Steady-State Modeling of Modular Multilevel Converter Under Unbalanced Grid Conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Xiaojie M.; Wang, Zhiqiang; Liu, Bo

This paper presents a steady-state model of MMC for the second-order phase voltage ripple prediction under unbalanced conditions, taking the impact of negative-sequence current control into account. From the steady-state model, a circular relationship is found among current and voltage quantities, which can be used to evaluate the magnitudes and initial phase angles of different circulating current components. Moreover, in order to calculate the circulating current in a point-to-point MMC-based HVdc system under unbalanced grid conditions, the derivation of equivalent dc impedance of an MMC is discussed as well. According to the dc impedance model, an MMC inverter can bemore » represented as a series connected R-L-C branch, with its equivalent resistance and capacitance directly related to the circulating current control parameters. Experimental results from a scaled-down three-phase MMC system under an emulated single-line-to-ground fault are provided to support the theoretical analysis and derived model. In conclusion, this new models provides an insight into the impact of different control schemes on the fault characteristics and improves the understanding of the operation of MMC under unbalanced conditions.« less

Steady-State Modeling of Modular Multilevel Converter Under Unbalanced Grid Conditions

DOE PAGES

Shi, Xiaojie M.; Wang, Zhiqiang; Liu, Bo; ...

2016-11-16

This paper presents a steady-state model of MMC for the second-order phase voltage ripple prediction under unbalanced conditions, taking the impact of negative-sequence current control into account. From the steady-state model, a circular relationship is found among current and voltage quantities, which can be used to evaluate the magnitudes and initial phase angles of different circulating current components. Moreover, in order to calculate the circulating current in a point-to-point MMC-based HVdc system under unbalanced grid conditions, the derivation of equivalent dc impedance of an MMC is discussed as well. According to the dc impedance model, an MMC inverter can bemore » represented as a series connected R-L-C branch, with its equivalent resistance and capacitance directly related to the circulating current control parameters. Experimental results from a scaled-down three-phase MMC system under an emulated single-line-to-ground fault are provided to support the theoretical analysis and derived model. In conclusion, this new models provides an insight into the impact of different control schemes on the fault characteristics and improves the understanding of the operation of MMC under unbalanced conditions.« less

Activation of rat intestinal mucosal mast cells by fat absorption.

PubMed

Ji, Yong; Sakata, Yasuhisa; Yang, Qing; Li, Xiaoming; Xu, Min; Yoder, Stephanie; Langhans, Wolfgang; Tso, Patrick

2012-06-01

Previous studies have linked certain types of gut mucosal immune cells with fat intake. We determined whether fat absorption activates intestinal mucosal mast cells (MMC), a key component of the gut mucosal immune system. Conscious intestinal lymph fistula rats were used. The mesenteric lymph ducts were cannulated, and the intraduodenal (i.d.) tubes were installed for the infusion of Liposyn II 20% (an intralipid emulsion). Lymphatic concentrations of histamine, rat MMC protease II (RMCPII), a specific marker of rat intestinal MMC degranulation, and prostaglandin D(2) (PGD(2)) were measured by ELISA. Intestinal MMC degranulation was visualized by immunofluorescent microscopy of jejunum sections taken at 1 h after Liposyn II gavage. Intraduodenal bolus infusion of Liposyn II 20% (4.4 kcal/3 ml) induced approximately a onefold increase in lymphatic histamine and PGD(2), ∼20-fold increase in lymphatic RMCPII, but only onefold increase in peripheral serum RMCPII concentrations. Release of RMCPII into lymph increased dose dependently with the amount of lipid fed. In addition, i.d. infusion of long-chain triacylglycerol trilinolein (C18:2 n-6, the major composite in Liposyn II) significantly increased the lymphatic RMCPII concentration, whereas medium-chain triacylglycerol tricaprylin (C8:0) did not alter lymph RMCPII secretion. Immunohistochemistry image revealed the degranulation of MMC into lamina propria after lipid feeding. These novel findings indicate that intestinal MMC are activated and degranulate to release MMC mediators to the circulation during fat absorption. This action of fatty acid is dose and chain length dependent.

Activation of rat intestinal mucosal mast cells by fat absorption

PubMed Central

Sakata, Yasuhisa; Yang, Qing; Li, Xiaoming; Xu, Min; Yoder, Stephanie; Langhans, Wolfgang; Tso, Patrick

2012-01-01

Previous studies have linked certain types of gut mucosal immune cells with fat intake. We determined whether fat absorption activates intestinal mucosal mast cells (MMC), a key component of the gut mucosal immune system. Conscious intestinal lymph fistula rats were used. The mesenteric lymph ducts were cannulated, and the intraduodenal (i.d.) tubes were installed for the infusion of Liposyn II 20% (an intralipid emulsion). Lymphatic concentrations of histamine, rat MMC protease II (RMCPII), a specific marker of rat intestinal MMC degranulation, and prostaglandin D2 (PGD2) were measured by ELISA. Intestinal MMC degranulation was visualized by immunofluorescent microscopy of jejunum sections taken at 1 h after Liposyn II gavage. Intraduodenal bolus infusion of Liposyn II 20% (4.4 kcal/3 ml) induced approximately a onefold increase in lymphatic histamine and PGD2, ∼20-fold increase in lymphatic RMCPII, but only onefold increase in peripheral serum RMCPII concentrations. Release of RMCPII into lymph increased dose dependently with the amount of lipid fed. In addition, i.d. infusion of long-chain triacylglycerol trilinolein (C18:2 n-6, the major composite in Liposyn II) significantly increased the lymphatic RMCPII concentration, whereas medium-chain triacylglycerol tricaprylin (C8:0) did not alter lymph RMCPII secretion. Immunohistochemistry image revealed the degranulation of MMC into lamina propria after lipid feeding. These novel findings indicate that intestinal MMC are activated and degranulate to release MMC mediators to the circulation during fat absorption. This action of fatty acid is dose and chain length dependent. PMID:22461027

Online Systems for Oversize and Overweight Freight Permitting and Motor Carrier Credentialing : Transportation Research Synthesis.

DOT National Transportation Integrated Search

2017-09-01

MnDOT uses two online systems implemented in the 1990s to issue and manage permits for oversize/overweight (OS/OW) freight and motor carrier credentials: - RouteBuilder, an OS/OW permitting system with a routing component. - Motor Carrier Information...

Mission Management Computer Software for RLV-TD

NASA Astrophysics Data System (ADS)

Manju, C. R.; Joy, Josna Susan; Vidya, L.; Sheenarani, I.; Sruthy, C. N.; Viswanathan, P. C.; Dinesh, Sudin; Jayalekshmy, L.; Karuturi, Kesavabrahmaji; Sheema, E.; Syamala, S.; Unnikrishnan, S. Manju; Ali, S. Akbar; Paramasivam, R.; Sheela, D. S.; Shukkoor, A. Abdul; Lalithambika, V. R.; Mookiah, T.

2017-12-01

The Mission Management Computer (MMC) software is responsible for the autonomous navigation, sequencing, guidance and control of the Re-usable Launch Vehicle (RLV), through lift-off, ascent, coasting, re-entry, controlled descent and splashdown. A hard real-time system has been designed for handling the mission requirements in an integrated manner and for meeting the stringent timing constraints. Redundancy management and fault-tolerance techniques are also built into the system, in order to achieve a successful mission even in presence of component failures. This paper describes the functions and features of the components of the MMC software which has accomplished the successful RLV-Technology Demonstrator mission.

Metal-Matrix Composite Parts With Metal Inserts

NASA Technical Reports Server (NTRS)

Majkowski, T.; Kashalikar, U.

1995-01-01

Developmental fabrication process produces metal-matrix composite (MMC) parts with integral metal inserts. With inserts, MMC parts readily joined to similar parts by use of brazing, welding, or mechanical fasteners. Process conceived to make strong, lightweight components of structures erected in outer space. Also useful on Earth, in such automotive parts as rocker arms, cylinder liners, and pistons. Potential industrial applications include parts subjected to high stresses at high temperatures, as in power-generation, mining, and oil-drilling equipment.

AMP-activated protein kinase is involved in the activation of the Fanconi anemia/BRCA pathway in response to DNA interstrand crosslinks.

PubMed

Chun, Min Jeong; Kim, Sunshin; Hwang, Soo Kyung; Kim, Bong Sub; Kim, Hyoun Geun; Choi, Hae In; Kim, Jong Heon; Goh, Sung Ho; Lee, Chang-Hun

2016-08-16

Fanconi anemia complementation group (FANC) proteins constitute the Fanconi Anemia (FA)/BRCA pathway that is activated in response to DNA interstrand crosslinks (ICLs). We previously performed yeast two-hybrid screening to identify novel FANC-interacting proteins and discovered that the alpha subunit of AMP-activated protein kinase (AMPKα1) was a candidate binding partner of the FANCG protein, which is a component of the FA nuclear core complex. We confirmed the interaction between AMPKα and both FANCG using co-immunoprecipitation experiments. Additionally, we showed that AMPKα interacted with FANCA, another component of the FA nuclear core complex. AMPKα knockdown in U2OS cells decreased FANCD2 monoubiquitination and nuclear foci formation upon mitomycin C-induced ICLs. Furthermore, AMPKα knockdown enhanced cellular sensitivity to MMC. MMC treatment resulted in an increase in AMPKα phosphorylation/activation, indicating AMPK is involved in the cellular response to ICLs. FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway. Our data suggest AMPK is involved in the activation of the FA/BRCA pathway.

Modulated Modularity Clustering as an Exploratory Tool for Functional Genomic Inference

PubMed Central

Stone, Eric A.; Ayroles, Julien F.

2009-01-01

In recent years, the advent of high-throughput assays, coupled with their diminishing cost, has facilitated a systems approach to biology. As a consequence, massive amounts of data are currently being generated, requiring efficient methodology aimed at the reduction of scale. Whole-genome transcriptional profiling is a standard component of systems-level analyses, and to reduce scale and improve inference clustering genes is common. Since clustering is often the first step toward generating hypotheses, cluster quality is critical. Conversely, because the validation of cluster-driven hypotheses is indirect, it is critical that quality clusters not be obtained by subjective means. In this paper, we present a new objective-based clustering method and demonstrate that it yields high-quality results. Our method, modulated modularity clustering (MMC), seeks community structure in graphical data. MMC modulates the connection strengths of edges in a weighted graph to maximize an objective function (called modularity) that quantifies community structure. The result of this maximization is a clustering through which tightly-connected groups of vertices emerge. Our application is to systems genetics, and we quantitatively compare MMC both to the hierarchical clustering method most commonly employed and to three popular spectral clustering approaches. We further validate MMC through analyses of human and Drosophila melanogaster expression data, demonstrating that the clusters we obtain are biologically meaningful. We show MMC to be effective and suitable to applications of large scale. In light of these features, we advocate MMC as a standard tool for exploration and hypothesis generation. PMID:19424432

The Adult Training and Education Survey (ATES) Pilot Study. Technical Report. NCES 2013-190

ERIC Educational Resources Information Center

Bielick, Stacey; Cronen, Stephanie; Stone, Celeste; Montaquila, Jill M.; Roth, Shelley Brock

2013-01-01

Education and training beyond high school are important for securing opportunities for high-wage jobs in the United States. Academic degrees awarded by institutions of higher education represent a key component of the post-high-school credentials available to the American labor force. Other credentials, such as industry-recognized certifications,…

Spina Bifida

PubMed Central

Copp, Andrew J.; Adzick, N. Scott; Chitty, Lyn S.; Fletcher, Jack M.; Holmbeck, Grayson N.; Shaw, Gary M.

2016-01-01

Spina bifida is a birth defect in which the vertebral column is open (bifid), often with spinal cord involvement. Clinically most significant is myelomeningocele (MMC; open spina bifida) in which the spinal neural tube fails to close during embryonic development. The exposed neural tissue degenerates in utero, resulting in neurological deficit that varies with level of the lesion. Occurring in around 1 per 1000 births worldwide, MMC is one of the commonest congenital malformations, yet its causation is largely unknown. The genetic component of MMC is estimated at 60-70% but few genes have yet been identified, despite much information from mouse models. Non-genetic risk factors include reduced folate intake, maternal anticonvulsant therapy, diabetes mellitus and obesity. Primary prevention by peri-conceptional folic acid has been demonstrated in clinical trials, leading to food fortification programmes in many countries. Prenatal diagnosis is by ultrasound enabling termination of pregnancy. Individuals who survive to birth have their lesions closed surgically, with subsequent management of associated defects, including the Chiari II malformation, hydrocephalus, and urological and orthopaedic sequelae. Fetal surgical repair of MMC has been associated with improved early neurological outcome compared with postnatal operation. MMC affects quality of life during childhood, adolescence, and into adulthood, posing a challenge for individuals, families and society as a whole. PMID:27189655

Research of facial feature extraction based on MMC

NASA Astrophysics Data System (ADS)

Xue, Donglin; Zhao, Jiufen; Tang, Qinhong; Shi, Shaokun

2017-07-01

Based on the maximum margin criterion (MMC), a new algorithm of statistically uncorrelated optimal discriminant vectors and a new algorithm of orthogonal optimal discriminant vectors for feature extraction were proposed. The purpose of the maximum margin criterion is to maximize the inter-class scatter while simultaneously minimizing the intra-class scatter after the projection. Compared with original MMC method and principal component analysis (PCA) method, the proposed methods are better in terms of reducing or eliminating the statistically correlation between features and improving recognition rate. The experiment results on Olivetti Research Laboratory (ORL) face database shows that the new feature extraction method of statistically uncorrelated maximum margin criterion (SUMMC) are better in terms of recognition rate and stability. Besides, the relations between maximum margin criterion and Fisher criterion for feature extraction were revealed.

ANN-PSO Integrated Optimization Methodology for Intelligent Control of MMC Machining

NASA Astrophysics Data System (ADS)

Chandrasekaran, Muthumari; Tamang, Santosh

2017-08-01

Metal Matrix Composites (MMC) show improved properties in comparison with non-reinforced alloys and have found increased application in automotive and aerospace industries. The selection of optimum machining parameters to produce components of desired surface roughness is of great concern considering the quality and economy of manufacturing process. In this study, a surface roughness prediction model for turning Al-SiCp MMC is developed using Artificial Neural Network (ANN). Three turning parameters viz., spindle speed ( N), feed rate ( f) and depth of cut ( d) were considered as input neurons and surface roughness was an output neuron. ANN architecture having 3 -5 -1 is found to be optimum and the model predicts with an average percentage error of 7.72 %. Particle Swarm Optimization (PSO) technique is used for optimizing parameters to minimize machining time. The innovative aspect of this work is the development of an integrated ANN-PSO optimization method for intelligent control of MMC machining process applicable to manufacturing industries. The robustness of the method shows its superiority for obtaining optimum cutting parameters satisfying desired surface roughness. The method has better convergent capability with minimum number of iterations.

AMP-activated protein kinase is involved in the activation of the Fanconi anemia/BRCA pathway in response to DNA interstrand crosslinks

PubMed Central

Hwang, Soo Kyung; Kim, Bong Sub; Kim, Hyoun Geun; Choi, Hae In; Kim, Jong Heon; Goh, Sung Ho; Lee, Chang-Hun

2016-01-01

Fanconi anemia complementation group (FANC) proteins constitute the Fanconi Anemia (FA)/BRCA pathway that is activated in response to DNA interstrand crosslinks (ICLs). We previously performed yeast two-hybrid screening to identify novel FANC-interacting proteins and discovered that the alpha subunit of AMP-activated protein kinase (AMPKα1) was a candidate binding partner of the FANCG protein, which is a component of the FA nuclear core complex. We confirmed the interaction between AMPKα and both FANCG using co-immunoprecipitation experiments. Additionally, we showed that AMPKα interacted with FANCA, another component of the FA nuclear core complex. AMPKα knockdown in U2OS cells decreased FANCD2 monoubiquitination and nuclear foci formation upon mitomycin C-induced ICLs. Furthermore, AMPKα knockdown enhanced cellular sensitivity to MMC. MMC treatment resulted in an increase in AMPKα phosphorylation/activation, indicating AMPK is involved in the cellular response to ICLs. FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway. Our data suggest AMPK is involved in the activation of the FA/BRCA pathway. PMID:27449087

Keystroke Dynamics-Based Credential Hardening Systems

NASA Astrophysics Data System (ADS)

Bartlow, Nick; Cukic, Bojan

abstract Keystroke dynamics are becoming a well-known method for strengthening username- and password-based credential sets. The familiarity and ease of use of these traditional authentication schemes combined with the increased trustworthiness associated with biometrics makes them prime candidates for application in many web-based scenarios. Our keystroke dynamics system uses Breiman’s random forests algorithm to classify keystroke input sequences as genuine or imposter. The system is capable of operating at various points on a traditional ROC curve depending on application-specific security needs. As a username/password authentication scheme, our approach decreases the system penetration rate associated with compromised passwords up to 99.15%. Beyond presenting results demonstrating the credential hardening effect of our scheme, we look into the notion that a user’s familiarity to components of a credential set can non-trivially impact error rates.

Metal Matrix Composites for Rocket Engine Applications

NASA Technical Reports Server (NTRS)

McDonald, Kathleen R.; Wooten, John R.

2000-01-01

This document is from a presentation about the applications of Metal Matrix Composites (MMC) in rocket engines. Both NASA and the Air Force have goals which would reduce the costs and the weight of launching spacecraft. Charts show the engine weight distribution for both reuseable and expendable engine components. The presentation reviews the operating requirements for several components of the rocket engines. The next slide reviews the potential benefits of MMCs in general and in use as materials for Advanced Pressure Casting. The next slide reviews the drawbacks of MMCs. The reusable turbopump housing is selected to review for potential MMC application. The presentation reviews solutions for reusable turbopump materials, pointing out some of the issues. It also reviews the development of some of the materials.

Curcumin enhances the mitomycin C-induced cytotoxicity via downregulation of MKK1/2-ERK1/2-mediated Rad51 expression in non-small cell lung cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ko, Jen-Chung; Department of Nursing, Yuanpei University, HsinChu, Taiwan; Graduate Institute of Technology Law, National Chiao Tung University, Taiwan

2011-09-15

Curcumin (diferuloylmethane), a major active component of turmeric (Curcuma longa), has been reported to suppress the proliferation of a wide variety of tumor cells. Rad51 is a key protein in the homologous recombination (HR) pathway of DNA double-strand break repair, and HR represents a novel target for cancer therapy. A high expression of Rad51 has been reported in chemo- or radio-resistant carcinomas. Therefore, in the current study, we will examine whether curcumin could enhance the effects of mitomycin C (MMC), a DNA interstrand cross-linking agent, to induce cytotoxicity by decreasing Rad51 expression. Exposure of two human non-small lung cancer (NSCLC)more » cell lines (A549 and H1975) to curcumin could suppress MMC-induced MKK1/2-ERK1/2 signal activation and Rad51 protein expression. Enhancement of ERK1/2 activation by constitutively active MKK1/2 (MKK1/2-CA) increased Rad51 protein levels in curcumin and MMC co-treated human lung cells. Moreover, the synergistic cytotoxic effect induced by curcumin combined with MMC was decreased by MKK1-CA-mediated enhancement of ERK1/2 activation by a significant degree. In contrast, MKK1/2 inhibitor, U0126 was shown to augment the cytotoxicity of curcumin and MMC through downregulation of ERK1/2 activation and Rad51 expression. Depletion of endogenous Rad51 expression by siRad51 RNA transfection significantly enhanced MMC and/or curcumin induced cell death and cell growth inhibition. In contrast, an overexpression of Rad51 protected lung cancer cells from synergistic cytotoxic effects induced by curcumin and MMC. We concluded that Rad51 inhibition may be an additional action mechanism for enhancing the chemosensitization of MMC by curcumin in NSCLC. - Highlights: > Curcumin downregulates MKK-ERK-mediated Rad51 expression. > Curcumin enhances mitomycin C-induced cytotoxicity. > Rad51 protects cells from cytotoxic effects induced by curcumin and mitomycin C. > Rad51 inhibition enhances the chemosensitization of mitomycin C by curcumin.« less

Macromolecular Crowding Amplifies Adipogenesis of Human Bone Marrow-Derived Mesenchymal Stem Cells by Enhancing the Pro-Adipogenic Microenvironment

PubMed Central

Ang, Xiu Min; Lee, Michelle H.C.; Blocki, Anna; Chen, Clarice; Ong, L.L. Sharon; Asada, H. Harry; Sheppard, Allan

2014-01-01

The microenvironment plays a vital role in both the maintenance of stem cells in their undifferentiated state (niche) and their differentiation after homing into new locations outside this niche. Contrary to conventional in-vitro culture practices, the in-vivo stem cell microenvironment is physiologically crowded. We demonstrate here that re-introducing macromolecular crowding (MMC) at biologically relevant fractional volume occupancy during chemically induced adipogenesis substantially enhances the adipogenic differentiation response of human bone marrow-derived mesenchymal stem cells (MSCs). Both early and late adipogenic markers were significantly up-regulated and cells accumulated 25–40% more lipid content under MMC relative to standard induction cocktails. MMC significantly enhanced deposition of extracellular matrix (ECM), notably collagen IV and perlecan, a heparan sulfate proteoglycan. As a novel observation, MMC also increased the presence of matrix metalloproteinase −2 in the deposited ECM, which was concomitant with geometrical ECM remodeling typical of adipogenesis. This suggested a microenvironment that was richer in both matrix components and associated ligands and was conducive to adipocyte maturation. This assumption was confirmed by seeding undifferentiated MSCs on decellularized ECM deposited by adipogenically differentiated MSCs, Adipo-ECM. On Adipo-ECM generated under crowding, MSCs differentiated much faster under a classical differentiation protocol. This was evidenced throughout the induction time course, by a significant up-regulation of both early and late adipogenic markers and a 60% higher lipid content on MMC-generated Adipo-ECM in comparison to standard induction on tissue culture plastic. This suggests that MMC helps build and endow the nascent microenvironment with adipogenic cues. Therefore, MMC initiates a positive feedback loop between cells and their microenvironment as soon as progenitor cells are empowered to build and shape it, and, in turn, are informed by it to respond by attaining a stable differentiated phenotype if so induced. This work sheds new light on the utility of MMC to tune the microenvironment to augment the generation of adipose tissue from differentiating human MSCs. PMID:24147829

Changing interdigestive migrating motor complex in rats under acute liver injury.

PubMed

Liu, Mei; Zheng, Su-Jun; Xu, Weihong; Zhang, Jianying; Chen, Yu; Duan, Zhongping

2014-01-01

Gastrointestinal motility disorder is a major clinical manifestation of acute liver injury, and interdigestive migrating motor complex (MMC) is an important indicator. We investigated the changes and characteristics of MMC in rats with acute liver injury. Acute liver injury was created by d-galactosamine, and we recorded the interdigestive MMC using a multichannel physiological recorder and compared the indexes of interdigestive MMC. Compared with normal controls, antral MMC Phase I duration was significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The duodenal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The jejunal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury compared with normal controls. Compared with the normal controls, rats with acute liver injury had a significantly prolonged interdigestive MMC cycle, related mainly to longer MMC Phases I and IV, shortened MMC Phase III, and MMC Phase II characterized by increased migrating clustered contractions, which were probably major contributors to the gastrointestinal motility disorders.

Improving 2D and 3D Skin In Vitro Models Using Macromolecular Crowding.

PubMed

Benny, Paula; Badowski, Cedric; Lane, E Birgitte; Raghunath, Michael

2016-08-22

The glycoprotein family of collagens represents the main structural proteins in the human body, and are key components of biomaterials used in modern tissue engineering. A technical bottleneck is the deposition of collagen in vitro, as it is notoriously slow, resulting in sub-optimal formation of connective tissue and subsequent tissue cohesion, particularly in skin models. Here, we describe a method which involves the addition of differentially-sized sucrose co-polymers to skin cultures to generate macromolecular crowding (MMC), which results in a dramatic enhancement of collagen deposition. Particularly, dermal fibroblasts deposited a significant amount of collagen I/IV/VII and fibronectin under MMC in comparison to controls. The protocol also describes a method to decellularize crowded cell layers, exposing significant amounts of extracellular matrix (ECM) which were retained on the culture surface as evidenced by immunocytochemistry. Total matrix mass and distribution pattern was studied using interference reflection microscopy. Interestingly, fibroblasts, keratinocytes and co-cultures produced cell-derived matrices (CDM) of varying composition and morphology. CDM could be used as "bio-scaffolds" for secondary cell seeding, where the current use of coatings or scaffolds, typically from xenogenic animal sources, can be avoided, thus moving towards more clinically relevant applications. In addition, this protocol describes the application of MMC during the submerged phase of a 3D-organotypic skin co-culture model which was sufficient to enhance ECM deposition in the dermo-epidermal junction (DEJ), in particular, collagen VII, the major component of anchoring fibrils. Electron microscopy confirmed the presence of anchoring fibrils in cultures developed with MMC, as compared to controls. This is significant as anchoring fibrils tether the dermis to the epidermis, hence, having a pre-formed mature DEJ may benefit skin graft recipients in terms of graft stability and overall wound healing. Furthermore, culture time was condensed from 5 weeks to 3 weeks to obtain a mature construct, when using MMC, reducing costs.

Single-step assembly of polymer-lipid hybrid nanoparticles for mitomycin C delivery

PubMed Central

2014-01-01

Mitomycin C is one of the most effective chemotherapeutic agents for a wide spectrum of cancers, but its clinical use is still hindered by the mitomycin C (MMC) delivery systems. In this study, the MMC-loaded polymer-lipid hybrid nanoparticles (NPs) were prepared by a single-step assembly (ACS Nano 2012, 6:4955 to 4965) of MMC-soybean phosphatidyhlcholine (SPC) complex (Mol. Pharmaceutics 2013, 10:90 to 101) and biodegradable polylactic acid (PLA) polymers for intravenous MMC delivery. The advantage of the MMC-SPC complex on the polymer-lipid hybrid NPs was that MMC-SPC was used as a structural element to offer the integrity of the hybrid NPs, served as a drug preparation to increase the effectiveness and safety and control the release of MMC, and acted as an emulsifier to facilitate and stabilize the formation. Compared to the PLA NPs/MMC, the PLA NPs/MMC-SPC showed a significant accumulation of MMC in the nuclei as the action site of MMC. The PLA NPs/MMC-SPC also exhibited a significantly higher anticancer effect compared to the PLA NPs/MMC or free MMC injection in vitro and in vivo. These results suggested that the MMC-loaded polymer-lipid hybrid NPs might be useful and efficient drug delivery systems for widening the therapeutic window of MMC and bringing the clinical use of MMC one step closer to reality. PMID:25324707

Effects of Control Mode and R-Ratio on the Fatigue Behavior of a Metal Matrix Composite

NASA Technical Reports Server (NTRS)

2005-01-01

Composite Because of their high specific stiffness and strength at elevated temperatures, continuously reinforced metal matrix composites (MMC's) are under consideration for a future generation of aeropropulsion systems. Since components in aeropropulsion systems experience substantial cyclic thermal and mechanical loads, the fatigue behavior of MMC's is of great interest. Almost without exception, previous investigations of the fatigue behavior of MMC's have been conducted in a tension-tension, load-controlled mode. This has been due to the fact that available material is typically less than 2.5-mm thick and, therefore, unable to withstand high compressive loads without buckling. Since one possible use of MMC's is in aircraft skins, this type of testing mode may be appropriate. However, unlike aircraft skins, most engine components are thick. In addition, the transient thermal gradients experienced in an aircraft engine will impose tension-compression loading on engine components, requiring designers to understand how the MMC will behave under fully reversed loading conditions. The increased thickness of the MMC may also affect the fatigue life. Traditionally, low-cycle fatigue (LCF) tests on MMC's have been performed in load control. For monolithic alloys, low-cycle fatigue tests are more typically performed in strain control. Two reasons justify this choice: (1) the critical volume from which cracks initiate and grow is generally small and elastically constrained by the larger surrounding volume of material, and (2) load-controlled, low-cycle fatigue tests of monolithics invariably lead to unconstrained ratcheting and localized necking--an undesired material response because the failure mechanism is far more severe than, and unrelated to, the fatigue mechanism being studied. It is unknown if this is the proper approach to composite testing. However, there is a lack of strain-controlled data on which to base any decisions. Consequently, this study addresses the isothermal, LCF behavior of a [0]_32 MMC tested under strain- and load-controlled conditions for both zero-tension and tension-compression loading conditions. These tests were run at 427 C on thick specimens of SiC-reinforced Ti-15-3. For the fully-reversed tests, no difference was observed in the lives between the load- and strain-controlled tests. However, for the zero-tension tests, the strain-controlled tests had longer lives by a factor of 3 in comparison to the load-controlled tests. This was due to the fact that under strain-control the specimens cyclically softened, reducing the cracking potential. In contrast, the load-controlled tests ratcheted toward larger tensile strains leading to an eventual overload of the fibers. Fatigue tests revealed that specimens tested under fully-reversed conditions had lives approximately an order of magnitude longer than for those specimens tested under zero tension. When examined on a strain-range basis, the fully reversed specimens had similar, but still shorter lives than those of the unreinforced matrix material. However, the composite had a strain limitation at short lives because of the limited strain capacity of the brittle ceramic fiber. The composite also suffered at very high lives because of the lack of an apparent fatigue limit in comparison to the unreinforced matrix. The value of adding fibers to the matrix is apparent when the fatigue lives are plotted as a function of stress range. Here, the composite is far superior to the unreinforced matrix because of the additional load-carrying capacity of the fibers.

Acceptability, Knowledge, Beliefs, and Partners as Determinants of Zambian Men's Readiness to Undergo Medical Male Circumcision

PubMed Central

Jones, Deborah; Cook, Ryan; Arheart, Kris; Redding, Colleen A.; Zulu, Robert; Castro, Jose; Weiss, Stephen M.

2013-01-01

There is limited information about the influence of partners on medical male circumcision (MMC) uptake. This study aimed to evaluate attitudes, knowledge, and preferences about MMC among men and their partners, and their relative impact on male readiness to undergo the MMC procedure. Male participants (n = 354) and their partners (n = 273) were recruited from community health centers in Lusaka, Zambia. Men reported their readiness to undergo MMC, and both men and women were assessed regarding their attitudes and knowledge regarding MMC. Men who had discussed MMC with their partners, those who endorsed MMC for HIV risk reduction, and those viewing MMC as culturally acceptable reported increased readiness to undergo MMC. Additionally, endorsement of MMC by female partners was associated with increased men’s readiness. Results support promotion of cultural acceptability of MMC, and efforts to increase MMC uptake may benefit from incorporating partners in the decision making process. PMID:23757123

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shao Wei; Zhao Shan; Liu Zhaofei

Anti-EGFR monoclonal antibodies LA22 and Erbitux bind to different epitopes of EGFR. The chemimmunoconjugates of MMC with LA22 or Erbitux were prepared, and in vitro cytotoxicity assays with A549 cells showed that LA22-MMC was much more potent than Erbitux or Erbitux-MMC. Viabilities of A549 cells treated with LA22-MMC, Erbitux or Erbitux-MMC were 35%, 94%, and 81%, respectively. Immunoscintigraphy of xenografts of human A431 and A549 cells in nude mice both showed that {sup 125}I-labeled-LA22-MMC enriched in tumor sites prominently. Most importantly, in vivo assays showed LA22-MMC was significantly more effective than free drug MMC in the treatment of subcutaneous xenograftsmore » of human A431 cells in nude mice (83% inhibition for LA22-MMC and 30% for MMC). We concluded that LA22-MMC could be a very potent drug for treatment of solid tumors.« less

Patient credentialing as a population health management strategy: a diabetes case study.

PubMed

Watson, Lindsay L; Bluml, Benjamin M; Skoufalos, Alexandria

2015-06-01

When given the opportunity to become actively involved in the decision-making process, patients can positively impact their health outcomes. Understanding how to empower patients to become informed consumers of health care services is an important strategy for addressing disparities and variability in care. Patient credentialing identifies people who have a certain diagnosis and have achieved certain levels of competency in understanding and managing their disease. Patient credentialing was developed to meet 3 core purposes: (1) enhance patient engagement by increasing personal accountability for health outcomes, (2) create a mass customization strategy for providers to deliver high-quality, patient-centered collaborative care, and (3) provide payers with a foundation for properly aligning health benefit incentives. The Patient Self-Management Credential for Diabetes, a first-of-its-kind, psychometrically validated tool, has been deployed within 3 practice-based research initiatives as a component of innovative diabetes care. Results from these projects show improved clinical outcomes, reduced health care costs, and a relationship between credential achievement levels and clinical markers of diabetes. Implementing patient credentialing as part of collaborative care delivered within various settings across the health care system may be an effective way to reduce disparities, improve access to care and appropriate treatments, incentivize patient engagement in managing their health, and expend time and resources in a customized way to meet individual needs.

MMC controlled-release membranes attenuate epidural scar formation in rat models after laminectomy.

PubMed

Xie, Hao; Wang, Binbin; Shen, Xun; Qin, Jian; Jiang, Longhai; Yu, Chen; Geng, Dawei; Yuan, Tangbo; Wu, Tao; Cao, Xiaojian; Liu, Jun

2017-06-01

Epidural scar formation after laminectomy impede surgical outcomes of decompression. Mitomycin C (MMC) has been demonstrated to have significant inhibitory effects on epidural scar. This study was undertaken to develop an effective MMC controlled‑release membrane and to investigate its effects on epidural scar in rat models of laminectomy. A total of 72 rats that underwent laminectomy were divided into three groups. Among them, 24 were treated with mitomycin C‑polylactic acid (MMC-PLA) controlled‑release membrane, 24 with mitomycin C-polyethylene glycol (MMC-PEG) controlled-release membrane, and no treatment was performed for the remaining 24 rats (control group). In the following 4 weeks, magnetic resonance image (MRI), macroscopic observation, histology and hydroxyproline (Hyp) concentration analysis were performed to explore the effects of these three therapies on epidural scar. MRI revealed a significant reduction of epidural fibrosis in MMC-PLA and MMC-PEG treatment groups, compared with the control group. Histological results also showed that collagen deposition was significantly reduced after being treated with MMC-PLA or MMC-PEG membranes. Likewise, Hyp concentrations of the epidural scar tissue in MMC-PLA and MMC-PEG groups were markedly lower than those in the control group. However, regarding the effects on reducing epidural scar, no significant difference was found between the MMC-PLA and MMC-PEG groups. In conclusion, MMC-PLA and MMC-PEG membranes are safe and effective in reducing fibrosis. Thus, MMC-controlled-release membranes promises to be a potential therapeutic in preventing epidural scar formation after laminectomy.

Potential of Progressive Construction Systems in Slovakia

NASA Astrophysics Data System (ADS)

Kozlovska, Maria; Spisakova, Marcela; Mackova, Daniela

2017-10-01

Construction industry is a sector with rapid development. Progressive technologies of construction and new construction materials also called modern methods of construction (MMC) are developed constantly. MMC represent the adoption of construction industrialisation and the use of prefabrication of components in building construction. One of these modern methods is also system Varianthaus, which is based on, insulated concrete forms principle and provides complete production plant for wall, ceiling and roof elements for a high thermal insulation house construction. Another progressive construction system is EcoB, which represents an insulated precast concrete panel based on combination of two layers, insulation and concrete, produced in a factory as a whole. Both modern methods of construction are not yet known and wide-spread in the Slovak construction market. The aim of this paper is focused on demonstration of MMC using potential in Slovakia. MMC potential is proved based on comparison of the selected parameters of construction process - construction costs and construction time. The subject of this study is family house modelled in three material variants - masonry construction (as a representative of traditional methods of construction), Varianthaus and EcoB (as the representatives of modern methods of construction). The results of this study provide the useful information in decision-making process for potential investors of construction.

Inhibitory effects of marine-derived DNA-binding anti-tumour tetrahydroisoquinolines on the Fanconi anaemia pathway.

PubMed

Martínez, Sandra; Pérez, Laura; Galmarini, Carlos M; Aracil, Miguel; Tercero, Juan C; Gago, Federico; Albella, Beatriz; Bueren, Juan A

2013-10-01

We have previously shown that cells with a defective Fanconi anaemia (FA) pathway are hypersensitive to trabectedin, a DNA-binding anti-cancer tetrahydroisoquinoline (DBAT) whose adducts functionally mimic a DNA inter-strand cross link (ICL). Here we expand these observations to new DBATs and investigate whether our findings in primary untransformed cells can be reproduced in human cancer cells. Initially, the sensitivity of transformed and untransformed cells, deficient or not in one component of the FA pathway, to mitomycin C (MMC) and three DBATs, trabectedin, Zalypsis and PM01183, was assessed. Then, the functional interaction of these drugs with the FA pathway was comparatively investigated. While untransformed FA-deficient haematopoietic cells were hypersensitive to both MMC and DBATs, the response of FA-deficient squamous cell carcinoma (SCC) cells to DBATs was similar to that of their respective FA-competent counterparts, even though these FA-deficient SCC cells were hypersensitive to MMC. Furthermore, while MMC always activated the FA pathway, the DBATs inhibited the FA pathway in the cancer cell lines tested and this enhanced their response to MMC. Our data show that although DBATs functionally interact with DNA as do agents that generate classical ICL, these drugs should be considered as FA pathway inhibitors rather than activators. Moreover, this effect was most significant in a variety of cancer cells. These inhibitory effects of DBATs on the FA pathway could be exploited clinically with the aim of 'fanconizing' cancer cells in order to make them more sensitive to other anti-tumour drugs. © 2013 The British Pharmacological Society.

Inhibitory effects of marine-derived DNA-binding anti-tumour tetrahydroisoquinolines on the Fanconi anaemia pathway

PubMed Central

Martínez, Sandra; Pérez, Laura; Galmarini, Carlos M; Aracil, Miguel; Tercero, Juan C; Gago, Federico; Albella, Beatriz; Bueren, Juan A

2013-01-01

BACKGROUND AND PURPOSE We have previously shown that cells with a defective Fanconi anaemia (FA) pathway are hypersensitive to trabectedin, a DNA-binding anti-cancer tetrahydroisoquinoline (DBAT) whose adducts functionally mimic a DNA inter-strand cross link (ICL). Here we expand these observations to new DBATs and investigate whether our findings in primary untransformed cells can be reproduced in human cancer cells. EXPERIMENTAL APPROACH Initially, the sensitivity of transformed and untransformed cells, deficient or not in one component of the FA pathway, to mitomycin C (MMC) and three DBATs, trabectedin, Zalypsis and PM01183, was assessed. Then, the functional interaction of these drugs with the FA pathway was comparatively investigated. KEY RESULTS While untransformed FA-deficient haematopoietic cells were hypersensitive to both MMC and DBATs, the response of FA-deficient squamous cell carcinoma (SCC) cells to DBATs was similar to that of their respective FA-competent counterparts, even though these FA-deficient SCC cells were hypersensitive to MMC. Furthermore, while MMC always activated the FA pathway, the DBATs inhibited the FA pathway in the cancer cell lines tested and this enhanced their response to MMC. CONCLUSIONS AND IMPLICATIONS Our data show that although DBATs functionally interact with DNA as do agents that generate classical ICL, these drugs should be considered as FA pathway inhibitors rather than activators. Moreover, this effect was most significant in a variety of cancer cells. These inhibitory effects of DBATs on the FA pathway could be exploited clinically with the aim of ‘fanconizing’ cancer cells in order to make them more sensitive to other anti-tumour drugs. PMID:23937566

Effect of exposure to mitomycin C on cultured tympanic membrane fibroblasts.

PubMed

Jang, Chul Ho; Song, Chang-Hun; Pak, Sok Cheon

2003-02-01

Recently, attempts have been made to prolong the patency of myringotomy site with topical use of mitomycin C (MMC). It has been shown that MMC inhibits mitosis and proliferation of ocular fibroblasts, however, there are no studies of MMC's effect on tympanic membrane fibroblasts. To investigate the effects of MMC on cultured human tympanic membrane fibroblasts and understand the cellular basis of MMC for maintain myringotomy patency, cultured fibroblasts were exposed to various concentrations of MMC for periods of 5-10 min. Effect of MMC on cultured fibroblasts was assessed by microscopic observation and cell viability test. Dose-, time- dependent relationship of MMC on cultured fibroblasts was revealed. There was a significant difference between the inhibition effects of MMC at concentrations of 0.4 mg/ml and control following 5 and 10 min exposure intervals. Phase-contrast microscopy showed consistency with the antiproliferative effect of MMC at higher concentration. Therefore, it would appear that intraoperative use of MMC could be effective in delaying the healing of the myringotomy site and extending the period of time for myringotomy patency.

Influence of Brain Stem on Axial and Hindlimb Spinal Locomotor Rhythm Generating Circuits of the Neonatal Mouse.

PubMed

Jean-Xavier, Céline; Perreault, Marie-Claude

2018-01-01

The trunk plays a pivotal role in limbed locomotion. Yet, little is known about how the brain stem controls trunk activity during walking. In this study, we assessed the spatiotemporal activity patterns of axial and hindlimb motoneurons (MNs) during drug-induced fictive locomotor-like activity (LLA) in an isolated brain stem-spinal cord preparation of the neonatal mouse. We also evaluated the extent to which these activity patterns are affected by removal of brain stem. Recordings were made in the segments T7, L2, and L5 using calcium imaging from individual axial MNs in the medial motor column (MMC) and hindlimb MNs in lateral motor column (LMC). The MN activities were analyzed during both the rhythmic and the tonic components of LLA, the tonic component being used as a readout of generalized increase in excitability in spinal locomotor networks. The most salient effect of brain stem removal was an increase in locomotor rhythm frequency and a concomitant reduction in burst durations in both MMC and LMC MNs. The lack of effect on the tonic component of LLA indicated specificity of action during the rhythmic component. Cooling-induced silencing of the brain stem reproduced the increase in rhythm frequency and accompanying decrease in burst durations in L2 MMC and LMC, suggesting a dependency on brain stem neuron activity. The work supports the idea that the brain stem locomotor circuits are operational already at birth and further suggests an important role in modulating trunk activity. The brain stem may influence the axial and hindlimb spinal locomotor rhythm generating circuits by extending their range of operation. This may represent a critical step of locomotor development when learning how to walk in different conditions and environments is a major endeavor.

Influence of Brain Stem on Axial and Hindlimb Spinal Locomotor Rhythm Generating Circuits of the Neonatal Mouse

PubMed Central

Jean-Xavier, Céline; Perreault, Marie-Claude

2018-01-01

The trunk plays a pivotal role in limbed locomotion. Yet, little is known about how the brain stem controls trunk activity during walking. In this study, we assessed the spatiotemporal activity patterns of axial and hindlimb motoneurons (MNs) during drug-induced fictive locomotor-like activity (LLA) in an isolated brain stem-spinal cord preparation of the neonatal mouse. We also evaluated the extent to which these activity patterns are affected by removal of brain stem. Recordings were made in the segments T7, L2, and L5 using calcium imaging from individual axial MNs in the medial motor column (MMC) and hindlimb MNs in lateral motor column (LMC). The MN activities were analyzed during both the rhythmic and the tonic components of LLA, the tonic component being used as a readout of generalized increase in excitability in spinal locomotor networks. The most salient effect of brain stem removal was an increase in locomotor rhythm frequency and a concomitant reduction in burst durations in both MMC and LMC MNs. The lack of effect on the tonic component of LLA indicated specificity of action during the rhythmic component. Cooling-induced silencing of the brain stem reproduced the increase in rhythm frequency and accompanying decrease in burst durations in L2 MMC and LMC, suggesting a dependency on brain stem neuron activity. The work supports the idea that the brain stem locomotor circuits are operational already at birth and further suggests an important role in modulating trunk activity. The brain stem may influence the axial and hindlimb spinal locomotor rhythm generating circuits by extending their range of operation. This may represent a critical step of locomotor development when learning how to walk in different conditions and environments is a major endeavor. PMID:29479302

Knowledge of HIV and benefits of male medical circumcision amongst clients in an urban area

PubMed Central

2014-01-01

Abstract Background Male medical circumcision (MMC) has been shown to reduce the risk of HIV transmission in circumcised men by up to 60%. Following recommendations from the World Health Organization, South Africa adopted MMC as a preventative strategy against HIV in 2010 and set up circumcision camps across the country. Concerns have been raised about condom avoidance following MMC because of a mistaken belief about the benefits of MMC. Aim and setting The aim of this study was to describe the profile and knowledge about HIV and circumcision amongst men presenting for MMC in an urban area in KwaZulu-Natal. Methods This was a cross-sectional descriptive study of 394 clients over the age of 18 years who presented to two MMC sites in Durban between November 2012 and March 2013. A validated questionnaire was used to collect data. Results The mean age of clients presenting for MMC was 28 years. Most clients were black, single, unemployed and sexually active. The majority presented for MMC because they believed that MMC would reduce their risk of acquiring HIV infection. Knowledge about HIV transmission was very good and 86.3% of clients were aware that risky sexual behaviour such as condom avoidance could reverse the benefits of MMC. Conclusion The knowledge of HIV and benefits of MMC was very good amongst those presenting for MMC. However as MMC is primarily a preventative strategy, innovative methods to promote MMC prior to first sexual encounter need to be explored. Further research is needed to determine whether the benefits of MMC on the reduction of HIV transmission are sustained in routine practice. PMID:26245426

Effects of Gelatin Hydrogel Loading Mitomycin C on Conjunctival Scarring in a Canine Filtration Surgery Model.

