateral epicondylitis on clinical outcomes. We performed a comprehensive search of the PubMed, Medline, Cochrane, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Embase databases using various combinations of the commercial names of each PRP preparation and "lateral epicondylitis" (with its associated terms), looking specifically at human studies. Data validity was assessed and collected on clinical outcome. Nine studies met the inclusion criteria, of which 5 were randomized controlled trials. Two cohort studies showed that PRP improved clinical satisfaction scores. One case-control study showed that PRP yielded a significantly greater improvement in symptoms compared with bupivacaine. Two randomized controlled trials compared the effect of injections of PRP and blood. Only 1 of the studies noted a significant difference at the 6-week time point. Three randomized controlled trials compared corticosteroids with PRP. Two of the smaller trials, which had follow-up periods of 6 weeks and 3 months, showed no significant difference between treatment groups. The largest randomized controlled trial found that PRP had significant benefit compared with corticosteroids with regard to pain and Disabilities of the Arm, Shoulder and Hand scores at 1- and 2-year time points. This review highlights the limited but evolving evidence for the use of PRP in lateral epicondylitis; however, further research is required to understand the concentration and preparation that facilitate the best clinical outcome. Characterizing the timing of the intervention would optimize the health economics behind the decision to treat for the patient and health care provider. Level III, systematic review of Level I to III studies. Copyright © 2013 Arthroscopy Association of North America. Published by

Optimized Motor Imagery Paradigm Based on Imagining Chinese Characters Writing Movement.

Science.gov (United States)

Qiu, Zhaoyang; Allison, Brendan Z; Jin, Jing; Zhang, Yu; Wang, Xingyu; Li, Wei; Cichocki, Andrzej

2017-07-01

motor imagery (MI) is a mental representation of motor behavior. The MI-based brain computer interfaces (BCIs) can provide communication for the physically impaired. The performance of MI-based BCI mainly depends on the subject's ability to self-modulate electroencephalogram signals. Proper training can help naive subjects learn to modulate brain activity proficiently. However, training subjects typically involve abstract motor tasks and are time-consuming. to improve the performance of naive subjects during motor imagery, a novel paradigm was presented that would guide naive subjects to modulate brain activity effectively. In this new paradigm, pictures of the left or right hand were used as cues for subjects to finish the motor imagery task. Fourteen healthy subjects (11 male, aged 22-25 years, and mean 23.6±1.16) participated in this study. The task was to imagine writing a Chinese character. Specifically, subjects could imagine hand movements corresponding to the sequence of writing strokes in the Chinese character. This paradigm was meant to find an effective and familiar action for most Chinese people, to provide them with a specific, extensively practiced task and help them modulate brain activity. results showed that the writing task paradigm yielded significantly better performance than the traditional arrow paradigm (p paradigm was easier. the proposed new motor imagery paradigm could guide subjects to help them modulate brain activity effectively. Results showed that there were significant improvements using new paradigm, both in classification accuracy and usability.

Critical evaluation of paradigms for modelling integrated supply chains

NARCIS (Netherlands)

Van Dam, K.H.; Adhitya, A.; Srinivasan, R.; Lukszo, Z.

2009-01-01

Contemporary problems in process systems engineering often require model-based decision support tool. Among the various modelling paradigms, equation-based models and agent-based models are widely used to develop dynamic models of systems. Which is the most appropriate modelling paradigm for a

A Comparison of Two Paradigms for Distributed Shared Memory

NARCIS (Netherlands)

Levelt, W.G.; Kaashoek, M.F.; Bal, H.E.; Tanenbaum, A.S.

1992-01-01

Two paradigms for distributed shared memory on loosely‐coupled computing systems are compared: the shared data‐object model as used in Orca, a programming language specially designed for loosely‐coupled computing systems, and the shared virtual memory model. For both paradigms two systems are

Marketing communications: Qualitative and quantitative paradigm

Directory of Open Access Journals (Sweden)

Uzelac Nikola

2005-01-01

Full Text Available This paper focuses on key issues in relation to the choice of basic language of communication of marketing as a practical and academic field. Principally, marketing managers prefer descriptive way of expression, but they should use the advantages of language of numbers much more. By doing so, they will advance decision-making process - and the communication with finance and top management. In this regard, models offered by academic community could be helpful. This especially pertains to those positive or normative verbal approaches and models in which mathematics and statistical solutions have been embedded, as well as to those which emphasize financial criteria in decision-making. Concerning the process of creation and verification of scientific knowledge, the choice between languages of words and numbers is the part of much wider dimension, because it is inseparable from the decision on basic research orientation. Quantitative paradigm is more appropriate for hypotheses testing, while qualitative paradigm gives greater contribution in their generation. Competition factor could become the key driver of changes by which existing "parallel worlds" of main paradigms would be integrating, for the sake of disciplinary knowledge advancement.

Contemporary paradigms for research related to women's mental health.