PubMed

Kojima, Shota; Sugiyama, Tetsuya; Takai, Shinji; Jin, Denan; Ueki, Mari; Oku, Hidehiro; Tabata, Yasuhiko; Ikeda, Tsunehiko

2015-04-01

To investigate the effects and toxicities of gelatin hydrogel (GH) loading mitomycin C (MMC) on IOP and conjunctival scarring in a canine model of glaucoma surgery in comparison with conventional MMC application. Glaucoma surgery models were made in six beagles. An MMC-loaded GH was implanted under the conjunctiva of one eye (GH-MMC group) and 0.04% MMC-soaked sponges were placed under the conjunctiva of the other eye (MMC group) for 5 minutes. Intraocular pressures and bleb features were then assessed for 4 weeks postoperative, followed by histological evaluation. The ratio of conjunctival area to scleral area, the densities of collagen and the numbers of fibroblasts, vessels, and proliferative cell nuclear antigen (PCNA)-positive cells were then quantified. In both groups, IOP reduction and bleb formation were maintained in a similar manner for 4 weeks postoperative. No significant difference in the ratio of conjunctival area to scleral area was found between the two groups. Collagen density and the numbers of fibroblasts and vessels were significantly lower in the MMC-treated group than in the GH-MMC-treated group. No significant difference in PCNA-positive cells was found between the two groups. Implantation of MMC-loaded GH ameliorated toxicity to conjunctiva compared with the 5-minute placement of MMC, whereas its effect on IOP reduction and bleb formation was similar. These results suggest that using GH for the application of MMC is a safer method than the conventional application of MMC in glaucoma filtration surgery.

Two-Port Fetoscopic Repair of Myelomeningocele in Fetal Lambs.

PubMed

Guilbaud, Lucie; Garabedian, Charles; Roux, Nathalie; Friszer, Stéphanie; Dhombres, Ferdinand; Vialle, Raphaël; Shah, Zoobia; Bessières, Bettina; Di Rocco, Federico; Zerah, Michel; Jouannic, Jean-Marie

2018-02-21

The aim of this study was to assess the feasibility and the effectiveness of a fetoscopic myelomeningocele (MMC) repair with a running single suture using a 2-port access in the sheep model. Eighteen fetuses underwent surgical creation of a MMC defect at day 75. Fetuses were then randomized into 3 groups. Four fetuses remained untreated (control group). In the other 14 fetuses, a prenatal repair was performed at day 90: 7 fetuses had an open repair (oMMC), and 7 fetuses had a fetoscopic repair (fMMC) using a single-layer running suture through a 2-port access. Lambs were sacrificed at term, and histological examinations were performed. Hindbrain herniation was observed in all live lambs in the control group. A complete closure of the defect was achieved in all the lambs of the fMMC group. A complete healing of the defect and no hindbrain herniation were observed in all live lambs of the oMMC and fMMC groups. The durations of surgeries were not statistically different between the oMMC and the fMMC groups (60 vs. 53 min, p = 0.40), as was the risk of fetal loss (fMMC: 1/7, oMMC: 3/7, p = 0.56). Fetoscopic repair of MMC can be performed using a single-layer running suture through a 2-port access and may be promising to reduce the risk of premature rupture of membranes. © 2018 S. Karger AG, Basel.

Recommended oral sodium bicarbonate administration for urine alkalinization did not affect the concentration of mitomycin-C in non-muscle invasive bladder cancer patients.

PubMed

Seo, Ho Kyung; Kim, Sung Han; Ahn, Kyung-Ohk; Lee, Sang-Jin; Park, Weon Seo; Kim, Sohee; Hwang, Sang-Hyun; Lee, Do Hoon; Joung, Jae Young; Chung, Jinsoo; Joo, Jungnam; Jeong, Kyung-Chae

2017-11-10

Sodium bicarbonate has been reported to maximize the efficacy of intravesical instillation of mitomycin-C (IVI-MMC) therapy by urine alkalinization in non-muscle-invasive bladder cancer (NMIBC). This study aimed to analyze the changes in MMC concentration according to urinary pH and evaluate the efficacy of sodium bicarbonate to maintain the concentration of active form of MMC during IVI-MMC. We prospectively enrolled 26 patients with NMIBC after transurethral resection of bladder tumor. Patients with very high-risk and low-risk NMIBC were excluded. Urinary creatinine, volume, pH, and concentrations of MMC and its degraded form were measured immediately before and after IVI-MMC. The patients were administered 1.5 g of oral sodium bicarbonate during the preceding evening, in the morning, and immediately before the fourth cycle of the six-cycle IVI-MMC. The correlation between MMC concentration and urinary pH changes was explored with or without oral bicarbonate therapy. Recurrence without progression to muscle-invasive disease was noted in 4 of 26 patients in a 23.7-month follow-up. The mean urinary pH before and after the therapy increased from 6.03 to 6.50, and 6.46 to 7.24, without or with oral SB therapy, respectively. Despite this increase, the concentration of active form of MMC did not change significantly. No correlation was found between urinary pH and MMC concentration. Urine alkalinization by SB administration did not maintain the high concentration of urinary MMC. Urine alkalinization by sodium bicarbonate administration for IVI-MMC did not maintain the high concentration of active urinary MMC in NMIBC.

The Roles of Alpha-Momorcharin and Jasmonic Acid in Modulating the Response of Momordica charantia to Cucumber Mosaic Virus.

PubMed

Yang, Ting; Meng, Yao; Chen, Li-Juan; Lin, Hong-Hui; Xi, De-Hui

2016-01-01

Alpha-momorcharin (α-MMC) is a type-I ribosome inactivating protein with a molecular weight of 29 kDa that is found in Momordica charantia , and has been shown to be effective against a broad range of human viruses as well as having anti-tumor activities. However, the role of endogenous α-MMC under viral infection and the mechanism of the anti-viral activities of α-MMC in plants are still unknown. To study the effect of α-MMC on plant viral defense and how α-MMC increases plant resistance to virus, the M. charantia - cucumber mosaic virus (CMV) interaction system was investigated. The results showed that the α-MMC level was positively correlated with the resistance of M. charantia to CMV. α-MMC treatment could alleviate photosystem damage and enhance the ratio of glutathione/glutathione disulfide in M. charantia under CMV infection. The relationship of α-MMC and defense related phytohormones, and their roles in plant defense were further investigated. α-MMC treatment led to a significant increase of jasmonic acid (JA) and vice versa, while there was no obvious relevance between salicylic acid and α-MMC. In addition, reactive oxygen species (ROS) were induced in α-MMC-pretreated plants, in a similar way to the ROS burst in JA-pretreated plants. The production of ROS in both ibuprofen (JA inhibitor) and (α-MMC+ibuprofen)-pretreated plants was reduced markedly, leading to a greater susceptibility of M. charantia to CMV. Our results indicate that the anti-viral activities of α-MMC in M. charantia may be accomplished through the JA related signaling pathway.

The Roles of Alpha-Momorcharin and Jasmonic Acid in Modulating the Response of Momordica charantia to Cucumber Mosaic Virus

PubMed Central

Yang, Ting; Meng, Yao; Chen, Li-Juan; Lin, Hong-Hui; Xi, De-Hui

2016-01-01

Alpha-momorcharin (α-MMC) is a type-I ribosome inactivating protein with a molecular weight of 29 kDa that is found in Momordica charantia, and has been shown to be effective against a broad range of human viruses as well as having anti-tumor activities. However, the role of endogenous α-MMC under viral infection and the mechanism of the anti-viral activities of α-MMC in plants are still unknown. To study the effect of α-MMC on plant viral defense and how α-MMC increases plant resistance to virus, the M. charantia–cucumber mosaic virus (CMV) interaction system was investigated. The results showed that the α-MMC level was positively correlated with the resistance of M. charantia to CMV. α-MMC treatment could alleviate photosystem damage and enhance the ratio of glutathione/glutathione disulfide in M. charantia under CMV infection. The relationship of α-MMC and defense related phytohormones, and their roles in plant defense were further investigated. α-MMC treatment led to a significant increase of jasmonic acid (JA) and vice versa, while there was no obvious relevance between salicylic acid and α-MMC. In addition, reactive oxygen species (ROS) were induced in α-MMC-pretreated plants, in a similar way to the ROS burst in JA-pretreated plants. The production of ROS in both ibuprofen (JA inhibitor) and (α-MMC+ibuprofen)-pretreated plants was reduced markedly, leading to a greater susceptibility of M. charantia to CMV. Our results indicate that the anti-viral activities of α-MMC in M. charantia may be accomplished through the JA related signaling pathway. PMID:27881976

New Method to Prepare Mitomycin C Loaded PLA-Nanoparticles with High Drug Entrapment Efficiency

NASA Astrophysics Data System (ADS)

Hou, Zhenqing; Wei, Heng; Wang, Qian; Sun, Qian; Zhou, Chunxiao; Zhan, Chuanming; Tang, Xiaolong; Zhang, Qiqing

2009-07-01

The classical utilized double emulsion solvent diffusion technique for encapsulating water soluble Mitomycin C (MMC) in PLA nanoparticles suffers from low encapsulation efficiency because of the drug rapid partitioning to the external aqueous phase. In this paper, MMC loaded PLA nanoparticles were prepared by a new single emulsion solvent evaporation method, in which soybean phosphatidylcholine (SPC) was employed to improve the liposolubility of MMC by formation of MMC-SPC complex. Four main influential factors based on the results of a single-factor test, namely, PLA molecular weight, ratio of PLA to SPC (wt/wt) and MMC to SPC (wt/wt), volume ratio of oil phase to water phase, were evaluated using an orthogonal design with respect to drug entrapment efficiency. The drug release study was performed in pH 7.2 PBS at 37 °C with drug analysis using UV/vis spectrometer at 365 nm. MMC-PLA particles prepared by classical method were used as comparison. The formulated MMC-SPC-PLA nanoparticles under optimized condition are found to be relatively uniform in size (594 nm) with up to 94.8% of drug entrapment efficiency compared to 6.44 μm of PLA-MMC microparticles with 34.5% of drug entrapment efficiency. The release of MMC shows biphasic with an initial burst effect, followed by a cumulated drug release over 30 days is 50.17% for PLA-MMC-SPC nanoparticles, and 74.1% for PLA-MMC particles. The IR analysis of MMC-SPC complex shows that their high liposolubility may be attributed to some weak physical interaction between MMC and SPC during the formation of the complex. It is concluded that the new method is advantageous in terms of smaller size, lower size distribution, higher encapsulation yield, and longer sustained drug release in comparison to classical method.

Thermoviscoplastic nonlinear constitutive relationships for structural analysis of high temperature metal matrix composites

NASA Technical Reports Server (NTRS)

Chamis, C. C.; Hopkins, D. A.

1985-01-01

A set of thermoviscoplastic nonlinear constitutive relationships (1VP-NCR) is presented. The set was developed for application to high temperature metal matrix composites (HT-MMC) and is applicable to thermal and mechanical properties. Formulation of the TVP-NCR is based at the micromechanics level. The TVP-NCR are of simple form and readily integrated into nonlinear composite structural analysis. It is shown that the set of TVP-NCR is computationally effective. The set directly predicts complex materials behavior at all levels of the composite simulation, from the constituent materials, through the several levels of composite mechanics, and up to the global response of complex HT-MMC structural components.

Effects of Macromolecular Crowding on Human Adipose Stem Cell Culture in Fetal Bovine Serum, Human Serum, and Defined Xeno-Free/Serum-Free Conditions

PubMed Central

Lee, Michelle Hui Ching; Mäkinen, Laura; Ang, Xiu Min; Mannerström, Bettina; Raghunath, Michael; Miettinen, Susanna

2017-01-01

Microenvironment plays an important role for stem cell proliferation and differentiation. Macromolecular crowding (MMC) was recently shown to assist stem cells in forming their own matrix microenvironment in vitro. The ability of MMC to support adipose stem cell (ASC) proliferation, metabolism, and multilineage differentiation was studied under different conditions: fetal bovine serum- (FBS-) and human serum- (HS-) based media and xeno- and serum-free (XF/SF) media. Furthermore, the immunophenotype of ASCs under MMC was evaluated. The proliferative capacity of ASCs under MMC was attenuated in each condition. However, osteogenic differentiation was enhanced under MMC, shown by increased deposition of mineralized matrix in FBS and HS cultures. Likewise, significantly greater lipid droplet accumulation and increased collagen IV deposition indicated enhanced adipogenesis under MMC in FBS and HS cultures. In contrast, chondrogenic differentiation was attenuated in ASCs expanded under MMC. The ASC immunophenotype was maintained under MMC with significantly higher expression of CD54. However, MMC impaired metabolic activity and differentiation capacity of ASCs in XF/SF conditions. Both the supportive and inhibitory effects of MMC on ASC are culture condition dependent. In the presence of serum, MMC maintains ASC immunophenotype and enhances adipogenic and osteogenic differentiation at the cost of reduced proliferation. PMID:28465691

Effects of Macromolecular Crowding on Human Adipose Stem Cell Culture in Fetal Bovine Serum, Human Serum, and Defined Xeno-Free/Serum-Free Conditions.

PubMed

Patrikoski, Mimmi; Lee, Michelle Hui Ching; Mäkinen, Laura; Ang, Xiu Min; Mannerström, Bettina; Raghunath, Michael; Miettinen, Susanna

2017-01-01

Microenvironment plays an important role for stem cell proliferation and differentiation. Macromolecular crowding (MMC) was recently shown to assist stem cells in forming their own matrix microenvironment in vitro. The ability of MMC to support adipose stem cell (ASC) proliferation, metabolism, and multilineage differentiation was studied under different conditions: fetal bovine serum- (FBS-) and human serum- (HS-) based media and xeno- and serum-free (XF/SF) media. Furthermore, the immunophenotype of ASCs under MMC was evaluated. The proliferative capacity of ASCs under MMC was attenuated in each condition. However, osteogenic differentiation was enhanced under MMC, shown by increased deposition of mineralized matrix in FBS and HS cultures. Likewise, significantly greater lipid droplet accumulation and increased collagen IV deposition indicated enhanced adipogenesis under MMC in FBS and HS cultures. In contrast, chondrogenic differentiation was attenuated in ASCs expanded under MMC. The ASC immunophenotype was maintained under MMC with significantly higher expression of CD54. However, MMC impaired metabolic activity and differentiation capacity of ASCs in XF/SF conditions. Both the supportive and inhibitory effects of MMC on ASC are culture condition dependent. In the presence of serum, MMC maintains ASC immunophenotype and enhances adipogenic and osteogenic differentiation at the cost of reduced proliferation.

Characteristic investigation and control of a modular multilevel converter-based HVDC system under single-line-to-ground fault conditions

DOE PAGES

Shi, Xiaojie; Wang, Zhiqiang; Liu, Bo; ...

2014-05-16

This paper presents the analysis and control of a multilevel modular converter (MMC)-based HVDC transmission system under three possible single-line-to-ground fault conditions, with special focus on the investigation of their different fault characteristics. Considering positive-, negative-, and zero-sequence components in both arm voltages and currents, the generalized instantaneous power of a phase unit is derived theoretically according to the equivalent circuit model of the MMC under unbalanced conditions. Based on this model, a novel double-line frequency dc-voltage ripple suppression control is proposed. This controller, together with the negative-and zero-sequence current control, could enhance the overall fault-tolerant capability of the HVDCmore » system without additional cost. To further improve the fault-tolerant capability, the operation performance of the HVDC system with and without single-phase switching is discussed and compared in detail. Lastly, simulation results from a three-phase MMC-HVDC system generated with MATLAB/Simulink are provided to support the theoretical analysis and proposed control schemes.« less

Corneal haze following PRK with mitomycin C as a retreatment versus prophylactic use in the contralateral eye.

PubMed

Netto, Marcelo V; Chalita, Maria Regina; Krueger, Ronald R

2007-01-01

To report photorefractive keratectomy (PRK) treated with mitomycin C (MMC) for previous corneal haze in one eye and PRK with MMC to prevent corneal haze formation in the fellow eye. A 40-year-old woman underwent PRK with MMC to treat previous corneal haze (secondary to previous PRK without MMC) for residual refractive error of +0.50 +0.25 x 165 in the left eye and PRK with MMC to prevent corneal haze in the right eye. Postoperative slit-lamp examination revealed no haze in the right eye, but continued mild haze in the left eye. Treatment with PRK and MMC for previous corneal haze is not as effective as primary PRK with MMC in preventing postoperative corneal haze formation.

The effects of intradermal and topical mitomycin C on wound healing.

PubMed

Porter, Glen T; Gadre, Swarupa A; Calhoun, Karen H

2006-07-01

To determine the effect of intradermal and topical mitomycin C (MMC) on skin wound healing. A prospective, controlled study in a rat wound model performed in an academic medical center. Intradermal and topical MMC application decreased wound integrity when compared with saline-treated animals at 1 week, 2 weeks, 1 month, and 6 months. Skin necrosis occurred in animals that received intradermal MMC. Hemotoxylin and eosin and immunohistochemical staining showed no consistent difference between treatment arms. Fibrosis and collagen deposition were reduced in MMC-treated wounds on trichrome staining. MMC-treated wounds showed decreased wound strength compared with controls. Intradermal MMC can cause skin necrosis. Histologic findings did not always correspond with clinical data. The data suggest cautious use of MMC in clinical situations when wound breaking strength is critical.

Effect of mitomycin C on IL-1R expression, IL-1-related hepatocyte growth factor secretion and corneal epithelial cell migration.

PubMed

Chen, Tsan-Chi; Chang, Shu-Wen

2010-03-01

To investigate how mitomycin C (MMC) modulates hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) secretions in human corneal fibroblasts and regulates human corneal epithelial (HCE) cell migration. Primary human corneal fibroblasts were treated with MMC (0.05, 0.1, or 0.2 mg/mL for 5 minutes) and were cultivated with or without interleukin (IL)-1beta. Transcript and secretion of HGF and KGF were determined by quantitative real-time RT-PCR and Western blot analysis, respectively. The effect of MMC-treated fibroblasts on HCE cell migration was evaluated using a transwell migration assay. The influence of MMC on HGF expression/secretion and HCE cell migration was further confirmed by RNA interference. The number of IL-1 receptors (IL-1R) on the fibroblast surface was analyzed by flow cytometry. MMC alone did not affect endogenous HGF expression, whereas IL-1beta alone significantly upregulated HGF transcripts and secretion. By modifying IL-1R numbers, MMC further upregulated IL-1beta-related HGF expression at a concentration of 0.05 mg/mL but to a lesser extent at 0.1 and 0.2 mg/mL. KGF transcripts and intracellular expression were suppressed by MMC dose dependently in the presence or absence of IL-1beta, whereas KGF secretion was not affected. Conditioned medium from MMC-treated fibroblasts exerted a similar concentration-dependent effect on HCE cell migration, enhancing migration most significantly at 0.05 mg/mL MMC in the presence of IL-1beta. The MMC dose-dependent modulation of HCE cell migration was abolished in HGF-silenced fibroblasts. MMC differentially modulated IL-1R expression at various concentrations and regulated HGF and KGF differently. MMC alone did not alter HGF expression. In the presence of IL-1beta, MMC-treated corneal fibroblasts modified HCE cell migration through IL-1beta-induced HGF secretion.

The effect of mitomycin C after long-term storage on human Tenon's fibroblast proliferation.

PubMed

Hu, D; Chen, P P; Oda, D

1999-10-01

To investigate the effect of mitomycin C (MMC) after long-term storage on proliferation of human Tenon's fibroblasts in vitro. Human Tenon's fibroblasts in tissue culture were exposed for 5 minutes to MMC (0.4 mg/mL) that was either freshly prepared or had been stored for as long as 18 months at either 4 degrees C or -20 degrees C. The MTT colorimetric assay was used to determine the inhibition of proliferation as measured indirectly by mitochondrial activity. The inhibition rate was 88% using fresh MMC, and declined to a mean of 73% when using MMC that had been stored for as long as 18 months at 4 degrees C; this decrease was not statistically significant. The mean inhibition for MMC stored at -20 degrees C was 68%, and this was significantly less than inhibition with fresh MMC. Inhibition did not vary significantly with MMC after different storage times. Mitomycin C continues to have strong in vitro antiproliferative effects when stored for as long as 18 months at 4 degrees C or -20 degrees C. A significant decline in potency compared with fresh MMC occurs when MMC is stored at -20 degrees C.

Space structures concepts and materials

NASA Technical Reports Server (NTRS)

Nowitzky, A. M.; Supan, E. C.

1988-01-01

An extension is preseted of the evaluation of graphite/aluminum metal matrix composites (MMC) for space structures application. A tubular DWG graphite/aluminum truss assembly was fabricated having the structural integrity and thermal stability needed for space application. DWG is a proprietary thin ply continuous graphite reinforced aluminum composite. The truss end fittings were constructed using the discontinuous ceramic particulate reinforced MMC DWAl 20 (trademark). Thermal stability was incorporated in the truss by utilizing high stiffness, negative coefficient of thermal expansion (CTE) P100 graphite fibers in a 6061 aluminum matrix, crossplied to provide minimized CTE in the assembled truss. Tube CTE was designed to be slightly negative to offset the effects of the end fitting and sleeve, CTE values of which are approx. 1/2 that of aluminum. In the design of the truss configuration, the CTE contribution of each component was evaluated to establish the component dimension and layup configuration required to provide a net zero CTE in the subassemblies which would then translate to a zero CTE for the entire truss bay produced.

Robotic Surgery Training in an OB/GYN Residency Program: A Survey Investigating the Optimal Training and Credentialing of OB/GYN Residents.

PubMed

Peterson, Shannon; Mayer, Allan; Nelson, Beth; Roland, Phillip

2015-08-01

Many community hospital gynecologic surgery training programs now include robotics.At St. Francis Hospital and Medical Center, we have integrated robotic surgical training since 2006. This study is designed to assess the success in training gynecology residents in robotic surgery. An anonymous web-based survey tool (www. survey monkey. com) was sent to all Ob/Gyn residency graduates from 2007-2010 (n = 17). From 2011-2014, we emailed three reevaluation questions to all 2007-2014 graduates (N = 32). Design Classification: II-3. The response rate was 95%, and 11 of 17 initial graduates (65%) indicated that they had received adequate robotic training. Currently, 24 of 32 (75%) graduates practice in hospitals with robotic availability. Twenty of the 32 graduates (63%) are using robotics in their surgical practices. Nine of these 20 graduates (45%) were fully credentialed following their residency. The other 11 graduates (55%)required further proctoring to obtain full robotic credentials. Robotic surgical training is a component of modern gynecologic surgical training. Postresidency robotic credentialing is a realistic graduation goal for residents who plan to practice gynecologic surgery.

Functional characterization of two SOS-regulated genes involved in mitomycin C resistance in Caulobacter crescentus.

PubMed

Lopes-Kulishev, Carina O; Alves, Ingrid R; Valencia, Estela Y; Pidhirnyj, María I; Fernández-Silva, Frank S; Rodrigues, Ticiane R; Guzzo, Cristiane R; Galhardo, Rodrigo S

2015-09-01

The SOS response is a universal bacterial regulon involved in the cellular response to DNA damage and other forms of stress. In Caulobacter crescentus, previous work has identified a plethora of genes that are part of the SOS regulon, but the biological roles of several of them remain to be determined. In this study, we report that two genes, hereafter named mmcA and mmcB, are involved in the defense against DNA damage caused by mitomycin C (MMC), but not against lesions induced by other common DNA damaging agents, such as UVC light, methyl methanesulfonate (MMS) and hydrogen peroxide. mmcA is a conserved gene that encodes a member of the glyoxalases/dioxygenases protein family, and acts independently of known DNA repair pathways. On the other hand, epistasis analysis showed that mmcB acts in the same pathway as imuC (dnaE2), and is required specifically for MMC-induced mutagenesis, but not for that induced by UV light, suggesting a role for MmcB in translesion synthesis-dependent repair of MMC damage. We show that the lack of MMC-induced mutability in the mmcB strain is not caused by lack of proper SOS induction of the imuABC operon, involved in translesion synthesis (TLS) in C. crescentus. Based on this data and on structural analysis of a close homolog, we propose that MmcB is an endonuclease which creates substrates for ImuABC-mediated TLS patches. Copyright © 2015 Elsevier B.V. All rights reserved.

A reduced organic carbon component in martian basalts.

PubMed

Steele, A; McCubbin, F M; Fries, M; Kater, L; Boctor, N Z; Fogel, M L; Conrad, P G; Glamoclija, M; Spencer, M; Morrow, A L; Hammond, M R; Zare, R N; Vicenzi, E P; Siljeström, S; Bowden, R; Herd, C D K; Mysen, B O; Shirey, S B; Amundsen, H E F; Treiman, A H; Bullock, E S; Jull, A J T

2012-07-13

The source and nature of carbon on Mars have been a subject of intense speculation. We report the results of confocal Raman imaging spectroscopy on 11 martian meteorites, spanning about 4.2 billion years of martian history. Ten of the meteorites contain abiotic macromolecular carbon (MMC) phases detected in association with small oxide grains included within high-temperature minerals. Polycyclic aromatic hydrocarbons were detected along with MMC phases in Dar al Gani 476. The association of organic carbon within magmatic minerals indicates that martian magmas favored precipitation of reduced carbon species during crystallization. The ubiquitous distribution of abiotic organic carbon in martian igneous rocks is important for understanding the martian carbon cycle and has implications for future missions to detect possible past martian life.

Research on MMC-SST Oriented AC/DC Distribution System

NASA Astrophysics Data System (ADS)

Xie, Xifeng; Shi, Hua; Zuo, Jianglin; Zhang, Zhigang

2018-01-01

A modular multilevel converter-solid state transformer (MMC-SST) oriented AC/DC Distribution System is designed. Firstly, the topology structure is introduced, MMC is adopted in the input stage, multiple DC-DC converters are adopted in the isolation stage, and a Three-Phase Four-Leg inverter is adopted in the output stage. Then, the control strategy is analysed. Finally, simulation model and an experimental prototype of MMC-SST are built, simulation and experimental results show that topology and control strategy of MMC-SST are feasible.

Acute toxic responses of the freshwater planarian, Dugesia dorotocephala, to methylmercury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Best, J.B.; Morita, M.; Ragin, J.

1981-07-01

Toxic responses of planaria to various aquatic habitat concentrations of methylmercury chloride (MMC) were investigated. One hundred percent lethality occurred within 5 h in 2 ppM MMC, 24 h in 1 ppM MMC, and 5 days in 0.5 ppM MMC. No deaths occurred in 0.2 ppM MMC over a 10 day period, however, non-lethal toxic responses were observed. Varying degrees of head resorption, progressing caudally from the snout were observed. With continuing exposure, partial head regeneration and recovery toward more normal appearance occurred by 10 days. Teratogenic effects were observed in surgical decapitation experiments. Head regeneration was retarded in 0.1more » and 0.2 ppM MMC. Malformations, visible lesions, or gross behavioral abnormalities were produced by 2 week exposure of planaria to concentrations of 20 ppB MMC or lower. (RJC)« less

Market and beneficiary characteristics associated with enrollment in Medicare managed care plans and fee-for-service.

PubMed

Shimada, Stephanie L; Zaslavsky, Alan M; Zaborski, Lawrence B; O'Malley, A James; Heller, Amy; Cleary, Paul D

2009-05-01

Risk selection in the Medicare managed care program ("Medicare Advantage") is an important policy concern. Past research has shown that Medicare managed care plans tend to attract healthier beneficiaries and that market characteristics such as managed care penetration may also affect risk selection. To assess whether patient enrollment in Medicare managed care (MMC) or traditional fee-for-service (FFS) Medicare is related to beneficiary and market characteristics and provide a baseline for understanding how changes in Medicare policy affect MMC enrollment over time. Data sources were the 2004 Medicare MMC and FFS CAHPS surveys, the Social Security Administration's Master Beneficiary Record, MMC Market Penetration Files, and 2000 Census data. We estimated logistic regression models to assess what beneficiary characteristics predict enrollment in MMC and the moderating effects of market characteristics. Enrollees in MMC plans tend to have better health than those in FFS. This effect is weaker in areas with more competition. Latinos and beneficiaries with less education and lower income, as indicated by earnings history or local-area median income, are more likely to enroll in MMC. Enrollment in MMC is related to beneficiary characteristics, including health status and socioeconomic status, and is modified by MMC presence in the local market. Because vulnerable subgroups are more likely to enroll in MMC plans, the Centers for Medicare & Medicaid Services should monitor how changes to Medicare Advantage policies and payment methods may affect beneficiaries in those groups.

High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: neural consequences and comparison with methamphetamine.

PubMed

Motbey, Craig P; Clemens, Kelly J; Apetz, Nadine; Winstock, Adam R; Ramsey, John; Li, Kong M; Wyatt, Naomi; Callaghan, Paul D; Bowen, Michael T; Cornish, Jennifer L; McGregor, Iain S

2013-09-01

Mephedrone (MMC) is a relatively new recreational drug that has rapidly increased in popularity in recent years. This study explored the characteristics of intravenous MMC self-administration in the rat, with methamphetamine (METH) used as a comparator drug. Male Sprague-Dawley rats were trained to nose poke for intravenous MMC or METH in daily 2 h sessions over a 10 d acquisition period. Dose-response functions were then established under fixed- and progressive-ratio (FR and PR) schedules over three subsequent weeks of testing. Brains were analyzed ex vivo for striatal serotonin (5-HT) and dopamine (DA) levels and metabolites, while autoradiography assessed changes in the regional density of 5-HT and serotonin transporter (SERT) and DA transporter (DAT) and induction of the inflammation marker translocator protein (TSPO). Results showed that MMC was readily and vigorously self-administered via the intravenous route. Under a FR1 schedule, peak responding for MMC was obtained at 0.1 mg/kg/infusion, versus 0.01 mg/kg/infusion for METH. Break points under a PR schedule peaked at 1 mg/kg/infusion MMC versus 0.3 mg/kg/infusion for METH. Final intakes of MMC were 31.3 mg/kg/d compared to 4 mg/kg/d for METH. Rats self-administering MMC, but not METH, gained weight at a slower rate than control rats. METH, but not MMC, self-administration elevated TSPO receptor density in the nucleus accumbens and hippocampus, while MMC, but not METH, self-administration decreased striatal 5-hydroxyindolacetic acid (5-HIAA) concentrations. In summary, MMC supported high levels of self-administration, matching or exceeding those previously reported with other drugs of abuse.

Cytological and histological changes in the urothelium produced by electromotive drug administration (EMDA) and by the combination of intravescical hyperthermia and chemotherapy (thermochemotherapy).

PubMed

Pierconti, Francesco; Straccia, Patrizia; Emilio, Sacco; Bassi, Pier Francesco; De Pascalis, Ivana; Marques, Rita C; Volavsek, Metka; Larocca, Luigi M; Lopez-Beltran, Antonio

2017-09-01

The treatment of non muscle-invasive bladder cancer (NMIBC) encompasses a range of different procedures. Electromotive drug administration (EMDA) and chemo-hyperthermia (C-HT; Synergo) represent a minimally-invasive methods of intravesical instillation of therapeutic agents as mitomycin C (MMC). We selected patients with high grade NMIBC, BCG non responder, treated with EMDA/MMC and C-HT/MMC and we also examined the morphological changes in urine cytology samples. During the period from 2012 to 2014, 110 patients with high grade NMIBC, BCG refractory were selected. All cases examined were classified according to The Paris System Classification as negative for high urothelial carcinoma (NHGUC) or atypical urothelial cells (AUC) with a mean of follow-up of 15 months and the cytological diagnosis were confirmed by histological biopsies. In particular 50 patients were treated with EMDA/MMC and 60 patients underwent to C-HT/MMC. The morphological changes were evaluated in urine samples processed by Thin Prep method. In the 50 patients treated with EMDA/MMC, 35 samples were classified as NHGUC and 15 cases were classified as AUC, while in the 60 patients treated with C-HT/MMC, 43 samples were NHGUC and 17 cases were classified AUC. The increase of cellularity and nuclear size with the alteration of nuclear/cytoplasmatic ratio (N/C) were common in patients treated with EMDA/MMC and C-HT/MMC without clinical and histological evidence of recurrence of neoplasia. The hyperchromasia and irregular nuclear chromatin were rarely observed. The irregular nuclear membrane rarely identified in urine cytology after EMDA/MMC treatment, is a feature present in patients C-HT/MMC treated. Copyright © 2017 Elsevier GmbH. All rights reserved.

Efficacy and safety of mitomycin C as an agent to treat corneal scarring in horses using an in vitro model.

PubMed

Buss, Dylan G; Sharma, Ajay; Giuliano, Elizabeth A; Mohan, Rajiv R

2010-07-01

Mitomycin C (MMC) is used clinically to treat corneal scarring in human patients. We investigated the safety and efficacy of MMC to treat corneal scarring in horses by examining its effects at the early and late stages of disease using an in vitro model. An in vitro model of equine corneal fibroblast (ECF) developed was used. The ECF or myofibroblast cultures were produced by growing primary ECF in the presence or absence of transforming growth factor beta-1 (TGFbeta1) under serum-free conditions. The MMC dose for the equine cornea was defined with dose-dependent trypan blue exclusion and (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays after applying MMC to the cultures once for 2 min. The efficacy of MMC to control corneal scarring in horses was determined by measuring mRNA and protein expression of corneal scarring markers (alpha-smooth muscle actin and F-actin) with western blotting, immunocytochemistry and/or quantitative real-time polymerase chain reactions. A single 2-min treatment of 0.02% or less MMC did not alter ECF phenotype, viability, or cellular proliferation whereas 0.05% or higher MMC doses showed mild-to-moderate cellular toxicity. The TGFbeta1 at 1 ng/mL showed significant myofibroblast formation in ECF under serum-free conditions. A single 2-min, 0.02% MMC treatment 24 h (early) after TGFbeta1 stimulation significantly reduced conversion of ECF to myofibroblasts, however, a single 0.02% MMC treatment 11 days after TGFbeta1 stimulation showed moderate myofibroblast inhibition. That MMC safely and effectively reduced scarring in ECF by reducing the degree of transdifferentiation of corneal fibroblasts to myofibroblasts in vitro. Further clinical in vivo investigations are warranted using MMC in horses.

Mitomycin C induces apoptosis in cultured corneal fibroblasts derived from type II granular corneal dystrophy corneas.

PubMed

Kim, Tae-im; Choi, Seung-il; Lee, Hyung Keun; Cho, Young Jae; Kim, Eung Kweon

2008-06-30

The present study investigated the effect of mitomycin C (MMC) on cell viability, apoptosis, and transforming growth factor beta-induced protein (TGFBIp) expression in cultured normal corneal fibroblasts and heterozygote or homozygote granular corneal dystrophy type II (GCD II) corneal fibroblasts. Keratocytes were obtained from normal cornea or from heterozygote or homozygote GCD II patients after lamellar or penetrating keratoplasty. To measure cell viability, corneal fibroblasts were incubated with 0.02% MMC for 3 h, 6 h, and 24 h or with 0%, 0.01%, 0.02%, and 0.04% MMC for 24 h and then tested using lactate dehydrogenase (LDH) and 3-[4,5-demethylthiazol-2,5-diphenyl-2H-tetrazolium bromide] (MTT) assays. To measure apoptosis, cells were analyzed by FACS analysis and annexin V staining. Bcl-xL, Bax, and TGFBI mRNA expression was measured using reverse transcription polymerase chain reaction (RT-PCR) assays. Cellular and media levels of TGFBIp protein were measured by immunoblotting. MTT and LDH assays showed that MMC reduced cell viability in all three cell types in a dose-dependent and time-dependent manner (p<0.05). FACS analysis and annexin V staining showed that MMC caused apoptosis with GCD II homozygote cells being most affected. RT-PCR analysis showed that MMC decreased Bcl-xL mRNA expression and increased Bax mRNA expression in all cell types. RT-PCR and immunoblotting analysis showed that MMC reduced TGFBI mRNA levels and cellular and media TGFBIp protein levels in all cell types. MMC induced apoptosis, and the effects of MMC were greatest in GCD II homozygote cells. MMC also reduced the production of TGFBIp in all three types of corneal fibroblasts. These findings may explain the additional therapeutic effect of MMC in GCD II patients.

Remote magnetic control of a wireless capsule endoscope in the esophagus is safe and feasible: results of a randomized, clinical trial in healthy volunteers.

PubMed

Keller, Jutta; Fibbe, Christiane; Volke, Frank; Gerber, Jeremy; Mosse, Alexander C; Reimann-Zawadzki, Meike; Rabinovitz, Elisha; Layer, Peter; Swain, Paul

2010-11-01

Remote control of esophageal capsule endoscopes could enhance diagnostic accuracy. To assess the safety and efficacy of remote magnetic manipulation of a modified capsule endoscope (magnetic maneuverable capsule [MMC]; Given Imaging Ltd, Yoqneam, Israel) in the esophagus of healthy humans. Randomized, controlled trial. Academic hospital. This study involved 10 healthy volunteers. All participants swallowed a conventional capsule (ESO2; Given Imaging) and a capsule endoscope with magnetic material, the MMC, which is activated by a thermal switch, in random order (1 week apart). An external magnetic paddle (EMP; Given Imaging) was used to manipulate the MMC within the esophageal lumen. MMC responsiveness was evaluated on a screen showing the MMC film in real time. Safety and tolerability of the procedure (questionnaire), responsiveness of the MMC to the EMP, esophageal transit time, and visualization of the Z-line. No adverse events occurred apart from mild retrosternal pressure (n = 5). The ability to rotate the MMC around its longitudinal axis and to tilt it by defined movements of the EMP was clearly demonstrated in 9 volunteers. Esophageal transit time was highly variable for both capsules (MMC, 111-1514 seconds; ESO2, 47-1474 seconds), but the MMC stayed longer in the esophagus in 8 participants (P < .01). Visualization of the Z-line was more efficient with the ESO2 (inspection of 73% ± 18% of the circumference vs 33% ± 27%, P = .01). Magnetic forces were not strong enough to hold the MMC against peristalsis when the capsule approached the gastroesophageal junction. Remote control of the MMC in the esophagus of healthy volunteers is safe and feasible, but higher magnetic forces may be needed. Copyright © 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

[Mitomycin C in head and neck surgical procedures].

PubMed

Scheithauer, M O; Riechelmann, H

2007-05-01

Mitomycin C (MMC) is frequently used in combination chemotherapy. Its metabolites bind to DNA-molecules and causes DNA crosslinking, which interferes with the synthesis of DNA, RNA and proteins. MMC is thus able to reduce fibroblast proliferation. Moreover, MMC particularly inhibits the synthesis of extracellular matrix proteins including fibronectin and various collagens. These properties have been demonstrated in several experimental studies. Beside its merits in treatment of malignancies, MMC may thus be useful to prevent hypertrophic scars and keloids, adhesions and ostial restenosis following head and neck surgical procedures. Clinically, MMC has been applied to prevent scarring after ophthalmologic surgery. Recent experimental and clinical trials investigating the effects of MMC on wound healing following head and neck surgical procedures are reviewed.

SU-E-P-02: Imaging and Radiation Oncology Core (IROC) Houston QA Center (RPC) Credentialing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amador, C; Keith, T; Nguyen, T

2014-06-01

Purpose: To provide information pertaining to IROC Houston QA Center's (RPC) credentialing process for institutions participating in NCI-sponsored clinical trials. Methods: IROC Houston issues credentials for NCI sponsored study groups. Requirements for credentialing might include any combination of questionnaires, knowledge assessment forms, benchmarks, or phantom irradiations. Credentialing requirements for specific protocols can be found on IROC Houston's website (irochouston.mdanderson.org). The website also houses the credentialing status inquiry (CSI) form. Once an institution has reviewed the protocol's credentialing requirements, a CSI form should be completed and submitted to IROC Houston. This form is used both to request whether requirements have beenmore » met as well as to notify IROC Houston that the institution requests credentialing for a specific protocol. IROC Houston will contact the institution to discuss any delinquent requirements. Once the institution has met all requirements IROC Houston issues a credentialing letter to the institution and will inform study groups and other IROC offices of the credentials. Institutions can all phone the IROC Houston office to initiate credentialing or ask any credentialing related questions. Results: Since 2010 IROC has received 1313 credentialing status inquiry forms. We received 317 in 2010, 266 in 2011, 324 in 2012, and 406 in 2013. On average we receive 35 phone calls per week with multiple types of credentialing questions. Decisions regarding credentialing status are based on the protocol specifications and previous completed credentialing by the institution. In some cases, such as for general IMRT credentialing, up to 5 sites may be credentialed based on the credentialing of one main center. Each of these situations is handled individually. Conclusion: IROC Houston will issue radiation therapy credentials for the NCI trials in the National Clinical Trials Network. Credentialing requirements and the CSI form can be found online at the IROC Houston's website. Work supported by PHS grant CA10953 and CA081647 (NCI, DHHS)« less

DNA methylation analysis of Homeobox genes implicates HOXB7 hypomethylation as risk factor for neural tube defects

PubMed Central

Rochtus, Anne; Izzi, Benedetta; Vangeel, Elise; Louwette, Sophie; Wittevrongel, Christine; Lambrechts, Diether; Moreau, Yves; Winand, Raf; Verpoorten, Carla; Jansen, Katrien; Van Geet, Chris; Freson, Kathleen

2015-01-01

Neural tube defects (NTDs) are common birth defects of complex etiology. Though family- and population-based studies have confirmed a genetic component, the responsible genes for NTDs are still largely unknown. Based on the hypothesis that folic acid prevents NTDs by stimulating methylation reactions, epigenetic factors, such as DNA methylation, are predicted to be involved in NTDs. Homeobox (HOX) genes play a role in spinal cord development and are tightly regulated in a spatiotemporal and collinear manner, partly by epigenetic modifications. We have quantified DNA methylation for the different HOX genes by subtracting values from a genome-wide methylation analysis using leukocyte DNA from 10 myelomeningocele (MMC) patients and 6 healthy controls. From the 1575 CpGs profiled for the 4 HOX clusters, 26 CpGs were differentially methylated (P-value < 0.05; β-difference > 0.05) between MMC patients and controls. Seventy-seven percent of these CpGs were located in the HOXA and HOXB clusters, with the most profound difference for 3 CpGs within the HOXB7 gene body. A validation case-control study including 83 MMC patients and 30 unrelated healthy controls confirmed a significant association between MMC and HOXB7 hypomethylation (-14.4%; 95% CI: 11.9–16.9%; P-value < 0.0001) independent of the MTHFR 667C>T genotype. Significant HOXB7 hypomethylation was also present in 12 unaffected siblings, each related to a MMC patient, suggestive of an epigenetic change induced by the mother. The inclusion of a neural tube formation model using zebrafish showed that Hoxb7a overexpression but not depletion resulted in deformed body axes with dysmorphic neural tube formation. Our results implicate HOXB7 hypomethylation as risk factor for NTDs and highlight the importance for future genome-wide DNA methylation analyses without preselecting candidate pathways. PMID:25565354

Effectiveness of combination packages for HIV-1 prevention in sub-Saharan Africa depends on partnership network structure: a mathematical modelling study.