Science.gov (United States)

Doucet, Shelley Anne; Letourneau, Nicole Lyn; Stoppard, Janet M

2010-04-01

Mental health problems are serious health concerns that affect women across diverse settings internationally. Knowledge of this population historically has been informed by research using a positivist approach. This article is a critical examination of contemporary paradigms for research related to women's mental health. We begin the article with an introduction to women's mental health, followed by an overview of the postpositivist, critical theory, and constructivist paradigms. We then present a critical examination of the benefits and limitations of these paradigms in relation to the study of women's mental health. We conclude with implications for research and practice.

[Reconstituting evaluation methods based on both qualitative and quantitative paradigms].

Science.gov (United States)

Miyata, Hiroaki; Okubo, Suguru; Yoshie, Satoru; Kai, Ichiro

2011-01-01

Debate about the relationship between quantitative and qualitative paradigms is often muddled and confusing and the clutter of terms and arguments has resulted in the concepts becoming obscure and unrecognizable. In this study we conducted content analysis regarding evaluation methods of qualitative healthcare research. We extracted descriptions on four types of evaluation paradigm (validity/credibility, reliability/credibility, objectivity/confirmability, and generalizability/transferability), and classified them into subcategories. In quantitative research, there has been many evaluation methods based on qualitative paradigms, and vice versa. Thus, it might not be useful to consider evaluation methods of qualitative paradigm are isolated from those of quantitative methods. Choosing practical evaluation methods based on the situation and prior conditions of each study is an important approach for researchers.

A nonmusical paradigm for identifying absolute pitch possessors

Science.gov (United States)

Ross, David A.; Olson, Ingrid R.; Marks, Lawrence E.; Gore, John C.

2004-09-01

The ability to identify and reproduce sounds of specific frequencies is remarkable and uncommon. The etiology and defining characteristics of this skill, absolute pitch (AP), have been very controversial. One theory suggests that AP requires a specific type of early musical training and that the ability to encode and remember tones depends on these learned musical associations. An alternate theory argues that AP may be strongly dependent on hereditary factors and relatively independent of musical experience. To date, it has been difficult to test these hypotheses because all previous paradigms for identifying AP have required subjects to employ knowledge of musical nomenclature. As such, these tests are insensitive to the possibility of discovering AP in either nonmusicians or musicians of non-Western training. Based on previous literature in pitch memory, a paradigm is presented that is intended to distinguish between AP possessors and nonpossessors independent of the subjects' musical experience. The efficacy of this method is then tested with 20 classically defined AP possessors and 22 nonpossessors. Data from these groups strongly support the validity of the paradigm. The use of a nonmusical paradigm to identify AP may facilitate research into many aspects of this phenomenon.

Platelet-rich plasma in orthopedic therapy: a comparative systematic review of clinical and experimental data in equine and human musculoskeletal lesions.

Science.gov (United States)

Brossi, Patrícia M; Moreira, Juliana J; Machado, Thaís S L; Baccarin, Raquel Y A

2015-04-22

This systematic review aimed to present and critically appraise the available information on the efficacy of platelet rich plasma (PRP) in equine and human orthopedic therapeutics and to verify the influence of study design and methodology on the assumption of PRP's efficacy. We searched Medline, PubMed, Embase, Bireme and Google Scholar without restrictions until July 2013. Randomized trials, human cohort clinical studies or case series with a control group on the use of PRP in tendons, ligaments or articular lesions were included. Equine clinical studies on the same topics were included independently of their design. Experimental studies relevant to the clarification of PRP's effects and mechanisms of action in tissues of interest, conducted in any animal species, were selected. This review included 123 studies. PRP's beneficial effects were observed in 46.7% of the clinical studies, while the absence of positive effects was observed in 43.3%. Among experimental studies, 73% yielded positive results, and 7.9% yielded negative results. The most frequent flaws in the clinical trials' designs were the lack of a true placebo group, poor product characterization, insufficient blinding, small sampling, short follow-up periods, and adoption of poor outcome measures. The methods employed for PRP preparation and administration and the selected outcome measures varied greatly. Poor study design was a common feature of equine clinical trials. From studies in which PRP had beneficial effects, 67.8% had an overall high risk of bias. From the studies in which PRP failed to exhibit beneficial effects, 67.8% had an overall low risk of bias. Most experimental studies revealed positive effects of PRP. Although the majority of equine clinical studies yielded positive results, the human clinical trials' results failed to corroborate these findings. In both species, beneficial results were more frequently observed in studies with a high risk of bias. The use of PRP in musculoskeletal

Effect of platelet rich plasma and fibrin sealant on facial nerve regeneration in a rat model.

Science.gov (United States)

Farrag, Tarik Y; Lehar, Mohamed; Verhaegen, Pauline; Carson, Kathryn A; Byrne, Patrick J

2007-01-01

To investigate the effects of platelet rich plasma (PRP) and fibrin sealant (FS) on facial nerve regeneration. Prospective, randomized, and controlled animal study. Experiments involved the transection and repair of facial nerve of 49 male adult rats. Seven groups were created dependant on the method of repair: suture; PRP (with/without suture); platelet poor plasma (PPP) (with/without suture); and FS (with/without suture) groups. Each method of repair was applied immediately after the nerve transection. The outcomes measured were: 1) observation of gross recovery of vibrissae movements within 8-week period after nerve transection and repair using a 5-point scale and comparing the left (test) side with the right (control) side; 2) comparisons of facial nerve motor action potentials (MAP) recorded before and 8 weeks after nerve transection and repair, including both the transected and control (untreated) nerves; 3) histologic evaluation of axons counts and the area of the axons. Vibrissae movement observation: the inclusion of suturing resulted in overall improved outcomes. This was found for comparisons of the suture group with PRP group; PRP with/without suture groups; and PPP with/without suture groups (P .05). The movement recovery of the suture group was significantly better than the FS group (P = .014). The recovery of function of the PRP groups was better than that of the FS groups, although this did not reach statistical significance (P = .09). Electrophysiologic testing: there was a significantly better performance of the suture group when compared with the PRP and PPP without suture groups in nerve conduction velocity (P facial nerve axotomy models occurred when the nerve ends were sutured together. At the same time, the data demonstrated a measurable neurotrophic effect when PRP was present, with the most favorable results seen with PRP added to suture. There was an improved functional outcome with the use of PRP in comparison with FS or no bioactive

Exploring paradigms in postpartum depression research: the need for feminist pragmatism.

Science.gov (United States)

Mollard, Elizabeth

2015-01-01

Postpartum depression (PPD) is an important area of women's health research internationally and across disciplines. There is no guiding paradigm, however, to ensure that PPD research results translate to women on a global level. This commentary builds on the work of Doucet, Letourneau, and Stoppard ( 2010 ) to determine a "best fit" paradigm with which to guide PPD research. Postpositivism, critical theory, constructivism, and pragmatism are combined with a feminist ideology and critiqued as potential guiding paradigms for PPD research. After thorough examination, I conclude the need for further use of a feminist pragmatist paradigm in PPD research.

Operations Strategy under Chaos –Lessons to be learned from a new Paradigm

DEFF Research Database (Denmark)

Koch, Christian

2004-01-01

The purpose of this paper is to introduce a new paradigm being able to conceptualize content and process aspects of Operations Strategy. Based on a critical reading of literature; two opposing paradigms of Operations Strategy are identified and described. The first focuses on content issues...... of Operations Strategy and relies on a normative orientation and the second focuses on process issues of Operations Strategy and relies on a descriptive orientation. To compare and evaluate the two paradigms; the results of a longitudinal case-study of Operations Strategy formulation and implementation...... in practice are shown. These results promote the need for a new or third paradigm to integrate and balance the two former paradigms. The new paradigm is labeled as a moderate constructivist paradigm using the metaphor of chaos and seems suitable for conceptualizing Operations Strategy as it is in practice...

Paradigms: How Far Does Research in Distributed Leadership "Stretch"?

Science.gov (United States)

Hartley, David

2010-01-01

Burrell and Morgan's widely-cited "Sociological Paradigms and Organizational Analysis" is applied here to research on distributed leadership in education. Nearly all of the extant research is regulatory, not radical; and the evidence which it has generated falls broadly within the paradigm of interpretivism. Few studies have generated the…

Interface between problem-based learning and a learner-centered paradigm

Directory of Open Access Journals (Sweden)

Karimi R

2011-05-01

Full Text Available Reza KarimiPacific University School of Pharmacy, Hillsboro, OR, USABackground: Problem-based learning (PBL has made a major shift in support of student learning for many medical school curricula around the world. Since curricular development of PBL in the early 1970s and its growth in the 1980s and 1990s, there have been growing numbers of publications providing positive and negative data in regard to the curricular effectiveness of PBL. The purpose of this study was to explore supportive data for the four core objectives of PBL and to identify an interface between the objectives of PBL and a learner-centered paradigm.Methods: The four core PBL objectives, ie, structuring of knowledge and clinical context, clinical reasoning, self-directed learning, and intrinsic motivation, were used to search MEDLINE, the Education Resources Information Center, the Educator’s Reference Complete, and PsycINFO from January 1969 to January 2011. The literature search was facilitated and narrowed if the published study included the following terms: “problem-based learning”, “medical education”, “traditional curriculum”, and one of the above four PBL objectives.Results: Through a comprehensive search analysis, one can find supportive data for the effectiveness of a PBL curriculum in achieving the four core objectives of PBL. A further analysis of these four objectives suggests that there is an interface between PBL objectives and criteria from a learner-centered paradigm. In addition, this review indicates that promotion of teamwork among students is another interface that exists between PBL and a learner-centered paradigm.Conclusion: The desire of medical schools to enhance student learning and a need to provide an environment where students construct knowledge rather than receive knowledge have encouraged many medical schools to move into a learner-centered paradigm. Implementation of a PBL curriculum can be used as a prevailing starting point to

A dual-task paradigm for behavioral and neurobiological studies in nonhuman primates.