PubMed

Jenness, Samuel M; Goodreau, Steven M; Morris, Martina; Cassels, Susan

2016-12-01

Combination packages for HIV prevention can leverage the effectiveness of biomedical and behavioural elements to lower disease incidence with realistic targets for individual and population risk reduction. We investigated how sexual network structures can maximise the effectiveness of a package targeting sexually active adults in sub-Saharan Africa (SSA) with intervention components for medical male circumcision (MMC) and sexual partnership concurrency (having >1 ongoing partner). Network-based mathematical models of HIV type 1 (HIV-1) transmission dynamics among heterosexual couples were used to explore how changes to MMC alone and in combination with changes to concurrency impacted endemic HIV-1 prevalence and incidence. Starting from a base model parameterised from empirical data from West Africa, we simulated the prevalence of circumcision from 10% to 90% and concurrency was modelled at four discrete levels corresponding to values observed across SSA. MMC and concurrency could contribute to the empirical variation in HIV-1 disease prevalence across SSA. Small reductions in concurrency resulted in large declines in HIV-1 prevalence. Scaling up circumcision in low-concurrency settings yields a greater relative benefit, but the absolute number of infections averted depends on both the circumcision coverage and baseline incidence. Epidemic extinction with this package will require substantial scale-up of MMC in low-concurrency settings. Dynamic sexual network structure should be considered in the design and targeting of MMC within combination HIV-1 prevention packages. Realistic levels of coverage for these packages within southern Africa could lead to a reduction of incidence to the low levels observed in western Africa, and possibly, epidemic extinction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The effects of repetitious topical use of mitomycin C on antrostomy patency in maxillary antrostomy created rabbit model.

PubMed

Kavuzlu, Ali; Arslan, Necmi; Tastan, Eren; Islam, Ahmet; Ustun, Huseyin; Aydogan, Filiz

2011-11-01

The aim of our study was to investigate the effect of the topical use of mitomycin C (MMC) intraoperatively in single dose and intra-postoperatively in two doses on the narrowing of antrostomy in maxillary rabbit sinus antrostomies created experimentally. And also to determine the local and systemic side effects of topical MMC. With this objective, 0.6 mg/ml MMC was used to the first group at single dose and to the second group intraoperatively and on third day postoperatively in two doses topically for 5 min. After 8 weeks, although the mean area of antrostomy was larger than that in the control side in the first group, which received single dose MMC, the difference was not statistically significant (p = 0.287). The second group received two doses, and the antrostomy areas were found to be significantly larger than the controls (p = 0.05). Overall, the sides that received MMC were significantly larger (p = 0.029). From the point of histopathological examination of the tissue, it was seen that two-dose MMC increased the edema indicating inflammation and antrostomy resolved with normal respiratory tract epithelium. It was shown by measuring the blood values that nephrotoxic and myelosupressant effect of MMC occurring in systemic use did not occur with single or double dose topical use. Our results demonstrate that even if the number of cases was low, two doses of topical MMC usage prevent the narrowing of antrostomy while single dose MMC does not. And two-dose topical MMC usage does not have local and systemic side effects.

A Generalized Precharging Strategy for Soft Startup Process of the Modular Multilevel Converter-Based HVDC Systems

DOE PAGES

Zhang, Lei; Qin, Jiangchao; Wu, Xiajie; ...

2017-01-01

The modular multilevel converter (MMC) has become one of the most promising converter technologies for medium/high-power applications, specifically for highvoltage direct current (HVDC) transmission systems. One of the technical challenges associated with the operation and control of the MMC-based system is to precharge the submodule (SM) capacitors to their nominal voltage during the startup process. In this paper, considering various SM circuits, a generalized precharging strategy is proposed for the MMC-based systems, which can implement soft stratup from dc or ac side. Furthermore, the proposed precharging strategy can be applicabe for various SM circuits and MMC configurations. The proposed startupmore » strategy does not require extra measurements and/or auxiliary power supplies. The charging current is controlled by adjusting the changing rate of the number of blocked and bypassed SM capacitors. Based on the proposed startup strategy, the startup processes of MMC/MMC-HVDC systems based on various SM circuits are analyzed and a generalized startup procedure for various MMC-HVDC systems is proposed. In addition, the uncontrollable steady-state SM capacitor voltages of various MMC-based systems are analyzed and determined, potentially useful in SM design. Our performance of the proposed strategy for various MMC-HVDC systems is evaluated based on time-domain simulation studies in the PSCAD/EMTDC software environment and experimental results based on a scaled-down prototype.« less

A Generalized Precharging Strategy for Soft Startup Process of the Modular Multilevel Converter-Based HVDC Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Lei; Qin, Jiangchao; Wu, Xiajie

The modular multilevel converter (MMC) has become one of the most promising converter technologies for medium/high-power applications, specifically for highvoltage direct current (HVDC) transmission systems. One of the technical challenges associated with the operation and control of the MMC-based system is to precharge the submodule (SM) capacitors to their nominal voltage during the startup process. In this paper, considering various SM circuits, a generalized precharging strategy is proposed for the MMC-based systems, which can implement soft stratup from dc or ac side. Furthermore, the proposed precharging strategy can be applicabe for various SM circuits and MMC configurations. The proposed startupmore » strategy does not require extra measurements and/or auxiliary power supplies. The charging current is controlled by adjusting the changing rate of the number of blocked and bypassed SM capacitors. Based on the proposed startup strategy, the startup processes of MMC/MMC-HVDC systems based on various SM circuits are analyzed and a generalized startup procedure for various MMC-HVDC systems is proposed. In addition, the uncontrollable steady-state SM capacitor voltages of various MMC-based systems are analyzed and determined, potentially useful in SM design. Our performance of the proposed strategy for various MMC-HVDC systems is evaluated based on time-domain simulation studies in the PSCAD/EMTDC software environment and experimental results based on a scaled-down prototype.« less

Melanocortin Antagonist Tetrapeptides with Minimal Agonist Activity at the Mouse Melanocortin-3 Receptor

PubMed Central

2014-01-01

The melanocortin system regulates many important functions in the body. There are five melanocortin G protein-coupled receptor subtypes known to date. Herein, we report a structure–activity relationship (SAR) study of a tetrapeptide lead discovered through a double substitution strategy at the melanocortin core His-Phe-Arg-Trp sequence. Several compounds were identified with micromolar agonist activity at the mouse melanocortin-1 (mMC1R) and mouse melanocortin-5 receptor (mMC5R) subtypes, weak antagonist activity at the mouse melanocortin-3 receptor (mMC3R), and potent antagonist activity at the mouse melanocortin-4 receptor (mMC4R). Two compounds (2 and 3) were nanomolar mMC4R antagonists with no mMC3R antagonist activity observed. Additionally, we identified three tetrapeptide MC3R antagonists (1, 6, and 7) that possess minimal mMC3R agonist activity only at 100 μM, not commonly observed for mMC3R/mMC4R antagonists. These novel molecular templates have the potential as molecular probes to better differentiate the roles of the centrally expressed MC3 and MC4 receptors. PMID:25699138

Differences in irradiation susceptibility and turnover between mucosal and connective tissue-type mast cells of mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fukuzumi, T.; Waki, N.; Kanakura, Y.

Although precursors of mast cells are derived from the bone marrow, phenotypes of mast cells are influenced by the tissues in which final differentiation occurs. Connective tissue-type mast cells (CTMC) and mucosal mast cells (MMC) are different in morphological, biochemical, immunological, and functional criteria. The purpose of the present study was to obtain information about the differentiation process of MMC. First, we compared changes in irradiation susceptibility in mice during the differentiation process of CTMC and MMC. The decrease in irradiation susceptibility was remarkable in the CTMC differentiation process, but it was moderate in that of MMC. Some morphologically identifiablemore » CTMC in the peritoneal cavity had proliferative potential and were highly radioresistant, whereas such a radioresistant population of MMC was not detectable in the gastric mucosa. Second, we estimated the turnover of CTMC and MMC by determining the proportion of mast cells that were labeled with continuously administered bromodeoxyuridine. The turnover of MMC was significantly faster than that of CTMC. The absence of the radioresistant mast cell population in the gastric mucosa appeared to be related to the short life span of MMC.« less

Antioxidant and antigenotoxic role of recombinant human erythropoeitin against alkylating agents: cisplatin and mitomycin C in cultured Vero cells.

PubMed

Rjiba-Touati, Karima; Ayed-Boussema, Imen; Soualeh, Nidhal; Achour, Abdellatif; Bacha, Hassen; Abid, Salwa

2013-08-01

Cisplatin (CDDP) and mitomycin C (MMC), two alkylating agents used against various solid tumours, are a common source of acute kidney injury. Thus, strategies for minimizing CDDP and MMC toxicity are of a clinical interest. In this study, we aimed to investigate the protective role of recombinant human erythropoietin (rhEPO) against oxidative stress and genotoxicity induced by CDDP and MMC in cultured Vero cells. Three types of treatments were performed: (i) cells were treated with rhEPO 24 h before exposure to CDDP/MMC (pre-treatment), (ii) cells were treated with rhEPO and CDDP/MMC simultaneously (co-treatment), (iii) cells were treated with rhEPO 24 h after exposure to CDDP/MMC (post-treatment). Our results showed that rhEPO decreased the reactive oxygen species levels, the malondialdehyde levels and ameliorated glutathione (reduced and oxidized glutathione) modulation induced by CDDP and MMC in cultured Vero cells. Furthermore, rhEPO administration prevented alkylating agents-induced DNA damage accessed by comet test. Altogether, our results suggested a protective role of rhEPO, against CDDP- and MMC-induced oxidative stress and genotoxicity, especially in pre-treatment condition.

Voluntary Professional Credentialing Programs. A Resource Handbook for Continuing Educators.

ERIC Educational Resources Information Center

Hanniford, Barbara, Ed.

This handbook describes 77 voluntary programs offering professional credentialing for people in a wide range of professional and occupational fields. Each description lists credentials, organization offering credentials, initial credentialing requirements, credential renewal requirements (if any), continuing education approval process, and other…

TRUSTBUILDER2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Adam J.; Perano, Kenneth J.

In trust negotiation, resource providers specify access control policies in terms of the attributes that should be possessed by authorized users, rather than the identities of these users. Users can prove ownership of certain attributes through the use of digital credentials issued by trusted entities. For example, the Department of Motor Vehicles might issue vehicle owners X.509 driver's licenses that can be used to demonstrate proof of their current age, address, or ability to drive. These types of digital credentials may also be protected by user-specified policies controlling their release to remote parties; for example, Alice might only be willingmore » to show her VISA card credential to members of the Better Business Bureau. In this way, a request to access a given resource can result in a bilateral and iterative exchange of policies and credentials that represents a negotiation between the participating parties. To date, research interest in trust negotiation has been primarily theoretical and any implementations have been largely proofs of concept; experimenting with these prototypes is often not a straightforward task. TrustBuilder2 is a flexible framework for supporting research in the area trust negotiation protocols, designed to allow researchers to quickly prototype and experiment with various approaches to trust negotiation. In TrustBuilder2, the primary components of a trust negotiation system are represented using abstract interfaces.« less

Mitomycin C induces apoptosis in cultured corneal fibroblasts derived from type II granular corneal dystrophy corneas

PubMed Central

Choi, Seung-il; Lee, Hyung Keun; Cho, Young Jae

2008-01-01

Purpose The present study investigated the effect of mitomycin C (MMC) on cell viability, apoptosis, and transforming growth factor beta-induced protein (TGFBIp) expression in cultured normal corneal fibroblasts and heterozygote or homozygote granular corneal dystrophy type II (GCD II) corneal fibroblasts. Methods Keratocytes were obtained from normal cornea or from heterozygote or homozygote GCD II patients after lamellar or penetrating keratoplasty. To measure cell viability, corneal fibroblasts were incubated with 0.02% MMC for 3 h, 6 h, and 24 h or with 0%, 0.01%, 0.02%, and 0.04% MMC for 24 h and then tested using lactate dehydrogenase (LDH) and 3-[4,5-demethylthiazol-2,5-diphenyl-2H-tetrazolium bromide] (MTT) assays. To measure apoptosis, cells were analyzed by FACS analysis and annexin V staining. Bcl-xL, Bax, and TGFBI mRNA expression was measured using reverse transcription polymerase chain reaction (RT–PCR) assays. Cellular and media levels of TGFBIp protein were measured by immunoblotting. Results MTT and LDH assays showed that MMC reduced cell viability in all three cell types in a dose-dependent and time-dependent manner (p<0.05). FACS analysis and annexin V staining showed that MMC caused apoptosis with GCD II homozygote cells being most affected. RT–PCR analysis showed that MMC decreased Bcl-xL mRNA expression and increased Bax mRNA expression in all cell types. RT–PCR and immunoblotting analysis showed that MMC reduced TGFBI mRNA levels and cellular and media TGFBIp protein levels in all cell types. Conclusions MMC induced apoptosis, and the effects of MMC were greatest in GCD II homozygote cells. MMC also reduced the production of TGFBIp in all three types of corneal fibroblasts. These findings may explain the additional therapeutic effect of MMC in GCD II patients. PMID:18615204

Efficacy and safety of mitomycin C as an agent to treat corneal scarring in horses using an in vitro model

PubMed Central

Buss, Dylan G.; Sharma, Ajay; Giuliano, Elizabeth A.; Mohan, Rajiv R.

2010-01-01

Objective Mitomycin C (MMC) is used clinically to treat corneal scarring in human patients. We investigated the safety and efficacy of MMC to treat corneal scarring in horses by examining its effects at the early and late stages of disease using an in-vitro model. Procedure An in-vitro model of equine corneal fibroblast (ECF) developed was used. The equine corneal fibroblast or myofibroblast cultures were produced by growing primary ECF in the presence or absence of transforming growth factor beta-1 (TGFβ1) under serum-free conditions. The MMC dose for the equine cornea was defined with dose-dependent trypan blue exclusion and MTT [(3-4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays after applying MMC to the cultures once for 2 minutes. The efficacy of MMC to control corneal scarring in horses was determined by measuring mRNA and protein expression of corneal scarring markers (α-smooth muscle actin and F-actin) with western blotting, immunocytochemistry and/or quantitative real-time polymerase chain reactions. Results A single 2 minutes treatment of 0.02% or less MMC did not alter ECF phenotype, viability, or cellular proliferation whereas 0.05% or higher MMC doses showed mild-to-moderate cellular toxicity. The TGFβ1 at 1ng/ml showed significant myofibroblast formation in ECF under serum-free conditions. A single 2 minute, 0.02% MMC treatment 24 hours (early) after TGFβ1 stimulation significantly reduced conversion of ECF to myofibroblasts, however, a single 0.02% MMC treatment 11 days after TGFβ1 stimulation showed moderate myofibroblast inhibition. Conclusions That MMC safely and effectively reduced scarring in ECF by reducing the degree of transdifferentiation of corneal fibroblasts to myofibroblasts in vitro. Further clinical in-vivo investigations are warranted using MMC in horses. PMID:20618797

The Application of Metal Matrix Composite Materials in Propulsion System Valves

NASA Technical Reports Server (NTRS)

Laszar, John; Shah, Sandeep; Kashalikar, Uday; Rozenoyer, Boris

2003-01-01

Metal Matrix Composite (MMC) materials have been developed and used in many applications to reduce the weight of components where weight and deflection are the driving design requirement. MMC materials are being developed for use in some propulsion system components, such as turbo-pumps and thrust chambers. However, to date, no propulsion system valves have been developed that take advantage of the materials unique properties. The stiffness of MMC's could help keep valves light or improve life where deflection is the design constraint (such as seal and bearing locations). The low CTE of the materials might allow the designer to reduce tolerances and clearances producing better performance and lighter weight valves. Using unique manufacturing processes allow parts to be plated/coated for longer life and allow joining either by welding or threading/bolting. Additionally, casting of multi part pre-forms to form a single part can lead to designs that would be hard or impossible to manufacture with other methods. Therefore, NASA's Marshall Space Flight Center (MSFC) has developed and tested a prototype propulsion system valve that utilizes these materials to demonstrate these advantages. Through design and testing, this effort will determine the best use of these materials in valves designed to achieve the goal of a highly reliable and lightweight propulsion system. This paper is a continuation of the paper, The Application of Metal Matrix Composite Materials In Propulsion System Valves, presented at the JANNAF Conference held in April, 2002. Fabrication techniques employed, valve development, and valve test results will be discussed in this paper.

The effect of thermochemotherapy with mitomycin C on normal bladder urothelium, an experimental study.

PubMed

Uçar, Murat; Altok, Muammer; Umul, Mehmet; Bayram, Dilek; Armağan, İlkay; Güneş, Mustafa; Çapkin, Tahsin; Soyupek, Sedat

2016-01-01

To investigate the effects of thermochemotherapy with mitomycin C (MMC) on normal rabbit bladder urothelium and to compare it with standard intravesical MMC and hyperthermia with normal saline. Twenty-four male New Zealand rabbits, with a mean weight of 2.7 kg (in weight of 2.1–4.3 kg), were divided into three groups, each containing eight rabbits. Thermotherapy with only normal saline was performed in the first group, standard intravesical MMC was performed in the second group, and thermotherapy with MMC was performed in the last group. A week after the primary procedure, total cystectomy was performed and tissue samples were evaluated. The presence of epithelial vacuolar degeneration (p = 0.001), epithelial hyperplasia (p = 0.000), subepithelial fibrosis (p = 0.001) and hemorrhagic areas in the connective tissue (p = 0.002) was observed statistically significantly higher in the standard MMC group than in thermotherapy with normal saline group. There was almost a significant difference among standard MMC and normal saline group in terms of vascular congestion in the connective tissue (p = 0.08). Presence of epithelial vacuolar degeneration (p = 0.002), epithelial hyperplasia (p = 0.002), subepithelial fibrosis (p = 0.030), hemorrhagic areas (p = 0.011) and vascular congestion (p = 0.36) in the connective tissue was observed statistically significantly higher in the thermochemotherapy with MMC group than in standard intravesical MMC group. Polymorphonuclear cell infiltration was not considerable in any of the groups, and there was no significant difference between each groups (p = 0.140). Administration of intravesical MMC causes a toxic effect on the normal urothelium of the bladder rather than an inflammatory reaction. Heating MMC significantly increased this effect.

Mitomycin C retardation of corneal fibroblast migration via sustained dephosphorylation of paxillin at tyrosine 118.

PubMed

Chen, Tsan-Chi; Lai, Chien-Hsueh; Chang, Jie-Ling; Chang, Shu-Wen

2012-03-21

To investigate how mitomycin C (MMC) modulates corneal fibroblast migration and its molecular mechanisms in the wound healing process. After treatment with 0 and 0.2 mg · mL(-1) MMC for 5 minutes, effect of MMC on cell migration of human corneal fibroblasts (HCFs) was examined with a cell migration assay. Both focal adhesion kinase (FAK) and paxillin (PXN) expressions in HCFs were analyzed by semiquantitative real-time PCR, immunoblotting, and immunofluorescence confocal microscopy. Using gene silencing or gene overexpression with lentiviral-based pseudovirion infection, the phosphorylation level of FAK, PXN, and mutated PXNs at tyrosine sites 31 (Y31F-EGFP) and 118 (Y118F-EGFP) were verified in HCFs. MMC retarded HCF migration at 1 and 2 days posttreatment (dpt). MMC reduced levels of FAK transcript and FAK protein, but increased both transcript and protein expression of PXN at 1 and 2 dpt. Furthermore, MMC upregulated FAK-pY397, which subsequently enhanced PXN-pY31 in a dose-dependent manner at 1 dpt. Concurrently, MMC downregulated PXN-pY118 at 1 dpt. However, MMC treatment resulted in dephosphorylation of FAK-pY397, PXN-pY31, and PXN-pY118 at 2 dpt. The FAK/PXN complex in MMC-treated HCFs was detected at focal adhesion sites more than at the leading edge at 1 and 2 dpt, contributing to retardation of HCF migration. Y118F-EGFP-expressing HCFs exhibited lower mobility than that of PXN-EGFP- or Y31F-EGFP-expressing HCFs. The sustained PXN-pY118 dephosphorylation resulted in steadfastness of an incompletely active FAK/PXN complex at focal adhesion sites and played a pivotal role in MMC-retarded HCF migration.

Interferon-alpha and interferon-gamma sensitize human tenon fibroblasts to mitomycin-C.

PubMed

Wang, Xiao Yang; Crowston, Jonathan G; Zoellner, Hans; Healey, Paul R

2007-08-01

To investigate the effect of interferon (IFN)-alpha and IFN-gamma pretreatment on mitomycin C (MMC)-induced cell death in human Tenon fibroblasts (HTFs) and the mechanisms by which IFN-alpha and IFN-gamma modulate the susceptibility of HTFs to MMC. HTFs were pretreated with IFN-alpha and IFN-gamma for 48 hours before 5-minute application of 0.4 mg/mL MMC. Cell death after 48 hours was determined by Annexin V/propidium iodide (PI) staining and lactate dehydrogenase (LDH) release assay. Fas, Fas-ligand, and Bcl-2 expression were determined by flow cytometry. Fas associated death domain (FADD), Bax, cytochrome c, and caspase expression were determined by Western blot analysis and immunofluorescence staining. MMC treatment increased cell death and upregulated Fas and FADD expression, but had no effect on Fas-Ligand, Bax, Bcl-2, or cytochrome c. Neither IFN-alpha nor IFN-gamma alone induced HTF death, but each increased cell death 2 days after MMC treatment in a dose-dependent fashion. Combination IFN-alpha and IFN-gamma had a synergistic effect. IFN-alpha and IFN-gamma pretreatment increased Fas expression. Fas upregulation was associated with increased sensitivity to MMC. IFN pretreatment increased procaspase-8, procaspase-9, and procaspase-3 expression, and caspase-3 activation. Caspase-8, caspase-3, and broad caspase inhibitors, but not caspase-9 inhibitor, inhibited MMC-induced cell death in nonpretreated and IFN-pretreated cells. IFN-alpha and IFN-gamma enhance the susceptibility of HTFs to MMC-induced cell death through a Fas-mediated and a caspase-3-dependent pathway. Pretreatment with IFN primed HTFs to MMC, providing a potential means for initially slowing the healing response with IFN and subsequently terminating fibroblast activity through MMC-induced cell death.

Effect of mitomycin-C on the variance in refractive outcomes after photorefractive keratectomy.

PubMed

Sy, Mary Ellen; Zhang, Lijun; Yeroushalmi, Allen; Huang, Derek; Hamilton, D Rex

2014-12-01

To compare the variance in manifest refraction spherical equivalent (MRSE) after photorefractive keratectomy (PRK) with mitomycin-C (MMC), PRK without MMC, and laser in situ keratomileusis (LASIK) for the treatment of myopic astigmatism. Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, California, USA. Retrospective case series. Patients were classified into 3 groups of preoperative refraction-matched eyes as follows: PRK with MMC 0.02%, PRK without MMC, and LASIK. The preoperative and postoperative MRSE, preoperative corrected distance visual acuity, and postoperative uncorrected distance visual acuity (UDVA) were analyzed. Each group comprised 30 eyes. Follow-up was at least 6 months in the LASIK group and 12 months in the 2 PRK groups. There were no statistically significant differences in the mean preoperative MRSE (P=.95) or postoperative MRSE (P=.06) between the 3 groups. The mean postoperative MRSE was -0.07 diopter (D) ± 0.47 (SD), -0.14 ± 0.26 D, and 0.02 ± 0.25 D in the PRK with MMC 0.02% group, PRK without MMC group, and LASIK group, respectively. The variance in the postoperative MRSE in the PRK with MMC 0.02% group was significantly higher than that in the PRK without MMC group (P=.002) and in the LASIK group (P=.001). There was no statistically significant difference in the mean postoperative UDVA between the 3 groups (P=.47). Refractive outcomes after PRK for myopia were more variable when MMC 0.02% was used. This should be weighed against the advantage of intraoperative MMC use in reducing haze after PRK. Copyright © 2014 ASCRS and ESCRS. All rights reserved.

One-year outcomes of a bilateral randomised prospective clinical trial comparing PRK with mitomycin C and LASIK.

PubMed

Wallau, A D; Campos, M

2009-12-01

To compare 1-year follow-up results of photorefractive keratectomy (PRK) with mitomycin C (MMC) and laser in situ keratomileusis (LASIK) for custom correction of myopia. Eighty-eight eyes of 44 patients with moderate myopia were randomised to PRK with 0.002% MMC for 1 min in one eye and LASIK in the fellow eye. The 1-year follow-up was evaluated. There were no differences between LASIK and MMC-PRK eyes preoperatively. Forty-two patients completed the 1-year follow-up. MMC-PRK eyes achieved better uncorrected visual acuity (p = 0.03) and better best-spectacle-corrected visual acuity (p<0.001) 1 year after surgery. SE did not differ in the two groups during follow-up (p = 0.12). Clinically significant haze was not found in surface ablation eyes. LASIK eyes showed a greater higher-order aberration (p = 0.01) and lower contrast sensitivity (p<0.05) than MMC-PRK eyes postoperatively. Excellent vision was reported in 64% of LASIK and 74% of MMC-PRK eyes 1 year after surgery. The corneal resistance factor and corneal hysteresis (ORA, Reichert) were higher in LASIK than in MMC-PRK eyes (p<0.01) at the last follow-up. Wavefront-guided PRK with 0.002% MMC was more effective than wavefront-guided LASIK for correction of moderate myopia. Further research is necessary to determine the optimal concentration, exposure time and long-term corneal side effect of MMC.

One-year outcomes of a bilateral randomised prospective clinical trial comparing PRK with mitomycin C and LASIK

PubMed Central

Wallau, A D; Campos, M

2009-01-01

Aim: To compare 1-year follow-up results of photorefractive keratectomy (PRK) with mitomycin C (MMC) and laser in situ keratomileusis (LASIK) for custom correction of myopia. Methods: Eighty-eight eyes of 44 patients with moderate myopia were randomised to PRK with 0.002% MMC for 1 min in one eye and LASIK in the fellow eye. The 1-year follow-up was evaluated. Results: There were no differences between LASIK and MMC-PRK eyes preoperatively. Forty-two patients completed the 1-year follow-up. MMC-PRK eyes achieved better uncorrected visual acuity (p = 0.03) and better best-spectacle-corrected visual acuity (p<0.001) 1 year after surgery. SE did not differ in the two groups during follow-up (p = 0.12). Clinically significant haze was not found in surface ablation eyes. LASIK eyes showed a greater higher-order aberration (p = 0.01) and lower contrast sensitivity (p<0.05) than MMC-PRK eyes postoperatively. Excellent vision was reported in 64% of LASIK and 74% of MMC-PRK eyes 1 year after surgery. The corneal resistance factor and corneal hysteresis (ORA, Reichert) were higher in LASIK than in MMC-PRK eyes (p<0.01) at the last follow-up. Conclusions: Wavefront-guided PRK with 0.002% MMC was more effective than wavefront-guided LASIK for correction of moderate myopia. Further research is necessary to determine the optimal concentration, exposure time and long-term corneal side effect of MMC. PMID:19889831

Effects of mitomycin C on the expression of chymase and mast cells in the conjunctival scar of a monkey trabeculectomy model

PubMed Central

Okada, Kouhei; Takai, Shinji; Jin, Denan; Ishida, Osamu; Fukmoto, Masanori; Oku, Hidehiro; Miyazaki, Mizuo; Ikeda, Tsunehiko

2009-01-01

Purpose To determine the effects of mitomycin C (MMC) on the expression of chymase and mast cells in the conjunctival scar after trabeculectomy. Methods Ten eyes of five monkeys were used. Three eyes underwent trabeculectomy with MMC (MMC-treated), four eyes had trabeculectomy without MMC (placebo-treated), and three eyes served as control eyes. Intraocular pressure was measured before and three weeks after surgery. The scores of the degree of conjunctival adhesion were evaluated. Immunohistochemistry was used to analyze the densities of proliferative cell nuclear antigen-positive cells, chymase-positive cells, and mast cells. The ratio of collagen fiber areas to conjunctival and scleral lesions was analyzed by Mallory-Azan staining. Results After trabeculectomy, the intraocular pressure reduction of MMC-treated eyes was significantly different from placebo-treated and control eyes (p=0.032, 0.035). The adhesion score of MMC-treated eyes was also significantly lower than that of placebo-treated eyes (p=0.034). Densities of proliferative cell nuclear antigen-positive cells, chymase-positive cells, and areas of collagen fiber in conjunctival and scleral lesions were significantly decreased in MMC-treated eyes, compared with placebo-treated eyes (p=0.034, 0.034, 0.049, respectively). There was a tendency for the density of mast cells to be suppressed in MMC-treated eyes (p=0.157). Conclusions Chymase might be involved in one of the mechanisms by which MMC suppresses scar formation after trabeculectomy. PMID:19844588

Binding of mitomycin C to blood proteins: A spectroscopic analysis and molecular docking

NASA Astrophysics Data System (ADS)

Jang, Jongchol; Liu, Hui; Chen, Wei; Zou, Guolin

2009-06-01

Mitomycin C (MMC) was the first recognized bioreductive alkylating agent, and has been widely used clinically for antitumor therapy. The binding of MMC to two human blood proteins, human serum albumin (HSA) and human hemoglobin (HHb), have been investigated by fluorescence quenching, synchronous fluorescence, circular dichroism (CD) spectroscopy and molecular docking methods. The fluorescence data showed that binding of MMC to proteins caused strong fluorescence quenching of proteins through a static quenching way, and each protein had only one binding site for the drug. The binding constants of MMC to HSA and HHb at 298 K were 2.71 × 10 4 and 2.56 × 10 4 L mol -1, respectively. Thermodynamic analysis suggested that both hydrophobic interaction and hydrogen bonding played major roles in the binding of MMC to HSA or HHb. The CD spectroscopy indicated that the secondary structures of the two proteins were not changed in the presence of MMC. The study of molecular docking showed that MMC was located in the entrance of site I of HSA, and in the central cavity of HHb.

Controlled release of mitomycin C from PHEMAH-Cu(II) cryogel membranes.

PubMed

Bakhshpour, Monireh; Yavuz, Handan; Denizli, Adil

2018-02-19

Molecular imprinting technique was used for the preparation of antibiotic and anti-neoplastic chemotherapy drug (mitomycin C) imprinted cryogel membranes (MMC-ICM). The membranes were synthezied by using metal ion coordination interactions with N-methacryloyl-(l)-histidine methyl ester (MAH) functional monomer and template molecules (i.e. MMC). The 2-hydroxyethyl methacrylate (HEMA) monomer and methylene bisacrylamide (MBAAm) crosslinker were used for the preparation of mitomycin C imprinted cryogel membranes by radical suspension polymerization technique. The imprinted cryogel membranes were characterized by scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR) and swelling degree measurements. Cytotoxicity of MMC-ICMs was investigated using mouse fibroblast cell line L929. Time-dependent release of MMC was demonstrated within 150 h from cryogel membranes. Cryogels demonstrated very high MMC loading efficiency (70-80%) and sustained MMC release over hours.

Mitomycin C upregulates IL-8 and MCP-1 chemokine expression via mitogen-activated protein kinases in corneal fibroblasts.

PubMed

Chou, San-Fang; Chang, Shu-Wen; Chuang, Jia-Ling

2007-05-01

To investigate the expression of chemokines and their signaling pathways after application of mitomycin C (MMC) to corneal fibroblasts. Primary porcine and human corneal fibroblasts from passages 3 to 6 were treated with MMC at concentrations of 0.05, 0.1, or 0.2 mg/mL for 1, 2, 5, or 10 minutes. The relative expression of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were investigated with reverse transcription, and quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA). The effects of MMC on the activation of kinases were analyzed by Western blot analysis with specific antiphosphokinase antibodies. The signaling pathways by which MMC regulates the expression of IL-8 and MCP-1 were evaluated by pharmacological kinase-specific inhibitors. The expression of IL-8 and MCP-1 were upregulated after MMC treatment in a time- and concentration-dependent manner. Furthermore, the upregulated expression of IL-8 and MCP-1 increased with longer incubation time. MMC treatment enhanced the phosphorylation of p38, JNK, and ERK at different time points. The MMC-related IL-8 and MCP-1 expression was inhibited by both a p38 inhibitor (SB203580) and an ERK inhibitor (PD98059). A JNK inhibitor (SP600125) reduced the expression of MMC-induced MCP-1 but not of IL-8. MMC treatment upregulated the expression of IL-8 and MCP-1 mRNA and protein secretion by the activation of mitogen-activated protein kinases (MAPKs) in corneal fibroblasts.

P-glycoprotein Blockers Augment the Effect of Mitomycin C on Human Tenon's Fibroblasts.

PubMed

White, Andrew J R; Kelly, Elizabeth; Healey, Paul R; Crowston, Jonathan G; Mitchell, Paul; Zoellner, Hans

2013-08-01

Mitomycin C (MMC), which induces apoptosis in human Tenon's fibroblasts (HTF), is frequently used to retard wound healing after glaucoma surgery. The aim of this in vitro study was to examine whether adjunctive Verapamil and Cyclosporine could augment the cytotoxic effect of MMC on HTF. Fibroblast cell lines were established by explant culture from human tissue biopsy samples obtained during trabeculectomy procedures. Cells were exposed to MMC at varying concentrations (0.01-0.4 mg/ml) for 3 minutes, prior to washing in the presence or absence of the following drugs: Staurosporine (0.003mg/ml), Verapamil (2.5-0.25 mg/ml), or Cyclosporine (50-0.5 mg/ml). Following exposure, cells were cultured for 6 hours and surviving cells quantitated by haemocytometer counts. Both Verapamil and Staurosporine exhibited mild toxic effects on their own, but greatly enhanced the apoptotic effect of MMC. Staurosporine is too toxic to be considered clinically, so its augmentive effect on the activity of MMC was not studied further here. Doses as low as 0.25 mg/ml of Verapamil continued to show significant augmentation of the apoptotic effect of MMC Cyclosporine at a clinically used concentration (5 mg/ml) exhibited modest augmentation of the effect of MMC. Verapamil and Cyclosporine in clinically acceptable concentrations potentiate the effect of MMC and may obviate the need for high dose antimetabolites in trabeculectomy; however, further preclinical study is required. Adjunctive Verapamil or Cyclosporine may allow lower dose MMC to be used in glaucoma filtration surgery while maintaining the same antifibrotic effects.

Quality in ethics consultations.

PubMed

Magill, Gerard

2013-11-01

There is an increasing need for quality in ethics consultations, though there have been significant achievements in the United States and Europe. However, fundamental concerns that place the profession in jeopardy are discussed from the perspective of the U.S. in a manner that will be helpful for other countries. The descriptive component of the essay (the first two points) explains the achievements in ethics quality (illustrated by the IntegratedEthics program of the Veterans Health Administration) and the progress on standards and competencies for ethics consultations (represented by the Core Competencies of the American Society for Bioethics and Humanities). Based on these achievements, the analytical component of the essay (the final three points) identifies and seeks to resolve three fundamental concerns (with increasing levels of importance) that compromise quality in ethics consultations: standards of quality; professionalism; and credentialing. The analysis argues for clearer standards of quality in ethics consultation and urges further professionalism by explaining the need for the following: interpreting the ASBH core competencies in a normative manner, developing a Code of Ethics, and clarifying the meaning of best practices. However, the most serious concern that threatens quality in ethics consultations is the lack of a credentialing process. This concern can be resolved effectively by developing an independent Ethics Consultation Accreditation Council to accredit and standardize graduate degree programs, fellowship experiences, and qualifying examinations. This credentialing process is indispensable if we are to strategically enhance quality in ethics consultations.

Ex Vivo Maintenance of Primary Human Multiple Myeloma Cells through the Optimization of the Osteoblastic Niche.

PubMed

Zhang, Wenting; Gu, Yexin; Sun, Qiaoling; Siegel, David S; Tolias, Peter; Yang, Zheng; Lee, Woo Y; Zilberberg, Jenny

2015-01-01

We previously reported a new approach for culturing difficult-to-preserve primary patient-derived multiple myeloma cells (MMC) using an osteoblast (OSB)-derived 3D tissue scaffold constructed in a perfused microfluidic environment and a culture medium supplemented with patient plasma. In the current study, we used this biomimetic model to show, for the first time, that the long-term survival of OSB is the most critical factor in maintaining the ex vivo viability and proliferative capacity of MMC. We found that the adhesion and retention of MMC to the tissue scaffold was meditated by osteoblastic N-cadherin, as one of potential mechanisms that regulate MMC-OSB interactions. However, in the presence of MMC and patient plasma, the viability and osteogenic activity of OSB became gradually compromised, and consequently MMC could not remain viable over 3 weeks. We demonstrated that the long-term survival of both OSB and MMC could be enhanced by: (1) optimizing perfusion flow rate and patient-derived plasma composition in the culture medium and (2) replenishing OSB during culture as a practical means of prolonging MMC's viability beyond several weeks. These findings were obtained using a high-throughput well plate-based perfusion device from the perspective of optimizing the ex vivo preservation of patient-derived MM biospecimens for downstream use in biological studies and chemosensitivity analyses.

Mucous Membrane Grafting Augmented with Topical Mitomycin C Application in Contracted Socket Repair Surgeries.

PubMed

Mandour, Sameh S; Elmazar, Hesham M; Marey, Hatem M; Rahman, Ahmed K Abdel; Sakr, Rokia A

2016-12-01

To evaluate the use of intraoperative topical application of mitomycin C (MMC) for managing cases of recurrent socket contraction. A prospective comparative randomized study was carried out on 40 patients suffering from contracted sockets. They were randomly enrolled into 2 groups. Group A included 20 patients who had a surgery to treat contracted socket without augmentation with MMC. Group B patients had an MMC-augmented repair for the contracted socket. Patients were followed up over a period of 12 months for changes in inferior fornix (IF) depth and ability to retain the ocular prosthesis. At the end of the follow-up period, postoperative IF depth was significantly deeper in group B (with MMC) than in group A (without MMC). As well, 75% of the patients in group B could maintain the prosthetic eye shell, whereas only 35% of group A could maintain the prosthesis. This study shows that using intraoperative MMC (0.2 mg/mL) in contracted socket reconstruction plays a significant role in maintaining prosthetic eye. To the best of our knowledge, this study is the first to use MMC on a relatively large scale of patients with contracted socket. However, the follow-up period was relatively short and further work is required to verify the effect of MMC on a longer follow-up period.

Efficacy and Safety Comparison Between Suberoylanilide Hydroxamic Acid and Mitomycin C in Reducing the Risk of Corneal Haze After PRK Treatment In Vivo.

PubMed

Anumanthan, Govindaraj; Sharma, Ajay; Waggoner, Michael; Hamm, Chuck W; Gupta, Suneel; Hesemann, Nathan P; Mohan, Rajiv R

2017-12-01

This study compared the efficacy and safety of suberoylanilide hydroxamic acid (SAHA) and mitomycin C (MMC) up to 4 months in the prevention of corneal haze induced by photorefractive keratectomy (PRK) in rabbits in vivo. Corneal haze in rabbits was produced with -9.00 diopter PRK. A single application of SAHA (25 μM) or MMC (0.02%) was applied topically immediately after PRK. Effects of the two drugs were analyzed by slit-lamp microscope, specular microscope, TUNEL assay, and immunofluorescence. Single topical adjunct use of SAHA (25 μM) or MMC (0.02%) after PRK attenuated more than 95% corneal haze and myofibroblast formation (P < .001). SAHA did not reduce keratocyte density, cause keratocyte apoptosis, or increase immune cell infiltration compared to MMC (P < .01 or .001). Furthermore, SAHA dosing did not compromise corneal endothelial phenotype, density, or function in rabbit eyes, whereas MMC application did (P < .01 or .001). SAHA and MMC significantly decreased corneal haze after PRK in rabbits in vivo. SAHA exhibited significantly reduced short- and long-term damage to the corneal endothelium compared to MMC in rabbits. SAHA is an effective and potentially safer alternative to MMC for the prevention of corneal haze after PRK. Clinical trials are warranted. [J Refract Surg. 2017;33(12):834-839.]. Copyright 2017, SLACK Incorporated.

Effect of brief exposure to mitomycin C on cultured human nasal mucosa fibroblasts.

PubMed

Hu, D; Sires, B S; Tong, D C; Royack, G A; Oda, D

2000-03-01

To observe the effect of mitomycin C (MMC) on cultured human nasal mucosa fibroblasts. Cultured human nasal mucosa fibroblasts were exposed to MMC (0.1-0.4 mg/ml) for 1 to 5 minutes. The viability of the fibroblasts was determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay; DNA fragmentation (apoptosis) by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL); apoptotic percentage by flow cytometry; and morphology by light microscopy. A portion of the fibroblasts survived the mitomycin treatment and showed evidence of regrowth within 2 to 3 days. These cells reached confluence in 5 to 7 days. The inhibition rates by MTT assay of 0.4 mg/ml MMC for 5-minute exposures was 31.3%. Dose-response effect was noted with the lower concentrations and shorter exposure times where the inhibition rates were lower (but not significantly so). DNA fragmentation was observed in fibroblasts 24 hours after MMC exposure (0.4 mg/ml) for 5 minutes compared with normal control. The apoptotic rate of fibroblasts treated by 0.4 mg/ml MMC was significantly higher than the control (p < 0.05). Short MMC exposure times have a variable cytotoxic effect and inhibit proliferation of cultured nasal mucosa fibroblasts. MMC also can induce apoptosis with a 5-minute exposure time. Therefore, it is possible that MMC has a complex effect in dacryocystorhinostomy.

IGBT Switching Characteristic Curve Embedded Half-Bridge MMC Modelling and Real Time Simulation Realization

NASA Astrophysics Data System (ADS)

Zhengang, Lu; Hongyang, Yu; Xi, Yang

2017-05-01

The Modular Multilevel Converter (MMC) is one of the most attractive topologies in recent years for medium or high voltage industrial applications, such as high voltage dc transmission (HVDC) and medium voltage varying speed motor drive. The wide adoption of MMCs in industry is mainly due to its flexible expandability, transformer-less configuration, common dc bus, high reliability from redundancy, and so on. But, when the sub module number of MMC is more, the test of MMC controller will cost more time and effort. Hardware in the loop test based on real time simulator will save a lot of time and money caused by the MMC test. And due to the flexible of HIL, it becomes more and more popular in the industry area. The MMC modelling method remains an important issue for the MMC HIL test. Specifically, the VSC model should realistically reflect the nonlinear device switching characteristics, switching and conduction losses, tailing current, and diode reverse recovery behaviour of a realistic converter. In this paper, an IGBT switching characteristic curve embedded half-bridge MMC modelling method is proposed. This method is based on the switching curve referring and sample circuit calculation, and it is sample for implementation. Based on the proposed method, a FPGA real time simulation is carried out with 200ns sample time. The real time simulation results show the proposed method is correct.

Experimental and theoretical study on the excited-state dynamics of ortho-, meta-, and para-methoxy methylcinnamate.

PubMed

Miyazaki, Yasunori; Yamamoto, Kanji; Aoki, Jun; Ikeda, Toshiaki; Inokuchi, Yoshiya; Ehara, Masahiro; Ebata, Takayuki

2014-12-28

The S1 state dynamics of methoxy methylcinnamate (MMC) has been investigated under supersonic jet-cooled conditions. The vibrationally resolved S1-S0 absorption spectrum was recorded by laser induced fluorescence and mass-resolved resonant two-photon ionization spectroscopy and separated into conformers by UV-UV hole-burning (UV-UV HB) spectroscopy. The S1 lifetime measurements revealed different dynamics of para-methoxy methylcinnamate from ortho-methoxy methylcinnamate and meta-methoxy methylcinnamate (hereafter, abbreviated as p-, o-, and m-MMCs, respectively). The lifetimes of o-MMC and m-MMC are on the nanosecond time scale and exhibit little tendency of excess energy dependence. On the other hand, p-MMC decays much faster and its lifetime is conformer and excess energy dependent. In addition, the p-MMC-H2O complex was studied to explore the effect of hydration on the S1 state dynamics of p-MMC, and it was found that the hydration significantly accelerates the nonradiative decay. Quantum chemical calculation was employed to search the major decay route from S1(ππ(∗)) for three MMCs and p-MMC-H2O in terms of (i) trans → cis isomerization and (ii) internal conversion to the (1)nπ(∗) state. In o-MMC and m-MMC, the large energy barrier is created for the nonradiative decay along (i) the double-bond twisting coordinate (∼1000 cm(-1)) in S1 as well as (ii) the linear interpolating internal coordinate (∼1000 cm(-1)) from S1 to (1)nπ(∗) states. The calculation on p-MMC decay dynamics suggests that both (i) and (ii) are available due to small energy barrier, i.e., 160 cm(-1) by the double-bond twisting and 390 cm(-1) by the potential energy crossing. The hydration of p-MMC raises the energy barrier of the IC route to the S1/(1)nπ(∗) conical intersection, convincing that the direct isomerization is more likely to occur.

Subconjunctival mitomycin C before pterygium excision: an ultrastructural study.

PubMed

Chang, Yi-Sheng; Chen, Wen-Chung; Tseng, Sung-Huei; Sze, Chun-I; Wu, Chao-Liang

2008-05-01

Subconjunctival injection of mitomycin C (MMC) before pterygium excision is a new adjunctive therapy to decrease pterygium recurrence. This study aimed to investigate the ultrastructural changes in pterygium after subconjunctival injection of MMC. Four patients underwent subconjunctival injection of 0.1 mL of 0.15 mg/mL MMC 1 month before pterygium excision, and 2 patients served as controls without preoperative MMC injection. The excised specimens of pterygium were examined under transmission electron microscopy. Epithelial cells of the treated pterygium remained unchanged. However, stromal fibroblasts were decreased in number, were oval rather than spindle-shaped, and had shrunken cytoplasmic processes; some were degenerating or apoptotic. Collagen and elastic fibers were decreased in density, disorganized, and degenerated. Capillary endothelial cells were thickened and swollen, with narrow or obliterated lumens. Axonal swelling and demyelination were observed. Subconjunctival injection of MMC inhibits fibrovascular activity in the pterygial stroma, leading to degeneration of the extracellular matrix and nerve axons. These ultrastructural changes are consistent with the clinical observation of reduced vascularity in the pterygium after MMC injection and verify the effectiveness of subconjunctival MMC injection 1 month before pterygium excision in decreasing the risk of pterygium recurrence.

The migrating myoelectric complex of the small intestine

NASA Astrophysics Data System (ADS)

Telford, Gordon L.; Sarna, Sushil K.

1991-10-01

Gastric and small intestinal myoelectric and motor activity is divided into two main patterns, fed and fasted. During fasting, the predominant pattern of activity is the migrating myoelectric complex (MMC), a cyclically occurring pattern of electric and mechanical activity that is initiated in the stomach and duodenum almost simultaneously and, from there, propagates the length of the small intestine. Cyclic motor activity also occurs in the lower esophageal sphincter, the gallbladder, and the sphincter of Oddi with a duration that is related to the MMC in the small intestine. Of the possible mechanisms for initiation of the MMC in the small intestine (extrinsic neural control, intrinsic neural control, and hormonal control), intrinsic neural control via a series of coupled is the most likely. The keep this sentence in! hormone motilin also plays a role in the initiation of MMCs. After a meal, in man the MMC is disrupted and replaced by irregular contractions. The physiologic role of the MMC is to clear the stomach and small intestine of residual food, secretions, and desquamated cells and propel them to the colon. Disruption of the MMC cycle is associated with bacterial overgrowth in some patients, an observation that supports the proposed cleansing function of the MMC cycle.

Fatigue In Continuous-Fiber/Metal-Matrix Composites

NASA Technical Reports Server (NTRS)

Johnson, William S.

1992-01-01

Report describes experimental approaches to quantification of fatigue damage in metal-matrix composites (MMC's). Discusses number of examples of development of damage and failure along with associated analytical models of behavior of MMC. Objectives of report are twofold. First, present experimental procedures and techniques for conducting meaningful fatigue tests to detect and quantify fatigue damage in MMC's. Second, present examples of how fatigue damage initiated and grows in various MMC's. Report furnishes some insight into what type of fatigue damage occurs and how damage quantified.

Care coordination experiences of people with disabilities enrolled in medicaid managed care.

PubMed

Bowers, Anne; Owen, Randall; Heller, Tamar

2017-10-01

To understand the impact of experience and contacts with care coordinators on Medicaid Managed Care (MMC) enrollees with disabilities. Primary data was collected from a random sample of 6000 out of the 100,000 people with disabilities enrolled in one state's mandatory MMC program. Surveys were conducted through the mail, telephone, and Internet; 1041 surveys were completed. The sample used for analysis included 442 MMC enrollees who received care coordination. Regression analyses were conducted with the outcomes of number of unmet health care needs and enrollee appraisal of the health services they received. Race, age, gender, and disability variables controlled for demographic differences, and the independent variables included enrollee experience with a care coordinator (coordinator knowledge of enrollee medical history and whether the coordinator took into account enrollee wishes and input) and frequency of contact with a care coordinator. Positive enrollee experiences with care coordinators significantly related to more positive enrollee health service appraisals and fewer unmet health care needs; frequency of contact did not have any significant impacts. People with mental health disabilities and intellectual/developmental disabilities had significantly lower health service appraisals. People with mental health disabilities had significantly more unmet needs. Quality of care coordination, but not frequency of contact alone, is associated with better health outcomes for MMC enrollees. Implications for rehabilitation Care coordination is a core component of managed care and facilitates effective healthcare management for people with complex chronic conditions and disabilities. Better experiences with care coordinators is related to fewer unmet healthcare needs and more positive health care service appraisals for Medicaid managed care enrollees. The continuous development of person-centered care coordination strategies and training programs emphasizing quality relationships between coordinators and consumers should be prioritized.

Changes in ambient temperature differentially alter the thermoregulatory, cardiac and locomotor stimulant effects of 4-methylmethcathinone (mephedrone).

PubMed

Miller, M L; Creehan, K M; Angrish, D; Barlow, D J; Houseknecht, K L; Dickerson, T J; Taffe, M A

2013-01-01

The substituted cathinone compound known as mephedrone (4-methylmethcathinone; 4-MMC) has become popular with recreational users of psychomotor-stimulant compounds. Only recently have the first preclinical studies provided information about this drug in the scientific literature; nevertheless, media reports have led to drug control actions in the UK and across several US states. Rodent studies indicate that 4-MMC exhibits neuropharmacological similarity to 3,4-methylenedioxymethamphetamine (MDMA) and prompt investigation of the thermoregulatory, cardiac and locomotor effects of 4-MMC. This study focuses on the role of ambient temperature, which has been shown to shift the effects of MDMA from hyperthermic to hypothermic. Male Sprague-Dawley rats were monitored after subcutaneous administration of 4-MMC (1.0-5.6 mg/kg) using an implantable radiotelemetry system under conditions of low (20 °C) and high (30 °C) ambient temperature. A pharmacokinetic study found a T(max) of 0.25 h and a C(max) of 1206 ng/ml after 5.6 mg/kg 4-MMC. A dose-dependent reduction of body temperature was produced by 4-MMC at 20 °C but there was no temperature change at 30 °C. Increased locomotor activity was observed after 4-MMC administration under both ambient temperatures, however, significantly more activity was observed at 30 °C. Heart rate was slowed by 1.0 and 5.6 mg/kg 4-MMC at 20°C, and was slower in the 30 °C vs. 20 °C condition across all treatments. These results show that the cathinone analog 4-MMC exhibits in vivo thermoregulatory properties that are distinct from those produced by MDMA. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Enhancement of mitomycin C-induced cytotoxicity by curcumin results from down-regulation of MKK1/2-ERK1/2-mediated thymidine phosphorylase expression.

PubMed

Weng, Shao-Hsing; Tsai, Min-Shao; Chiu, Yu-Fan; Kuo, Ya-Hsun; Chen, Huang-Jen; Lin, Yun-Wei

2012-03-01

Curcumin (diferuloylmethane), a phenolic compound obtained from the rhizome of Curcuma longa, has been found to inhibit cell proliferation in various human cancer cell lines, including non-small cell lung cancer (NSCLC). Thymidine phosphorylase (TP) is considered an attractive therapeutic target, because increased TP expression can suppress cancer cell death induced by DNA-damaging agents. Mitomycin C (MMC), a chemotherapeutic agent used to treat NSCLC, inhibits tumour growth through DNA cross-linking and breaking. Whether MMC can affect TP expression in NSCLC is unknown. Therefore, in this study, we suggested that curcumin enhances the effects of MMC-mediated cytotoxicity by decreasing TP expression and ERK1/2 activation. Exposure of human NSCLC cell lines H1975 and H1650 to curcumin decreased MMC-elicited phosphorylated MKK1/2-ERK1/2 protein levels. Moreover, curcumin significantly decreased MMC-induced TP protein levels by increasing TP mRNA and protein instability. Enhancement of ERK1/2 activation by constitutively active MKK1/2 (MKK1/2-CA) increased TP protein levels and cell viability in curcumin- and MMC-co-treated cells. In contrast, U0126, a MKK1/2 inhibitor, augmented the cytotoxic effect and the down-regulation of TP by curcumin and MMC. Specific inhibition of TP by siRNA significantly enhanced MMC-induced cell death and cell growth inhibition. Our results suggest that suppression of TP expression or administration of curcumin along with MMC may be a novel lung cancer therapeutic modality in the future. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Solubilization and Stability of Mitomycin C Solutions Prepared for Intravesical Administration.

PubMed

Myers, Alan L; Zhang, Yan-Ping; Kawedia, Jitesh D; Zhou, Ximin; Sobocinski, Stacey M; Metcalfe, Michael J; Kramer, Mark A; Dinney, Colin P N; Kamat, Ashish M

2017-06-01

Mitomycin C (MMC) is an antitumor agent that is often administered intravesically to treat bladder cancer. Pharmacologically optimized studies have suggested varying methods to optimize delivery, with drug concentration and solution volume being the main drivers. However, these MMC concentrations (e.g. 2.0 mg/mL) supersede its solubility threshold, raising major concerns of inferior drug delivery. In this study, we seek to confirm that the pharmacologically optimized MMC concentrations are achievable in clinical practice through careful modifications of the solution preparation methods. MMC admixtures (1.0 and 2.0 mg/mL) were prepared in normal saline using conventional and alternative compounding methods. Conventional methodology resulted in poorly soluble solutions, with many visible particulates and crystallates. However, special compounding methods, which included incubation of solutions at 50 °C for 50 min followed by storage at 37 °C, were sufficient to solubilize drug. Chemical degradation of MMC solutions was determined over 6 h using high-performance liquid chromatography (HPLC) analytics, while physical stability was tested in parallel. Immediately following the 50 min incubation, both MMC solutions exhibited approximately 5-7% drug degradation. Based on the measured concentrations and linear regression of degradation plots, additional storage of these solutions at 37 °C for 5 h retained chemical stability criterion (< 10% overall drug loss). No physical changes were observed in any solutions at any test time points. We recommend that the described alternative preparation methods may improve intravesicular delivery of MMC in this urological setting, and advise that clinicians employing these changes should closely monitor patients for MMC toxicities and pharmacodynamics (change in clinical outcomes) that result from the potential enhancement of MMC exposure in the bladder.

Alpha-momorcharin, a RIP produced by bitter melon, enhances defense response in tobacco plants against diverse plant viruses and shows antifungal activity in vitro.

PubMed

Zhu, Feng; Zhang, Ping; Meng, Yan-Fa; Xu, Fei; Zhang, Da-Wei; Cheng, Jian; Lin, Hong-Hui; Xi, De-Hui

2013-01-01

Alpha-momorcharin (α-MMC) is type-1 ribosome inactivating proteins (RIPs) with molecular weight of 29 kDa and has lots of biological activity. Our recent study indicated that the α-MMC purified from seeds of Momordica charantia exhibited distinct antiviral and antifungal activity. Tobacco plants pre-treated with 0.5 mg/mL α-MMC 3 days before inoculation with various viruses showed less-severe symptom and less reactive oxygen species (ROS) accumulation compared to that inoculated with viruses only. Quantitative real-time PCR analysis revealed that the replication levels of viruses were lower in the plants treated with the α-MMC than control plants at 15 days post inoculation. Moreover, the coat protein expression of viruses was almost completely inhibited in plants which were treated with the α-MMC compared with control plants. Furthermore, the SA-responsive defense-related genes including non-expressor of pathogenesis-related genes 1 (NPR1), PR1, PR2 were up-regulated and activities of some antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) were increased after the α-MMC treatment. In addition, the α-MMC (500 μg/mL) revealed remarkable antifungal effect against phytopathogenic fungi, in the growth inhibition range 50.35-67.21 %, along with their MIC values ranging from 100 to 500 μg/mL. The α-MMC had also a strong detrimental effect on spore germination of all the tested plant pathogens along with concentration as well as time-dependent kinetic inhibition of Sclerotinia sclerotiorum. The α-MMC showed a remarkable antiviral and antifungal effect and hence could possibly be exploited in crop protection for controlling certain important plant diseases.

Endoplasmic reticulum stress signaling is involved in mitomycin C (MMC)-induced apoptosis in human fibroblasts via PERK pathway.

PubMed

Shi, Kun; Wang, Daode; Cao, Xiaojian; Ge, Yingbin

2013-01-01

Endoplasmic reticulum (ER) stress-mediated cell apoptosis has been implicated in various cell types, including fibroblasts. Previous studies have shown that mitomycin C (MMC)-induced apoptosis occurs in fibroblasts, but the effects of MMC on ER stress-mediated apoptosis in fibroblasts have not been examined. Here, MMC-induced apoptosis in human primary fibroblasts was investigated by exposing cells to a single dose of MMC for 5 minutes. Significant inhibition of cell proliferation and increased apoptosis were observed using a cell viability assay, Annexin V/propidium iodide double staining, cell cycle analysis, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining. Upregulation of proapoptotic factors, including cleaved caspase-3 and poly ADP-ribose polymerase (PARP), was detected by Western blotting. MMC-induced apoptosis was correlated with elevation of 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP), which are hallmarks of ER stress. Three unfolded protein response (UPR) sensors (inositol-requiring enzyme 1, IRE1; activating transcription factor 6, ATF6; and PKR-like ER kinase, PERK) and their downstream signaling pathways were also activated. Knockdown of CHOP attenuated MMC-induced apoptosis by increasing the ratio of BCL-2/BAX and decreasing BIM expression, suggesting that ER stress is involved in MMC-induced fibroblast apoptosis. Interestingly, knockdown of PERK significantly decreased ER stress-mediated apoptosis by reducing the expression of CHOP, BIM and cleaved caspase-3. Reactive oxygen species (ROS) scavenging also decreased the expression of GRP78, phospho-PERK, CHOP, and BIM. These results demonstrate that MMC-induced apoptosis is triggered by ROS generation and PERK activation.

Endoplasmic Reticulum Stress Signaling Is Involved in Mitomycin C(MMC)-Induced Apoptosis in Human Fibroblasts via PERK Pathway

PubMed Central

Cao, Xiaojian; Ge, Yingbin

2013-01-01

Endoplasmic reticulum (ER) stress-mediated cell apoptosis has been implicated in various cell types, including fibroblasts. Previous studies have shown that mitomycin C (MMC)-induced apoptosis occurs in fibroblasts, but the effects of MMC on ER stress-mediated apoptosis in fibroblasts have not been examined. Here, MMC-induced apoptosis in human primary fibroblasts was investigated by exposing cells to a single dose of MMC for 5 minutes. Significant inhibition of cell proliferation and increased apoptosis were observed using a cell viability assay, Annexin V/propidium iodide double staining, cell cycle analysis, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining. Upregulation of proapoptotic factors, including cleaved caspase-3 and poly ADP-ribose polymerase (PARP), was detected by Western blotting. MMC-induced apoptosis was correlated with elevation of 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP), which are hallmarks of ER stress. Three unfolded protein response (UPR) sensors (inositol-requiring enzyme 1, IRE1; activating transcription factor 6, ATF6; and PKR-like ER kinase, PERK) and their downstream signaling pathways were also activated. Knockdown of CHOP attenuated MMC-induced apoptosis by increasing the ratio of BCL-2/BAX and decreasing BIM expression, suggesting that ER stress is involved in MMC-induced fibroblast apoptosis. Interestingly, knockdown of PERK significantly decreased ER stress-mediated apoptosis by reducing the expression of CHOP, BIM and cleaved caspase-3. Reactive oxygen species (ROS) scavenging also decreased the expression of GRP78, phospho-PERK, CHOP, and BIM. These results demonstrate that MMC-induced apoptosis is triggered by ROS generation and PERK activation. PMID:23533616

Dexamethasone modifies mitomycin C-triggered interleukin-8 secretion in isolated human Tenon's capsule fibroblasts.

PubMed

Ho, Wei-Ting; Chen, Tsan-Chi; Chou, San-Fang; Chang, Shu-Wen

2014-07-01

Intraoperative mitomycin C (MMC) is widely used to prevent pterygium recurrence and glaucoma filtering bleb failure, but it has been shown to induce corneal inflammation and cell death. Postoperative dexamethasone (DEX) is advocated to reduce MMC-related inflammation and cell death in corneal fibroblasts. Nevertheless, its long-term regulation mechanism in Tenon's capsule remains to be explored. The purpose of this study was to investigate how DEX modifies MMC's effects in human Tenon's capsule fibroblasts (HTFs). HTFs isolated from the pterygium surgical patients (n = 6) were treated with MMC at 0, 0.1, 0.2, and 0.4 mg/ml for 5 min and incubated in DEX at 10 μM for 0, 1, 2, and 3 days. Recombinant interleukin-8 (IL-8) was used to verify the effect of MMC-related IL-8 secretion. Cell proliferation of all the treated cells was analyzed by WST-1 assay. The amount of IL-8 secretion in HTFs was determined by enzyme-linked immunosorbent assay. Immunoblotting assay was used to analyze the expression of peroxisome-proliferator-activated receptor gamma (PPARγ) and B-cell lymphoma-extra large (Bcl-xL). Our results revealed that MMC significantly reduced the HTF cell proliferation rate. Additionally, MMC significantly upregulated IL-8 secretion in HTFs concentration-dependently. At 3 days post treatment (dpt), 5-min exposures to 0.1, 0.2, and 0.4 mg/ml MMC resulted in 1.4-fold (p = 0.012), 1.6-fold (p = 0.012), and 2.5-fold (p = 0.001) increases of IL-8 secretion. In contrast, DEX reversed the MMC-retarded cell proliferation rate (p = 0.036) and repressed MMC-related IL-8 secretion by 33.5% at 3 dpt (p = 0.003). Addition of recombinant IL-8 noticeably suppressed HTF cell proliferation in a concentration-dependent manner. DEX stimulated upregulation of both PPARγ and Bcl-xL at 1 dpt in normal HTFs and at 2 dpt in MMC-treated HTFs. PPARγ silencing reduced expression of PPARγ and Bcl-xL, but enhanced IL-8 secretion (p < 0.001). On the other hand, Bcl-xL silencing enhanced IL-8 secretion (p < 0.001), but did not affect PPARγ expression. These revealed that IL-8 secretion in HTFs is modulated by PPARγ-dependent Bcl-xL signaling. We conclude that DEX reversed the MMC-inhibited HTF cell proliferation via diminishing the MMC-induced IL-8 secretion, which resulted from a late-phase upregulation of the PPARγ and Bcl-xL. These long-term effects suggest a beneficial postoperative DEX treatment following intraoperative MMC application. Copyright © 2014 Elsevier Ltd. All rights reserved.

Operational Test and Evaluation Manual

DTIC Science & Technology

2011-06-28

Fiscal Office manages all funds received throughout the year for Operations and Maintenance Marine Corps (O&MMC); Research , Development, Test, and... Research , Development, and Acquisition) Assistant Secretary of the Navy ( Research , Development, and Acquisition) (ASN (RDA)) is the DOD’s Component...entire acquisition cycle (SECNAV 2008). This accumulation of data starts with early research and developmental testing and Other tests and

Minichromosome maintenance complex component 8 mutations cause primary ovarian insufficiency.

PubMed

Dou, Xiaoyun; Guo, Ting; Li, Guangyu; Zhou, LiGuang; Qin, Yingying; Chen, Zi-Jiang

2016-11-01

To investigate whether mutations in the minichromosome maintenance complex component 8 (MCM8) gene were present in 192 patients with sporadic primary ovarian insufficiency (POI). Retrospective case-control cohort study. University-based reproductive medicine center. A total of 192 patients with sporadic POI and 312 control women with regular menstruation (192 age-matched women and 120 women >45 years old). Sanger sequencing was performed in patients with sporadic POI, and potentially pathogenic variants were confirmed in matched controls. DNA damage was induced by mitomycinC (MMC) treatment, and DNA repair capacity was evaluated by histone H2AX phosphorylation level. Sanger sequencing for MCM8 was performed in 192 patients with sporadic POI, and functional experiments were performed to explore the deleterious effects of mutations identified. Two novel missense variants in MCM8, c. A950T (p. H317L), and c. A1802G (p. H601R), were identified in two patients with POI but absent in 312 controls (the upper 90% confidence limit for the proportion 2/192 is 2.24%). The HeLa cells overexpressing mutant p. H317L and p. H601R showed higher sensitivity to MMC compared with wild type. Furthermore, mutant p. H317L showed decreased repair capacity after MMC treatment with much more histone H2AX phosphorylation remaining after 2 hours of recovery. Our result suggests novel mutations p. H317L and p. H601R in the MCM8 gene are potentially causative for POI by dysfunctional DNA repair. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Approximate Entropy Values Demonstrate Impaired Neuromotor Control of Spontaneous Leg Activity in Infants with Myelomeningocele

PubMed Central

Smith, Beth A.; Teulier, Caroline; Sansom, Jennifer; Stergiou, Nicholas; Ulrich, Beverly D.

2012-01-01

Purpose One obstacle to providing early intervention to infants with myelomeningocele (MMC) is the challenge of quantifying impaired neuromotor control of movements early in life. Methods We used the nonlinear analysis tool Approximate Entropy (ApEn) to analyze periodicity and complexity of supine spontaneous lower extremity movements of infants with MMC and typical development (TD) at 1, 3, 6 and 9 months of age. Results Movements of infants with MMC were more regular and repeatable (lower ApEn values) than movements of infants with TD indicating less adaptive and flexible movement patterns. For both groups ApEn values decreased with age, and the movements of infants with MMC were less complex than movements of infants with TD. Further, for infants with MMC, lesion level and age of walking onset correlated negatively with ApEn values. Conclusions Our study begins to demonstrate the feasibility of ApEn to identify impaired neuromotor control in infants with MMC. PMID:21829116

Mitomycin-C in dacryocystorhinostomy: From experimentation to implementation and the road ahead: A review.

PubMed

Nair, Akshay Gopinathan; Ali, Mohammad Javed

2015-04-01

Dacryocystorhinostomy (DCR) is the procedure of choice in patients with epiphora due to primary acquired nasolacrimal duct obstruction. The evolution of surgical tools, fiber-optic endoscopes, effective anesthesia techniques, and the adjunct use of antimetabolites intraoperatively; namely mitomycin-C (MMC) have significantly contributed to the advancement of DCR surgery. MMC is a systemic chemotherapeutic agent derived from Streptomyces caespitosus that inhibits the synthesis of DNA, cellular RNA, and protein by inhibiting the synthesis of collagen by fibroblasts. Even the cellular changes in the human nasal mucosal fibroblasts induced by MMC at an ultrastructural level have been documented. There, however, seems to be a lack of consensus regarding MMC: The dosage, the route of delivery/application, the time of exposure and subsequently what role each of these variables plays in the final outcome of the surgery. In this review, an attempt is made to objectively examine all the evidence regarding the role of MMC in DCR. MMC appears to improve the success rate of DCR.

Mitomycin-C in dacryocystorhinostomy: From experimentation to implementation and the road ahead: A review

PubMed Central

Nair, Akshay Gopinathan; Ali, Mohammad Javed

2015-01-01

Dacryocystorhinostomy (DCR) is the procedure of choice in patients with epiphora due to primary acquired nasolacrimal duct obstruction. The evolution of surgical tools, fiber-optic endoscopes, effective anesthesia techniques, and the adjunct use of antimetabolites intraoperatively; namely mitomycin-C (MMC) have significantly contributed to the advancement of DCR surgery. MMC is a systemic chemotherapeutic agent derived from Streptomyces caespitosus that inhibits the synthesis of DNA, cellular RNA, and protein by inhibiting the synthesis of collagen by fibroblasts. Even the cellular changes in the human nasal mucosal fibroblasts induced by MMC at an ultrastructural level have been documented. There, however, seems to be a lack of consensus regarding MMC: The dosage, the route of delivery/application, the time of exposure and subsequently what role each of these variables plays in the final outcome of the surgery. In this review, an attempt is made to objectively examine all the evidence regarding the role of MMC in DCR. MMC appears to improve the success rate of DCR. PMID:26044474

Trends in epidemiology and hospitalization utilization for myelomeningocele repair from 2000 to 2009.

PubMed

Harris, Dominic A; Cherian, Jacob; LoPresti, Melissa; Jea, Andrew; Lam, Sandi

2016-07-01

Although the incidence of myelomeningocele (MMC) has declined over the past decades with folic acid supplementation and prenatal screening, neural tube defects remain the most common birth defect in the USA. A majority of affected neonates require surgical repair. To characterize US trends in the epidemiology and hospital utilization of MMC repair over the past decade, we analyzed a nationally representative database. We queried the Healthcare Cost and Utilization Project (HCUP) Kid's Inpatient Database (KID) for all discharges with procedure code for MMC repair for the years 2000, 2003, 2006, and 2009. The cohorts from these time points were compared for their demographic and in-hospital variables. Results are reported as estimated frequencies and means with 95 % confidence intervals (CI). Sex, race, insurance status, family income level, and mortality of affected infants have not changed significantly over the decade. A majority of neonatal MMC repairs occur in larger hospital bed size and more specialized children's hospital centers. Of patients, 52.3 to 60 % receive VPS placement during the same admission as the primary MMC repair. Total hospital costs for the MMC hospitalizations have remained relatively stable from 42,843 dollars in 2003 to 46,749 dollars in 2009 (adjusted to 2009 dollars). Demographics of children having MMC repair have not changed significantly over the past decade, while these surgeries have become more concentrated in pediatric-specialized centers. There appears to be a plateau in public health and access advances with relatively stable cost of MMC hospital care.

Rural Zulu women's knowledge of and attitudes towards medical male circumcision.

PubMed

Ikwegbue, Joseph N; Ross, Andrew; Ogbonnaya, Harbor

2015-03-31

Medical male circumcision (MMC) is a key strategy in the South African HIV infection prevention package. Women may have a potentially powerful role in supporting such a strategy. Circumcision is not a traditional part of Zulu society, and Zulu women may have limited knowledge and ambivalent or negative attitudes towards MMC. This study employs quantitative data to expand insight into rural Zulu women's knowledge of and attitudes towards MMC, and is important as women could potentially yield a powerful positive or negative influence over the decisions of their partners and sons. A hospital-based antenatal clinic in rural KwaZulu-Natal. Participants were 590 pregnant, mostly isiZulu-speaking women. Data on their knowledge of and attitude towards MMC were collected using a questionnaire and were analysed descriptively. The majority of the women supported MMC; however, knowledge of the potential benefits was generally poor. Most would encourage their partners and sons to undergo MMC. The preferred place for the procedure was a hospital. Zulu participants supported MMC and would support their partners and children being circumcised. Knowledge around potential benefits was worryingly poor, and further research into disseminating information is essential. The findings highlight the need for an expanded campaign of health education for women, and innovative means are suggested to enhance information accessibility. Reasons for preferring that MMC be carried out in hospital need to be explored further.

Comparison of the effects of Mitomycin-C and sodium hyaluronate/carboxymethylcellulose [NH/CMC] (Seprafilm) on abdominal adhesions.

PubMed

Ozerhan, Ismail Hakkı; Urkan, Murat; Meral, Ulvi Mehmet; Unlu, Aytekin; Ersöz, Nail; Demirag, Funda; Yagci, Gokhan

2016-01-01

Intra-abdominal adhesions (IA) may occur after abdominal surgery and also may lead to complications such as infertility, intestinal obstruction and chronic pain. The aim of this study was to compare the effects of Mitomycin-C (MM-C) and sodium hyaluronate/carboxymethylcellulose [NH/CMC] on abdominal adhesions in a cecal abrasion model and to investigate the toxicity of MM-C on complete blood count (CBC) and bone marrow analyses. The study comprised forty rats in four groups (Control, Sham, Cecal abrasion + MM-C, and Cecal abrasion + NH/CMC). On postoperative day 21, all rats except for the control (CBC + femur resection) group, were sacrificed. Macroscopical and histopathological evaluations of abdominal adhesions were performed. In order to elucidate the side effects of MM-C; CBC analyses and femur resections were performed to examine bone marrow cellularity. CBC analyses and bone marrow cellularity assessment revealed no statistically significant differences between MM-C, NH/CMC and control groups. No significant differences in inflammation scores were observed between the groups. The MM-C group had significantly lower fibrosis scores compared to the NH/CMC and sham groups. Although the adhesion scores were lower in the MM-C group, the differences were not statistically significant. Despite its potential for systemic toxicity, MM-C may show some anti-fibrosis and anti-adhesive effects. MM-C is a promising agent for the prevention of IAs, and as such, further trials are warranted to study efficacy.

The effect of ICG on mitomycin C cytotoxicity in human tenon fibroblasts.

PubMed

Reeves, Graham; Wallis, Richard; Crowston, Jonathan G; Small, Keith M; Wells, Anthony P

2007-08-01

To examine the effects of indocyanine green (ICG) with and without mitomycin C (MMC) on proliferation of cultured human Tenon fibroblasts. Fibroblast monolayers were exposed to either MMC [0.4 mg/mL in phosphate buffered saline (PBS)] or PBS containing ICG (0.0625%, 0.125%, 0.25%, and 0.5% in 200 microL PBS) or a combination of MMC (0.4 mg/mL in PBS) and ICG (0.25% and 0.5%) for 5 minutes. Controls were exposed for 5 minutes to MMC, PBS, or culture medium containing no ICG. After treatment, the monolayers were washed and incubated in culture medium for 24, 48, 72 hours, and 1 week periods after which the number of viable cells was quantified. The presence of ICG alone, at concentrations ranging from 0.0625% to 0.5%, had no effect on the rate of fibroblast proliferation measured at any of the incubation periods. As expected, MMC treatment resulted in a significant reduction in viable fibroblast number (8.4+/-0.13x10(3)). ICG in combination with MMC did not significantly alter fibroblast numbers (8.5+/-0.05x10(3)) up to 1 week compared with MMC alone (8.4+/-0.12x10(3)). ICG at concentrations of 0.5% and below do not reduce proliferation of Tenon capsule fibroblasts. ICG did not potentiate or diminish the effect of MMC on Tenon capsule fibroblast proliferation.

Electron microscopic features of nasal mucosa treated with topical and circumostial injection of mitomycin C: implications in dacryocystorhinostomy.

PubMed

Ali, Mohammad Javed; Baig, Farhana; Lakshman, Mekala; Naik, Milind N

2015-01-01

To evaluate the ultrastructural effects of topical and circumostial injection of mitomycin C (COS-MMC) on nasal mucosa and compare them with the controls. The study also aimed at classifying the subcellular effects in detail. The nasal mucosa of 6 patients were subjected to 0.02% of mitomycin C for 3 minutes (3 patients) and 0.02% COS-MMC (3 patients) as per standard protocol, during endoscopic dacryocystorhinostomy. Normal nasal mucosa from untreated areas (2 each from topical and COS-MMC groups) were taken as controls after harvesting the treated areas. Full thickness tissues (5 mm × 5 mm) were collected for transmission electron microscopy, and ultrastructural effects were evaluated. Both topical and COS-MMC showed significant and distinct ultrastructural changes involving the epithelial, glandular, vascular, and fibrocollagenous tissues compared with the controls. There were profound changes within fibroblasts with intracellular edema, pleomorphic and vesicular mitochondria, dilated smooth and rough endoplasmic reticulum, and chromatin condensation. In addition, COS-MMC samples showed subepithelial hypocellularity with limited disorganization of structure. The changes in both the MMC groups were restricted to treated areas only. Both topical and COS-MMC show profound changes in nasal mucosa with more marked changes in COS-MMC group. These changes being limited in nature may help in enhancing the success of dacryocystorhinostomy by preventing cicatricial changes of the ostium, especially in high-risk cases such as revision and post-traumatic dacryocystorhinostomy.

Dexamethasone reduces mitomycin C-related inflammatory cytokine expression without inducing further cell death in corneal fibroblasts.

PubMed

Chang, Shu-Wen; Chou, San-Fang; Yu, Shuen-Yuen

2010-01-01

The purpose of this study was to investigate the effect of dexamethasone (DEX) on mitomycin C (MMC)-induced inflammatory cytokine expression in corneal fibroblasts. Primary human corneal fibroblasts were treated with MMC, dexamethasone, or in combination. Morphological changes and cell growth were documented using phase-contrast microscopy and PicoGreen assay, respectively. Cell apoptosis was evaluated by annexin V/propidium iodide staining, whereas viability was tested by the live/dead assay and analyzed by flow cytometry. The relative expression of interleukin-8 and monocyte chemoattractant protein-1 was investigated with quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Mitogen-activated protein kinase activation and mitogen-activated protein kinase phosphatase-1 expression were documented by Western blot analysis. We found that MMC induced corneal fibroblast elongation, apoptosis, and retarded cell growth, whereas DEX did not significantly alter cell morphology or viability. The combination of DEX and MMC did not induce additional apoptosis and cell death. DEX dose dependently down-regulated basal and MMC-induced interleukin-8 and monocyte chemoattractant protein-1 mRNA expression and protein secretion. DEX attenuated MMC-induced p38 and Jun N-terminal kinases activation and up-regulated expression. These suggested that DEX may inhibit MMC-induced interleukin-8 and monocyte chemoattractant protein-1 by up-regulating MKP-1 expression, which subsequently deactivated p38 and Jun N-terminal kinases activation. Combined MMC and DEX treatment may facilitate corneal wound healing.

Outcome and Life Satisfaction of Adults with Myelomeningocele

PubMed Central

Cope, Heidi; McMahon, Kelly; Heise, Elizabeth; Eubanks, Sonja; Garrett, Melanie; Gregory, Simon; Ashley-Koch, Allison

2013-01-01

Background Myelomeningocele (MMC) commonly causes impairments in body structure and functions as well as cognitive disabilities that can have an adverse effect on adult life. Improved medical care has resulted in increased numbers of individuals with MMC surviving to adulthood, however little is known about the impact of MMC on the lives of adults age 25 years or older. Objective To gain a better understanding of outcomes in education, employment, relationships, reproduction and life satisfaction of adults with MMC. Methods A primarily quantitative multiple-choice questionnaire designed to capture outcomes in education, employment, relationships and reproduction, along with a previously validated life satisfaction checklist (LiSat-11), was completed by adults with MMC. Relationships between demographic variables, outcomes and life satisfaction were determined using cross tabulation analysis, logistic regression and linear regression. Results Ninety adults with MMC, age 25 to 85 years (median age 32), reported a diverse range of outcomes in education, employment, relationships and reproduction. The most consistent variable associated with difficulty attaining adult milestones was hydrocephalus, the presence of which reduced the likelihood of living independently (p=<0.001), having a partner (p=0.003) and reproducing (p=<0.001), but did not contribute to reduced life satisfaction. Conclusions Adults with MMC, especially those without hydrocephalus, can obtain gainful employment, live independently, form partner relationships and have children, and these achievements contribute to life satisfaction. While MMC does not affect overall reported life satisfaction for adults, attention should be paid to specific domains with less reported satisfaction. PMID:23769483

Tribological coating of titanium alloys by laser processing

NASA Astrophysics Data System (ADS)

Pang, Wang

Titanium-based alloys have been used for aerospace materials for many years. Recently, these alloys are now being increasingly considered for automotive, industrial and consumer applications. Their excellent creep resistance, corrosion resistance and relative higher specific strength ratio are attractive for many applications. However, the main obstacle for the wide adoption of Ti alloys in various industries is their poor tribological properties. In slide wear, Ti deforms and adhesive wear readily occurs. Their poor tribological properties are mainly due to low hardness and absolute values of tensile and shear strength. Different surface modification techniques have been studied in order to improve the tribological characteristics of Ti alloys, i.e. PVD, nitrding, carburizing, boriding, plating etc. Coatings produced by these techniques have their own limitations such as thermal distortion and grain growth. A different approach is to introduce hard particles in the Ti alloy matrix to form a MMC coating, which has tailor-made hardness and wear resistance properties. Laser cladding or laser alloying techniques facilitate the fabrication of surface MMC on Ti alloys without thermal distortion to the substrate. In this project, the fabrication of hard and wear resistant layers of metal matrix composite on titanium alloys substrate by laser surface alloying was investigated. Powder mixtures of Mo and WC were used to form the MMC layer. By optimizing the processing parameters and pre-placed powder mixture compositions, surface MMC of different properties have been successfully fabricated on CP-Ti and Ti6A14V respectively. The structure and characteristics of the MMC surface were investigated by metallography, SEM, XRD, and E-DAX. It was found that the hardness of the laser alloyed Mo/WC MMC surface was 300% higher than that of the CP-Ti substrate Excellent metallurgical bonding with the MMC layer of the substrate has been achieved. The relative kinetic frictional tests were carried out and the results showed that the kinetic coefficient of friction of the laser fabricated Ti-Mo-WC MMC coatings was much lower than that of the CP-Ti and Ti6A14V substrate. The wear resistance of this Ti-Mo-WC MMC was found to be between 60 to 150 times better than those of CP-Ti. The experimental results also identified a key issue of mixing efficiency that the density of WC was much higher than that of Ti and Mo and this rendered poor mixing between the different constituents. This resulted in a relatively poor repeatability of the coating quality. To solve this issue, a lower density carbide phase, TiC, was used. The hardness and dry sliding wear resistance of the Ti-Mo-TiC MMC was found to be lower than those of Ti-Mo-WC MMC. The mixing efficiency of the TiC in the Ti-Mo-MMC was found to be better than the WC in Ti-Mo-WC MMC. This combination gave a harder and more wear resistant MMC with more uniform properties across the width and depth of the alloyed layer formed. A mathematical model for predicting the melt depth of the alloyed MMC layer was developed together with a heat transfer mechanism between layers of powders under the laser irradiation. The model facilitates the prediction of melt depth of the alloyed layer and the dilution ratio of the MMC layer. It thus enabled the composition of the MMC layer to be predicted and tailor made. The project results contribute significantly to the knowledge of improving the wear and frictional properties of one of the most important engineering metals for the automobile and aerospace industries.

Macromolecular crowding gives rise to microviscosity, anomalous diffusion and accelerated actin polymerization

NASA Astrophysics Data System (ADS)

Rashid, Rafi; Chee, Stella Min Ling; Raghunath, Michael; Wohland, Thorsten

2015-05-01

Macromolecular crowding (MMC) has been used in various in vitro experimental systems to mimic in vivo physiology. This is because the crowded cytoplasm of cells contains many different types of solutes dissolved in an aqueous medium. MMC in the extracellular microenvironment is involved in maintaining stem cells in their undifferentiated state (niche) as well as in aiding their differentiation after they have travelled to new locations outside the niche. MMC at physiologically relevant fractional volume occupancies (FVOs) significantly enhances the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells during chemically induced adipogenesis. The mechanism by which MMC produces this enhancement is not entirely known. In the context of extracellular collagen deposition, we have recently reported the importance of optimizing the FVO while minimizing the bulk viscosity. Two opposing properties will determine the net rate of a biochemical reaction: the negative effect of bulk viscosity and the positive effect of the excluded volume, the latter being expressed by the FVO. In this study we have looked more closely at the effect of viscosity on reaction rates. We have used fluorimetry to measure the rate of actin polymerization and fluorescence correlation spectroscopy (FCS) to measure diffusion of various probes in solutions containing the crowder Ficoll at physiological concentrations. Similar to its effect on collagen, Ficoll enhanced the actin polymerization rate despite increasing the bulk viscosity. Our FCS measurements reveal a relatively minor component of anomalous diffusion. In addition, our measurements do suggest that microviscosity becomes relevant in a crowded environment. We ruled out bulk viscosity as a cause of the rate enhancement by performing the actin polymerization assay in glycerol. These opposite effects of Ficoll and glycerol led us to conclude that microviscosity becomes relevant at the length scale of the reacting molecules within a crowded microenvironment. The excluded volume effect (arising from crowding) increases the effective concentration of actin, which increases the reaction rate, while the microviscosity does not increase sufficiently to lower the reaction rate. This study reveals finer details about the mechanism of MMC.

Macromolecular crowding gives rise to microviscosity, anomalous diffusion and accelerated actin polymerization.

PubMed

Rashid, Rafi; Chee, Stella Min Ling; Raghunath, Michael; Wohland, Thorsten

2015-04-30

Macromolecular crowding (MMC) has been used in various in vitro experimental systems to mimic in vivo physiology. This is because the crowded cytoplasm of cells contains many different types of solutes dissolved in an aqueous medium. MMC in the extracellular microenvironment is involved in maintaining stem cells in their undifferentiated state (niche) as well as in aiding their differentiation after they have travelled to new locations outside the niche. MMC at physiologically relevant fractional volume occupancies (FVOs) significantly enhances the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells during chemically induced adipogenesis. The mechanism by which MMC produces this enhancement is not entirely known. In the context of extracellular collagen deposition, we have recently reported the importance of optimizing the FVO while minimizing the bulk viscosity. Two opposing properties will determine the net rate of a biochemical reaction: the negative effect of bulk viscosity and the positive effect of the excluded volume, the latter being expressed by the FVO. In this study we have looked more closely at the effect of viscosity on reaction rates. We have used fluorimetry to measure the rate of actin polymerization and fluorescence correlation spectroscopy (FCS) to measure diffusion of various probes in solutions containing the crowder Ficoll at physiological concentrations. Similar to its effect on collagen, Ficoll enhanced the actin polymerization rate despite increasing the bulk viscosity. Our FCS measurements reveal a relatively minor component of anomalous diffusion. In addition, our measurements do suggest that microviscosity becomes relevant in a crowded environment. We ruled out bulk viscosity as a cause of the rate enhancement by performing the actin polymerization assay in glycerol. These opposite effects of Ficoll and glycerol led us to conclude that microviscosity becomes relevant at the length scale of the reacting molecules within a crowded microenvironment. The excluded volume effect (arising from crowding) increases the effective concentration of actin, which increases the reaction rate, while the microviscosity does not increase sufficiently to lower the reaction rate. This study reveals finer details about the mechanism of MMC.

Atomic force microscope-related study membrane-associated cytotoxicity in human pterygium fibroblasts induced by mitomycin C.

PubMed

Cai, Xiaofang; Yang, Xiaoxi; Cai, Jiye; Wu, Shixian; Chen, Qian

2010-03-25

Mitomycin C (MMC) has been shown to have a therapeutic effect against human pterygium fibroblasts (HPFs) by inducing apoptosis. However, there is little data about the effect of it on plasma membrane. In the present study, the cytotoxicity of MMC to HPFs including inhibiting cell growth, inducing apoptosis and bringing about membrane toxicity was investigated. It was found that MMC could significantly suppress the proliferation of HPFs in a dose-dependent manner by CCK-8 assay. Flow cytometric analysis also revealed that treatment with MMC resulted in increased percentages of apoptotic cells in a dose-dependent manner. Membrane lipid peroxidation level, lactate dehydrogenase (LDH) leakage, membrane surface topography, and membrane rigidity alterations were investigated to assess the membrane toxicity induced by MMC. Treatment with MMC at different concentrations accelerated membrane lipid peroxidation and potentiated LDH leakage, which was consistent with disturbance of membrane surface and decrease of membrane elasticity detected by atomic force microscopy. All the above changes led to the disturbed intracellular Ca(2+) homeostasis, which was an important signal triggering apoptosis. Hence, the membrane toxicity induced by MMC might play an important role in the process of apoptotic induction and the calcium channel may be one of the apoptosis mechanisms.

Predicting tumor responses to mitomycin C on the basis of DT-diaphorase activity or drug metabolism by tumor homogenates: implications for enzyme-directed bioreductive drug development.