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Watanabe, Kei; Funahashi, Shintaro

2015-05-15

The dual-task paradigm is a procedure in which subjects are asked to perform two behavioral tasks concurrently, each of which involves a distinct goal with a unique stimulus-response association. Due to the heavy demand on subject's cognitive abilities, human studies using this paradigm have provided detailed insights regarding how the components of cognitive systems are functionally organized and implemented. Although dual-task paradigms are widely used in human studies, they are seldom used in nonhuman animal studies. We propose a novel dual-task paradigm for monkeys that requires the simultaneous performance of two cognitively demanding component tasks, each of which uses an independent effector for behavioral responses (hand and eyes). We provide a detailed description of an optimal training protocol for this paradigm, which has been lacking in the existing literature. An analysis of behavioral performance showed that the proposed dual-task paradigm (1) was quickly learned by monkeys (less than 40 sessions) with step-by-step training protocols, (2) produced specific behavioral effects, known as dual-task interference in human studies, and (3) achieved rigid and independent control of the effectors for behavioral responses throughout the trial. The proposed dual-task paradigm has a scalable task structure, in that each of the two component tasks can be easily replaced by other tasks, while preserving the overall structure of the paradigm. This paradigm should be useful for investigating executive control that underlies dual-task performance at both the behavioral and neuronal levels. Copyright © 2015 Elsevier B.V. All rights reserved.

Different Research Paradigms Concerning Giftedness and Gifted Education: Shall Ever They Meet?

Science.gov (United States)

Heller, Kurt A.

2012-01-01

Knowledge regarding giftedness and gifted education is supplied by different sources of information and different research paradigms. Particularly relevant approaches are here the psychometric paradigm, the expert-novice paradigm, and the explanatory approaches from cognitive sciences, also the quasi-experimental social and developmental studies…

Interaction between Social Categories in the Composite Face Paradigm

Science.gov (United States)

Chen, Wenfeng; Ren, Naixin; Young, Andrew W.; Liu, Chang Hong

2018-01-01

The composite face paradigm (Young, Hellawell, & Hay, 1987) is widely used to demonstrate holistic perception of faces (Rossion, 2013). In the paradigm, parts from different faces (usually the top and bottom halves) are recombined. The principal criterion for holistic perception is that responses involving the component parts of composites in…

Are leader stereotypes masculine? A meta-analysis of three research paradigms.

Science.gov (United States)

Koenig, Anne M; Eagly, Alice H; Mitchell, Abigail A; Ristikari, Tiina

2011-07-01

This meta-analysis examined the extent to which stereotypes of leaders are culturally masculine. The primary studies fit into 1 of 3 paradigms: (a) In Schein's (1973) think manager-think male paradigm, 40 studies with 51 effect sizes compared the similarity of male and leader stereotypes and the similarity of female and leader stereotypes; (b) in Powell and Butterfield's (1979) agency-communion paradigm, 22 studies with 47 effect sizes compared stereotypes of leaders' agency and communion; and (c) in Shinar's (1975) masculinity-femininity paradigm, 7 studies with 101 effect sizes represented stereotypes of leadership-related occupations on a single masculinity-femininity dimension. Analyses implemented appropriate random and mixed effects models. All 3 paradigms demonstrated overall masculinity of leader stereotypes: (a) In the think manager-think male paradigm, intraclass correlation = .25 for the women-leaders similarity and intraclass correlation = .62 for the men-leaders similarity; (b) in the agency-communion paradigm, g = 1.55, indicating greater agency than communion; and (c) in the masculinity-femininity paradigm, g = 0.92, indicating greater masculinity than the androgynous scale midpoint. Subgroup and meta-regression analyses indicated that this masculine construal of leadership has decreased over time and was greater for male than female research participants. In addition, stereotypes portrayed leaders as less masculine in educational organizations than in other domains and in moderate- than in high-status leader roles. This article considers the relation of these findings to Eagly and Karau's (2002) role congruity theory, which proposed contextual influences on the incongruity between stereotypes of women and leaders. The implications for prejudice against women leaders are also considered.

Paradigms in object recognition

International Nuclear Information System (INIS)

Mutihac, R.; Mutihac, R.C.

1999-09-01

A broad range of approaches has been proposed and applied for the complex and rather difficult task of object recognition that involves the determination of object characteristics and object classification into one of many a priori object types. Our paper revises briefly the three main different paradigms in pattern recognition, namely Bayesian statistics, neural networks, and expert systems. (author)

Innovative character of marketing paradigm of education governance

OpenAIRE

E. G. Sytnychenko

2014-01-01

The most common methodological basis for creating marketing paradigm of public education management is the allocation of general forms of marketing to management activities. Immediate methodological basis for the formation of the said paradigm was synthesis of marketing concepts and management activities. Educational marketing is a cognitive foundation of values reorientation of all forms of regulation to meet the social and educational needs of the individual. In this sense, marketing manage...

Historical ESWT Paradigms Are Overcome: A Narrative Review

OpenAIRE

Lohrer, Heinz; Nauck, Tanja; Korakakis, Vasileios; Malliaropoulos, Nikos

2016-01-01

Extracorporeal Shock Wave Therapy (ESWT) is a conservative treatment modality with still growing interest in musculoskeletal disorders. This narrative review aims to present an overview covering 20-year development in the field of musculoskeletal ESWT. Eight historical paradigms have been identified and put under question from a current perspective: energy intensity, focus size, anesthesia, imaging, growth plates, acuteness, calcifications, and number of sessions. All paradigms as set in a hi...