PubMed

Phillips, R M; Burger, A M; Loadman, P M; Jarrett, C M; Swaine, D J; Fiebig, H H

2000-11-15

Mitomycin C (MMC) is a clinically used anticancer drug that is reduced to cytotoxic metabolites by cellular reductases via a process known as bioreductive drug activation. The identification of key enzymes responsible for drug activation has been investigated extensively with the ultimate aim of tailoring drug administration to patients whose tumors possess the biochemical machinery required for drug activation. In the case of MMC, considerable interest has been centered upon the enzyme DT-diaphorase (DTD) although conflicting reports of good and poor correlations between enzyme activity and response in vitro and in vivo have been published. The principle aim of this study was to provide a definitive answer to the question of whether tumor response to MMC could be predicted on the basis of DTD activity in a large panel of human tumor xenografts. DTD levels were measured in 45 human tumor xenografts that had been characterized previously in terms of their sensitivity to MMC in vitro and in vivo (the in vivo response profile to MMC was taken from work published previously). A poor correlation between DTD activity and antitumor activity in vitro as well as in vivo was obtained. This study also assessed the predictive value of an alternative approach based upon the ability of tumor homogenates to metabolize MMC. This approach is based on the premise that the overall rate of MMC metabolism may provide a better indicator of response than single enzyme measurements. MMC metabolism was evaluated in tumor homogenates (clarified by centrifugation at 1000 x g for 1 min) by measuring the disappearance of the parent compound by HPLC. In responsive [T/C <10% (T/C defined as the relative size of treated and control tumors)] and resistant (T/C >50%) tumors, the mean half life of MMC was 75+/-48.3 and 280+/-129.6 min, respectively. The difference between the two groups was statistically significant (P < 0.005). In conclusion, these results unequivocally demonstrate that response to MMC in vivo cannot be predicted on the basis of DTD activity. Measurement of MMC metabolism by tumor homogenates on the other hand may provide a better indicator of tumor response, and further studies are required to determine whether this approach has real clinical potential in terms of individualizing patient chemotherapy.

Experimental and theoretical study on the excited-state dynamics of ortho-, meta-, and para-methoxy methylcinnamate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyazaki, Yasunori; Yamamoto, Kanji; Aoki, Jun

The S{sub 1} state dynamics of methoxy methylcinnamate (MMC) has been investigated under supersonic jet-cooled conditions. The vibrationally resolved S{sub 1}-S{sub 0} absorption spectrum was recorded by laser induced fluorescence and mass-resolved resonant two-photon ionization spectroscopy and separated into conformers by UV-UV hole-burning (UV-UV HB) spectroscopy. The S{sub 1} lifetime measurements revealed different dynamics of para-methoxy methylcinnamate from ortho-methoxy methylcinnamate and meta-methoxy methylcinnamate (hereafter, abbreviated as p-, o-, and m-MMCs, respectively). The lifetimes of o-MMC and m-MMC are on the nanosecond time scale and exhibit little tendency of excess energy dependence. On the other hand, p-MMC decays much faster andmore » its lifetime is conformer and excess energy dependent. In addition, the p-MMC-H{sub 2}O complex was studied to explore the effect of hydration on the S{sub 1} state dynamics of p-MMC, and it was found that the hydration significantly accelerates the nonradiative decay. Quantum chemical calculation was employed to search the major decay route from S{sub 1}(ππ{sup ∗}) for three MMCs and p-MMC-H{sub 2}O in terms of (i) trans → cis isomerization and (ii) internal conversion to the {sup 1}nπ{sup ∗} state. In o-MMC and m-MMC, the large energy barrier is created for the nonradiative decay along (i) the double-bond twisting coordinate (∼1000 cm{sup −1}) in S{sub 1} as well as (ii) the linear interpolating internal coordinate (∼1000 cm{sup −1}) from S{sub 1} to {sup 1}nπ{sup ∗} states. The calculation on p-MMC decay dynamics suggests that both (i) and (ii) are available due to small energy barrier, i.e., 160 cm{sup −1} by the double-bond twisting and 390 cm{sup −1} by the potential energy crossing. The hydration of p-MMC raises the energy barrier of the IC route to the S{sub 1}/{sup 1}nπ{sup ∗} conical intersection, convincing that the direct isomerization is more likely to occur.« less

Evaluation strategy for the I-95 CC electronic credentialing program

DOT National Transportation Integrated Search

1999-03-01

The electronic credentialing field operational test will undertake the model deployment of electronic credentialing for commercial vehicles. The project will involve the development of state-specific electronic credentialing systems.

Safety and efficacy of Intraurethral Mitomycin C Hydrogel for prevention of post-traumatic anterior urethral stricture recurrence after internal urethrotomy.

PubMed

Moradi, Mahmoudreza; Derakhshandeh, Katayoun; Karimian, Babak; Fasihi, Mahtab

2016-07-01

Evaluation of the safety and efficacy of intraurethral Mitomycin C (MMC) hydrogel for prevention of post-traumatic anterior urethral stricture recurrence after internal urethrotomy. A thermoresponsive hydrogel base consisting of 0.8 mg MMC with 1cc water and propylene glycol to PF-127 poloxamer was used in theater. 40 male patients with short, non-obliterated, urethral stricture were randomized into 2 groups: control and MMC. After internal urethrotomy, the MMC group patients received the MMC-Hydrogel while the others were just catheterized. Both groups had their catheters for at least 1 week. After surgery, they were followed up by means of medical history and physical examination, monitoring voiding patterns and retrograde urethrogram at 1 month, 6 months and 1 year after surgery. 40 male patients between 14 to 89 years old (Mean = 54.15) underwent internal urethrotomy. The average age for the control and MMC group was 54.55±21.25 and 53.75±24.75 respectively. In a comparison of age between the two groups, they were matched (P=0.574). Stricture length was 10.7±5.9 and 9.55±4.15 mm for the control and MMC group respectively. There were no statistically meaningful differences between the two groups (P=0.485). Fifteen patients had a history of one previous internal urethrotomy which in a comparison between the two groups meant there was no meaningful difference (P=0.327). During postoperative follow up, total urethral stricture recurrence happened in 12 patients: 10 patients (50%) in control group and 2 patients (10%) in MMC group. The difference was statistically significant (P=0.001). There were no significant complications associated with the MMC injection in our patients. Based on our results, MMC Hydrogel may have an anti-fibrotic action preventing post-traumatic anterior urethral stricture recurrence with no side effects on pre-urethral tissue. Due to our study limitations, our follow up time and the small number of patients, our results were not conclusive and further studies will be needed with a longer follow up time. © 2016 KUMS, All rights reserved.

Fetal surgery for spina bifida: past, present, future.

PubMed

Adzick, N Scott

2013-02-01

Open spina bifida or myelomeningocele (MMC) is a common birth defect that is associated with significant lifelong morbidity. Little progress has been made in the postnatal surgical management of the child with spina bifida. Postnatal surgery is aimed at covering the exposed spinal cord, preventing infection, and treating hydrocephalus with a ventricular shunt. Experimental and clinical evidence suggest that the primary cause of the neurologic defects associated with MMC is not simply incomplete neurulation, but rather chronic, mechanical and amniotic-fluid induced chemical trauma that progressively damages the exposed neural tissue during gestation. The cerebrospinal fluid leak through the MMC leads to hindbrain herniation and hydrocephalus. In utero repair of open spina bifida is now performed in selected patients and presents an additional therapeutic alternative for expectant mothers carrying a fetus with MMC. In the past, studies in animal models and clinical case series laid the groundwork for a clinical trial to test the safety and efficacy of fetal MMC repair. In the present, a prospective, randomized study (the MOMS trial) has shown that fetal surgery for MMC before 26 weeks' gestation may preserve neurologic function, reverse the hindbrain herniation of the Chiari II malformation, and obviate the need for postnatal placement of a ventriculoperitoneal shunt. However, this study also demonstrates that fetal surgery is associated with significant risks related to the uterine scar and premature birth. In the future, research will expand our understanding of the pathophysiology of MMC, evaluate the long-term impact of in-utero intervention, and to refine timing and technique of fetal MMC surgery using tissue engineering technology. Copyright © 2013 Elsevier Inc. All rights reserved.

[Intraoperative chemotherapy against peritoneal dissemination of gastric cancer with intraperitoneal activated carbon particles adsorbing mitomycin C].

PubMed

Hagiwara, A; Takahashi, T; Sawai, K; Yamaguchi, T; Iwamoto, A; Yoneyama, C

1989-02-01

For prevention and therapy of peritoneal dissemination, a new dosage from (MMC-CH) comprising carbon particles adsorbing mitomycin C was given to 44 patients (the MMC-CH group) undergoing gastrectomy for gastric cancer, of which advancing stage was classified into the category of H0, and S2 or S3, and P0, P1, P2 or P3 according to the General Rules for the Gastric Cancer Study. MMC-CH, principally at 50 mg person in terms of mitomycin C was administered intraperitoneally before the surgical wound was closed. Historical control group was composed of 53 patients not given MMC-CH, who underwent gastrectomy for gastric cancer in the same advancing stage as those of the 44 patients. There was statistically no significant difference of age, sex, depth of infiltration, macroscopically and microscopically defined progression of lymph-nodal metastases, between the MMC-CH group and the historical control group. The survival rate of the overall patients, and each group of the patients with the lesion defined as P0, P1, P2, or P3 was compared with Kaplan-Meier's method between the MMC-CH group and the historical control group. In the MMC-CH group, the survival rates of the overall patients and the patients with P0, P1, or P2 lesion were statistically significantly higher than those in the historical control group. However, the rate of the P3 patients in the MMC-CH group was statistically significantly lower than in the historical control group.

Meet the new kids on the credentialing block.

PubMed

1998-12-01

The Washington, DC-based American Nurses Credentialing Center's nurse case manager credential continues to get a rocky reception. Following difficulties with last year's test and controversy over the credential's eligibility criteria, the number of applicants remains small. Meanwhile, the inaugural test for the Center for Case Management's new case management administrator certified credential took place on Oct. 24, 1998. While results are not yet available, officials at the South Natick, MA-based Center report that the diversity of candidates for the credential reflected the exam's cross-continuum focus. The Oakbrook Terrace, IL-based Joint Commission on Accreditation of Healthcare Organizations is still developing its upcoming "Diplomate of the Academy" credential, which will feature a formal curriculum and course work.

Improved Wear Resistance of Low Carbon Steel with Plasma Melt Injection of WC Particles

NASA Astrophysics Data System (ADS)

Liu, Aiguo; Guo, Mianhuan; Hu, Hailong

2010-08-01

Surface of a low carbon steel Q235 substrate was melted by a plasma torch, and tungsten carbide (WC) particles were injected into the melt pool. WC reinforced surface metal matrix composite (MMC) was synthesized. Dry sliding wear behavior of the surface MMC was studied and compared with the substrate. The results show that dry sliding wear resistance of low carbon steel can be greatly improved by plasma melt injection of WC particles. Hardness of the surface MMC is much higher than that of the substrate. The high hardness lowers the adhesion and abrasion of the surface MMC, and also the friction coefficient of it. The oxides formed in the sliding process also help to lower the friction coefficient. In this way, the dry sliding wear resistance of the surface MMC is greatly improved.

Preclinical Evaluation of Promitil, a Radiation-Responsive Liposomal Formulation of Mitomycin C Prodrug, in Chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Xi; Warner, Samuel B.; Wagner, Kyle T.

Purpose: To examine the effect of radiation on in vitro drug activation and release of Promitil, a pegylated liposomal formulation of a mitomycin C (MMC) lipid-based prodrug; and examine the efficacy and toxicity of Promitil with concurrent radiation in colorectal cancer models. Methods and Materials: Promitil was obtained from Lipomedix Pharmaceuticals (Jerusalem, Israel). We tested the effects of radiation on release of active MMC from Promitil in vitro. We next examined the radiosensitization effect of Promitil in vitro. We further evaluated the toxicity of a single injection of free MMC or Promitil when combined with radiation by assessing the effects on blood counts and in-fieldmore » skin and hair toxicity. Finally, we compared the efficacy of MMC and Promitil in chemoradiotherapy using mouse xenograft models. Results: Mitomycin C was activated and released from Promitil in a controlled-release profile, and the rate of release was significantly increased in medium from previously irradiated cells. Both Promitil and MMC potently radiosensitized HT-29 cells in vitro. Toxicity of MMC (8.4 mg/kg) was substantially greater than with equivalent doses of Promitil (30 mg/kg). Mice treated with human-equivalent doses of MMC (3.3 mg/kg) experienced comparable levels of toxicity as Promitil-treated mice at 30 mg/kg. Promitil improved the antitumor efficacy of 5-fluorouracil–based chemoradiotherapy in mouse xenograft models of colorectal cancer, while equitoxic doses of MMC did not. Conclusions: We demonstrated that Promitil is an attractive agent for chemoradiotherapy because it demonstrates a radiation-triggered release of active drug. We further demonstrated that Promitil is a well-tolerated and potent radiosensitizer at doses not achievable with free MMC. These results support clinical investigations using Promitil in chemoradiotherapy.« less

Ex Vivo Maintenance of Primary Human Multiple Myeloma Cells through the Optimization of the Osteoblastic Niche

PubMed Central

Zhang, Wenting; Gu, Yexin; Sun, Qiaoling; Siegel, David S.; Tolias, Peter; Yang, Zheng

2015-01-01

We previously reported a new approach for culturing difficult-to-preserve primary patient-derived multiple myeloma cells (MMC) using an osteoblast (OSB)-derived 3D tissue scaffold constructed in a perfused microfluidic environment and a culture medium supplemented with patient plasma. In the current study, we used this biomimetic model to show, for the first time, that the long-term survival of OSB is the most critical factor in maintaining the ex vivo viability and proliferative capacity of MMC. We found that the adhesion and retention of MMC to the tissue scaffold was meditated by osteoblastic N-cadherin, as one of potential mechanisms that regulate MMC-OSB interactions. However, in the presence of MMC and patient plasma, the viability and osteogenic activity of OSB became gradually compromised, and consequently MMC could not remain viable over 3 weeks. We demonstrated that the long-term survival of both OSB and MMC could be enhanced by: (1) optimizing perfusion flow rate and patient-derived plasma composition in the culture medium and (2) replenishing OSB during culture as a practical means of prolonging MMC’s viability beyond several weeks. These findings were obtained using a high-throughput well plate-based perfusion device from the perspective of optimizing the ex vivo preservation of patient-derived MM biospecimens for downstream use in biological studies and chemosensitivity analyses. PMID:25973790

Melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 modified at the para position of the benzyl side chain (DPhe): importance for mouse melanocortin-3 receptor agonist versus antagonist activity.

PubMed

Proneth, Bettina; Pogozheva, Irina D; Portillo, Federico P; Mosberg, Henry I; Haskell-Luevano, Carrie

2008-09-25

The melanocortin-3 and -4 receptors (MC3R, MC4R) have been implicated in energy homeostasis and obesity. Whereas the physiological role of the MC4R is extensively studied, little is known about the MC3R. One caveat is the limited availability of ligands that are selective for the MC3R. Previous studies identified Ac-His-DPhe(p-I)-Arg-Trp-NH 2, which possessed partial agonist/antagonist pharmacology at the mMC3R while retaining full nanomolar agonist pharmacology at the mMC4R. These data allowed for the hypothesis that the DPhe position in melanocortin tetrapeptides can be used to examine ligand side-chain determinants important for differentiation of mMC3R agonist versus antagonist activity. A series of 15 DPhe (7) modified Ac-His-DPhe (7)-Arg-Trp-NH 2 tetrapeptides has been synthesized and pharmacologically characterized. Most notable results include the identification of modifications that resulted in potent antagonists/partial agonists at the mMC3R and full, potent agonists at the mMC4R. These SAR studies provide experimental evidence that the molecular mechanism of antagonism at the mMC3R differentiates this subtype from the mMC4R.

Melanocortin Tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 Modified at the Para Position of the Benzyl Side Chain (DPhe): Importance for Mouse Melanocortin-3 Receptor Agonist versus Antagonist Activity

PubMed Central

Proneth, Bettina; Pogozheva, Irina D.; Portillo, Federico P.; Mosberg, Henry I.; Haskell-Luevano, Carrie

2010-01-01

The melanocortin-3 and -4 receptors (MC3R, MC4R) have been implicated in energy homeostasis and obesity. Whereas the physiological role of the MC4R is extensively studied, little is known about the MC3R. One caveat is the limited availability of ligands that are selective for the MC3R. Previous studies identified Ac-His-DPhe(p-I)-Arg-Trp-NH2, which possessed partial agonist/antagonist pharmacology at the mMC3R while retaining full nanomolar agonist pharmacology at the mMC4R. These data allowed for the hypothesis that the DPhe position in melanocortin tetrapeptides can be used to examine ligand side-chain determinants important for differentiation of mMC3R agonist versus antagonist activity. A series of 15 DPhe7 modified Ac-His-DPhe7-Arg-Trp-NH2 tetrapeptides has been synthesized and pharmacologically characterized. Most notable results include the identification of modifications that resulted in potent antagonists/partial agonists at the mMC3R and full, potent agonists at the mMC4R. These SAR studies provide experimental evidence that the molecular mechanism of antagonism at the mMC3R differentiates this subtype from the mMC4R. PMID:18800761

Biodegradable magnesium-hydroxyapatite metal matrix composites.

PubMed

Witte, Frank; Feyerabend, Frank; Maier, Petra; Fischer, Jens; Störmer, Michael; Blawert, Carsten; Dietzel, Wolfgang; Hort, Norbert

2007-04-01

Recent studies indicate that there is a high demand to design magnesium alloys with adjustable corrosion rates and suitable mechanical properties. An approach to this challenge might be the application of metal matrix composite (MMC) based on magnesium alloys. In this study, a MMC made of magnesium alloy AZ91D as a matrix and hydroxyapatite (HA) particles as reinforcements have been investigated in vitro for mechanical, corrosive and cytocompatible properties. The mechanical properties of the MMC-HA were adjustable by the choice of HA particle size and distribution. Corrosion tests revealed that HA particles stabilised the corrosion rate and exhibited more uniform corrosion attack in artificial sea water and cell solutions. The phase identification showed that all samples contained hcp-Mg, Mg(17)Al(12), and HA before and after immersion. After immersion in artificial sea water CaCO3 was found on MMC-HA surfaces, while no formation of CaCO3 was found after immersion in cell solutions with and without proteins. Co-cultivation of MMC-HA with human bone derived cells (HBDC), cells of an osteoblasts lineage (MG-63) and cells of a macrophage lineage (RAW264.7) revealed that RAW264.7, MG-63 and HBDC adhere, proliferate and survive on the corroding surfaces of MMC-HA. In summary, biodegradable MMC-HA are cytocompatible biomaterials with adjustable mechanical and corrosive properties.

Determination of in vivo behavior of mitomycin C-loaded o/w soybean oil microemulsion and mitomycin C solution via gamma camera imaging.

PubMed

Kotmakçı, Mustafa; Kantarcı, Gülten; Aşıkoğlu, Makbule; Ozkılıç, Hayal; Ertan, Gökhan

2013-09-01

In this study, a microemulsion system was evaluated for delivery of mitomycin C (MMC). To track the distribution of the formulated drug after intravenous administration, radiochemical labeling and gamma scintigraphy imaging were used. The aim was to evaluate a microemulsion system for intravenous delivery of MMC and to compare its in vivo behavior with that of the MMC solution. For microemulsion formulation, soybean oil was used as the oil phase. Lecithin and Tween 80 were surfactants and ethanol was the cosurfactant. To understand the whole body localization of MMC-loaded microemulsion, MMC was labeled with radioactive technetium and gamma scintigraphy was applied for visualization of drug distribution. Radioactivity in the bladder 30 minutes after injection of the MMC solution was observed, according to static gamma camera images. This shows that urinary excretion of the latter starts very soon. On the other hand, no radioactivity appeared in the urinary bladder during the 90 minutes following the administration of MMC-loaded microemulsion. The unabated radioactivity in the liver during the experiment shows that the localization of microemulsion formulation in the liver is stable. In the light of the foregoing, it is suggested that this microemulsion formulation may be an appropriate carrier system for anticancer agents by intravenous delivery in hepatic cancer chemotherapy.

Alpha-momorcharin enhances Tobacco mosaic virus resistance in tobaccoNN by manipulating jasmonic acid-salicylic acid crosstalk.

PubMed

Yang, Ting; Zhu, Li-Sha; Meng, Yao; Lv, Rui; Zhou, Zhuo; Zhu, Lin; Lin, Hong-Hui; Xi, De-Hui

2018-04-01

Alpha-momorcharin (α-MMC) is a type-I ribosome inactivating protein (RIP) with a molecular weight of 29 kDa found in plants. This protein has been shown to be effective against a broad range of human viruses and also has anti-tumor activities. However, the mechanism by which α-MMC induces plant defense responses and regulates the N gene to promote resistance to the Tobacco mosaic virus (TMV) is still not clear. By using pharmacological and infection experiments, we found that α-MMC enhances TMV resistance of tobacco plants containing the N gene (tobacco NN ). Our results showed that plants pretreated with 0.5 mg/ml α-MMC could relieve TMV-induced oxidative damage, had enhanced the expression of the N gene and increased biosynthesis of jasmonic acid (JA) and salicylic acid (SA). Moreover, transcription of JA and SA signaling pathway genes were increased, and their expression persisted for a longer period of time in plants pretreated with α-MMC compared with those pretreated with water. Importantly, exogenous application of 1-Aminobenzotriazole (ABT, SA inhibitor) and ibuprofen (JA inhibitor) reduced α-MMC induced plant resistance under viral infection. Thus, our results revealed that α-MMC enhances TMV resistance of tobacco NN plants by manipulating JA-SA crosstalk. Copyright © 2017 Elsevier GmbH. All rights reserved.

Antifibrotic effects of pirfenidone on Tenon's fibroblasts in glaucomatous eyes: comparison with mitomycin C and 5-fluorouracil.

PubMed

Na, Jung Hwa; Sung, Kyung Rim; Shin, Jin A; Moon, Jung Il

2015-09-01

The purpose of this study was to evaluate the antifibrotic effects of pirfenidone (PFD) on primary cultured human Tenon's fibroblasts (HTFs) from primary open-angle glaucoma (POAG) eyes, compared to mitomicin C (MMC) and 5-fluorouracil (5-FU). Samples of human Tenon's capsule were obtained during respective surgeries from three groups of patients: patients with cataract (CAT group), patients with POAG who underwent glaucoma filtration surgery (GFS) (POAG1 group), and patients with POAG who underwent GFS due to failed bleb of previous GFS (POAG2 group). Cell toxicity, cell migration, and the expression level of α-smooth muscle actin (α-SMA) protein were evaluated in primary cultured HTFs from the three patient groups after treatment (PFD, MMC, or 5-FU). Overall, cell viability after PFD treatment was higher compared to MMC treatment (82.3 ± 5.1 % vs 56.7 ± 3.8 %; p = 0.001) and comparable to 5-FU treatment (82.3 ± 5.1 % vs 85.7 ± 10.7 %, p = 0.214) at the same concentration (0.4 mg/ml). Both 0.3 mg/ml PFD and 0.1 mg/ml MMC inhibited cell migration compared to control (without treatment) cells (p = 0.014 and 0.005, respectively), while 0.2 mg/ml 5-FU showed the highest degree of cell migration among the three agents in the POAG1 group (PFD vs MMC vs 5-FU; 29.5 ± 2.1 % vs 34.5 ± 0.7 % vs 76.0 ± 8.5 %, PFD vs MMC; p = 1.000, PFD vs 5-FU; p = 0.008, MMC vs 5-FU; p = 0.011). PFD (0.1 or 0.3 mg/ml) and MMC (0.05 and 0.1 mg/ml) treatment significantly reduced the protein expression level of α-SMA in the POAG 1 group (all p < 0.05), and the α-SMA protein level following treatment with 0.3 mg/ml PFD was lower than that of 0.1 mg/ml MMC (p = 0.040). PFD showed less cytotoxicity compared to MMC. PFD and MMC inhibited cell migration and reduced α-SMA protein expression levels, while 5-FU showed neither inhibition of cell migration nor reduction in α-SMA expression level. These findings indicate PFD as a potential adjunctive antifibrotic agent to prevent bleb failure during GFS.

Two-year survival of Ahmed valve implantation in the first 2 years of life with and without intraoperative mitomycin-C.

PubMed

Al-Mobarak, Faisal; Khan, Arif O

2009-10-01

To evaluate the effect of intraoperative mitomycin-C (MMC) on polypropylene Ahmed glaucoma valve (AGV) survival 2 years after implantation during the first 2 years of life. Retrospective institutional comparative series (1995-2005). Thirty-one eyes of 27 patients (23 unilateral, 4 bilateral; 16 boys, 11 girls) undergoing AGV implantation at a mean age of 11.1 months (standard deviation [SD], 5.46), all of which had 2 years of regular postoperative follow-up. MMC was applied intraoperatively in those cases in the area of AGV implantation in 16 (52%) and was not applied in 15 (48%). In some eyes, MMC was applied intraoperatively in cases done by the surgeons who routinely used MMC for all AGV implantation in young children. Failure was defined as intraocular pressure (IOP) > 22 mmHg with or without glaucoma medications, the need for an additional procedure for IOP control, or the occurrence of significant complications (e.g., endophthalmitis, retinal detachment, persistent hypotony [IOP < 5 mmHg]). Survival was the absence of failure. Failure or significant complications as defined. Mean survival for the non-MMC eyes (22.15 months; standard error [SE], 1.93) was significantly longer than survival for the MMC eyes (16.25 months; SE, 2.17) by the log-rank test (P = 0.025). The difference in cumulative survival at 2 years was also significantly different by log-rank test (P = 0.001): 80.0% (SE 10.3) and 31.3% (SE 11.6), respectively. Rather than improved survival, intraoperative use of MMC was associated with shorter survival 2 years after AGV implantation during the first 2 years of life. We speculate that MMC-induced tissue death can stimulate a reactive fibrosis around the AGV in very young eyes.

Tumorigenic risk of human induced pluripotent stem cell explants cultured on mouse SNL76/7 feeder cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamada, Mizuna; Mitsui, Youji, E-mail: y-mitsui8310@hb.tp1.jp; Kumazaki, Tsutomu

2014-10-24

Highlights: • hiPS cell explants formed malignant tumors when SNL76/7 feeder cells were used. • Multi type tumors developed by interaction of SNL76/7 feeder cells with hiPS cells. • Tumorigenic risk occurs by co-culture of hiPS cells with SNL76/7 feeder cells. - Abstract: The potential for tumor formation from transplanted human induced pluripotent stem cell (hiPSC) derivatives represents a high risk in their application to regenerative medicine. We examined the genetic origin and characteristics of tumors, that were formed when 13 hiPSC lines, established by ourselves, and 201B7 hiPSC from Kyoto University were transplanted into severe combined immune-deficient (SCID) mice.more » Though teratomas formed in 58% of mice, five angiosarcomas, one malignant solitary fibrous tumor and one undifferentiated pleomorphic sarcoma formed in the remaining mice. Three malignant cell lines were established from the tumors, which were derived from mitomycin C (MMC)-treated SNL76/7 (MMC-SNL) feeder cells, as tumor development from fusion cells between MMC-SNL and hiPSCs was negative by genetic analysis. While parent SNL76/7 cells produced malignant tumors, neither MMC-SNL nor MMC-treated mouse embryo fibroblast (MEF) produced malignant tumors. When MMC-SNL feeder cells were co-cultured with hiPSCs, growing cell lines were generated, that expressed genes similar to the parent SNL76/7 cells. Thus, hiPSCs grown on MMC-SNL feeder cells have a high risk of generating feeder-derived malignant tumors. The possible mechanism(s) of growth restoration and the formation of multiple tumor types are discussed with respect of the interactions between MMC-SNL and hiPSC.« less

Evaluating acetate metabolism for imaging and targeting in multiple myeloma

PubMed Central

Fontana, Francesca; Ge, Xia; Su, Xinming; Hathi, Deep; Xiang, Jingyu; Cenci, Simone; Civitelli, Roberto; Shoghi, Kooresh I.; Akers, Walter J.; D’avignon, Andre

2016-01-01

Purpose We hypothesized that in multiple myeloma cells (MMC), high membrane biosynthesis will induce acetate uptake in vitro and in vivo. Here, we studied acetate metabolism and targeting in MMC in vitro and tested the efficacy of 11C-acetate-PET (positron emission tomography) to detect and quantitatively image myeloma treatment response in vivo. Experimental design Acetate fate tracking using 13C-edited-1H NMR (nuclear magnetic resonance) was performed to study in vitro acetate uptake and metabolism in MMC. Effects of pharmacological modulation of acetate transport or acetate incorporation into lipids on MMC cell survival and viability were assessed. Preclinical mouse MM models of subcutaneous and bone tumors were evaluated using 11C-acetate-PET/CT imaging and tissue biodistribution. Results In vitro, NMR showed significant uptake of acetate by MMC, and acetate incorporation into intracellular metabolites and membrane lipids. Inhibition of lipid synthesis and acetate transport was toxic to MMC, while sparing resident bone cells or normal B cells. In vivo, 11C-acetate uptake by PET imaging was significantly enhanced in subcutaneous and bone MMC tumors compared to unaffected bone or muscle tissue. Likewise, 11C-acetate uptake was significantly reduced in MM tumors after treatment. Conclusions Uptake of acetate from the extracellular environment was enhanced in MMC and was critical to cellular viability. 11C-acetate-PET detected the presence of myeloma cells in vivo, including uptake in intramedullary bone disease. 11C-acetate-PET also detected response to therapy in vivo. Our data suggested that acetate metabolism and incorporation into lipids was crucial to MM cell biology and that 11C-acetate-PET is a promising imaging modality for MM. PMID:27486177

The U.S. Army Surface Ablation Study: comparison of PRK, MMC-PRK, and LASEK in moderate to high myopia.

PubMed

Sia, Rose K; Ryan, Denise S; Edwards, Jayson D; Stutzman, Richard D; Bower, Kraig S

2014-04-01

To compare visual outcomes following photorefractive keratectomy (PRK), PRK with mitomycin C (MMC-PRK), and LASEK in moderate and high myopia in military personnel. This prospective, randomized contralateral eye study included 167 patients 21 years or older with manifest spherical equivalent -5.99 ± 1.40 diopters (D) (range: -3.88 to -9.38 D) randomized to either MMC-PRK or LASEK treatment in their dominant eye and conventional PRK without MMC in the fellow eye. All procedures were performed using the LADARVision 4000 Excimer Laser System (Alcon Surgical Inc., Ft. Worth, TX). High- and low-contrast visual acuities, manifest refraction, endothelial cell count, and corneal haze were evaluated up to 12 months postoperatively. At 12 months postoperatively, visual outcomes were comparable among the treatment groups. Corneal haze of any grade was less common in MMC-PRK compared to PRK at 1 month (21.4% vs 31.0%; P < .01) and 3 months (12.8% vs 35.9%; P = .03) postoperatively; it was also less common in MMC-PRK compared to LASEK at 1 month (21.4% vs 55.9%; P < .01), 3 months (12.8% vs 42.4%; P < .01), and 6 months (12.2% vs 36.4%; P = .03) postoperatively. Haze rate (grade 0.5 or higher) was comparable between LASEK and PRK. Clinically significant haze (grade 2 or higher) developed after PRK (4 eyes) and LASEK (2 eyes), but not after MMC-PRK. MMC-PRK showed some benefits in minimizing corneal haze formation. One year after surgery, there was no discernible difference in the postoperative refractive outcomes among the three methods. Copyright 2014, SLACK Incorporated.

Mitomycin C induces fibroblasts apoptosis and reduces epidural fibrosis by regulating miR-200b and its targeting of RhoE.

PubMed

Sun, Yu; Ge, Yingbin; Fu, Yuxuan; Yan, Lianqi; Cai, Jun; Shi, Kun; Cao, Xiaojian; Lu, Chun

2015-10-15

Mitomycin C (MMC) is known to reduce epidural fibrosis, but the underlying mechanisms have not yet been elucidated. Aberrant miR-200b expressions have been reported in multiple types of fibrotic tissues from many diseases. The aim of this study was to clarify the mechanism by which MMC induces fibroblasts apoptosis and reduces epidural fibrosis. The expression of miR-200b in human fibroblasts was determined after MMC treatment, and the targeted association between miR-200b and RhoE was determined using the luciferase activity assay. The effects of MMC and miR-200b on human fibroblasts apoptosis were evaluated using flow cytometry and western blot analysis. The effects of MMC and miR-200b on epidural fibrosis were evaluated using the Rydell classification, hydroxyproline content, apoptotic cell count and histological analysis. The study revealed that MMC could significantly downregulate miR-200b expression and induce human fibroblasts apoptosis. The direct downregulation of miR-200b could induce human fibroblasts apoptosis. Furthermore, we identified the binding sequence for miR-200b within the 3' untranslated region of RhoE. RhoE was confirmed to be a direct target of miR-200b, and RhoE itself acted as a promoter of fibroblasts apoptosis. The inhibition of miR-200b increased fibroblasts apoptosis and reduced epidural fibrosis in rats, which was in accordance with the effect of MMC. This study suggests that MMC induces fibroblasts apoptosis and reduces epidural fibrosis by regulating miR-200b expression and its targeting of RhoE. Copyright © 2015 Elsevier B.V. All rights reserved.

The Fanconi anemia pathway sensitizes to DNA alkylating agents by inducing JNK-p53-dependent mitochondrial apoptosis in breast cancer cells.

PubMed

Zhao, Lin; Li, Yanlin; He, Miao; Song, Zhiguo; Lin, Shu; Yu, Zhaojin; Bai, Xuefeng; Wang, Enhua; Wei, Minjie

2014-07-01

The Fanconi anemia/BRCA (FA/BRCA) DNA damage repair pathway plays a pivotal role in the cellular response to DNA alkylating agents and greatly influences drug response in cancer treatment. However, the molecular mechanisms underlying the FA/BRCA pathway reversed resistance have received limited attention. In the present study, we investigated the effect of Fanconi anemia complementation group F protein (FANCF), a critical factor of the FA/BRCA pathway, on cancer cell apoptosis induced by DNA alkylating agents such as mitomycin c (MMC). We found that FANCF shRNA potentiated MMC-induced cytotoxicity and apoptosis in MCF-7 and MDA-MB-231 breast cancer cells. At a mechanistic level, FANCF shRNA downregulated the anti-apoptotic protein Bcl-2 and upregulated the pro-apoptotic protein Bax, accompanied by release of cyt-c and smac into the cytosol in MMC-treated cells. Furthermore, activation of caspase-3 and -9, other than caspase-8, cleavage of poly(ADP ribose) polymerase (PARP), and a decrease of mitochondrial membrane potential (MMP) indicated that involvement of the mitochondrial apoptotic pathway in FANCF silencing of MMC-treated breast cancer cells. A decrease in IAP family proteins XIAP and survivin were also observed following FANCF silencing in MMC-treated breast cancer cells. Notably, FANCF shRNA was able to increase p53 levels through activation of the JNK pathway in MMC-treated breast cancer cells. Furthermore, p53 inhibition using pifithrin-α abolished the induction of caspase-3 and PARP by FANCF shRNA and MMC, indicating that MMC-induced apoptosis is substantially enhanced by FANCF shRNA via p53-dependent mechanisms. To our knowledge, we provide new evidence for the potential application of FANCF as a chemosensitizer in breast cancer therapy.

Development of Metal Matrix Composites for NASA'S Advanced Propulsion Systems

NASA Technical Reports Server (NTRS)

Lee, Jonathan A.

2000-01-01

The state-of-the-art development of several aluminum and copper based Metal Matrix Composites (MMC) for NASA's advanced propulsion systems will be presented. The presentation's goal is to provide an overview of NASA-Marshall Space Flight Center's planned and on-going activities in MMC for advanced liquid rocket engines such as the X-33 vehicle's Aerospike and X-34 Fastrac engine. The focus will be on lightweight and environmental compatibility with oxygen and hydrogen of key MMC materials, within each NASA's new propulsion application, that will provide a high payoff for NASA's reusable launch vehicle systems and space access vehicles. Advanced MMC processing techniques such as plasma spray, centrifugal casting, pressure infiltration casting will be discussed. Development of a novel 3D printing method for low cost production of composite preform, and functional gradient MMC to enhanced rocket engine's dimensional stability will be presented.

Stimulation of Mucosal Mast Cell Growth in Normal and Nude Rat Bone Marrow Cultures

NASA Astrophysics Data System (ADS)

Haig, David M.; McMenamin, Christine; Gunneberg, Christian; Woodbury, Richard; Jarrett, Ellen E. E.

1983-07-01

Mast cells with the morphological and biochemical properties of mucosal mast cells (MMC) appear and proliferate to form the predominant cell type in rat bone marrow cultures stimulated with factors from antigen- or mitogen-activated lymphocytes. Conditioned media causing a selective proliferation of MMC were derived from mesenteric lymph node cells of Nippostrongylus brasiliensis-infected rats restimulated in vitro with specific antigen or from normal or infected rat mesenteric lymph node cells stimulated with concanavalin A. MMC growth factor is not produced by T-cell-depleted mesenteric lymph node cells or by the mesenteric lymph node cells of athymic rats. By contrast, MMC precursors are present in the bone marrow of athymic rats and are normally receptive to the growth factor produced by the lymphocytes of thymus-intact rats. The thymus dependence of MMC hyperplasia is thus based on the requirement of a thymus-independent precursor for a T-cell-derived growth promoter.

Mass Medication Clinic (MMC) Patient Medical Assistant (PMA) System Training Initiative

DTIC Science & Technology

2007-06-01

AD_________________ Award Number: W81XWH-06-2-0045 TITLE: Mass Medication Clinic (MMC) Patient ...SUBTITLE 5a. CONTRACT NUMBER Mass Medication Clinic (MMC) Patient Medical Assistant (PMA) System Training Initiative 5b. GRANT NUMBER W81XWH-06-2...sections will describe the events, results, and accomplishments of this study. With validation through this project the Patient Medical Assistant

Capitated Medicaid Managed Care in a Rural Area: The Impact of Minnesota's PMAP Program

ERIC Educational Resources Information Center

Long, Sharon K.; Coughlin, Teresa A.; King, Jennifer

2005-01-01

Although states have had difficulty extending Medicaid managed care (MMC) to rural areas, rural models of capitated MMC are expected to grow in response to new federal regulations and the serious budget problems facing nearly all states. As such, understanding the effects of capitated MMC in rural settings is important for policy considerations.…

The influence of the learning climate on learning outcomes from Marte Meo counselling in dementia care.

PubMed

Alnes, Rigmor Einang; Kirkevold, Marit; Skovdahl, Kirsti

2013-01-01

  To identify factors that affected the learning outcomes from Marte Meo counselling (MMC).   Although MMC has shown promising results regarding learning outcomes for staff working in dementia-specific care units, the outcomes differ.   Twelve individual interviews and four focus group interviews with staff who had participated in MMC were analysed through a qualitative content analysis.   The learning climate has considerable significance for the experienced benefit of MMC and indicate that this learning climate depends on three conditions: establishing a common understanding of the content and form of MMC, ensuring staff's willingness to participate and the opportunity to do so, and securing an arena in the unit for discussion and interactions.   Learning outcomes from MMC in dementia-specific care units appear to depend on the learning climate in the unit. Implication for nursing management  The learning climate needs attention from the nursing management when establishing Marte Meo intervention in nursing homes. The learning climate can be facilitated through building common understandings in the units regarding why and how this intervention should take place, and by ensuring clarity in the relationship between the intervention and the organization's objectives. © 2012 Blackwell Publishing Ltd.

A multilingual mass communication intervention for seniors and people with disabilities on Medicaid: a randomized controlled trial.

PubMed

Kurtovich, Elaine; Ivey, Susan L; Neuhauser, Linda; Graham, Carrie; Constantine, Wendy; Barkan, Howard

2010-04-01

To evaluate the following: (1) baseline knowledge, attitudes, and behavioral intentions about Medicaid managed care (MMC) among seniors and people with disabilities (SPD) receiving Medicaid benefits; (2) SPD Medicaid beneficiaries' use of and satisfaction with a user-designed MMC guidebook; and (3) guidebook effects on changes in MMC knowledge, attitudes, and intended behaviors of SPD beneficiaries. Survey data collected between February and May 2008 from a random sample of SPD receiving Medicaid benefits in three California counties. This randomized controlled trial of 319 intervention and 373 control SPD Medicaid beneficiaries used pre- and postintervention telephone surveys to compare changes in MMC knowledge, attitudes, and intended behaviors. Baseline and follow-up telephone interviews were conducted in English, Spanish, Cantonese, and Mandarin. Seventy-seven percent of intervention participants reported using the guidebook. Nearly all (97.9 percent) found it somewhat or very useful. Intervention participants showed gains in knowledge, positive attitudes, and intentions to enroll in MMC that are statistically significant compared with control participants. However, knowledge levels remained low even among intervention participants. Findings suggest that the guidebook is an effective way to improve recipients' MMC knowledge, confidence, and behavioral intentions.

Human serum reduces mitomycin-C cytotoxicity in human tenon's fibroblasts.

PubMed

Crowston, Jonathan G; Wang, Xiao Y; Khaw, Peng T; Zoellner, Hans; Healey, Paul R

2006-03-01

To determine the effect of human serum factors on mitomycin-C (MMC) cytotoxicity in cultured human subconjunctival Tenon's capsule fibroblasts. Fibroblast monolayers were treated with 5-minute applications of mitomycin-C (0.4 mg/mL) and incubated in culture medium with or without additional human serum. Fibroblast apoptosis was quantified by direct cell counts based on nuclear morphology, flow cytometry with annexin-V/propidium iodide, and a lactate dehydrogenase release assay. The number of viable fibroblasts and fibroblast proliferation were measured with a colorimetric MTT assay and by bromodeoxyuridine (BrdU) labeling. Mitomycin-C induced significant levels of fibroblast apoptosis. The addition of human serum resulted in a 40% reduction in MMC-induced fibroblast apoptosis (range, 31.3%-55.3%; P = 0.021) as determined by nuclear morphology and a 32.4% reduction measured by annexin-V/PI. There was a corresponding dose-dependent increase in the number of viable fibroblasts. Serum did not restore proliferation in MMC-treated fibroblasts. Factors present in human serum reduce MMC cytotoxicity in cultured human Tenon's fibroblasts. Human serum increased the number of viable fibroblasts by inhibiting MMC-induced fibroblast apoptosis. Serum factors access aqueous humor after trabeculectomy and may therefore influence the clinical outcome of MMC treatment.

Enhancement of lutetium texaphyrin phototherapy with Mitomycin C

NASA Astrophysics Data System (ADS)

Thiemann, Patricia A.; Woodburn, Kathryn W.

1998-05-01

Lutetium texaphyrin (Lu-Tex) photodynamic therapy (PDT) relies on the presence of the water-soluble Lu-Tex, oxygen, and light (activation around 730 nm). Cytotoxic oxygen species are produced that cause irreversible damage to biological substrates. Damage may be inflicted via direct cell kill mechanisms or through vasculature effects that cause hypoxia. The addition of hypoxia enhanced drugs, such as Mitomycin C (MMC), can potentially increase the anti-tumor response. RIF-1 bearing C3H mice received 10 micrometers ol Lu-Tex/kg and were illuminated with 100 J/cm2 3 hours postinjection. Mice received MMC (2.5 or 5 mg/kg, before and after light) in conjunction with PDT and were compared to subsets of drug alone controls. A significant improvement in PDT response was observed when MMC was added to the dosing regimen; the effect was more pronounced at the highest MMC dose of 5 mg/kg: MMC prior to PDT gave a median tumor regrowth time (10X original volume) of 28 days compared to MMC and PDT alone, 16.3 and 14.9 days, respectively. The anti-tumor activity of lutetium texaphyrin induced PDT was improved by the addition of the bioreductive alkylating agent mitomycin C.

Placental Mesenchymal Stromal Cells Rescue Ambulation in Ovine Myelomeningocele

PubMed Central

Brown, Erin G.; Lankford, Lee; Keller, Benjamin A.; Pivetti, Christopher D.; Sitkin, Nicole A.; Beattie, Michael S.; Bresnahan, Jacqueline C.; Farmer, Diana L.

2015-01-01

Myelomeningocele (MMC)—commonly known as spina bifida—is a congenital birth defect that causes lifelong paralysis, incontinence, musculoskeletal deformities, and severe cognitive disabilities. The recent landmark Management of Myelomeningocele Study (MOMS) demonstrated for the first time in humans that in utero surgical repair of the MMC defect improves lower limb motor function, suggesting a capacity for improved neurologic outcomes in this disorder. However, functional recovery was incomplete, and 58% of the treated children were unable to walk independently at 30 months of age. In the present study, we demonstrate that using early gestation human placenta-derived mesenchymal stromal cells (PMSCs) to augment in utero repair of MMC results in significant and consistent improvement in neurologic function at birth in the rigorous fetal ovine model of MMC. In vitro, human PMSCs express characteristic MSC markers and trilineage differentiation potential. Protein array assays and enzyme-linked immunosorbent assay show that PMSCs secrete a variety of immunomodulatory and angiogenic cytokines. Compared with adult bone marrow MSCs, PMSCs secrete significantly higher levels of brain-derived neurotrophic factor and hepatocyte growth factor, both of which have known neuroprotective capabilities. In vivo, functional and histopathologic analysis demonstrated that human PMSCs mediate a significant, clinically relevant improvement in motor function in MMC lambs and increase the preservation of large neurons within the spinal cord. These preclinical results in the well-established fetal ovine model of MMC provide promising early support for translating in utero stem cell therapy for MMC into clinical application for patients. Significance This study presents placenta-derived mesenchymal stromal cell (PMSC) treatment as a potential therapy for myelomeningocele (MMC). Application of PMSCs can augment current in utero surgical repair in the well-established and rigorously applied fetal lamb model of MMC. Treatment with human PMSCs significantly and dramatically improved neurologic function and preserved spinal cord neuron density in experimental animals. Sixty-seven percent of the PMSC-treated lambs were able to ambulate independently, with two exhibiting no motor deficits whatsoever. In contrast, none of the lambs treated with the vehicle alone were capable of ambulation. The locomotor rescue demonstrated in PMSC-treated lambs indicates great promise for future clinical trials to improve paralysis in children afflicted with MMC. PMID:25911465

Design of a Dry Dilution Refrigerator for MMC Gamma Detector Arrays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Friedrich, Stephan; Boyd, Stephen; Cantor, Robin

2017-04-03

The goal of this LCP is to develop an ultra-high resolution gamma detector based on magnetic microcalorimeters (MMCs) for accurate non-destructive analysis (NDA) of nuclear materials. For highest energy resolution, we will introduce erbium-doped silver (Ag:Er) as a novel sensor material to replace current Au:Er sensors. The detector sensitivity will be increased by developing arrays of 32 Ag:Er pixels read out by 16 SQUID preamplifiers. MMC detectors require operating temperatures of ~15 mK and thus the use of a dilution refrigerator, and the desire for user-friendly operation without cryogenic liquids requires that this refrigerator use pulse-tube pre-cooling to ~4 K.more » For long-term reliability, we intend to re-design the heat switch that is needed to apply the magnetizing current to the Ag:Er sensor and that used to fail in earlier designs after months of operation. A cryogenic Compton veto will be installed to reduce the spectral background of the MMC, especially at low energies where ultra-high energy resolution is most important. The goals for FY16 were 1) to purchase a liquid-cryogen-free dilution refrigerator and adapt it for MMC operation, and 2) to fabricate Ag:Er-based MMC γ-detectors with improved performance and optimize their response. This report discusses the design of the instruments, and progress in MMC detector fabrication. Details of the MMC fabrication have been discussed in an April 2016 report to DOE.« less

Mitomycin C induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via a mitochondrial-mediated pathway.

PubMed

Yan, Chuqi; Kong, Dechao; Ge, Dong; Zhang, Yanming; Zhang, Xishan; Su, Changhui; Cao, Xiaojian

2015-01-01

Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterised by prominent synoviocyte hyperplasia and a potential imbalance between the growth and death of fibroblast-like synoviocytes (FLS). Mitomycin C (MMC) has previously been demonstrated to inhibit fibroblast proliferation and to induce fibroblast apoptosis. However, the effects of MMC on the proliferation and apoptosis of human RA FLS and the potential mechanisms underlying its effects remain unknown. Cell viability was determined using the Cell Counting Kit-8 assay. Apoptotic cell death was analysed via Annexin V-FITC/PI double staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling. The production of intracellular reactive oxygen species (ROS) was assessed via flow cytometry, and the changes in mitochondrial membrane potential (ΔΨm) were visualized based on JC-1 staining via fluorescence microscopy. The expression of apoptosis-related proteins was determined via Western blot. Treatment with MMC significantly reduced cell viability and induced apoptosis in RA FLS. Furthermore, MMC exposure was found to stimulate the production of ROS and to disrupt the ΔΨm compared to the control treatment. Moreover, MMC increased the release of mitochondrial cytochrome c, the ratio of Bax/Bcl-2, the activation of caspase-9 and caspase-3, and the subsequent cleavage of poly(ADP-ribose) polymerase. Our findings suggest that MMC inhibits cell proliferation and induces apoptosis in RA FLS, and the mechanism underlying this MMC-induced apoptosis may involve a mitochondrial signalling pathway. © 2015 S. Karger AG, Basel.

Drug Program Report: Credentialing.

ERIC Educational Resources Information Center

Contee, Jerome A., Ed.

This report contains several articles on drug abuse worker credentialing, and provides an update on information about credentialing policies and reciprocity efforts of the states. The first article reports on a meeting of the credentialing/reciprocity task force comprised of representatives from 10 states which have exhibited leadership in the…

Setting Course: The Case for the Credentialing of Forensic Interviewers

ERIC Educational Resources Information Center

Haney, Mike; Vieth, Victor I.; Campos, Hector M.

2010-01-01

The article provides a history of efforts to develop a credentialing or certification process for forensic interviewers and reviews the multitiered credentialing process offered by the National Association of Certified Child Forensic Interviewers. The authors argue the benefits of a credentialing process for forensic interviewers and respond to…

42 CFR 422.204 - Provider selection and credentialing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Provider selection and credentialing. 422.204... Provider selection and credentialing. (a) General rule. An MA organization must have written policies and procedures for the selection and evaluation of providers. These policies must conform with the credential and...

46 CFR 10.201 - General characteristics of the merchant mariner credential.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false General characteristics of the merchant mariner credential. 10.201 Section 10.201 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE... § 10.201 General characteristics of the merchant mariner credential. (a) A merchant mariner credential...

New Pathways to Credentialing: The Digital Badge

ERIC Educational Resources Information Center

DiSalvio, Philip

2016-01-01

With an increasing number of higher education institutions now offering "digital badges," some suggest that this credential has become a practical commodity in the world of college credentials. Colleges and universities are in a unique position to be the gatekeepers of many of those credentials. Among the many institutions of higher…

Advancing Health Professions Education Research by Creating a Network of Networks.

PubMed

Carney, Patricia A; Brandt, Barbara; Dekhtyar, Michael; Holmboe, Eric S

2018-02-27

Producing the best evidence to show educational outcomes, such as competency achievement and credentialing effectiveness, across the health professions education continuum will require large multisite research projects and longitudinal studies. Current limitations that must be overcome to reach this goal include the prevalence of single-institution study designs, assessments of a single curricular component, and cross-sectional study designs that provide only a snapshot in time of a program or initiative rather than a longitudinal perspective.One solution to overcoming these limitations is to develop a network of networks that collaborates, using longitudinal approaches, across health professions and regions of the United States. Currently, individual networks are advancing educational innovation toward understanding the effectiveness of educational and credentialing programs. Examples of such networks include: (1) the American Medical Association's Accelerating Change in Medical Education initiative, (2) the National Center for Interprofessional Practice and Education, and (3) the Accreditation Council for Graduate Medical Education's Accreditation System. In this Invited Commentary, the authors briefly profile these existing networks, identify their progress and the challenges they have encountered, and propose a vigorous way forward toward creating a national network of networks designed to determine the effectiveness of health professions education and credentialing.

Impact of Medicaid Managed Care on Illinois's Acute Health Services Expenditures for Adults with Intellectual and Developmental Disabilities

ERIC Educational Resources Information Center

Yamaki, Kiyoshi; Wing, Coady; Mitchell, Dale; Owen, Randall; Heller, Tamar

2018-01-01

States have increasingly transitioned Medicaid enrollees with disabilities from fee-for-service (FFS) to Medicaid Managed Care (MMC), intending to reduce state Medicaid spending and to provide better access to health services. Yet, previous studies on the impact of MMC are limited and findings are inconsistent. We analyzed the impact of MMC on…

Virtual skeletal complex model- and landmark-guided orthognathic surgery system.

PubMed

Lee, Sang-Jeong; Woo, Sang-Yoon; Huh, Kyung-Hoe; Lee, Sam-Sun; Heo, Min-Suk; Choi, Soon-Chul; Han, Jeong Joon; Yang, Hoon Joo; Hwang, Soon Jung; Yi, Won-Jin

2016-05-01

In this study, correction of the maxillofacial deformities was performed by repositioning bone segments to an appropriate location according to the preoperative planning in orthognathic surgery. The surgery was planned using the patient's virtual skeletal models fused with optically scanned three-dimensional dentition. The virtual maxillomandibular complex (MMC) model of the patient's final occlusal relationship was generated by fusion of the maxillary and mandibular models with scanned occlusion. The final position of the MMC was simulated preoperatively by planning and was used as a goal model for guidance. During surgery, the intraoperative registration was finished immediately using only software processing. For accurate repositioning, the intraoperative MMC model was visualized on the monitor with respect to the simulated MMC model, and the intraoperative positions of multiple landmarks were also visualized on the MMC surface model. The deviation errors between the intraoperative and the final positions of each landmark were visualized quantitatively. As a result, the surgeon could easily recognize the three-dimensional deviation of the intraoperative MMC state from the final goal model without manually applying a pointing tool, and could also quickly determine the amount and direction of further MMC movements needed to reach the goal position. The surgeon could also perform various osteotomies and remove bone interference conveniently, as the maxillary tracking tool could be separated from the MMC. The root mean square (RMS) difference between the preoperative planning and the intraoperative guidance was 1.16 ± 0.34 mm immediately after repositioning. After surgery, the RMS differences between the planning and the postoperative computed tomographic model were 1.31 ± 0.28 mm and 1.74 ± 0.73 mm for the maxillary and mandibular landmarks, respectively. Our method provides accurate and flexible guidance for bimaxillary orthognathic surgery based on intraoperative visualization and quantification of deviations for simulated postoperative MMC and landmarks. The guidance using simulated skeletal models and landmarks can complement and improve conventional navigational surgery for bone repositioning in the craniomaxillofacial area. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Fabrication of Gamma Detectors Based on Magnetic Ag:Er Microcalorimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Friedrich, Stephan; Boyd, Stephen; Cantor, Robin

2016-05-06

This report discusses the photolithographic fabrication of ultra-high resolution gamma-ray detectors based on magnetic microcalorimeters (MMCs). The MMC uses a novel Er-doped silver sensor (Ag:Er) that is expected to have higher sensitivity than the Er-doped gold (Au:Er) sensors currently in use. The MMC also integrates the first-stage SQUID preamplifier on the same chip as the MMC gamma detector to increase its signal-to-noise ratio. In addition, the MMC uses a passive Ta-Nb heat switch to replace one of the common long-term failure points in earlier detectors. This report discusses the fabrication process we have developed to implement the proposed improvements.

Fabrication of Gamma Detectors Based on Magnetic Ag:Er Microcalorimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Friedrich, Stephan; Boyd, Stephen; Cantor, Robin

2015-11-25

This report discusses the photolithographic fabrication of ultra-high resolution gamma-ray detectors based on magnetic microcalorimeters (MMCs). The MMC uses a novel Er-doped silver sensor (Ag:Er) that is expected to have higher sensitivity than the Er-doped gold (Au:Er) sensors currently in use. The MMC also integrates the first-stage SQUID preamplifier on the same chip as the MMC gamma detector to increase its signal-to-noise ratio. In addition, the MMC uses a passive Ta-Nb heat switch to replace one of the common long-term failure points in earlier detectors. This report discusses the fabrication process we have developed to implement the proposed improvements.

The role of optics in secure credentials

NASA Astrophysics Data System (ADS)

Lichtenstein, Terri L.

2006-02-01

The global need for secure ID credentials has grown rapidly over the last few years. This is evident both in government and commercial sectors. Governmental programs include national ID card programs, permanent resident cards for noncitizens, biometric visas or border crossing cards, foreign worker ID programs and secure vehicle registration programs. The commercial need for secure credentials includes secure banking and financial services, security and access control systems and digital healthcare record cards. All of these programs necessitate the use of multiple tamper and counterfeit resistant features for credential authentication and cardholder verification. It is generally accepted that a secure credential should include a combination of overt, covert and forensic security features. The LaserCard optical memory card is a proven example of a secure credential that uses a variety of optical features to enhance its counterfeit resistance and reliability. This paper will review those features and how they interact to create a better credential.

14 CFR 121.548 - Aviation safety inspector's credentials: Admission to pilot's compartment.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Aviation safety inspector's credentials... Operations § 121.548 Aviation safety inspector's credentials: Admission to pilot's compartment. Whenever, in... presents form FAA 110A, “Aviation Safety Inspector's Credential,” to the pilot in command of an aircraft...

Adjuvant treatment or primary topical monotherapy for ocular surface squamous neoplasia: a systematic review.

PubMed

Viani, Gustavo Arruda; Fendi, Ligia Issa de

2017-01-01

In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN). The findings were: (i) adjuvant 5-fluorouracil (5-FU) reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR) A]. (ii) Primary topical mitomycin (MMC) produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A). (iii) Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B). (iv) Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C). (v) Primary topical 5-FU versus MMC versus interferon (IFN) showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C).

SU-F-J-49: IGRT Credentialing in NCTN Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowenstein, J; Molineu, A; Followill, D

Purpose: To make Image Guided Radiation Therapy (IGRT) credentialing a more unified, consistent and efficient process across the entire National Clinical Trial Network (NCTN). Methods: IGRT plays a role in several advanced NCTN trials. Previously an institution had to be IGRT credentialed for each protocol. When institutions were allowed to use previous credentials for new protocols it was limited to the same disease site as the original credentialing. The credentialing was analyzed by the physics PI of the protocol. We consulted with several of these physicists to determine what is important to consider when reviewing submissions and to learn waysmore » to apply credentialing more broadly. Results: For trials open in 2016, IGRT credentialing can be simplified to cover either boney anatomy or soft tissue. This revised credentialing will cover all disease sites based on the type of anatomy, unless otherwise stated within the protocol. Institutions will submit will complete an online questionnaire about their IGRT procedures. Boney anatomy requirements will include submission of data from 2 sequential fraction of both a patient aligned with boney anatomy and pelvic patient. Soft tissue will require similar submissions for a patient aligned using soft tissue and a pelvic patient. Institutions will only be required to submit the pelvic patient once. Data should be in DICOM format and includes planning CT set, RT structure set, RT plan file, RT dose file, localization images and spatial registration file (if available). Reviews will be done by IROC-Houston staff who will continue to provide feedback to the sites. Conclusion: This revised IGRT credentialing process will bring consistency, a savings in time and effort for both the IROC Houston QA office and to those institutions wanting to be credentialed to participate in NCTN Trials. Sponsored by NIH/NCI CA10953.« less

Does Medicaid Managed Care Help Equalize Racial and Ethnic Disparities in Utilization?

PubMed

Marton, James; Yelowitz, Aaron; Shores, Meredith; Talbert, Jeffery C

2016-06-01

To estimate the impact of different forms of Medicaid managed care (MMC) delivery on racial and ethnic disparities in utilization. Longitudinal, administrative data on 101,649 children in Kentucky continuously enrolled in Medicaid between January 1997 and June 1999. Outcomes considered are monthly professional, outpatient, and inpatient utilization. We apply an intent-to-treat, instrumental variables analysis using the staggered geographic implementation of MMC to create treatment and control groups of children. The implementation of MMC reduced monthly professional visits by a smaller degree for non-whites than whites (3.8 percentage points vs. 6.2 percentage points), thereby helping to equalize the initial racial/ethnic disparity in utilization. The Passport MMC program in the Louisville-centered region statistically significantly reduced disparities for professional visits (closing the gap by 8.0 percentage points), while the Kentucky Health Select MMC program in the Lexington-centered region did not. No substantive impact on disparities was found for either outpatient or inpatient utilization in either program. We find evidence that MMC has the possibility to reduce racial/ethnic disparities in professional utilization. More work is needed to determine which managed care program characteristics drive this result. © 2015 The Authors. Health Services Research published by Wiley Periodicals, Inc. on behalf of Health Research and Educational Trust.

Culture scale-up and immobilisation of a mixed methanotrophic consortium for methane remediation in pilot-scale bio-filters.

PubMed

Karthikeyan, Obulisamy Parthiba; Saravanan, Nadarajan; Cirés, Samuel; Alvarez-Roa, Carlos; Razaghi, Ali; Chidambarampadmavathy, Karthigeyan; Velu, Chinnathambi; Subashchandrabose, Gobalakrishnan; Heimann, Kirsten

2017-02-01

Robust methanotrophic consortia for methane (CH 4 ) remediation and by-product development are presently not readily available for industrial use. In this study, a mixed methanotrophic consortium (MMC), sequentially enriched from a marine sediment, was assessed for CH 4 removal efficiency and potential biomass-generated by-product development. Suitable packing material for bio-filters to support MMC biofilm establishment and growth was also evaluated. The enriched MMC removed ∼7-13% CH 4 under a very high gas flow rate (2.5 L min -1 ; 20-25% CH 4 ) in continuous-stirred tank reactors (∼10 L working volume) and the biomass contained long-chain fatty acids (i.e. C 16 and C 18 ). Cultivation of the MMC on plastic bio-balls abated ∼95-97% CH 4 in pilot-scale non-sterile outdoor-operated bio-filters (0.1 L min -1 ; 1% CH 4 ). Contamination by cyanobacteria had beneficial effects on treating low-level CH 4 , by providing additional oxygen for methane oxidation by MMC, suggesting that the co-cultivation of MMC with cyanobacterial mats does not interfere with and may actually be beneficial for remediation of CH 4 and CO 2 at industrial scale.

A Multilingual Mass Communication Intervention for Seniors and People with Disabilities on Medicaid: A Randomized Controlled Trial

PubMed Central

Kurtovich, Elaine; Ivey, Susan L; Neuhauser, Linda; Graham, Carrie; Constantine, Wendy; Barkan, Howard

2010-01-01

Objectives To evaluate the following: (1) baseline knowledge, attitudes, and behavioral intentions about Medicaid managed care (MMC) among seniors and people with disabilities (SPD) receiving Medicaid benefits; (2) SPD Medicaid beneficiaries' use of and satisfaction with a user-designed MMC guidebook; and (3) guidebook effects on changes in MMC knowledge, attitudes, and intended behaviors of SPD beneficiaries. Data Sources/Study Setting Survey data collected between February and May 2008 from a random sample of SPD receiving Medicaid benefits in three California counties. Study Design This randomized controlled trial of 319 intervention and 373 control SPD Medicaid beneficiaries used pre- and postintervention telephone surveys to compare changes in MMC knowledge, attitudes, and intended behaviors. Data Collection Methods Baseline and follow-up telephone interviews were conducted in English, Spanish, Cantonese, and Mandarin. Principal Findings Seventy-seven percent of intervention participants reported using the guidebook. Nearly all (97.9 percent) found it somewhat or very useful. Intervention participants showed gains in knowledge, positive attitudes, and intentions to enroll in MMC that are statistically significant compared with control participants. However, knowledge levels remained low even among intervention participants. Conclusions Findings suggest that the guidebook is an effective way to improve recipients' MMC knowledge, confidence, and behavioral intentions. PMID:20070389

Anomalous Buckling Characteristics of Laminated Metal-Matrix Composite Plates with Central Square Holes

NASA Technical Reports Server (NTRS)

Ko, William L.

1998-01-01

Compressive buckling analysis was performed on metal-matrix composite (MMC) plates with central square holes. The MMC plates have varying aspect ratios and hole sizes and are supported under different boundary conditions. The finite-element structural analysis method was used to study the effects of plate boundary conditions, plate aspect ratio, hole size, and the composite stacking sequence on the compressive buckling strengths of the perforated MMC plates. Studies show that by increasing the hole sizes, compressive buckling strengths of the perforated MMC plates could be considerably increased under certain boundary conditions and aspect ratios ("anomalous" buckling behavior); and that the plate buckling mode could be symmetrical or antisymmetrical, depending on the plate boundary conditions, aspect ratio, and the hole size. For same-sized plates with same-sized holes, the compressive buckling strengths of the perforated MMC plates with [90/0/0/90]2 lamination could be as much as 10 percent higher or lower than those of the [45/- 45/- 45/45]2 laminations, depending on the plate boundary conditions, plate aspect ratios, and the hole size. Clamping the plate edges induces far stronger "anomalous" buckling behavior (enhancing compressive buckling strengths at increasing hole sizes) of the perforated MMC plates than simply supporting the plate edges.

The SOS and RpoS Regulons Contribute to Bacterial Cell Robustness to Genotoxic Stress by Synergistically Regulating DNA Polymerase Pol II.

PubMed

Dapa, Tanja; Fleurier, Sébastien; Bredeche, Marie-Florence; Matic, Ivan

2017-07-01

Mitomycin C (MMC) is a genotoxic agent that induces DNA cross-links, DNA alkylation, and the production of reactive oxygen species (ROS). MMC induces the SOS response and RpoS regulons in Escherichia coli SOS-encoded functions are required for DNA repair, whereas the RpoS regulon is typically induced by metabolic stresses that slow growth. Thus, induction of the RpoS regulon by MMC may be coincidental, because DNA damage slows growth; alternatively, the RpoS regulon may be an adaptive response contributing to cell survival. In this study, we show that the RpoS regulon is primarily induced by MMC-induced ROS production. We also show that RpoS regulon induction is required for the survival of MMC-treated growing cells. The major contributor to RpoS-dependent resistance to MMC treatment is DNA polymerase Pol II, which is encoded by the polB gene belonging to the SOS regulon. The observation that polB gene expression is controlled by the two major stress response regulons that are required to maximize survival and fitness further emphasizes the key role of this DNA polymerase as an important factor in genome stability. Copyright © 2017 by the Genetics Society of America.

Topical Silver Nanoparticles Result in Improved Bleb Function by Increasing Filtration and Reducing Fibrosis in a Rabbit Model of Filtration Surgery

PubMed Central

Butler, Michelle R.; Prospero Ponce, Claudia M.; Weinstock, Y. Etan; Orengo-Nania, Silvia; Chevez-Barrios, Patricia; Frankfort, Benjamin J.

2013-01-01

Purpose. To compare the effects of silver nanoparticles (AgNPs) and mitomycin C (MMC) on intraocular pressure (IOP) and external, histologic, and immunohistochemical bleb characteristics in a rabbit model of filtration surgery. Methods. Filtration surgery with concurrent topical application of either AgNPs or MMC was performed on 14 pigmented Dutch Belted rabbits. IOP and bleb characteristics were compared on postoperative day 1 and at weeks 1 through 6. Hematoxylin and eosin staining and smooth muscle actin (SMA) immunohistochemistry were performed at postoperative week 6. Results. Average IOP across all time points was reduced 5.8 and 3.8 mm Hg in AgNP- and MMC-treated eyes, respectively. At week 6, IOP was reduced 4.1 and 0.2 mm Hg in AgNP- and MMC-treated eyes, respectively. Blebs were smaller, thicker, and less ischemic in AgNP-treated eyes. AgNP-treated eyes showed less fibrosis and more stromal edema, suggesting increased filtration, and also had fewer SMA-positive myofibroblasts, suggesting reduced bleb contraction. AgNP-treated eyes showed more lymphocytes than MMC-treated eyes. There were few complications in both groups. Conclusions. In a rabbit model of filtration surgery, AgNPs are a reasonable alternative to MMC as adjunctive therapy. Compared to MMC, AgNPs result in an improved and sustained reduction of IOP and promote blebs with decreased fibrosis and ischemia as well as increased filtration despite a smaller overall size. This combination may offer an opportunity to promote long-term surgical IOP reduction with an improved complication profile. PMID:23766475

Resistance of uveal melanoma to the interstrand cross-linking agent mitomycin C is associated with reduced expression of CYP450R

PubMed Central

Gravells, P; Hoh, L; Canovas, D; Rennie, I G; Sisley, K; Bryant, H E

2011-01-01

Background: Uveal melanoma (UM) is the most common primary intraocular tumour of adults, frequently metastasising to the liver. Hepatic metastases are difficult to treat and are mainly unresponsive to chemotherapy. To investigate why UM are so chemo-resistant we explored the effect of interstrand cross-linking agents mitomycin C (MMC) and cisplatin in comparison with hydroxyurea (HU). Methods: Sensitivity to MMC, cisplatin and HU was tested in established UM cell lines using clonogenic assays. The response of UM to MMC was confirmed in MTT assays using short-term cultures of primary UM. The expression of cytochrome P450 reductase (CYP450R) was analysed by western blotting, and DNA cross-linking was assessed using COMET analysis supported by γ-H2AX foci formation. Results: Both established cell lines and primary cultures of UM were resistant to the cross-linking agent MMC (in each case P<0.001 in Student's t-test compared with controls). In two established UM cell lines, DNA cross-link damage was not induced by MMC (in both cases P<0.05 in Students's t-test compared with damage induced in controls). In all, 6 out of 6 UMs tested displayed reduced expression of the metabolising enzyme CYP450R and transient expression of CYP450R increased MMC sensitivity of UM. Conclusion: We suggest that reduced expression of CYP450R is responsible for MMC resistance of UM, through a lack of bioactivation, which can be reversed by complementing UM cell lines with CYP450R. PMID:21386838

Transcriptome Analysis of the Arabidopsis Megaspore Mother Cell Uncovers the Importance of RNA Helicases for Plant Germline Development

PubMed Central

Schmidt, Anja; Wuest, Samuel E.; Vijverberg, Kitty; Baroux, Célia; Kleen, Daniela; Grossniklaus, Ueli

2011-01-01

Germ line specification is a crucial step in the life cycle of all organisms. For sexual plant reproduction, the megaspore mother cell (MMC) is of crucial importance: it marks the first cell of the plant “germline” lineage that gets committed to undergo meiosis. One of the meiotic products, the functional megaspore, subsequently gives rise to the haploid, multicellular female gametophyte that harbours the female gametes. The MMC is formed by selection and differentiation of a single somatic, sub-epidermal cell in the ovule. The transcriptional network underlying MMC specification and differentiation is largely unknown. We provide the first transcriptome analysis of an MMC using the model plant Arabidopsis thaliana with a combination of laser-assisted microdissection and microarray hybridizations. Statistical analyses identified an over-representation of translational regulation control pathways and a significant enrichment of DEAD/DEAH-box helicases in the MMC transcriptome, paralleling important features of the animal germline. Analysis of two independent T-DNA insertion lines suggests an important role of an enriched helicase, MNEME (MEM), in MMC differentiation and the restriction of the germline fate to only one cell per ovule primordium. In heterozygous mem mutants, additional enlarged MMC-like cells, which sometimes initiate female gametophyte development, were observed at higher frequencies than in the wild type. This closely resembles the phenotype of mutants affected in the small RNA and DNA-methylation pathways important for epigenetic regulation. Importantly, the mem phenotype shows features of apospory, as female gametophytes initiate from two non-sister cells in these mutants. Moreover, in mem gametophytic nuclei, both higher order chromatin structure and the distribution of LIKE HETEROCHROMATIN PROTEIN1 were affected, indicating epigenetic perturbations. In summary, the MMC transcriptome sets the stage for future functional characterization as illustrated by the identification of MEM, a novel gene involved in the restriction of germline fate. PMID:21949639

Use of Mitomycin C to reduce the incidence of encapsulated cysts following ahmed glaucoma valve implantation in refractory glaucoma patients: a new technique.

PubMed

Zhou, Minwen; Wang, Wei; Huang, Wenbin; Zhang, Xiulan

2014-09-06

To evaluate the surgical outcome of Ahmed glaucoma valve (AGV) implantation with a new technique of mitomycin C (MMC) application. This is a retrospective study. All patients with refractory glaucoma underwent FP-7 AGV implantation. Two methods of MMC application were used. In the traditional technique, 6 × 4 mm cotton soaked with MMC (0.25-0.33 mg/ml) was placed in the implantation area for 2-5mins; in the new technique, the valve plate first was encompassed with a thin layer of cotton soaked with MMC, then inserted into the same area. A 200 ml balanced salt solution was applied for irrigation of MMC. The surgical success rate, intraocular pressure (IOP), number of anti-glaucoma medications used, and postoperative complications were analyzed between the groups. The surgical outcomes of two MMC applied techniques were compared. The new technique group had only one case (2.6%) of encapsulated cyst formation out of 38 eyes, while there were eight (19.5%) cases out of 41 eyes the in traditional group. The difference was statistically significant (P = 0.030). According to the definition of success rate, there was 89.5% in the new technique group and 70.7% in the traditional group at the follow-up end point. There was a significant difference between the two groups (P = 0.035). Mean IOP in the new technique group were significantly lower than those of the traditional group at 3 and 6 months (P < 0.05). By using a thin layer of cotton soaked with MMC to encompass the valve plate, the new MMC application technique could greatly decrease the incidence of encapsulated cyst and increase the success rate following AGV implantation.

Chimeric NDP-MSH and MTII melanocortin peptides with agouti-related protein (AGRP) Arg-Phe-Phe amino acids possess agonist melanocortin receptor activity.

PubMed

Joseph, Christine G; Wilczynski, Andrzej; Holder, Jerry R; Xiang, Zhimin; Bauzo, Rayna M; Scott, Joseph W; Haskell-Luevano, Carrie

2003-12-01

Agouti-related protein (AGRP) is one of only two known endogenous antagonists of G-protein coupled receptors (GPCRs). Specifically, AGRP antagonizes the brain melanocortin-3 and -4 receptors involved in energy homeostasis, regulation of feeding behavior, and obesity. Alpha-melanocyte stimulating hormone (alpha-MSH) is one of the known endogenous agonists for these receptors. It has been hypothesized that the Arg-Phe-Phe (111-113) human AGRP amino acids may be mimicking the melanocortin agonist Phe-Arg-Trp (7-9) residue interactions with the melanocortin receptors that are important for both receptor molecular recognition and stimulation. To test this hypothesis, we generated thirteen chimeric peptide ligands based upon the melanocortin agonist peptides NDP-MSH (Ac-Ser-Tyr-Ser-Nle4-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2) and MTII (Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH2). In these chimeric ligands, the agonist DPhe-Arg-Trp amino acids were replaced by the AGRP Arg-Phe-Phe residues, and resulted in agonist activity at the mouse melanocortin receptors (mMC1R and mMC3-5Rs), supporting the hypothesis that the AGRP antagonist ligand Arg-Phe-Phe residues mimic the agonist Phe-Arg-Trp amino acids. Interestingly, the Ac-Ser-Tyr-Ser-Nle4-Glu-His-Arg-DPhe-Phe-Gly-Lys-Pro-Val-NH2 peptide possessed 7 nM mMC1R agonist potency, and is 850-fold selective for the mMC1R versus the mMC3R, 2300-fold selective for the mMC1R versus the mMC4R, and 60-fold selective for the MC1R versus the mMC5R, resulting in the discovery of a new peptide template for the design of melanocortin receptor selective ligands.

Structure-activity relationships of the unique and potent agouti-related protein (AGRP)-melanocortin chimeric Tyr-c[beta-Asp-His-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH2 peptide template.

PubMed

Wilczynski, Andrzej; Wilson, Krista R; Scott, Joseph W; Edison, Arthur S; Haskell-Luevano, Carrie

2005-04-21

The melanocortin receptor system consists of endogenous agonists, antagonists, G-protein coupled receptors, and auxiliary proteins that are involved in the regulation of complex physiological functions such as energy and weight homeostasis, feeding behavior, inflammation, sexual function, pigmentation, and exocrine gland function. Herein, we report the structure-activity relationship (SAR) of a new chimeric hAGRP-melanocortin agonist peptide template Tyr-c[beta-Asp-His-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) that was characterized using amino acids previously reported in other melanocortin agonist templates. Twenty peptides were examined in this study, and six peptides were selected for (1)H NMR and computer-assisted molecular modeling structural analysis. The most notable results include the identification that modification of the chimeric template at the His position with Pro and Phe resulted in ligands that were nM mouse melanocortin-3 receptor (mMC3R) antagonists and nM mouse melanocortin-4 receptor (mMC4R) agonists. The peptides Tyr-c[beta-Asp-His-DPhe-Ala-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) and Tyr-c[beta-Asp-His-DNal(1')-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) resulted in 730- and 560-fold, respectively, mMC4R versus mMC3R selective agonists that also possessed nM agonist potency at the mMC1R and mMC5R. Structural studies identified a reverse turn occurring in the His-DPhe-Arg-Trp domain, with subtle differences observed that may account for the differences in melanocortin receptor pharmacology. Specifically, a gamma-turn secondary structure involving the DPhe(4) in the central position of the Tyr-c[beta-Asp-Phe-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) peptide may differentiate the mixed mMC3R antagonist and mMC4R agonist pharmacology.

Effect of mitomycin-C on contraction and migration of human nasal mucosa fibroblasts: implications in dacryocystorhinostomy.

PubMed

Kumar, Vinay; Ali, Mohammad Javed; Ramachandran, Charanya

2015-09-01

To determine the effect of mitomycin-C (MMC) on the contraction and migration of human nasal mucosal fibroblasts (HNMFs) in vitro in order to identify the least concentration of MMC required to prevent cicatrix development following dacryocystorhinostomy (DCR). Primary cultures of HNMFs were established from nasal mucosal tissues of patients undergoing DCR. Myofibroblast transformation of HNMFs was induced using transforming growth factor-β (TGF-β1) and confirmed by immunostaining for α-smooth muscle actin (α-SMA). Collagen gel contraction assay was employed to study contraction in the presence or absence of TGF-β1 (5 and 10 ng/mL) and MMC (0.2 and 0.4 mg/mL). Scratch wound assay was employed to determine the influence of MMC treatment on cell migration. Quantification of gel contraction and wound closure was done using Image J software. α-SMA expression increased with TGF-β1 treatment in a time- and dose-dependent manner indicating myofibroblast transformation of HNMFs. MMC inhibited TGF-β1- induced collagen gel contraction in a dose-dependent manner (0.4 mg/mL>0.2 mg/mL). Further, there was a decrease in the migration of MMC-treated HNMFs, resulting in delayed wound closure that corroborated with the loss of actin stress fibres. MMC successfully inhibited TGF-β1-induced myofibroblast transformation, collagen gel contraction and significantly reduced the migration of HNMFs to cover the wound even at a low concentration of 0.2 mg/mL. This study provides evidence that low concentration and short duration of MMC treatment is efficient in reducing increased contraction and migration of HMNFs in response to injury. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Modular Dual-Labeling Scaffold That Retains Agonistic Properties for Somatostatin Receptor Targeting

PubMed Central

Ghosh, Sukhen C.; Rodriguez, Melissa; Carmon, Kendra S.; Voss, Julie; Wilganowski, Nathaniel L.; Schonbrunn, Agnes

2017-01-01

Fluorescence-guided surgery is an emerging imaging technique that can enhance the ability of surgeons to detect tumors when compared with visual observation. To facilitate characterization, fluorescently labeled probes have been dual-labeled with a radionuclide to enable cross-validation with nuclear imaging. In this study, we selected the somatostatin receptor imaging agent DOTATOC as the foundation for developing a dual-labeled analog. We hypothesized that a customized dual-labeling approach with a multimodality chelation (MMC) scaffold would minimize steric effects of dye conjugation and retain agonist properties. Methods: An MMC conjugate (MMC-TOC) was synthesized on solid-phase and compared with an analog prepared using conventional methods (DA-TOC). Both analogs were conjugated to IRDye 800 using copper-free click chemistry. The resulting compounds, MMC(IR800)-TOC and DA(IR800)-TOC, were labeled with Cu and 64Cu and tested in vitro in somatostatin receptor subtype 2–overexpressing HEK-293 cells to assess agonist properties, and in AR42J rat pancreatic cancer cells to determine receptor binding characteristics. Multimodality imaging was performed in AR42J xenografts. Results: Cu-MMC(IR800)-TOC demonstrated higher potency for cyclic adenosine monophosphate inhibition (half maximal effective concentration [EC50]: 0.21 ± 0.18 vs. 1.38 ± 0.54 nM) and receptor internalization (EC50: 41.9 ± 29.8 vs. 455 ± 299 nM) than Cu-DA(IR800)-TOC. Radioactive uptake studies showed that blocking with octreotide caused a dose-dependent reduction in 64Cu-MMC(IR800)-TOC uptake whereas 64Cu-DA(IR800)-TOC was not affected. In vivo studies revealed higher tumor uptake for 64Cu-MMC(IR800)-TOC than 64Cu-DA(IR800)-TOC (5.2 ± 0.2 vs. 3.6 ± 0.4 percentage injected dose per gram). In vivo blocking studies with octreotide reduced tumor uptake of 64Cu-MMC(IR800)-TOC by 66%. Excretion of 64Cu-MMC(IR800)-TOC was primarily through the liver and spleen whereas 64Cu-DA(IR800)-TOC was cleared through the kidneys. Ex vivo analysis at 24 h confirmed PET/CT data by showing near-infrared fluorescence signal in tumors and a tumor-to-muscle ratio of 5.3 ± 0.8 as determined by γ-counting. Conclusion: The findings demonstrate that drug design affected receptor pharmacology and suggest that the MMC scaffold is a useful tool for the development of dual-labeled imaging agents. PMID:28572490

[Intraoperative chemotherapy with intraperitoneal activated carbon particles adsorbing mitomycin C against peritoneal dissemination of gastric cancer].

PubMed

Iwamoto, A; Takahashi, T; Sasabe, T; Itoh, M; Kondoh, S; Seiki, K; Yoneyama, C; Shimotsuma, M; Hagiwara, A; Yamaguchi, T

1989-08-01

A new form of dosage (MMC-CH) was composed of activated carbon particles adsorbing mitomycin C. Intraperitoneal administration of MMC-CH was tested clinically for prophylactic and therapeutic effects on peritoneal carcinomatosis of gastric cancer. The criteria of MMC-CH's administration were equal or less than 70 years old, more than 40 kg in body weight, no disfunction of liver and kidney, no particular findings in electrocardiography, S2 or S3 in the grade of serosal invasion, P0, P1, P2 or P3 in the grade of peritoneal dissemination, according to the General Rules for the Gastric Cancer Study in Surgery and Pathology by the Japanese Research Society for Gastric Cancer. MMC-CH was given to 44 patients undergoing gastrectomy for gastric cancer in our department from 1985 to 1988. The 44 patients were composed of 12 patients with P0 findings (P0 patients), 8 patients with P1 findings (P1 patients), 12 patients with P2 findings (P2 patients), and 12 patients with P3 findings (P3 patients). MMC-CH at 50 mg/person in terms of mitomycin C was administered intraperitoneally before the operation wound was closed. Fifty-seven patients in our department from 1983 to 1987 for whom the same criteria were applicable and did not receive MMC-CH therapy, served as the control group. The 57 patients were composed of 23 P0 patients, 21 P1 patients, 10 P2 patients, and 3 P3 patients. There was statistically with chi 2 test no significant difference of age, sex, depth of infiltration macroscopically and microscopically defined progression of lymph-nodal metastases between the MMC-CH group and the control group. Survival rate was calculated with Kaplan-Meier's method in the overall patients in each of the MMC-CH group or the control group. The overall survival rate in the MMC-CH group was statistically significantly (p less than 0.01-0.05) higher from day 460 to day 552 and from day 736 to day 800 than that in the control group. Next, the patients were classified into two subgroups, namely the subgroup composed of P0 patients and the subgroup composed of P1, P2, and P3 patients, in order to examine each of the MMC-CH's prophylactic effects on subsequent dissemination or its therapeutic effects on established dissemination. Survival rate was calculated with Kaplan-Meier's method in the two subgroups through the same procedures used for the overall survival rate.(ABSTRACT TRUNCATED AT 400 WORDS)

The Future of University Credentials: New Developments at the Intersection of Higher Education and Hiring

ERIC Educational Resources Information Center

Gallagher, Sean R.

2016-01-01

"The Future of University Credentials" offers a thorough and urgently needed overview of the burgeoning world of university degrees and credentials. At a time of heightened attention to how universities and colleges are preparing young people for the working world, questions about the meaning and value of university credentials have…

Credentialing School Based Teacher Educators: Bases for Decisioning. School Based Teacher Educators, Number 8.

ERIC Educational Resources Information Center

Houston, W. Robert; And Others

The basic question addressed in this monograph is whether credentialing the preservice or inservice school based teacher educator is necessary and/or desirable. To study this question, a series of related issues were posed and investigated: (1) Is there a need for credentialing? (2) What institution would award the credential, and should…

The automotive application of discontinuously reinforced TiB-Ti composites

NASA Astrophysics Data System (ADS)

Saito, Takashi

2004-05-01

In 1998, Toyota Motor Corporation adopted intake valves and exhaust valves made of titanium-based alloys for the engine of its Altezza. Both valves were manufactured via a newly developed cost-effective powder metallurgy process. The exhaust valve is made of a newly developed titanium metal-matrix composite (MMC). The valve has achieved sufficient durability and reliability with a manufacturing cost acceptable for the mass-produced automobile engine components.

Menstrual blood closely resembles the uterine immune micro-environment and is clearly distinct from peripheral blood.

PubMed

van der Molen, R G; Schutten, J H F; van Cranenbroek, B; ter Meer, M; Donckers, J; Scholten, R R; van der Heijden, O W H; Spaanderman, M E A; Joosten, I

2014-02-01

Is menstrual blood a suitable source of endometrial derived lymphocytes? Mononuclear cells isolated from menstrual samples (menstrual blood mononuclear cells (MMC)) are clearly distinct from peripheral blood mononuclear cells (PBMC) and show a strong resemblance with biopsy-derived endometrial mononuclear cells. A critical event in the onset of pregnancy is the implantation of the embryo in the uterine wall. The immune cell composition in the endometrium at the time of implantation is considered pivotal for success. Despite advancing knowledge on the composition of the immune cell population in the uterus, the role of endometrial immune cells in reproductive disorders is still not fully resolved, mainly due to the fact that this type of research requires invasive techniques. Here, we collected menstrual fluid and validated this unique non-invasive technique to obtain and study the endometrium-derived immune cells which would be present around the time of implantation. Five healthy non-pregnant females with regular menstruation cycles and not using oral contraceptives collected their menstrual blood using a menstrual cup in five consecutive cycles. Sampling took place over the first 3 days of menses, with 12 h intervals. Peripheral blood samples, taken before and after each menstruation, were obtained for comparative analysis. MMC and PBMC samples were characterized for the different lymphocyte subsets by flow cytometry, with emphasis on NK cells and T cells. Next, the functional capacity of the MMC-derived NK cells was determined by measuring intracellular production of IFN-γ, granzyme B and perforin after culture in the presence of IL-2 and IL-15. In support of their endometrial origin, MMC samples contained the typical composition of mononuclear cells expected of endometrial tissue, were phenotypically similar to the reported phenotype for biopsy-derived endometrial cells, and were distinct from PBMC. Increased percentages of NK cells and decreased percentages of T cells were found in MMC when compared with PBMC from the same female. The MMC-derived NK cells were pre-dominantly CD56(bright)/CD16(-), in contrast to the primarily CD56(dim)/CD16(+) peripheral blood NK cells. MMC-derived NK cells expressed CD103, indicating their mucosal origin. In addition, the pattern of natural cytotoxicity receptor (NCR) expression in MMC-derived NK cells was comparable with that in endometrial biopsy-derived NK cells. Compared with PBMC, the NKp30 expression was decreased, while the percentage of NKp44 positive cells was increased in MMC samples. CXCR3 and CXCR4 were hardly expressed by MMC-derived NK cells, indicating that these cells are not of PBMC origin. NK cells from MMC samples were functional as shown by their capacity to produce IFN-γ, granzyme B and perforin, upon stimulation with IL-2 and IL-15. MMC-derived T cells revealed an increased expression of CD103, CD69 and CXCR4 compared with PBMC-derived T cells. Importantly, MMC collection using a menstrual cup proved highly reliable and reproducible between women and between cycles. Based on the parameters we studied, MMC appear similar to biopsy-derived endometrial mononuclear cells. However, sampling is not done at the exact same time in the menstrual cycle, and thus we cannot exclude some, as yet undetected, differences. Also, it should be considered that for some women, the use of the menstrual cup may be unpleasant. Menstrual blood may be a source of endometrial cells and may create new opportunities to study uterine immunological cells in fertility issues. No external funding was obtained for the present study. None of the authors have any conflict of interest to declare. NA.

Credentialing in Out-of-School Time Programs: A Discussion Paper. Making the MOST of Out-of-School Time.

ERIC Educational Resources Information Center

Morgan, Gwen G.

This discussion paper provides background information on credentialing, raises issues in the area of credentialing for out-of-school time programs, and suggests the important decisions that need to evolve in the out-of-school time field. The first part of the paper defines credentials, describes traditional and changing concepts of credentialing…

Credentials in Context: The Meaning and Use of Associate Degrees in the Employment of IT Technicians

ERIC Educational Resources Information Center

Van Noy, Michelle

2011-01-01

Educational credentials are clearly linked to economic success, but the reasons for this link are not clear. Common theoretical approaches provide explanations but lack direct employer perspectives on credentials' meaning and the context in which employers make sense of credentials. In this study, I used an alternative perspective based in Meyer's…

Credentialing Educational Accomplishment. Report and Recommendations of the Task Force on Educational Credit and Credentials.