Paradigm shift from cartography to geo-communication

DEFF Research Database (Denmark)

Brodersen, Lars

2007-01-01

This paper argues that the domain of GIS, cartography, geo-information etc. is facing a paradigm shift. The implication of a paradigm shift is a complete and necessary re-definition of e.g. the philosophical foundation of the system, as well as with a major upgrade and readjustment of procedures......-information is actually not possible at all without having a usage (a project identity and a purpose) in mind. Objective and neutral geo-information does not exist. Therefore the overall philosophy of the geo-domain will be that it is a communication discipline....

Understanding the land management paradigm

DEFF Research Database (Denmark)

Enemark, Stig

2006-01-01

There is a worldwide need to build understanding of the land management paradigm and for institutional development to establish sustainable national concepts. This includes creation and adoption of a policy on land development, and an approach that combines the land administration...

Manufacture of pooled platelets in additive solution and storage in an ELX container after an overnight warm temperature hold of platelet-rich plasma.

Science.gov (United States)

Alhumaidan, Hiba; Cheves, Tracey; Holme, Stein; Sweeney, Joseph D

2011-10-01

The processing of whole blood-derived platelet-rich plasma (PRP) to a platelet concentrate and platelet-poor plasma is currently performed within 8 hours to comply with the requirements to manufacture fresh frozen plasma. Maintaining PRP at room temperature for a longer period can have the advantage of shifting the completion of component manufacture onto day shifts. Pairs of ABO-identical prepooled platelets were manufactured by the PRP method, using the current approach with platelet storage in a CLX HP container (Pall Medical, Covina, CA) and plasma, or a novel approach with an 18- to a 24-hour room temperature hold of the PRP and the manufacture of pooled platelets in a glucose-containing additive solution (AS) and storage in a new ELX container (Pall Medical). Standard in vitro assays were performed on days 2, 5, and 7. The results showed that the AS platelets in ELX have in vitro characteristics that are equivalent or superior to those of the standard product.

The effect of platelet rich plasma from bone marrow aspirate with added bone morphogenetic protein-2 on the Achilles tendon-bone junction in rabbits.

Science.gov (United States)

Kim, Hak Jun; Nam, Hyok-Woo; Hur, Chang-Yong; Park, Misu; Yang, Hee Seok; Kim, Byung-Soo; Park, Jung-Ho

2011-12-01

To determine if exogenously injected bone marrow derived platelet-rich plasma (PRP) plus bone morphogenetic protein (BMP)-2 could accelerate the healing of bone-tendon junction injuries and increase the junction holding strength during the early regeneration period. A direct injury model of the bone-tendon junction was made using an Achilles tendon-calcaneus bone junction in a rabbit. In the PRP/BMP-2/fibrin group, 0.05 mL of bone marrow derived PRP and 100 ng/mL of BMP-2 both incorporated into 0.1 mL of fibrin glue were injected into Achilles tendon-calcaneus bone junctions. The effect of the intervention was tested by comparing the results of an intervention group to a control group. The results of biomechanical testing, and histological and gross analyses were compared between the 2 groups at the following time points after surgery: 2 weeks, 4 weeks, and 8 weeks. Histologic examinations showed that woven bone developed in tendon-bone junctions at 2 weeks after surgery in the PRP/BMP-2/fibrin group. Mechanical test results showed no significant difference between the PRP/BMP-2/fibrin and control groups at 2 and 4 weeks after surgery, but the mean maximal load in the PRP/BMP-2/fibrin group was significantly higher than in the control group (p rabbit model of tendon-bone junction injury.

Comparative study of the efficacy of Platelet-rich plasma combined with carboxytherapy vs its use with fractional carbon dioxide laser in atrophic acne scars.

Science.gov (United States)

Al Taweel, Abdul-Aziz Ibrahim; Al Refae, Abdul-Aziz Abdul-Salam; Hamed, Ahmed Mohamed; Kamal, Asmaa Mostafa

2018-04-22

Acne scars are a major concerning problem to all acne patients affecting their quality of life. Platelet-rich plasma (PRP) and fractional CO 2 laser are innovative treatment modalities for acne scars. Carboxytherapy can also be used to improve scar tissue through the increase in collagen deposition and reorganization, and the improvement in skin texture and tone. The aim of this work was to compare the efficacy, safety, and complications of the intradermal injection of PRP combined with carboxytherapy and PRP combined with fractional CO 2 laser, in the treatment of atrophic acne scars. Forty patients with atrophic acne scars were divided into 2 groups. Group A included 20 patients and was subjected to three fractional CO 2 laser sessions combined with PRP injection. Group B included 20 patients and was subjected to three sessions of carboxytherapy combined with PRP injection. Both fractional CO 2 laser and carboxytherapy combined with PRP showed improvement in acne scars and patients' satisfaction but the improvement with fractional CO 2 laser was significantly better than carboxytherapy but with more side effects. Improvement of acne scars was noted in both treatment modalities with obvious higher and statistically significant results in favor of fractional CO 2 laser but with more side effects. Carboxytherapy is a promising tool in treatment of acne scars with less complication. © 2018 Wiley Periodicals, Inc.

Disability Is Not Measles: New Research Paradigms in Disability.

Science.gov (United States)

Rioux, Marcia H., Ed.; Bach, Michael, Ed.

This book is the product of a forum titled New Research Directions and Paradigms, held at the Congress of the International Association for the Scientific Study of Mental Deficiency in Australia in August 1992. The book presents 13 chapters, all written within a critical paradigm for disability research which critiques the reification of…

Cloud Manufacturing Service Paradigm for Group Manufacturing Companies

Directory of Open Access Journals (Sweden)

Jingtao Zhou

2014-07-01

Full Text Available The continuous refinement of specialization requires that the group manufacturing company must be constantly focused on how to concentrate its core resources in special sphere to form its core competitive advantage. However, the resources in enterprise group are usually distributed in different subsidiary companies, which means they cannot be fully used, constraining the competition and development of the enterprise. Conducted as a response to a need for cloud manufacturing studies, systematic and detailed studies on cloud manufacturing schema for group companies are carried out in this paper. A new hybrid private clouds paradigm is proposed to meet the requirements of aggregation and centralized use of heterogeneous resources and business units distributed in different subsidiary companies. After the introduction of the cloud manufacturing paradigm for enterprise group and its architecture, this paper presents a derivation from the abstraction of paradigm and framework to the application of a practical evaluative working mechanism. In short, the paradigm establishes an effective working mechanism to translate collaborative business process composed by the activities into cloud manufacturing process composed by services so as to create a foundation resulting in mature traditional project monitoring and scheduling technologies being able to be used in cloud manufacturing project management.

Cryptocurrency Networks: A New P2P Paradigm

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Sergi Delgado-Segura

2018-01-01

Full Text Available P2P networks are the mechanism used by cryptocurrencies to disseminate system information while keeping the whole system as much decentralized as possible. Cryptocurrency P2P networks have new characteristics that propose new challenges and avoid some problems of existing P2P networks. By characterizing the most relevant cryptocurrency network, Bitcoin, we provide details on different properties of cryptocurrency networks and their similarities and differences with standard P2P network paradigms. Our study allows us to conclude that cryptocurrency networks present a new paradigm of P2P networks due to the mechanisms they use to achieve high resilience and security. With this new paradigm, interesting research lines can be further developed, both in the focused field of P2P cryptocurrency networks and also when such networks are combined with other distributed scenarios.

The "extended mind" approach for a new paradigm of psychology.

Science.gov (United States)

Kono, Tetsuya

2010-12-01

In this paper, I would like to propose the idea of "extended mind" for a new paradigm of psychology. Kohler (Integrative Psychology & Behavioral Science 44:39-57, 2010) correctly pointed out the serious problems of the machine paradigm, and proposed the "organic" view as a new paradigm. But the term "organic" signifying the processes inside the body, is inadequate to express the characteristic of human mind. The recent philosophy of mind suggests that the mind is realized neither only in the brain nor only in the body, but in the whole system of brain-body-environment, namely, in the "extended mind". The characteristic of human mind resides in the interaction with the mediating tools, artifacts, and the humanized environment. We should propose an "extended mind approach" or an "ecological approach to humanized environment" as a new paradigm for a psychology.

Researching Style: Epistemology, Paradigm Shifts and Research Interest Groups

Science.gov (United States)

Rayner, Stephen

2011-01-01

This paper identifies the need for a deliberate approach to theory building in the context of researching cognitive and learning style differences in human performance. A case for paradigm shift and a focus upon research epistemology is presented, building upon a recent critique of style research. A proposal for creating paradigm shift is made,…

A Critical Evaluation of the Paradigm Approach in Sepedi ...

African Journals Online (AJOL)

user

Abstract: This article gives a critical evaluation of the paradigm approach of the Groot Noord-. Sotho Woordeboek to the lemmatisation of verbs and nouns derived from verbs. The verb stem -roba. 'break' with its complicated system of derivations will be taken as a case in point. The paradigm presented for -roba will be ...

Comunication: the Paradigms of symmetry, antisymmetry anda asymmetry

OpenAIRE

Winfried Nöth

2011-01-01

The paper examines how the process of communication is represented (a) in the etymology of the conceptof communication, (b) in everyday metaphors of communication, and (c) in 20th century theories andmodels of communication. These reflect this paradox in three different scenarios: the paradigms ofsymmetry, antisymmetry and asymmetry. The dead end into which communication theory is led by theproponents of the latter paradigm is contrasted with some solutions offered by Charles S. Peirce’scommu...

Black hole mass formula in the membrane paradigm

Science.gov (United States)

Lemos, José P. S.; Zaslavskii, Oleg B.