ERIC Educational Resources Information Center

Miller, Jerry W., Ed.; Mills, Olive, Ed.

The Task Force on Educational Credit and Credentials of the American Council on Education undertook a two-year study to determine how postsecondary education's system for awarding credit and credentials can be changed or its adequacy improved to meet today's educational and social needs. This book sets forth the Task Force's report and…

Comparison of mitomycin C and limbal-conjunctival autograft in the prevention of pterygial recurrence in Turkish patients: A one-year, randomized, assessor-masked, controlled trial

PubMed Central

Ari, Şeyhmus; Çaca, Îhsan; Yildiz, Zennure Özdemir; Şakalar, Yildirim Bayezit; Dogan, Eyüp

2009-01-01

Background: A pterygium is a fibrovascular overgrowth of degenerative bulbar conjunctival tissue that grows over the limbus onto the cornea. Although various approaches have been proposed for the treatment of pterygium, the common problem after these treatments is recurrence. Objectives: The goals of this study were to compare the efficacy of mitomycin C (MMC) and limbal-conjunctival autograft (LCAU) in preventing recurrence of primary pterygia and to monitor long-term adverse effects (AEs). Methods: Patients undergoing pterygium surgery between February 2006 and May 2007 were assessed prospectively and randomly divided into 2 groups using a random number table. The MMC group underwent pterygium excision and received 0.02% MMC intraoperatively for 2 minutes. The LCAU group underwent pterygium excision and LCAU. Recurrence and AE rates of the 2 treatments were compared during the 1-year follow-up period. Assessors for pterygial recurrence were masked to treatment group. Results: One hundred thirteen eyes (57 patients in the MMC group and 56 patients in the LCAU group) were included in the study. Thirteen of the patients (7 in the MMC group and 6 in the LCAU group) were withdrawn due to irregular attendance at follow-up visits or lack of sufficient dose and duration for postoperative topical antibiotic and steroid administration; their data were excluded from analysis. Fifty patients (MMC group: 26 men, 24 women; mean [SD] age, 48.0 [12.3] years; age range, 30–73 years; LCAU group: 27 men, 23 women; mean age, 49.0 [12.6] years; age range, 28–71 years) in each group completed the study. The mean (SD) length of the pterygium across the limbus was similar in the MMC group and the LCAU group (4.18 [1.27] vs 4.07 [1.24] mm). The mean follow-up period was also similar in the 2 groups (16.0 [1.9] vs 15.0 [1.7] months). The rate of recurrence was significantly greater in the MMC group than in the LCAU group (10 [20.0%] vs 2 [4.0%] patients; P=0.035). Seven patients (14.0%) in the MMC group experienced AEs: conjunctival cyst (3 patients), symblepharon (2), conjunctival granuloma (1), and dellen (1). In the LCAU group, 1 patient (2.0%; P=0.032 vs MMC group) experienced permanent graft edema. All patients in the LCAU group experienced transient graft edema, with recovery occurring in 3 to 4 weeks. There were no intraoperative complications and there was no graft rejection. Conclusions: Recurrence and postoperative AEs were less frequently observed in primary excision with LCAU than with MMC in these Turkish patients who completed the study. This study found that pterygium excision with LCAU was well tolerated and effective in these patients. PMID:24683237

Polyhydroxyalkanoate synthesis by mixed microbial consortia cultured on fermented dairy manure: Effect of aeration on process rates/yields and the associated microbial ecology.

PubMed

Coats, Erik R; Watson, Benjamin S; Brinkman, Cynthia K

2016-12-01

Polyhydroxyalkanoates (PHAs) are biodegradable polymers that can substitute for petroleum-based plastics in a variety of applications. One avenue to commercial PHA production involves coupling waste-based synthesis with the use of mixed microbial consortia (MMC). In this regard, production requires maximizing the enrichment of a MMC capable of feast-famine PHA synthesis, with the metabolic response induced through imposition of aerobic-dynamic feeding (ADF) conditions. However, the concept of PHA production in complex matrices remains unrefined; process operational improvements are needed, along with an enhanced understanding of the MMC. Research presented herein investigated the effect of aeration on feast-famine PHA synthesis, with four independent aeration state systems studied; MMC were fed volatile fatty acid (VFA)-rich fermented dairy manure. Regardless of the aeration state, all MMC exhibited a feast-famine response based on observed carbon cycling. Moreover, there was no statistical difference in PHA synthesis rates, with q PHA ranging from 0.10 to 0.19 CmmolPHA gVSS -1 min -1 ; VFA uptake rates exhibited similar statistical indifferences. PHA production assessments on the enriched MMC resulted in maximum intracellular concentrations ranging from 22.5 to 90.7% (mgPHA mgVSS -1 ); at maximum concentration, the mean hydroxyvalerate mol content was 73 ± 0.6%. While a typical feast-famine dissolved oxygen (DO) pattern was observed at maximum aeration, less resolution was observed at decreasing aeration rates, suggesting that DO may not be an optimal process monitoring parameter. At lower aeration states, nitrogen cycling patterns, supported by molecular investigations targeting AOBs and NOBs, indicate that NO 2 and NO 3 sustained feast-famine PHA synthesis. Next-generation sequencing analysis of the respective MMC revealed numerous and diverse genera exhibiting the potential to achieve PHA synthesis, suggesting functional redundancy embedded in the diverse MMC. Ultimately, results demonstrate that aeration can be controlled in waste-based ADF systems to sustain PHA production potential, while enriching for a diverse MMC that exhibits potential functional redundancy. Reduced aeration could also enhance cost competitiveness of waste-based PHA production, with potential further benefits associated with nitrogen treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mitomycin C and the endoscopic treatment of laryngotracheal stenosis: are two applications better than one?

PubMed

Smith, Marshall E; Elstad, Mark

2009-02-01

Endoscopic treatment of laryngotracheal stenosis by airway dilation, despite short-term improvement, is often associated with long-term relapse. Mitomycin-C (MMC) inhibits fibroblast proliferation and synthesis of extracellular matrix proteins, and thereby modulates wound healing and scarring. MMC application at the time of endoscopic dilation and laser surgery has been suggested to improve outcomes, but this has not been studied in a rigorous manner. This study examines the hypothesis that two topical applications of MMC given 3-6 weeks apart will result in decreased scarring/restenosis of the airway, when compared to a single topical application. A randomized, prospective, double-blind, placebo-controlled clinical trial. Twenty-six patients with laryngotracheal stenosis due to idiopathic subglottic stenosis, postintubation stenosis, or Wegener's granulomatosis entered a protocol to receive three endoscopic CO(2) laser and dilation procedures over a 3-month interval. At the first procedure, after radial CO(2) laser incision and airway dilation, all patients received topical application of MMC (0.5 mg/mL) to the airway lesion. One month later, a second endoscopic incision and dilation was performed and the patients were randomized to either a second application of mitomycin-C or to application of saline placebo. A third dilation procedure was performed 2 months later, without MMC application. Patients were followed for up to 5 years for relapse of airway stenosis with clinical symptoms sufficient to require a subsequent procedure. The relapse rates at 1, 3, and 5 years were 7%, 36%, and 69% for patients treated with two applications of MMC compared to 33%, 58%, and 70% for patients treated with one application of MMC. The median interval to relapse was 3.8 years in the two-application group, compared with 2.4 years in the one-application group. This prospective randomized double-blind placebo-controlled trial suggests that, in the endoscopic management of laryngotracheal stenosis, two applications of MMC given 3-4 weeks apart after airway radial incision and dilation reduces the restenosis rate for 2 to 3 years after treatment when compared to a single application. However, restenosis and delayed symptom recurrence continues so that at 5 years the relapse rates are the same. Thus, MMC may postpone, but does not prevent, the recurrence of symptomatic stenosis in the majority of patients.

Four Ways to Avoid a Credentialing Cash Flow Crisis.

PubMed

Toth, Cheryl

2015-01-01

Credentialing a physician for Medicare and private plans is a detailed and time-consuming process, but it must be completed before a plan will reimburse a practice's billed services. Assign a person with the right skills for this project, and insist on regular progress reports to be certain credentialing has been successfully completed. Submit credentialing applications three to six months ahead of opening your practice doors, moving to a new location, or merging with another organization. If you're considering outsourcing the credentialing process to a service, verify its reputation and work products with its customers.

The Need for National Credentialing Standards for Addiction Counselors

ERIC Educational Resources Information Center

Miller, Geri; Scarborough, Jim; Clark, Catherine; Leonard, Justin C.; Keziah, Tyler B.

2010-01-01

The authors review the current state of credentialing for addiction counselors in the United States and provide recommendations to the addiction counseling field regarding national standards for credentialing.

Effect of ambient temperature on the thermoregulatory and locomotor stimulant effects of 4-methylmethcathinone in Wistar and Sprague-Dawley rats.

PubMed

Wright, M Jerry; Angrish, Deepshikha; Aarde, Shawn M; Barlow, Deborah J; Buczynski, Matthew W; Creehan, Kevin M; Vandewater, Sophia A; Parsons, Loren H; Houseknecht, Karen L; Dickerson, Tobin J; Taffe, Michael A

2012-01-01

The drug 4-methylmethcathinone (4-MMC; aka, mephedrone, MMCAT, "plant food", "bath salts") is a recent addition to the list of popular recreational psychomotor-stimulant compounds. Relatively little information about this drug is available in the scientific literature, but popular media reports have driven recent drug control actions in the UK and several US States. Online user reports of subjective similarity to 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") prompted the current investigation of the thermoregulatory and locomotor effects of 4-MMC. Male Wistar and Sprague-Dawley rats were monitored after subcutaneous administration of 4-MMC (1-10 mg/kg ) using an implantable radiotelemetry system under conditions of low (23°C) and high (27°C) ambient temperature. A reliable reduction of body temperature was produced by 4-MMC in Wistar rats at 23°C or 27°C with only minimal effect in Sprague-Dawley rats. Increased locomotor activity was observed after 4-MMC administration in both strains with significantly more activity produced in the Sprague-Dawley strain. The 10 mg/kg s.c. dose evoked greater increase in extracellular serotonin, compared with dopamine, in the nucleus accumbens. Follow-up studies confirmed that the degree of locomotor stimulation produced by 10 mg/kg 4-MMC was nearly identical to that produced by 1 mg/kg d-methamphetamine in each strain. Furthermore, hypothermia produced by the serotonin 1(A/7) receptor agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) was similar in each strain. These results show that the cathinone analog 4-MMC exhibits thermoregulatory and locomotor properties that are distinct from those established for methamphetamine or MDMA in prior work, despite recent evidence of neuropharmacological similarity with MDMA.

The ethyl acetate fraction of a methanolic extract of unripe noni (Morinda citrifolia Linn.) fruit exhibits a biphasic effect on the dopaminergic system in mice

PubMed Central

Pandy, Vijayapandi; Narasingam, Megala; Vijeepallam, Kamini; Mohan, Syam; Mani, Vasudevan; Mohamed, Zahurin

2017-01-01

In earlier ex vivo studies, we reported the biphasic effect of a methanolic extract of unripe Morinda citrifolia fruit (MMC) on dopamine-induced contractility in isolated rat vas deferens preparations. The present in vivo study was designed and undertaken to further explore our earlier ex vivo findings. This study examined the effect of the ethyl acetate fraction of a methanolic extract of unripe Morinda citrifolia Linn. fruit (EA-MMC; 5–100 mg/kg, p.o.) on the dopaminergic system using mouse models of apomorphine-induced climbing time and climbing behavior, methamphetamine-induced stereotypy (sniffing, biting, gnawing, and licking) and haloperidol-induced catalepsy using the bar test. Acute treatment with EA-MMC at a low dose (25 mg/kg, p.o.) significantly attenuated the apomorphine-induced climbing time and climbing behavior in mice. Similarly, EA-MMC (5 and 10 mg/kg, p.o.) significantly inhibited methamphetamine-induced stereotyped behavior in mice. These results demonstrated that the antidopaminergic effect of EA-MMC was observed at relatively lower doses (<25 mg/kg, p.o.). On the other hand, EA-MMC showed dopaminergic agonistic activity at a high dose (3,000 mg/kg, p.o.), which was evident from alleviation of haloperidol (a dopamine D2 blocker)-induced catalepsy in mice. Therefore, it is concluded that EA-MMC might possess a biphasic effect on the dopaminergic system, i.e., an antagonistic effect at lower doses (<25 mg/kg, p.o.) and an agonistic effect at higher doses (>1,000 mg/kg, p.o.). However, further receptor-ligand binding assays are necessary to confirm the biphasic effects of M. citrifolia fruit on the dopaminergic system. PMID:28450692

The ethyl acetate fraction of a methanolic extract of unripe noni (Morinda citrifolia Linn.) fruit exhibits a biphasic effect on the dopaminergic system in mice.

PubMed

Pandy, Vijayapandi; Narasingam, Megala; Vijeepallam, Kamini; Mohan, Syam; Mani, Vasudevan; Mohamed, Zahurin

2017-08-05

In earlier ex vivo studies, we reported the biphasic effect of a methanolic extract of unripe Morinda citrifolia fruit (MMC) on dopamine-induced contractility in isolated rat vas deferens preparations. The present in vivo study was designed and undertaken to further explore our earlier ex vivo findings. This study examined the effect of the ethyl acetate fraction of a methanolic extract of unripe Morinda citrifolia Linn. fruit (EA-MMC; 5-100 mg/kg, p.o.) on the dopaminergic system using mouse models of apomorphine-induced climbing time and climbing behavior, methamphetamine-induced stereotypy (sniffing, biting, gnawing, and licking) and haloperidol-induced catalepsy using the bar test. Acute treatment with EA-MMC at a low dose (25 mg/kg, p.o.) significantly attenuated the apomorphine-induced climbing time and climbing behavior in mice. Similarly, EA-MMC (5 and 10 mg/kg, p.o.) significantly inhibited methamphetamine-induced stereotyped behavior in mice. These results demonstrated that the antidopaminergic effect of EA-MMC was observed at relatively lower doses (<25 mg/kg, p.o.). On the other hand, EA-MMC showed dopaminergic agonistic activity at a high dose (3,000 mg/kg, p.o.), which was evident from alleviation of haloperidol (a dopamine D 2 blocker)-induced catalepsy in mice. Therefore, it is concluded that EA-MMC might possess a biphasic effect on the dopaminergic system, i.e., an antagonistic effect at lower doses (<25 mg/kg, p.o.) and an agonistic effect at higher doses (>1,000 mg/kg, p.o.). However, further receptor-ligand binding assays are necessary to confirm the biphasic effects of M. citrifolia fruit on the dopaminergic system.

Does mitomycin C cause toxicity in the cornea after photorefractive keratectomy? A comparative wound-healing study in a refractive surgery animal model.

PubMed

Blanco-Mezquita, Tomas; Espandar, Ladan; Torres, Rodrigo; Alvarez-Barcia, Angel; Cantalapiedra-Rodriguez, Roberto; Martinez-Garcia, Carmen; Merayo-Lloves, Jesus

2014-11-01

In this study, we investigated the wound-healing process after photorefractive keratectomy with mitomycin C (MMC) in hen corneas. In addition, we evaluated the synergistic effect of ethanol and MMC. Forty-eight adult hens were divided into 3 groups: A: ethanol-assisted debridement plus MMC; B: mechanical debridement plus MMC; and C: mechanical debridement (MMC-untreated control). Photorefractive keratectomy was performed, and the animals were followed up for up to 60 days. Epithelial healing was measured with fluorescein. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end-labeling assay and proliferation was measured by BrdU incorporation. Both myofibroblast differentiation and collagen deposition were evaluated by immunofluorescence and histology. Epithelial wound closure was similar in all 3 groups (P > 0.05). Significant reduction in haze was observed in groups A and B compared with C (P < 0.01), but there was no difference between groups A and B (P > 0.05). Furthermore, there was no difference in the number of apoptotic cells between groups. Proliferation was delayed in both groups A and B compared with C (P < 0.01), but groups A and B did not differ significantly (P > 0.05). Myofibroblasts, cellular density, and collagen deposition were lower in both groups A and B compared with C (P < 0.01), but they were not significantly different from each other (P > 0.05). Topical application of MMC in hen corneas reproduces the wound healing observed in humans by reducing haze, keratocyte proliferation, myofibroblast differentiation, and new collagen deposition. Synergistic cytotoxic effects of ethanol and MMC were not observed.

Results of the application of intraoperative mitomycin C in dacryocystorhinostomy.

PubMed

Roozitalab, M H; Amirahmadi, M; Namazi, M R

2004-01-01

Dacryocystorhinostomy (DCR) is widely accepted as the procedure of choice for surgical correction of lacrimal drainage system obstruction distal to common canaliculus in adulthood. The success rate of DCR has been reported to be from 63% to 99%. DCR failure has been attributed to membranous occlusion of the rhinostomy site caused by soft tissue scarring. More recently, use of mitomycin C (MMC) has been described in lacrimal drainage surgery. The beneficial effect of MMC as a surgical adjunct is thought to be related to its potent inhibition of fibroblast proliferation. To improve the success rate of DCR, the authors used MMC as an adjunct to surgery in 130 patients with nasolacrimal duct obstruction undergoing lacrimal surgery. They were assigned randomly into a MMC DCR group and a regular DCR group (control group). The mean age of the MMC group was 40+/-15 years and that of the control group was 42+/-16 years. The standard surgical techniques of an external DCR were used in all patients of both groups. Patients were followed for 6 months. The authors evaluated the patients with subjective symptoms (improvement in tearing) and objective findings such as the height of tear meniscus, fluorescein dye test, and patency at the time of irrigation. There was no significant difference in the age between the two groups (p=1.00). Six patients in the mitomycin group were symptomatic after 6 months' follow-up; probe and irrigation showed non-patency of lacrimal system. The success rate in the MMC group was therefore 90.5% (59/65), and in the conventional group it was 92.4% (60/65). No significant difference between the two groups was present (p=0.75). The authors conclude that the use of intraoperative MMC in DCR surgery does not change the success rate of this procedure.

Effect of Ambient Temperature on the Thermoregulatory and Locomotor Stimulant Effects of 4-Methylmethcathinone in Wistar and Sprague-Dawley Rats

PubMed Central

Wright, M. Jerry; Angrish, Deepshikha; Aarde, Shawn M.; Barlow, Deborah J.; Buczynski, Matthew W.; Creehan, Kevin M.; Vandewater, Sophia A.; Parsons, Loren H.; Houseknecht, Karen L.; Dickerson, Tobin J.; Taffe, Michael A.

2012-01-01

The drug 4-methylmethcathinone (4-MMC; aka, mephedrone, MMCAT, “plant food”, “bath salts”) is a recent addition to the list of popular recreational psychomotor-stimulant compounds. Relatively little information about this drug is available in the scientific literature, but popular media reports have driven recent drug control actions in the UK and several US States. Online user reports of subjective similarity to 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) prompted the current investigation of the thermoregulatory and locomotor effects of 4-MMC. Male Wistar and Sprague-Dawley rats were monitored after subcutaneous administration of 4-MMC (1–10 mg/kg ) using an implantable radiotelemetry system under conditions of low (23°C) and high (27°C) ambient temperature. A reliable reduction of body temperature was produced by 4-MMC in Wistar rats at 23°C or 27°C with only minimal effect in Sprague-Dawley rats. Increased locomotor activity was observed after 4-MMC administration in both strains with significantly more activity produced in the Sprague-Dawley strain. The 10 mg/kg s.c. dose evoked greater increase in extracellular serotonin, compared with dopamine, in the nucleus accumbens. Follow-up studies confirmed that the degree of locomotor stimulation produced by 10 mg/kg 4-MMC was nearly identical to that produced by 1 mg/kg d-methamphetamine in each strain. Furthermore, hypothermia produced by the serotonin 1A/7 receptor agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) was similar in each strain. These results show that the cathinone analog 4-MMC exhibits thermoregulatory and locomotor properties that are distinct from those established for methamphetamine or MDMA in prior work, despite recent evidence of neuropharmacological similarity with MDMA. PMID:22952999

Complete Reversibility of the Chiari Type II Malformation After Postnatal Repair of Myelomeningocele.

PubMed

Beuriat, Pierre-Aurélien; Szathmari, Alexandru; Rousselle, Christophe; Sabatier, Isabelle; Di Rocco, Federico; Mottolese, Carmine

2017-12-01

It was believed that Chiari type II malformation (CM-II) was always present in a myelomeningocele (MMC). In fact, it is associated in about 80% of cases. Improvement of the hindbrain herniation after prenatal closure of MMC has challenged the idea that this condition was irreversible. Only 2 studies report ascent of the cerebellar tonsil after postnatal closure. This work aimed to study a large group of patients with MMC who benefited from a postnatal repair to evaluate the rate of long-term total reversibility of CM-II. Sixty-one patients were included. Mean time of follow-up was 8.1 years. The presence of CM-II after closure of the MMC was assessed on the most recent brain scan available for each patient. Forty-seven patients (77%) had a CM-II at birth (confirmed before the MMC repair). There was a significant correlation between the level of the malformation and the presence of a CM-II at birth (P = 0.003). After MMC closure, only 28 (45.9%) patients had a remaining CM-II. The reversibility rate was 40.4%. The reversibility was higher in lower level malformations (P = 0.004). The number of patients treated for hydrocephalus was significantly higher in the group of patients with remaining CM-II (P = 0.004). Only 11.5% of the children needed surgery for a symptomatic CM-II. MMC is not always associated with CM-II. The outcome of CM-II has improved. Postnatal closure can reverse the CM-II. This must be kept in mind when analyzing the result of prenatal series. Copyright © 2017 Elsevier Inc. All rights reserved.

Conflicting Data on the Incidence of Leukopenia and Neutropenia After Heated Intraperitoneal Chemotherapy with Mitomycin C.

PubMed

Feferman, Yael; Bhagwandin, Shanel; Kim, Joseph; Aycart, Samantha N; Feingold, Daniela; Labow, Daniel M; Sarpel, Umut

2017-12-01

During heated intraperitoneal chemotherapy (HIPEC), neutropenia rates of 20 to 40% have been reported when mitomycin C (MMC) is dosed by weight or body surface area (BSA). This study investigated the authors' HIPEC experience using a fixed 40-mg dose of MMC, per consensus guidelines, and analyzed predictors for severe leukopenia and neutropenia. Patients who underwent MMC-HIPEC from 2007 to 2016 at a single tertiary care center were retrospectively reviewed. Among 314 MMC-HIPEC cases, 72 patients in the early era of the authors' program received routine prophylactic postoperative granulocyte-colony-stimulating factor (GCSF). This early cohort had five severe leukopenic reactions and one neutropenic reaction. In the subsequent 242 cases without GCSF prophylaxis, severe leukopenia developed in 16 patients (7%), with neutropenia occurring in 11 (4.5%) of these cases. A history of prior systemic chemotherapy was noted in 9 (56%) of the 16 leukopenic patients compared with 112 (46%) of the patients who had no leukopenia (nonsignificant difference). The median nadir of leukopenia was 5 days (range 1-11 days). Of the 11 neutropenic patients, 6 received therapeutic GCSF, and 5 recovered without intervention. The 30-day postoperative mortality of the patients with leukopenia was 0%. In this study, the incidence of neutropenia after HIPEC with 40 mg of MMC was markedly lower than reported in the literature for doses adjusted by BSA or weight. The authors report that GCSF is not necessary for routine prophylaxis of all MMC-HIPEC patients. The findings suggest that a fixed 40-mg dose of MMC allows HIPEC to be performed with less risk of immunosuppression.

A longitudinal evaluation of the effect of Medi-Cal managed care on supplemental security income and aid to families with dependent children enrollees in two California counties.

PubMed

Lo Sasso, A T; Freund, D A

2000-09-01

We examined the differential effect of Medicaid managed care (MMC) among Aid to Families With Dependent Children (AFDC) and Supplemental Security Income (SSI) enrollees over time by comparing the experiences of adult nonelderly enrollees in the Health Plan of San Mateo in California versus Ventura County's fee-for-service (FFS) enrollees. Four years of administrative claims data were used to construct a longitudinal data set and estimate panel data models to decompose the effect of managed care over time. AFDC MMC enrollees exhibited generally fewer ambulatory visits, lower expenditures, and higher monthly probabilities of a preventable hospitalization relative to comparably enrolled FFS patients. SSI MMC enrollees had more emergency department visits and higher monthly probabilities of hospitalization. However, SSI MMC enrollees had more ambulatory visits and more medications during the first year of enrollment relative to SSI FFS enrollees, although levels were similar in subsequent years. SSI MMC enrollees did not exhibit a significantly higher level of expenditures in the first year of enrollment, although in subsequent years, expenditure levels were significantly lower. The results for emergency department visits and preventable hospitalizations presented a decidedly downbeat picture of access to care for AFDC and SSI enrollees in MMC. However, some aspects of utilization under managed care exhibited results consistent with long-term- oriented treatment for enrollees with a greater likelihood of remaining in the system for a longer period of time (SSI enrollees). By contrast, enrollees more likely to be enrolled for shorter periods (AFDC enrollees) tended to exhibit care patterns under MMC consistent with lower levels of care relative to FFS.

Redefining the functional roles of the gastrointestinal migrating motor complex and motilin in small bacterial overgrowth and hunger signaling.

PubMed

Deloose, Eveline; Tack, Jan

2016-02-15

During the fasting state the upper gastrointestinal tract exhibits a specific periodic migrating contraction pattern that is known as the migrating motor complex (MMC). Three different phases can be distinguished during the MMC. Phase III of the MMC is the most active of the three and can start either in the stomach or small intestine. Historically this pattern was designated to be the housekeeper of the gut since disturbances in the pattern were associated with small intestinal bacterial overgrowth; however, its role in the involvement of hunger sensations was already hinted in the beginning of the 20th century by both Cannon (Cannon W, Washburn A. Am J Physiol 29: 441-454, 1912) and Carlson (Carlson A. The Control of Hunger in Health and Disease. Chicago, IL: Univ. of Chicago Press, 1916). The discovery of motilin in 1973 shed more light on the control mechanisms of the MMC. Motilin plasma levels fluctuate together with the phases of the MMC and induce phase III contractions with a gastric onset. Recent research suggests that these motilin-induced phase III contractions signal hunger in healthy subjects and that this system is disturbed in morbidly obese patients. This minireview describes the functions of the MMC in the gut and its regulatory role in controlling hunger sensations. Copyright © 2016 the American Physiological Society.

Effect of noni (Morinda citrifolia Linn.) fruit and its bioactive principles scopoletin and rutin on rat vas deferens contractility: an ex vivo study.

PubMed

Pandy, Vijayapandi; Narasingam, Megala; Kunasegaran, Thubasni; Murugan, Dharmani Devi; Mohamed, Zahurin

2014-01-01

This study examined the effect of methanolic extract of Morinda citrifolia Linn. (MMC) and its bioactive principles, scopoletin and rutin, on dopamine- and noradrenaline-evoked contractility in isolated rat vas deferens preparations. MMC (1-40 mg/mL), scopoletin (1-200 μg/mL), and rutin hydrate (0.6-312.6 μg/mL) dose-dependently inhibited the contractility evoked by submaximal concentrations of both dopamine and noradrenaline, respectively. Haloperidol and prazosin, reference dopamine D2, and α 1-adrenoceptors antagonists significantly reversed the dopamine- and noradrenaline-induced contractions, respectively, in a dose-dependent manner. Interestingly, MMC per se at higher doses (60-100 mg/mL) showed dose-dependent contractile response in rat vas deferens which was partially inhibited by high doses of haloperidol but not by prazosin. These results demonstrated the biphasic effects of MMC on dopaminergic system; that is, antidopaminergic effect at lower concentrations (<40 mg/mL) and dopaminergic agonistic effect at higher concentrations (>60 mg/mL). However, similar contractile response at high doses of scopoletin (0.5-5 mg/mL) and rutin hydrate (0.5-5 mg/mL) per se was not observed. Therefore, it can be concluded that the bioactive principles of MMC, scopoletin, and rutin might be responsible for the antidopaminergic and antiadrenergic activities of MMC.

A new system for cultivation of human keratinocytes on acellular dermal matrix substitute with the use of human fibroblast feeder layer.

PubMed

Xiao, S; Zhu, S; Ma, B; Xia, Z-F; Yang, J; Wang, G

2008-01-01

To improve the proliferative potential of human keratinocytes (HK) cultured on acellular dermal matrix (ADM), HK and mitomycin C-treated human fibroblasts (MMC-HF) were seeded onto ADM to form four types of composite skin: type I, HK were seeded onto the epidermal side of ADM; type II, both HK and MMC-HF were seeded onto the epidermal side; type III, MMC-HF were preseeded onto the dermal side of ADM, and then HK were seeded onto the epidermal side, and type IV, where MMC-HF were preseeded onto both sides, and then HK were seeded onto the epidermal side. Compared with type I and III, the proliferative potential of HK of type II and IV was significantly higher on day 3, 5, 7 and 9 in vitro. In type I and III, HK grew into one layer on day 7-9, while in type II and IV keratinocytes grew into a confluent monolayer by day 4-6. The adherence to ADM of HK in types II and IV was stronger than that in type I and III. The take rate of type II and IV composite skin was also significantly higher. In conclusion, when MMC-HF and HK were cocultured on the epidermal side of ADM, MMC-HF could serve as excellent feeder cells. Copyright 2007 S. Karger AG, Basel.

Transconjunctival penetration of mitomycin C.

PubMed

Velpandian, T; Sihota, Ramanjit; Sinha, Ankur; Gupta, Viney

2008-01-01

The study was performed to estimate transconjunctival penetration of mitomycin C (MMC) to Tenon's tissue following application over the intact conjunctiva before routine trabeculectomy. Institution-based case series. In 41 eyes of 41 patients, MMC (0.4 mg/ml for 3 min) was applied over the intact conjunctiva before beginning trabeculectomy. Tenon's capsule directly beneath the site of application was excised during trabeculectomy and was homogenized, centrifuged and MMC concentrations were analyzed using high-performance liquid chromatography (HPLC). Statistical analysis was performed using STATA 8.0 version software (STATA Corporation, Houston, TX, USA). In this study, P -values less than 0.05 were considered as statistically significant. The average weight of the sample of Tenon's tissue excised was 5.51+/-4.42 mg (range: 0.9-17.1) and the average estimated MMC concentration found to be present in Tenon's tissue using HPLC was 18.67+/-32.36 x 10(-6) moles/kg of the tissue (range: 0.38-197.05 x 10(-6)). In 36 of the 41 patients (87.80%), the MMC concentration reached above 2 x 10(-6) moles/kg of the tissue concentration required to inhibit human conjunctival fibroblasts. Mitomycin C does permeate into the subconjunctival tissue after supraconjunctival application for 3 min. Application of MMC over the conjunctiva may be a useful alternative to subconjunctival or subscleral application during routine trabeculectomy and as an adjunct for failing blebs.

Credentialing, Licensing, and Education

MedlinePlus

... et al. Credentialing complementary practitioners in a large academic cancer center . Journal of the Society for Integrative ... al. A framework for credentialing naturopathic physicians in academic health centers: Oregon Health and Science University . Journal ...

SU-E-CAMPUS-J-04: Image Guided Radiation Therapy (IGRT): Review of Technical Standards and Credentialing in Radiotherapy Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giaddui, T; Chen, W; Yu, J

2014-06-15

Purpose: To review IGRT credentialing experience and unexpected technical issues encountered in connection with advanced radiotherapy technologies as implemented in RTOG clinical trials. To update IGRT credentialing procedures with the aim of improving the quality of the process, and to increase the proportion of IGRT credentialing compliance. To develop a living disease site-specific IGRT encyclopedia. Methods: Numerous technical issues were encountered during the IGRT credentialing process. The criteria used for credentialing review were based on: image quality; anatomy included in fused data sets and shift results. Credentialing requirements have been updated according to the AAPM task group reports for IGRTmore » to ensure that all required technical items are included in the quality review process. Implementation instructions have been updated and expanded for recent protocols. Results: Technical issues observed during the credentialing review process include, but are not limited to: poor quality images; inadequate image acquisition region; poor data quality; shifts larger than acceptable; no soft tissue surrogate. The updated IGRT credentialing process will address these issues and will also include the technical items required from AAPM: TG 104; TG 142 and TG 179 reports. An instruction manual has been developed describing a remote credentialing method for reviewers. Submission requirements are updated, including images/documents as well as facility questionnaire. The review report now includes summary of the review process and the parameters that reviewers check. We have reached consensus on the minimum IGRT technical requirement for a number of disease sites. RTOG 1311(NRG-BR002A Phase 1 Study of Stereotactic Body Radiotherapy (SBRT) for the Treatment of Multiple Metastases) is an example, here; the protocol specified the minimum requirement for each anatomical sites (with/without fiducials). Conclusion: Technical issues are identified and reported. IGRT guidelines are updated, with the corresponding credentialing requirements. An IGRT encyclopedia describing site-specific implementation issues is currently in development.« less

Mitomycin C-induced pairing of heterochromatin reflects initiation of DNA repair and chromatid exchange formation.

PubMed

Abdel-Halim, H I; Natarajan, A T; Mullenders, L H F; Boei, J J W A

2005-04-15

Chromatid interchanges induced by the DNA cross-linking agent mitomycin C (MMC) are over-represented in human chromosomes containing large heterochromatic regions. We found that nearly all exchange breakpoints of chromosome 9 are located within the paracentromeric heterochromatin and over 70% of exchanges involving chromosome 9 are between its homologues. We provide evidence that the required pairing of chromosome 9 heterochromatic regions occurs in G(0)/G(1) and S-phase cells as a result of an active cellular process initiated upon MMC treatment. By contrast, no pairing was observed for a euchromatic paracentromeric region of the equal-sized chromosome 8. The MMC-induced pairing of chromosome 9 heterochromatin is observed in a subset of cells; its percentage closely mimics the frequency of homologous interchanges found at metaphase. Moreover, the absence of pairing in cells derived from XPF patients correlates with an altered spectrum of MMC-induced exchanges. Together, the data suggest that the heterochromatin-specific pairing following MMC treatment reflects the initiation of DNA cross-link repair and the formation of exchanges.

Toll-like receptor 6 and connective tissue growth factor are significantly upregulated in mitomycin-C-treated urothelial carcinoma cells under hydrostatic pressure stimulation.

PubMed

Chen, Shao-Kuan; Chung, Chih-Ang; Cheng, Yu-Che; Huang, Chi-Jung; Chen, Wen-Yih; Ruaan, Ruoh-Chyu; Li, Chuan; Tsao, Chia-Wen; Hu, Wei-Wen; Chien, Chih-Cheng

2014-06-01

Urothelial carcinoma (UC) is the most common histologic subtype of bladder cancer. The administration of mitomycin C (MMC) into the bladder after transurethral resection of the bladder tumor (TURBT) is a common treatment strategy for preventing recurrence after surgery. We previously applied hydrostatic pressure combined with MMC in UC cells and found that hydrostatic pressure synergistically enhanced MMC-induced UC cell apoptosis through the Fas/FasL pathways. To understand the alteration of gene expressions in UC cells caused by hydrostatic pressure and MMC, oligonucleotide microarray was used to explore all the differentially expressed genes. After bioinformatics analysis and gene annotation, Toll-like receptor 6 (TLR6) and connective tissue growth factor (CTGF) showed significant upregulation among altered genes, and their gene and protein expressions with each treatment of UC cells were validated by quantitative real-time PCR and immunoblotting. Under treatment with MMC and hydrostatic pressure, UC cells showed increasing apoptosis using extrinsic pathways through upregulation of TLR6 and CTGF.

Smart activatable and traceable dual-prodrug for image-guided combination photodynamic and chemo-therapy.

PubMed

Hu, Fang; Yuan, Youyong; Mao, Duo; Wu, Wenbo; Liu, Bin

2017-11-01

Activatable photosensitizers (PSs) and chemo-prodrugs are highly desirable for anti-cancer therapy to reduce systemic toxicity. However, it is difficult to integrate both together into a molecular probe for combination therapy due to the complexity of introducing PS, singlet oxygen quencher, chemo-drug, chemo-drug inhibitor and active linker at the same time. To realize activatable PS and chemo-prodrug combination therapy, we develop a smart therapeutic platform in which the chemo-prodrug serves as the singlet oxygen quencher for the PS. Specifically, the photosensitizing activity and fluorescence of the PS (TPEPY-SH) are blocked by the chemo-prodrug (Mitomycin C, MMC) in the probe. Meanwhile, the cytotoxicity of MMC is also inhibited by the electron-withdrawing acyl at the nitrogen position next to the linker. Upon glutathione activation, TPEPY-S-MMC can simultaneously release active PS and MMC for combination therapy. The restored fluorescence of TPEPY-SH is also used to report the activation for both PS and MMC as well as to guide the photodynamic therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of mitomycin-C on human foreskin fibroblasts used as feeders in human embryonic stem cells: immunocytochemistry MIB1 score and DNA ploidy and apoptosis evaluated by flow cytometry.

PubMed

Nieto, A; Cabrera, C M; Catalina, P; Cobo, F; Barnie, A; Cortés, J L; Barroso del Jesus, A; Montes, R; Concha, A

2007-03-01

Mitomycin C (MMC) treatment has been used to arrest cell proliferation but not much is known about the effect of MMC on human foreskin fibroblasts (HFF) used as feeders for human embryonic stem cells (hESC). We tested the ability of MMC to stop the proliferation of HFF and to induce apoptosis. MMC inhibited the proliferation of HFF at 10 microg/ml over 2.5h of MMC treatment showing a decrease in the proliferation index measured by Ki-67 and S and G2/M phases related to active HFF. A low percentage of cells showed necrotic or apoptotic features using different lengths of incubation. Over time, the majority of cells remained in a mitotically inactive state. The percentage of apoptotic cells increased from day 2 to day 10, at the same time as the necrotic ones increased. The HS181 hESC line grew in an undifferentiated state on inactive HFF throughout the study.

Encapsulation of methotrexate loaded magnetic microcapsules for magnetic drug targeting and controlled drug release

NASA Astrophysics Data System (ADS)

Chakkarapani, Prabu; Subbiah, Latha; Palanisamy, Selvamani; Bibiana, Arputha; Ahrentorp, Fredrik; Jonasson, Christian; Johansson, Christer

2015-04-01

We report on the development and evaluation of methotrexate magnetic microcapsules (MMC) for targeted rheumatoid arthritis therapy. Methotrexate was loaded into CaCO3-PSS (poly (sodium 4-styrenesulfonate)) doped microparticles that were coated successively with poly (allylamine hydrochloride) and poly (sodium 4-styrenesulfonate) by layer-by-layer technique. Ferrofluid was incorporated between the polyelectrolyte layers. CaCO3-PSS core was etched by incubation with EDTA yielding spherical MMC. The MMC were evaluated for various physicochemical, pharmaceutical parameters and magnetic properties. Surface morphology, crystallinity, particle size, zeta potential, encapsulation efficiency, loading capacity, drug release pattern, release kinetics and AC susceptibility studies revealed spherical particles of ~3 μm size were obtained with a net zeta potential of +24.5 mV, 56% encapsulation and 18.6% drug loading capacity, 96% of cumulative drug release obeyed Hixson-Crowell model release kinetics. Drug excipient interaction, surface area, thermal and storage stability studies for the prepared MMC was also evaluated. The developed MMC offer a promising mode of targeted and sustained release drug delivery for rheumatoid arthritis therapy.

Cornerstones of Completion: State Policy Support for Accelerated, Structured Pathways to College Credentials and Transfer. Executive Summary

ERIC Educational Resources Information Center

Couturier, Lara K.

2012-01-01

Completion by Design, funded by the Bill & Melinda Gates Foundation, is a partnership between participating colleges and state-level policy organizations. The initiative's strong policy component seeks both to change policies in ways that support the colleges' change strategies and to spread the learning and ideas stemming from Completion by…

Field of Study Choice by Community College Students in Canada

ERIC Educational Resources Information Center

Boudarbat, Brahim

2008-01-01

Community college education is a key component of Canadian postsecondary education, with 21% of the population aged 25-64 having college credentials. In order to understand educational decisions at this level, we estimate a model of choice of field of study and analyze, among other things, the effect of earnings on this choice. In this way, we…

Career Opportunities: Career Technical Education and the College Completion Agenda. Part IV: Aligning Policy with Mission for Better Outcomes

ERIC Educational Resources Information Center

Shulock, Nancy; Moore, Colleen

2013-01-01

The California Community Colleges are vital to closing the projected shortfall of Californians with a postsecondary credential and sustaining the state's economic competitiveness. Increasing the number of students who pursue and earn certificates and associate degrees in career technical education (CTE) fields is an important component of the…

Higher Education in Ohio: High Tuition, Low Aid, Too Little State Investment. Budget

ERIC Educational Resources Information Center

Patton, Wendy; Halbert, Hannah

2015-01-01

A skilled workforce is one essential component of a prosperous and inclusive state economy. Attaining a degree or other post-secondary credential has obvious benefits to graduates and their families. Higher education insulates against unemployment and can be a pathway out of the low-wage economy. Funding for higher education is correlated with…

Instructional climates in preschool children who are at-risk. Part II: perceived physical competence.

PubMed

Robinson, Leah E; Rudisill, Mary E; Goodway, Jacqueline D

2009-09-01

In Part II of this study, we examined the effect of two 9-week instructional climates (low-autonomy [LA] and mastery motivational climate [MMC]) on perceived physical competence (PPC) in preschoolers (N = 117). Participants were randomly assigned to an LA, MMC, or comparison group. PPC was assessed by a pretest, posttest, and retention test with the Pictorial Scale of Perceived Competence and Social Acceptance. A significant Treatment x Time interaction (p < .001) was present, supporting that MMC participants reported significantly higher PPC scores over time, while no positive changes were present in LA and comparison participants. The results show that an MMC leads to psychological benefits related to achievement motivation. These findings should encourage early childhood educators to consider the effect of instructional climates on children's self-perception.

A method of Modelling and Simulating the Back-to-Back Modular Multilevel Converter HVDC Transmission System

NASA Astrophysics Data System (ADS)

Wang, Lei; Fan, Youping; Zhang, Dai; Ge, Mengxin; Zou, Xianbin; Li, Jingjiao

2017-09-01

This paper proposes a method to simulate a back-to-back modular multilevel converter (MMC) HVDC transmission system. In this paper we utilize an equivalent networks to simulate the dynamic power system. Moreover, to account for the performance of converter station, core components of model of the converter station gives a basic model of simulation. The proposed method is applied to an equivalent real power system.

Use of adjunctive mitomycin C in external dacryocystorhinostomy surgery compared with surgery alone in patients with nasolacrimal duct obstruction: A prospective, double-masked, randomized, controlled trial.

PubMed

Ari, Seyhmus; Gun, Ramazan; Surmeli, Serdar; Atay, Ahmet Engin; Caca, Ihsan

2009-08-01

The most common cause for the failure of external dacryocystorhinostomy (DCR) surgery is the formation of granulation tissue at the osteotomy site or common canaliculus. The aims of this study were to assess the efficacy of intraoperative adjunctive mitomycin C (MMC) treatment in external DCR surgery and to compare this procedure with the standard DCR procedure alone in the long term (1 year). In this prospective, double-masked, randomized, controlled trial, patients with primary acquired nasolacrimal duct obstruction were randomized (using a random number table) into 2 groups based on surgical procedure. In the MMC group, intraoperative adjunctive MMC 0.2 mg/mL was applied to the osteotomy site for 30 minutes. The control group underwent standard DCR procedure only. The results of the DCR surgeries were assessed using objective findings (eg, cessation of excessive tearing via nasolacrimal duct irrigation and the improvement in height of tear meniscus) and subjective symptoms (asking patients to describe the degree of tearing improvement). Both the patients and the researchers who were assessing the study outcomes were masked to treatment group. One hundred eyes of 100 Turkish patients were assessed and equally randomized to the MMC (27 women, 23 men; mean [SD] age, 47.0 [7.6] years) and control (26 women, 24 men; mean age, 46.6 [8.8] years) groups. The follow-up period was not significantly different between the MMC and the control groups (13.1 [1.1] vs 13.2 [1.4] months). Significantly more eyes in the MMC group than the control group remained symptom-free throughout the 1-year follow-up period (45/50 [90%] vs 33/50 [66%]; P=0.005). Significantly more patients in the control group than the MMC group had an improvement in symptoms at the 1-year follow-up (8/50 [16%] vs 2/50 [4%] eyes; P=0.005). Based on the patency of the drainage system, the success rate was significantly greater in the MMC group than the control group (48/50 [96%] vs 42/50 [84%]; P=0.005). Based on nasolacrimal duct irrigation, significantly fewer patients in the MMC group than the control group had an enclosed naso-lacrimal duct (2/50 [4%] vs 8/50 [16%]). No adverse effects (eg, abnormal nasal bleeding, mucosal necrosis, infection) or any other surgical adverse events were observed. In the management of these patients with primary acquired nasolacrimal duct obstruction, adjunctive intraoperative MMC application with standard DCR surgery had a significantly higher success rate than did standard DCR surgery alone. Further large, double-masked, randomized studies are needed to confirm these findings.