2018-03-01

The membrane paradigm approach adopts a timelike surface, stretched out off the null event horizon, to study several important black hole properties. We use this powerful tool to give a direct derivation of the black hole mass formula in the static and stationary cases without and with electric field. Since here the membrane is a self-gravitating material system, we go beyond the usual applicability on test particles and test fields of the paradigm.

Sustainable intensification: A new paradigm for African agriculture

OpenAIRE

The Montpellier Panel

2013-01-01

Sub-Saharan Africa faces a rapid population growth that drives food demand and scarcity together with scarcity in natural resources such as land, water, and soil fertility. This Montpellier Panel report identifies the paradigm of sustainable intensification as a framework to address both of these issues. It provides a comprehensive overview of the sustainable intensification paradigm, which seeks to utilize existing land to maximize yields, incomes, and nutrition while minimizing negative ext...

Toward a Metatheoretical Integration of Developmental Paradigms

Directory of Open Access Journals (Sweden)

Mark W. Antley

2010-07-01

Full Text Available This paper shows how a partial consilience might be achieved in the field of human development by means of principles from general systems theory. The author concurs with Sameroff (1989 that it is possible to interpret the mechanistic, organisimic, and contextualist paradigms/worldviews (Goldhaber, 2000; Pepper, 1970 in terms of general systems theory. The author selects a major developmentalist from each paradigm and interprets that scholar’s work in terms of systems principles. The following developmentalists were selected: Arnold Sameroff (contextualism, Erik Erickson (organicism, and Albert Bandura (mechanism. The systems principles employed are wholeness and order, self-stabilization, self-reorganization, hierarchical interaction, and dialectical contradiction (Sameroff, 1989. The author addresses the conflicting presuppositions of the major paradigms in order to provide for their theoretical subsuming under systems theory. Finally, the author notes areas of inconsistency that will need to be resolved in the future and calls for further scholarship to translate developmental theory in terms of general systems theory for the benefit of students, scholars, consultants and other practitioners familiar with systems theory.

Three Paradigms of Social Assistance

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Pierre-Marc Daigneault

2014-11-01

Full Text Available “Ideas,” which are defined as the normative and cognitive beliefs of actors, are fundamental to a full understanding of the welfare state and, in particular, of social assistance. However, policy ideas have been neglected in most typologies of social assistance regimes. Based on a selective review of the literature, this article proposes a brief but systematic analysis of policy paradigms in the field of social assistance. Three ideal types that emphasize the ideational dimension of social assistance are analyzed, namely, the entitlement, workfare, and activation paradigms. The value of the typology lies in its utility for characterizing the ideational orientation of social assistance regimes. Specifically, the typology provides a yardstick for measuring the ideas of policy actors with respect to social assistance and can facilitate the conduct of case studies, comparative research, and causal analyses on this policy sector.

Cloud Computing and Multi Agent System to improve Learning Object Paradigm

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Ana B. Gil

2015-05-01

Full Text Available The paradigm of Learning Object provides Educators and Learners with the ability to access an extensive number of learning resources. To do so, this paradigm provides different technologies and tools, such as federated search platforms and storage repositories, in order to obtain information ubiquitously and on demand. However, the vast amount and variety of educational content, which is distributed among several repositories, and the existence of various and incompatible standards, technologies and interoperability layers among repositories, constitutes a real problem for the expansion of this paradigm. This study presents an agent-based architecture that uses the advantages provided by Cloud Computing platforms to deal with the open issues on the Learning Object paradigm.

Industry 4.0 and the New Simulation Modelling Paradigm

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Rodič Blaž

2017-08-01

Full Text Available Background and Purpose: The aim of this paper is to present the influence of Industry 4.0 on the development of the new simulation modelling paradigm, embodied by the Digital Twin concept, and examine the adoption of the new paradigm via a multiple case study involving real-life R&D cases involving academia and industry.

Evolution of the radiological protection paradigms; Evolucao dos paradigmas de protecao radiologica

Energy Technology Data Exchange (ETDEWEB)

Sordi, Gian Maria A.A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Programa de Pos-Graduacao em Tecnologia Nuclear], E-mail: gmsordi@ipen.br

2009-10-15

We consider as initial radiological protection paradigms those in vigour after the release of the atomic energy for pacific usages in 1955. In that occasion, only one paradigm was introduced, presently named dose limitation system. After arguing about the basis that raised the paradigm, we introduced the guidance, that is, the measurements to be implemented to comply with the paradigm. In that occasion, they were two, i.e., the radiation dose monitoring and the workplace classification. Afterwards, the reasons that caused the radiological protection paradigms changes in force until 1995 are discussed. The initial paradigm was modified introducing the justification and the optimization principles, adding that the radiological protection should be economical and effective. The guidance also increased to four: personal monitoring, workplace classification, reference level and workers classification. Afterwards, we give the main justifications for the present paradigms that besides the formers were added the dose constraints, the potential exposure and the annual risk limits. Due to these modifications, the workers classifications were eliminated from the guidance, but the potential exposure and the search for the dose constraints were added. Eventually, we discuss the tendencies for the next future and the main changes introduced by the ICRP in the Publication 103, 2007. (author)

Challenging paradigms in estuarine ecology and management

Science.gov (United States)

Elliott, M.; Whitfield, A. K.

2011-10-01

For many years, estuarine science has been the 'poor relation' in aquatic research - freshwater scientists ignored estuaries as they tended to get confused by salt and tides, and marine scientists were more preoccupied by large open systems. Estuaries were merely regarded by each group as either river mouths or sea inlets respectively. For the past four decades, however, estuaries (and other transitional waters) have been regarded as being ecosystems in their own right. Although often not termed as such, this has led to paradigms being generated to summarise estuarine structure and functioning and which relate to both the natural science and management of these systems. This paper defines, details and affirms these paradigms that can be grouped into those covering firstly the science (definitions, scales, linkages, productivity, tolerances and variability) and secondly the management (pressures, valuation, health and services) of estuaries. The more 'science' orientated paradigms incorporate the development and types of ecotones, the nature of stressed and variable systems (with specific reference to resilience and redundancy), the relationship between generalists and specialists produced by environmental tolerance, the relevance of scale in relation to functioning and connectivity, the sources of production and degree of productivity, the biodiversity-ecosystem functioning and the stress-subsidy debates. The more 'management' targeted paradigms include the development and effects of exogenic unmanaged pressures and endogenic managed pressures, the perception of health and the ability to manage estuaries (related to internal and external influences), and the influence of all of these on the production of ecosystem services and societal benefits.

Complexity: a potential paradigm for a health promotion discipline.

Science.gov (United States)

Tremblay, Marie-Claude; Richard, Lucie

2014-06-01

Health promotion underpins a distancing from narrow, simplifying health approaches associated with the biomedical model. However, it has not yet succeeded in formally establishing its theoretical, epistemological and methodological foundations on a single paradigm. The complexity paradigm, which it has yet to broach head-on, might provide it with a disciplinary matrix in line with its implicit stances and basic values. This article seeks to establish complexity's relevance as a paradigm that can contribute to the development of a health promotion discipline. The relevance of complexity is justified primarily by its matching with several implicit epistemological and methodological/theoretical stances found in the cardinal concepts and principles of health promotion. The transcendence of ontological realism and determinism as well as receptiveness in respect of the reflexivity that complexity encompasses are congruent with the values of social justice, participation, empowerment and the concept of positive health that the field promotes. Moreover, from a methodological and theoretical standpoint, complexity assumes a holistic, contextual and transdisciplinary approach, toward which health promotion is tending through its emphasis on ecology and interdisciplinary action. In a quest to illustrate our position, developmental evaluation is presented as an example of practice stemming from a complexity paradigm that can be useful in the evaluation of health promotion initiatives. In short, we argue that it would be advantageous for health promotion to integrate this paradigm, which would provide it with a formal framework appropriate to its purposes and concerns.

Guiding New Teacher Training towards the Acquisition of a Systemic Paradigm

Directory of Open Access Journals (Sweden)

Luis Guillermo Barrantes-Montero

2015-09-01

Full Text Available This paper distinguishes between positivist disciplinary paradigm, which classifies human knowledge into isolated disciplines, and systemic paradigm, which aims at integrating knowledge and an inter-and trans-disciplinarity approach. The need and convenience of preparing new professionals in the latter is discussed. An example on how to develop a training experience based on the systemic paradigm in an advanced English reading course, in a teacher-training career is also described.

E-learning paradigmer og e-learning strategiudvikling

DEFF Research Database (Denmark)

Duus, Henrik Johannsen

2003-01-01

E-learning området er meget varieret hvad angår produkter, holdninger ogmeninger, og indeholder også en del 'støj' og mytedannelser, som afspejles i såvel denakademisk-videnskabelige som den journalistisk-offentlige debat om området. Dennevariation i såvel produkter som udtrykte meninger søges...... systematiseret og ordnet i fireidealtypiske paradigmer. Det vises, hvorledes disse fire paradigmer har hver sinebestemte karakteristika og udviklingsgrænser. Dette har afgørende strategisk betydningfor virksomheders og læreanstalters udvikling af e-learning, idet forkerte paradigmevalgvil hæmme udviklingen....

Playing off the beat: Applying the jazz paradigm to psychotherapy.

Science.gov (United States)

Johnson, David Read

2018-02-01

A jazz paradigm is applied to traditional psychotherapy practice, illuminating the links between psychotherapy and the Romantic aesthetic tradition, primarily in the centrality of concepts such as attunement. Modernist disruptions of realism during the early 20 th century, such as jazz, elaborated dissonant and improvisational artistic impulses that brought new vitality to their art forms. The psychotherapeutic relationship also has potential avenues for multilevel and discrepant communication that open possibilities of freedom. However, the limitations imposed by the single channel nature of comprehended language, compared with the capacity of artistic media to express multiple sensory information simultaneously, remain the most significant obstacle to dimensionalizing the psychotherapeutic dialogue. Psychotherapy may have much to gain from embracing some of the concepts underlying the jazz aesthetic. © 2018 Wiley Periodicals, Inc.