Use of adjunctive mitomycin C in external dacryocystorhinostomy surgery compared with surgery alone in patients with nasolacrimal duct obstruction: A prospective, double-masked, randomized, controlled trial

PubMed Central

Ari, Şeyhmus; Gun, Ramazan; Surmeli, Serdar; Atay, Ahmet Engin; Çaca, Îhsan

2009-01-01

Background: The most common cause for the failure of external dacryocystorhinostomy (DCR) surgery is the formation of granulation tissue at the osteotomy site or common canaliculus. Objectives: The aims of this study were to assess the efficacy of intraoperative adjunctive mitomycin C (MMC) treatment in external DCR surgery and to compare this procedure with the standard DCR procedure alone in the long term (1 year). Methods: In this prospective, double-masked, randomized, controlled trial, patients with primary acquired nasolacrimal duct obstruction were randomized (using a random number table) into 2 groups based on surgical procedure. In the MMC group, intraoperative adjunctive MMC 0.2 mg/mL was applied to the osteotomy site for 30 minutes. The control group underwent standard DCR procedure only. The results of the DCR surgeries were assessed using objective findings (eg, cessation of excessive tearing via nasolacrimal duct irrigation and the improvement in height of tear meniscus) and subjective symptoms (asking patients to describe the degree of tearing improvement). Both the patients and the researchers who were assessing the study outcomes were masked to treatment group. Results: One hundred eyes of 100 Turkish patients were assessed and equally randomized to the MMC (27 women, 23 men; mean [SD] age, 47.0 [7.6] years) and control (26 women, 24 men; mean age, 46.6 [8.8] years) groups. The follow-up period was not significantly different between the MMC and the control groups (13.1 [1.1] vs 13.2 [1.4] months). Significantly more eyes in the MMC group than the control group remained symptom-free throughout the 1-year follow-up period (45/50 [90%] vs 33/50 [66%]; P=0.005). Significantly more patients in the control group than the MMC group had an improvement in symptoms at the 1-year follow-up (8/50 [16%] vs 2/50 [4%] eyes; P=0.005). Based on the patency of the drainage system, the success rate was significantly greater in the MMC group than the control group (48/50 [96%] vs 42/50 [84%]; P=0.005). Based on nasolacrimal duct irrigation, significantly fewer patients in the MMC group than the control group had an enclosed naso-lacrimal duct (2/50 [4%] vs 8/50 [16%]). No adverse effects (eg, abnormal nasal bleeding, mucosal necrosis, infection) or any other surgical adverse events were observed. Conclusions: In the management of these patients with primary acquired nasolacrimal duct obstruction, adjunctive intraoperative MMC application with standard DCR surgery had a significantly higher success rate than did standard DCR surgery alone. Further large, double-masked, randomized studies are needed to confirm these findings. PMID:24683236

Educational Credentials in Australia: Average Positional Value in Decline. Centre for the Study of Higher Education Research Working Papers, 93.4.

ERIC Educational Resources Information Center

Marginson, Simon

Since the 1960s there has been a major expansion in the number of people in Australia holding post school educational credentials and the proportion of the full time work force with those credentials. The penalties of not holding credentials, in terms of the incidence and duration of unemployment, are increasingly severe. At the same time, there…

Ultrasound use in Australasian emergency departments: a survey of Australasian College for Emergency Medicine Fellows and Trainees.

PubMed

Craig, Simon; Egerton-Warburton, Diana; Mellett, Tanya

2014-06-01

To describe current practice of EDUS by ACEM Trainees and Fellows; to describe potential barriers to US use in the Australasian setting; to determine compliance with current college guidelines regarding US credentialing. Data were collected by a cross-sectional online survey. Respondents were Trainees and Fellows of the ACEM. Outcome measures included the percentage of respondents currently undergoing or that had completed US credentialing for Focused Assessment with Sonography for Trauma (FAST) and assessment of abdominal aortic aneurysm (AAA) scans. The perceived barriers to use of emergency US were explored. There were 512 survey respondents, giving an overall response rate of 15%. Fellows were more likely to be credentialed compared with Trainees. There were 61% of respondents not credentialed for FAST and assessment of AAA scans. However, a significant proportion performed these scans regularly, and did not routinely seek independent confirmation of their findings. Barriers to credentialing included limited time and no credentialing programme at the individual's hospital. The present study showed that only a minority of ACEM Trainees and Fellows are credentialed to perform routine ED scans. Many non-credentialed ACEM Trainees and Fellows are performing scans, many without independent confirmation of their findings. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Steady-State Algorithmic Analysis M/M/c Two-Priority Queues with Heterogeneous Rates.

DTIC Science & Technology

1981-04-21

ALGORITHMIC ANALYSIS OF M/M/c TWO-PRIORITY QUEUES WITH HETEROGENEOUS RATES by Douglas R. Miller An algorithm for steady-state analysis of M/M/c nonpreemptive ...practical algorithm for systems involving more than two priority classes. The preemptive case is simpler than the nonpreemptive case; an algorithm for it...priority nonpreemptive queueing system with arrival rates 1 and X2 and service rates V and p42 * The state space can be described as follows. Let xi,j,k be

Considerations concerning fatigue life of metal matrix composites

NASA Technical Reports Server (NTRS)

Radhakrishnan, V. M.; Bartolotta, Paul A.

1993-01-01

Since metal matrix composites (MMC) are composed from two very distinct materials each having their own physical and mechanical properties, it is feasible that the fatigue resistance depends on the strength of the weaker constituent. Based on this assumption, isothermal fatigue lives of several MMC's were analyzed utilizing a fatigue life diagram approach. For each MMC, the fatigue life diagram was quantified using the mechanical properties of its constituents. The fatigue life regions controlled by fiber fracture and matrix were also quantitatively defined.

Cellular effects of mitomycin-C on human corneas after photorefractive keratectomy.

PubMed

Rajan, Madhavan S; O'Brart, David P S; Patmore, Anne; Marshall, John

2006-10-01

To investigate the effects of mitomycin-C (MMC) on epithelial and keratocyte cell kinetics after photorefractive keratectomy (PRK) using an in vitro human cornea model. Department of Academic Ophthalmology, Rayne Institute, St. Thomas' Hospital, London, United Kingdom. Twenty-four human eye-bank corneas were placed in a specially designed acrylic corneal holder and cultured using the air-interface organ culture technique for up to 4 weeks. The corneas were divided into 3 groups. Group 1 consisted of 8 human corneas that had -9.00 diopter (D) myopic PRK without MMC application. Group 2 consisted of 8 corneas that had -9.00 D PRK with MMC (0.2 microg/mL) application for 1 minute on the stromal surface after ablation. Group 3 consisted of 8 corneas that had -9.00 D PRK with 2-minute exposure to MMC (0.2 microg/mL). Temporal events in epithelial and keratocyte cell kinetics were evaluated using digital imaging, confocal microscopy, and light microscopy. Epithelial latency was significantly delayed with MMC application in Groups 2 and 3 (P<.001). Epithelial migration was delayed in Group 3 (2-minute exposure) compared to migration in Group 2 (P<.04), with a consequent delay in epithelial closure (P<.001). Group 3 corneas had poorly differentiated epithelium that was significantly thinner than in Groups 1 and 2 (P<.0001). A significant delay in keratocyte regeneration occurred after MMC application (P<.0005). At 4 weeks, the anterior stromal cell density was significantly lower in Group 3 than Group 2 (P<.001). There were no significant differences in the mid- and posterior stromal keratocyte density between the groups. Results suggest that epithelial healing after MMC is characterized by prolonged latency and decreased migration rate dependent on exposure time. Mitomycin C application did not result in increased loss of keratocytes, but it significantly delayed keratocyte repopulation in the anterior stroma. The use of MMC 0.2 microg/mL for 1 minute resulted in optimum modulation of healing characterized by reduced keratocyte activation with normal epithelial differentiation.

Correlating PMC-MMC Bonded Joint 3D FEA with Test

NASA Technical Reports Server (NTRS)

Jacobson, Mindy; Rodini, Benjamin; Chen, Wayne C.; Flom, Yury A.; Posey, Alan J.

2005-01-01

A viewgraph presentation on the correlation of Polymer Matrix Composites (PMC) and Metal Matrix Composites (MMC) bonded joints using three dimensional finite element analyses with materials tests is shown.

49 CFR 1572.500 - Scope.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF HOMELAND SECURITY MARITIME AND LAND TRANSPORTATION SECURITY CREDENTIALING AND SECURITY THREAT ASSESSMENTS Fees for Security Threat Assessments for Transportation Worker Identification Credential (TWIC... Transportation Worker Identification Credential and must undergo a security threat assessment under 49 CFR part...

Fraudulent Credentials: Federal Employees. A Report by the Chairman of the Subcommittee on Health and Long-Term Care of the Select Committee on Aging. House of Representatives, Ninety-Ninth Congress, Second Session.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Select Committee on Aging.

A House of Representatives report on the practice of a profession with fradulent credentials is presented. Attention is directed to the provision of medical care by unlicensed and unqualified people posing as doctors, fraudulent credentials across a range of occupations, especially those affecting the elderly, and fraudulent credentials held by…

Economic credentialing: the propriety of managing physician costs through privileging.

PubMed

Dahl, B A

1999-01-01

Hospital executives face the unique task of managing the costs of an institution in which they have no direct managerial authority over the primary cost drivers, namely, the physicians who practice in the hospital. Perhaps the most controversial method of controlling physician costs consists of the application of economic factors to the credentialing process. Using the credentialing process as a technique to exert fiscal control over physicians affords hospital executives and their governing boards a tremendous cost-management opportunity. The legal propriety of economic credentialing remains unsettled. Many commentators, relying on limited case law, conclude that hospitals can engage in economic credentialing. Nevertheless, hospitals should exercise care when employing an economic rationale to restrict privileges lest they stir up legal challenges. Moreover, if hospitals use economic credentialing to limit medicaid patients' access to hospitals by excluding these patients' physicians from the hospital, the federal government may have the last word on the propriety of the practice.

Full time adult credential students' instructional preferences at California State University, Long Beach: pedagogy orandragogy?

PubMed

Wang, Victor

2004-03-01

This study investigated the instructional preferences of full time adult credential students after they took a live course called Principles of Adult Education at California State University, Long Beach (CSULB) in the fall semester of 2002. These full time adult credential students had been working on their adult teaching credentials to meet the competencies specified by the California Commission on Teacher Credentialing. The course introduced students to Andragogy developed by Malcolm Knowles out of the andragogical model developed by Lindeman (1926). The study used Principles of Adult Learning Scales (PALS), advanced by Gary Conti in 1983 to measure instructional preferences. Data were collected from 30 (100% of 30) full time adult credential students enrolled in a live course to determine their instructional preferences of helping adults learn. The results of the study showed in most cases these adult learning professionals taught adult students andragogically; in some cases they taught adult students pedagogically.

Identification of putative agouti-related protein(87-132)-melanocortin-4 receptor interactions by homology molecular modeling and validation using chimeric peptide ligands.

PubMed

Wilczynski, Andrzej; Wang, Xiang S; Joseph, Christine G; Xiang, Zhimin; Bauzo, Rayna M; Scott, Joseph W; Sorensen, Nicholas B; Shaw, Amanda M; Millard, William J; Richards, Nigel G; Haskell-Luevano, Carrie

2004-04-22

Agouti-related protein (AGRP) is one of only two naturally known antagonists of G-protein-coupled receptors (GPCRs) identified to date. Specifically, AGRP antagonizes the brain melanocortin-3 and -4 receptors involved in energy homeostasis. Alpha-melanocyte stimulating hormone (alpha-MSH) is one of the known endogenous agonists for these melanocortin receptors. Insight into putative interactions between the antagonist AGRP amino acids with the melanocortin-4 receptor (MC4R) may be important for the design of unique ligands for the treatment of obesity related diseases and is currently lacking in the literature. A three-dimensional homology molecular model of the mouse MC4 receptor complex with the hAGRP(87-132) ligand docked into the receptor has been developed to identify putative antagonist ligand-receptor interactions. Key putative AGRP-MC4R interactions include the Arg111 of hAGRP(87-132) interacting in a negatively charged pocket located in a cavity formed by transmembrane spanning (TM) helices 1, 2, 3, and 7, capped by the acidic first extracellular loop (EL1) and specifically with the conserved melanocortin receptor residues mMC4R Glu92 (TM2), mMC4R Asp114 (TM3), and mMC4R Asp118 (TM3). Additionally, Phe112 and Phe113 of hAGRP(87-132) putatively interact with an aromatic hydrophobic pocket formed by the mMC4 receptor residues Phe176 (TM4), Phe193 (TM5), Phe253 (TM6), and Phe254 (TM6). To validate the AGRP-mMC4R model complex presented herein from a ligand perspective, we generated nine chimeric peptide ligands based on a modified antagonist template of the hAGRP(109-118) (Tyr-c[Asp-Arg-Phe-Phe-Asn-Ala-Phe-Dpr]-Tyr-NH(2)). In these chimeric ligands, the antagonist AGRP Arg-Phe-Phe residues were replaced by the melanocortin agonist His/D-Phe-Arg-Trp amino acids. These peptides resulted in agonist activity at the mouse melanocortin receptors (mMC1R and mMC3-5Rs). The most notable results include the identification of a novel subnanomolar melanocortin peptide template Tyr-c[Asp-His-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) that is equipotent to alpha-MSH at the mMC1, mMC3, and mMC5 receptors but is 30-fold more potent than alpha-MSH at the mMC4R. Additionally, these studies identified a new and novel >200-fold MC4R versus MC3R selective peptide Tyr-c[Asp-D-Phe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) template. Furthermore, when the His-DPhe-Arg-Trp sequence is used to replace the hAGRP Arg-Phe-Phe residues in the "mini"-AGRP (hAGRP87-120, C105A) template, a potent nanomolar agonist resulted at the mMC1R and MC3-5Rs.

Effect of Noni (Morinda citrifolia Linn.) Fruit and Its Bioactive Principles Scopoletin and Rutin on Rat Vas Deferens Contractility: An Ex Vivo Study

PubMed Central

Narasingam, Megala; Murugan, Dharmani Devi; Mohamed, Zahurin

2014-01-01

This study examined the effect of methanolic extract of Morinda citrifolia Linn. (MMC) and its bioactive principles, scopoletin and rutin, on dopamine- and noradrenaline-evoked contractility in isolated rat vas deferens preparations. MMC (1–40 mg/mL), scopoletin (1–200 μg/mL), and rutin hydrate (0.6–312.6 μg/mL) dose-dependently inhibited the contractility evoked by submaximal concentrations of both dopamine and noradrenaline, respectively. Haloperidol and prazosin, reference dopamine D2, and α 1-adrenoceptors antagonists significantly reversed the dopamine- and noradrenaline-induced contractions, respectively, in a dose-dependent manner. Interestingly, MMC per se at higher doses (60–100 mg/mL) showed dose-dependent contractile response in rat vas deferens which was partially inhibited by high doses of haloperidol but not by prazosin. These results demonstrated the biphasic effects of MMC on dopaminergic system; that is, antidopaminergic effect at lower concentrations (<40 mg/mL) and dopaminergic agonistic effect at higher concentrations (>60 mg/mL). However, similar contractile response at high doses of scopoletin (0.5–5 mg/mL) and rutin hydrate (0.5–5 mg/mL) per se was not observed. Therefore, it can be concluded that the bioactive principles of MMC, scopoletin, and rutin might be responsible for the antidopaminergic and antiadrenergic activities of MMC. PMID:25045753

Hydrostatic pressure enhances mitomycin C induced apoptosis in urothelial carcinoma cells.

PubMed

Chen, Shao-Kuan; Chung, Chih-Ang; Cheng, Yu-Che; Huang, Chi-Jung; Ruaan, Ruoh-Chyu; Chen, Wen-Yih; Li, Chuan; Tsao, Chia-Wen; Hu, Wei-Wen; Chien, Chih-Cheng

2014-01-01

Urothelial carcinoma (UC) of the bladder is the second most common cancer of the genitourinary system. Clinical UC treatment usually involves transurethral resection of the bladder tumor followed by adjuvant intravesical immunotherapy or chemotherapy to prevent recurrence. Intravesical chemotherapy induces fewer side effects than immunotherapy but is less effective at preventing tumor recurrence. Improvement to intravesical chemotherapy is, therefore, needed. Cellular effects of mitomycin C (MMC) and hydrostatic pressure on UC BFTC905 cells were assessed. The viability of the UC cells was determined using cellular proliferation assay. Changes in apoptotic function were evaluated by caspase 3/7 activities, expression of FasL, and loss of mitochondrial membrane potential. Reduced cell viability was associated with increasing hydrostatic pressure. Caspase 3/7 activities were increased following treatment of the UC cells with MMC or hydrostatic pressure. In combination with 10 kPa hydrostatic pressure, MMC treatment induced increasing FasL expression. The mitochondria of UC cells displayed increasingly impaired membrane potentials following a combined treatment with 10 μg/ml MMC and 10 kPa hydrostatic pressure. Both MMC and hydrostatic pressure can induce apoptosis in UC cells through an extrinsic pathway. Hydrostatic pressure specifically increases MMC-induced apoptosis and might minimize the side effects of the chemotherapy by reducing the concentration of the chemical agent. This study provides a new and alternative approach for treatment of patients with UC following transurethral resection of the bladder tumor. Copyright © 2014 Elsevier Inc. All rights reserved.

Transconjunctival penetration of mitomycin C

PubMed Central

Velpandian, T; Sihota, Ramanjit; Gupta, Viney

2008-01-01

Aims: The study was performed to estimate transconjunctival penetration of mitomycin C (MMC) to Tenon′s tissue following application over the intact conjunctiva before routine trabeculectomy. Settings and Design: Institution-based case series. Materials and Methods: In 41 eyes of 41 patients, MMC (0.4 mg/ml for 3 min) was applied over the intact conjunctiva before beginning trabeculectomy. Tenon′s capsule directly beneath the site of application was excised during trabeculectomy and was homogenized, centrifuged and MMC concentrations were analyzed using high-performance liquid chromatography (HPLC). Statistical Analysis Used: Statistical analysis was performed using stata0 8.0 version software (STATA Corporation, Houston, TX, USA). In this study, P -values less than 0.05 were considered as statistically significant. Results: The average weight of the sample of Tenon′s tissue excised was 5.51 ± 4.42 mg (range: 0.9-17.1) and the average estimated MMC concentration found to be present in Tenon′s tissue using HPLC was 18.67 ± 32.36 × 10−6 moles/kg of the tissue (range: 0.38-197.05 x 10−6 ). In 36 of the 41 patients (87.80%), the MMC concentration reached above 2 x 10−6 moles/kg of the tissue concentration required to inhibit human conjunctival fibroblasts. Conclusions: Mitomycin C does permeate into the subconjunctival tissue after supraconjunctival application for 3 min. Application of MMC over the conjunctiva may be a useful alternative to subconjunctival or subscleral application during routine trabeculectomy and as an adjunct for failing blebs. PMID:18417819

Synthesis of a novel CS-g-MMCs conjugate and the inhabitation on the proliferation of Tenon's capsule fibroblasts in vitro.

PubMed

Duan, Lihong; Li, Xiaoning; Ouyang, Liangqi; Quan, Daping; Zheng, Qiongjuan; Ma, Jian; Gao, Qianying; Ge, Jian

2012-08-15

A novel anti-proliferative macromolecular conjugate, CS-g-MMCs, was synthesized in order to decrease the cytotoxicity of Mitomycin C (MMC) which was a traditional anti-proliferative agent of fibroblast in trabeculectomy. The structure of CS-g-MMCs was characterized by (1)H NMR, FT-IR spectroscopy and GPC analysis. The grafting degree (dg) of MMC onto chitosan (CS) was determined to be in the range of 2.8-11.3%, which could be controlled by variation of the molar ratios of MMC to oxidized chitosan (CS-CHO). In the drug release profiles of CS-g-MMCs in vitro, an initial burst followed by slow leakage was observed, and addition of acid or lysozyme obviously accelerated the MMC release. The MTS assay indicated that CS-CHO of 8 mg/ml has no cytotoxicity against human Tenon's capsule fibroblasts (HTCFs). The inhibition of HTCFs proliferation by CS-g-MMCs increased along with increasing the dg of conjugate. The CS-g-MMCs also caused the apoptosis of HTCFs and interfered in the active DNA synthesis in HTCFs. Furthermore, the expression of a-SMA at gene and protein levels were obviously lower when HTCFs were treated with CS-g-MMCs, as compared to MMC or blend of MMC/CS-CHO (p<0.05). Our results primarily demonstrated that the CS-g-MMCs conjugates have low cytotoxicity and have the effect to inhibit fibroblast proliferation. Copyright © 2012 Elsevier B.V. All rights reserved.

A comparative study of the safety and efficacy effect of 5-fluorouracil or mitomycin C mounted biological delivery membranes in a rabbit model of glaucoma filtration surgery.

PubMed

Wu, Zhihong; Li, Shuning; Wang, Ningli; Liu, Wanshun; Liu, Wen

2013-01-01

To investigate the potential usage of biological delivery membranes containing mitomycin C (MMC) or 5-fluorouracil (5-FU) in the construction of glaucoma-filtering blebs, and to evaluate their safety and efficacy. Chitosan was selected as the biological membrane carrier to prepare sustained-released membranes. Twelve micrograms of 5-FU or MMC was covalently conjugated onto the membranes by solvent volatilization. Rabbits underwent glaucoma filtration surgery and were randomly allocated into one of the four treatment regimens: glaucoma filtration operation with no implantation of chitosan membrane group (as control), drug-free chitosan membrane implantation group (blank/placebo group), membrane containing 5-FU treatment group (5-FU group), and membrane containing MMC treatment group (MMC group). Each group consisted of 12 rabbits. Intraocular pressure (IOP) was measured and evaluated over a 28-day period follow-up preoperatively, then after surgery on days 1, 3, 5, 7, 14, 21, and 28 by Tono-Pen. The aqueous humor was analyzed in each experimental and control groups at days 4, 6, 8, 10, 12, 14, 16, and 20 after operation. Bleb survival and anterior segment were examined with a slit lamp microscope and photographed simultaneously. Two rabbits from each group were killed on day 28 and eight eye samples obtained for histopathological study. Corneas and lenses were examined by transmission and scanning electron microscopy. Both 5-FU and MMC significantly prolonged bleb survival compared with control groups. The filtering bleb's survival period was significantly more prolonged in the MMC and 5-FU groups (maintained 14 days) than the other two groups (maintained 7 days). Significantly lower IOP was observed within the control, blank, and 5-FU groups after surgery on day 14 compared with that before operation, with F-values of 6.567, 11.426, and 13.467, respectively (P < 0.01). The most significant lower IOP was recorded in the MMC group on day 28 postoperation (F-value 26.866, P < 0.01). No obvious abnormalities were found in cornea or anterior lens capsule 28 days after surgery. The study provided evidence that 5-FU and MMC biological delivery membranes could significantly improve the outcome of filtering procedures, the survival of the bleb, and maintenance of lower IOP. MMC membrane is superior to 5-FU, with regard to the more effective reduction of IOP. The results indicated a safe and effective treatment strategy in glaucoma surgery.

A comparative study of the safety and efficacy effect of 5-fluorouracil or mitomycin C mounted biological delivery membranes in a rabbit model of glaucoma filtration surgery

PubMed Central

Wu, Zhihong; Li, Shuning; Wang, Ningli; Liu, Wanshun; Liu, Wen

2013-01-01

Purpose To investigate the potential usage of biological delivery membranes containing mitomycin C (MMC) or 5-fluorouracil (5-FU) in the construction of glaucoma-filtering blebs, and to evaluate their safety and efficacy. Methods Chitosan was selected as the biological membrane carrier to prepare sustained-released membranes. Twelve micrograms of 5-FU or MMC was covalently conjugated onto the membranes by solvent volatilization. Rabbits underwent glaucoma filtration surgery and were randomly allocated into one of the four treatment regimens: glaucoma filtration operation with no implantation of chitosan membrane group (as control), drug-free chitosan membrane implantation group (blank/placebo group), membrane containing 5-FU treatment group (5-FU group), and membrane containing MMC treatment group (MMC group). Each group consisted of 12 rabbits. Intraocular pressure (IOP) was measured and evaluated over a 28-day period follow-up preoperatively, then after surgery on days 1, 3, 5, 7, 14, 21, and 28 by Tono-Pen. The aqueous humor was analyzed in each experimental and control groups at days 4, 6, 8, 10, 12, 14, 16, and 20 after operation. Bleb survival and anterior segment were examined with a slit lamp microscope and photographed simultaneously. Two rabbits from each group were killed on day 28 and eight eye samples obtained for histopathological study. Corneas and lenses were examined by transmission and scanning electron microscopy. Results Both 5-FU and MMC significantly prolonged bleb survival compared with control groups. The filtering bleb’s survival period was significantly more prolonged in the MMC and 5-FU groups (maintained 14 days) than the other two groups (maintained 7 days). Significantly lower IOP was observed within the control, blank, and 5-FU groups after surgery on day 14 compared with that before operation, with F-values of 6.567, 11.426, and 13.467, respectively (P < 0.01). The most significant lower IOP was recorded in the MMC group on day 28 postoperation (F-value 26.866, P < 0.01). No obvious abnormalities were found in cornea or anterior lens capsule 28 days after surgery. Conclusion The study provided evidence that 5-FU and MMC biological delivery membranes could significantly improve the outcome of filtering procedures, the survival of the bleb, and maintenance of lower IOP. MMC membrane is superior to 5-FU, with regard to the more effective reduction of IOP. The results indicated a safe and effective treatment strategy in glaucoma surgery. PMID:23576864

Ultrasound credentialing in North American emergency department systems with ultrasound fellowships: a cross-sectional survey.

PubMed

Bellamkonda, Venkatesh R; Shokoohi, Hamid; Alsaawi, Abdulmohsen; Ding, Ru; Campbell, Ronna L; Liu, Yiju Teresa; Boniface, Keith S

2015-10-01

To describe the credentialing systems of North American emergency department systems (EDS) with emergency ultrasound (EUS) fellowship programmes. This is a prospective, cross-sectional, survey-based study of North American EUS fellowships using a 62-item, pilot-tested, web-based survey instrument assessing credentialing and training systems. The American College of Emergency Physicians (ACEP) distributed the surveys using SNAP survey (Snap Surveys Ltd, Portsmouth, New Hampshire, USA). Over 6 months, 75 eligible programmes were surveyed, 55 responded (73% response rate); 1 declined to participate leaving 54 participating programmes. Less than 20% of EDS credential nurses, physician assistants, nurse practitioners and students in EUS. Respondent EDS reported having an average of 4.2 ± 3.3 ultrasound faculty members (faculty identifying their career focus as EUS). The median number of annual point-of-care ultrasounds reported was 5000 (IQR 3000-8000). 30 EDS (56%) credential each examination individually and 48 EDS (89%) use ACEP credentialing criteria. 61% of fellowship leadership believe their credentialing system is either satisfactory or very satisfactory (Cronbach's coefficient α=0.84). The data show heterogeneity among North American EDS with EUS fellowship programmes with regard to credentialing systems despite published guidelines from the ACEP and Canadian Emergency Ultrasound Society. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Modulation of radiation-induced and mitomycin C-induced chromosome damage by apigenin in human lymphocytes in vitro.

PubMed

Sharma, Narinder K

2013-09-01

Apigenin (APG), a flavone, is known to exhibit antioxidant, antimutagenic and antitumorigenic activity, both in vivo and in vitro. The aim of this study is to investigate the modulatory effects of APG on human lymphocytes after irradiation with gamma rays (3 Gy) or treatment with the antineoplastic agent, mitomycin C (MMC), in vitro. Cytogenetic biomarkers such as chromosome aberrations (CAs), sister chromatid exchanges (SCEs) and cytochalasin-B blocked micronuclei (CBMN), were studied in blood lymphocytes treated with radiation, or antineoplastic agent (MMC), and APG. Whole blood lymphocytes were cultured in vitro using a standard protocol. No significant differences were found in the frequency of CAs or micronuclei (MN) in human peripheral blood lymphocytes irradiated with gamma rays (3 Gy) and then post-treated with APG. There was an increase in the frequency of SCEs per cell in APG-treated samples compared with the controls. Lymphocytes treated with MMC in the presence of APG exhibited a significant decrease (P < 0.01) in the frequency of SCEs compared with MMC treatment alone. The data for the MN test indicated that APG treatment significantly reduced (P < 0.01) the frequency of MMC-induced MN.

Modulation of radiation-induced and mitomycin C-induced chromosome damage by apigenin in human lymphocytes in vitro

PubMed Central

Sharma, Narinder K.

2013-01-01

Apigenin (APG), a flavone, is known to exhibit antioxidant, antimutagenic and antitumorigenic activity, both in vivo and in vitro. The aim of this study is to investigate the modulatory effects of APG on human lymphocytes after irradiation with gamma rays (3 Gy) or treatment with the antineoplastic agent, mitomycin C (MMC), in vitro. Cytogenetic biomarkers such as chromosome aberrations (CAs), sister chromatid exchanges (SCEs) and cytochalasin-B blocked micronuclei (CBMN), were studied in blood lymphocytes treated with radiation, or antineoplastic agent (MMC), and APG. Whole blood lymphocytes were cultured in vitro using a standard protocol. No significant differences were found in the frequency of CAs or micronuclei (MN) in human peripheral blood lymphocytes irradiated with gamma rays (3 Gy) and then post-treated with APG. There was an increase in the frequency of SCEs per cell in APG-treated samples compared with the controls. Lymphocytes treated with MMC in the presence of APG exhibited a significant decrease (P < 0.01) in the frequency of SCEs compared with MMC treatment alone. The data for the MN test indicated that APG treatment significantly reduced (P < 0.01) the frequency of MMC-induced MN. PMID:23764456

Friction Stir Welding for Aluminum Metal Matrix Composites (MMC's) (Center Director's Discretionary Fund, Project No. 98-09)

NASA Technical Reports Server (NTRS)

Lee, J. A.; Carter, R. W.; Ding, J.

1999-01-01

This technical memorandum describes an investigation of using friction stir welding (FSW) process for joining a variety of aluminum metal matrix composites (MMC's) reinforced with discontinuous silicon-carbide (SiC) particulate and functional gradient materials. Preliminary results show that FSW is feasible to weld aluminum MMC to MMC or to aluminum-lithium 2195 if the SiC reinforcement is <25 percent by volume fraction. However, a softening in the heat-affected zone was observed and is known to be one of the major limiting factors for joint strength. The pin tool's material is made from a low-cost steel tool H-13 material, and the pin tool's wear was excessive such that the pin tool length has to be manually adjusted for every 5 ft of weldment. Initially, boron-carbide coating was developed for pin tools, but it did not show a significant improvement in wear resistance. Basically, FSW is applicable mainly for butt joining of flat plates. Therefore, FSW of cylindrical articles such as a flange to a duct with practical diameters ranging from 2-5 in. must be fully demonstrated and compared with other proven MMC joining techniques for cylindrical articles.

[Latex and banana allergies in children with myelomeningocele in the city of Rio de Janeiro].

PubMed

Machado, Marta; Sant'anna, Clemax; Aires, Vera; Rodrigues, Pedro Paulo; Pinheiro, Maria Fernanda; Teixeira, Marisa

2004-01-01

Recently, latex type I hypersensibility reactions were frequently described, mainly in children with myelomeningocele (MMC), which maintain earlier intimate and frequent contact with latex products. Allergic food cross-reactions are well known for many years. Nowadays, latex allergy is frequently associated with food allergies to avocado, banana, kiwi, grapefruit, papaya, chestnut and peach. The objective of this study consisted in identifying the number of patients with myelomeningocele (MMC) and banana-latex clinico-laboratorial sensitization. Questionnaires were applied to 33 children with MMC and blood was collected from 30 to perform latex IgE (RAST Pharmacia), and from 29 to banana IgE. Specific IgE equal or above class I was considered positive. Four children related histories of latex contact urticaria, and one child related a history of urticaria and diarrhea with banana. 14/30 (46.6%) were latex IgE positive, and 4/29 (13.7%) to banana. There was no statistically significant association between variables. We identified high prevalence of latex and banana allergies in patients with MMC and we need more studies to analyze the prevalence of food-latex allergic cross-reactions in children with MMC.

Liquid Metal Infiltration Processing of Metallic Composites: A Critical Review

NASA Astrophysics Data System (ADS)

Sree Manu, K. M.; Ajay Raag, L.; Rajan, T. P. D.; Gupta, Manoj; Pai, B. C.

2016-10-01

Metal matrix composites (MMC) are one of the advanced materials widely used for aerospace, automotive, defense, and general engineering applications. MMC can be tailored to have superior properties such as enhanced high-temperature performance, high specific strength and stiffness, increased wear resistance, better thermal and mechanical fatigue, and creep resistance than those of unreinforced alloys. To fabricate such composites with ideal properties, the processing technique has to ensure high volume fraction of reinforcement incorporation, uniform distribution of the reinforcement, and acceptable adhesion between the matrix and the reinforcing phase without unwanted interfacial reactions which degrades the mechanical properties. A number of processing techniques such as stir casting/vortex method, powder metallurgy, infiltration, casting etc. have been developed to synthesize MMC employing a variety of alloy and the reinforcement's combinations. Among these, infiltration process is widely used for making MMC with high volume fraction of reinforcements and offers many more advantages compared to other conventional manufacturing processes. The present paper critically reviews the various infiltration techniques used for making the MMC, their process parameters, characteristics, and selected studies carried out worldwide and by authors on the development of metal ceramic composites by squeeze infiltration process.

Trabeculectomy with mitomycin-C in neovascular galucoma patients.

PubMed

Caça, Ihsan; Ari, Seyhmus; Sakalar, Yildirim Bayezit; Unlü, Kaan; Dogan, Eyüp

2008-01-01

We sought to determine the effectiveness of trabeculectomy with mitomycin-C (MMC) in neovascular glaucoma (NVG) patients. Trabeculectomy with MMC in NVG patients is a method that has high rate of short-term success.

Metal- matrix composite processing technologies for aircraft engine applications

NASA Astrophysics Data System (ADS)

Pank, D. R.; Jackson, J. J.

1993-06-01

Titanium metal-matrix composites (MMC) are prime candidate materials for aerospace applications be-cause of their excellent high-temperature longitudinal strength and stiffness and low density compared with nickel- and steel-base materials. This article examines the steps GE Aircraft Engines (GEAE) has taken to develop an induction plasma deposition (IPD) processing method for the fabrication of Ti6242/SiC MMC material. Information regarding process methodology, microstructures, and mechani-cal properties of consolidated MMC structures will be presented. The work presented was funded under the GE-Aircraft Engine IR & D program.

Status and Significance of Credentialing.

ERIC Educational Resources Information Center

Musgrave, Dorothea

1984-01-01

Discusses the current status, significance, and future of credentialing in the field of environmental health. Also discusses four phases of a Bureau of Health Professions (BHP) Credentialing Program and BHP-funded projects related to their development and implementation. Phases include role delineation, resources development, examination…

Synergistic Effect of Combinatorial Treatment with Curcumin and Mitomycin C on the Induction of Apoptosis of Breast Cancer Cells: A cDNA Microarray Analysis

PubMed Central

Zhou, Qian-Mei; Chen, Qi-Long; Du, Jia; Wang, Xiu-Feng; Lu, Yi-Yu; Zhang, Hui; Su, Shi-Bing

2014-01-01

In order to explore the synergistic mechanisms of combinatorial treatment using curcumin and mitomycin C (MMC) for breast cancer, MCF-7 breast cancer xenografts were conducted to observe the synergistic effect of combinatorial treatment using curcumin and MMC at various dosages. The synergistic mechanisms of combinatorial treatment using curcumin and MMC on the inhibition of tumor growth were explored by differential gene expression profile, gene ontology (GO), ingenuity pathway analysis (IPA) and Signal–Net network analysis. The expression levels of selected genes identified by cDNA microarray expression profiling were validated by quantitative RT-PCR (qRT-PCR) and Western blot analysis. Effect of combinatorial treatment on the inhibition of cell growth was observed by MTT assay. Apoptosis was detected by flow cytometric analysis and Hoechst 33258 staining. The combinatorial treatment of 100 mg/kg curcumin and 1.5 mg/kg MMC revealed synergistic inhibition on tumor growth. Among 1501 differentially expressed genes, the expression of 25 genes exhibited an obvious change and a significant difference in 27 signal pathways was observed (p < 0.05). In addition, Mapk1 (ERK) and Mapk14 (MAPK p38) had more cross-interactions with other genes and revealed an increase in expression by 8.14- and 11.84-fold, respectively during the combinatorial treatment by curcumin and MMC when compared with the control. Moreover, curcumin can synergistically improve tumoricidal effect of MMC in another human breast cancer MDA-MB-231 cells. Apoptosis was significantly induced by the combinatorial treatment (p < 0.05) and significantly inhibited by ERK inhibitor (PD98059) in MCF-7 cells (p < 0.05). The synergistic effect of combinatorial treatment by curcumin and MMC on the induction of apoptosis in breast cancer cells may be via the ERK pathway. PMID:25226537

Effect of Medicaid Managed Care on racial disparities in health care access.

PubMed

Cook, Benjamin Lê

2007-02-01

To evaluate the impact of Medicaid Managed Care (MMC) on racial disparities in access to care consistent with the Institute of Medicine (IOM) definition of racial disparity, which excludes differences stemming from health status but includes socioeconomic status (SES)-mediated differences. Secondary data from the Adult Samples of the 1997-2001 National Health Interview Survey, metropolitan statistical area (MSA)-level Medicaid Health Maintenance Organization (MHMO) market share from the 1997 to 2001 InterStudy MSA Trend Dataset, and MSA characteristics from the 1997 to 2001 Area Resource File. I estimate multivariate regression models to compare racial disparities in doctor visits, emergency room (ER) use, and having a usual source of care between enrollees in MMC and Medicaid Fee-for-Service (FFS) plans. To contend with potential selection bias, I use a difference-in-difference analytical strategy and assess the impact of greater MHMO market share at the MSA level on Medicaid enrollees' access measures. To implement the IOM definition of racial disparity, I adjust for health status but not SES factors using a novel method to transform the distribution of health status for minority populations to approximate the white health status distribution. MMC enrollment is associated with lowered disparities in having any doctor visit in the last year for blacks, and in having any usual source of care for both blacks and Hispanics. Increasing Medicaid HMO market share lowered disparities in having any doctor visits in the last year for both blacks and Hispanics. Although disparities in most other measures were not much affected, black-white ER use disparities exist among MMC enrollees and in areas of high MHMO market share. MMC programs' reduction of some disparities suggests that recent shifts in Medicaid policy toward managed care plans have benefited minority enrollees. Future research should investigate whether black-white disparities in ER use within MMC groups represent the flexibility of MMC plans to locate primary care in ERs or an inefficient delivery of care.

Simulation of automotive wrist pin joint and tribological studies of tin coated Al-Si alloy, metal matrix composites and nitrogen ceramics under mixed lubrication

NASA Astrophysics Data System (ADS)

Wang, Qian

Development of automotive engines with high power output demands the application of high strength materials with good tribological properties. Metal matrix composites (MMC's) and some nitrogen ceramics are of interest to replace some conventional materials in the piston/pin/connecting rod design. A simulation study has been developed to explore the possibility to employ MMC's as bearing materials and ceramics as journal materials, and to investigate the related wear mechanisms and the possible journal bearing failure mechanisms. Conventional tin coated Al-Si alloy (Al-Si/Sn) have been studied for the base line information. A mixed lubrication model for journal bearing with a soft coating has been developed and applied to the contact and temperature analysis of the Al-Si/Sn bearing. Experimental studies were performed to reveal the bearing friction and wear behavior. Tin coating exhibited great a advantage in friction reduction, however, it suffered significant wear through pitting and debonding. When the tin wore out, the Al-Si/steel contact experienced higher friction. A cast and P/M MMC's in the lubricated contact with case hardened steel and ceramic journals were studied experimentally. Without sufficient material removal in the conformal contact situation, MMC bearings in the MMC/steel pairs gained weight due to iron transfer and surface tribochemical reactions with the lubricant additives and contact failure occurred. However, the MMC/ceramic contacts demonstrated promising tribological behavior with low friction and high wear resistance, and should be considered for new journal bearing design. Ceramics are wear resistant. Ceramic surface roughness is very crucial when the journals are in contact with the tin coated bearings. In contact with MMC bearings, ceramic surface quality and fracture toughness seem to play some important roles in affecting the friction coefficient. The wear of silicon nitride and beta sialon (A) journals is pitting due to grain boundary fracture and grain pull-out.

Mitomycin-C in corneal surface excimer laser ablation techniques: a report by the American Academy of Ophthalmology.

PubMed

Majmudar, Parag A; Schallhorn, Steven C; Cason, John B; Donaldson, Kendall E; Kymionis, George D; Shtein, Roni M; Verity, Steven M; Farjo, Ayad A

2015-06-01

To review the published literature assessing the efficacy and safety of mitomycin-C (MMC) as an adjunctive treatment in corneal surface excimer laser ablation procedures. Literature searches of the PubMed and Cochrane Library databases were last conducted on August 19, 2014, without language or date limitations. The searches retrieved a total of 239 references. Of these, members of the Ophthalmic Technology Assessment Committee Refractive Management/Intervention Panel selected 26 articles that were considered to be of high or medium clinical relevance, and the panel methodologist rated each article according to the strength of evidence. Ten studies were rated as level I evidence, 5 studies were rated as level II evidence, and the remaining 11 studies were rated as level III evidence. The majority of the articles surveyed in this report support the role of MMC as an adjunctive treatment in surface ablation procedures. When MMC is applied in the appropriate concentration and confined to the central cornea, the incidence of post-surface ablation haze is decreased. Although a minority of studies that evaluated endothelial cell density (ECD) reported an MMC-related decrease in ECD, no clinical adverse outcomes were reported. Over the past 15 years, the use of MMC during surgery in surface ablation has become widespread. There is good evidence of the effectiveness of MMC when used intraoperatively as prophylaxis against haze in higher myopic ablations. Although there are reports of decreased endothelial counts after the administration of MMC during surgery, the clinical significance of this finding remains uncertain, because no adverse outcomes were reported with as much as 5 years of follow-up. Optimal dosage, effectiveness as prophylaxis in lower myopic and hyperopic ablations, and long-term safety, particularly in eyes with reduced corneal endothelial cell counts from prior intraocular surgery, have yet to be established. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Structural characterization of the mitomycin 7-O-methyltransferase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Shanteri; Chang, Aram; Goff, Randal D.

2014-10-02

Mitomycins are quinone-containing antibiotics, widely used as antitumor drugs in chemotherapy. Mitomycin-7-O-methyltransferase (MmcR), a key tailoring enzyme involved in the biosynthesis of mitomycin in Streptomyces lavendulae, catalyzes the 7-O-methylation of both C9{beta}- and C9{alpha}-configured 7-hydroxymitomycins. We have determined the crystal structures of the MmcR-S-adenosylhomocysteine (SAH) binary complex and MmcR-SAH-mitomycin A (MMA) ternary complex at resolutions of 1.9 and 2.3 {angstrom}, respectively. The study revealed MmcR to adopt a common S-adenosyl-L-methionine-dependent O-methyltransferase fold and the presence of a structurally conserved active site general acid-base pair is consistent with a proton-assisted methyltransfer common to most methyltransferases. Given the importance of C7 alkylationmore » to modulate mitomycin redox potential, this study may also present a template toward the future engineering of catalysts to generate uniquely bioactive mitomycins.« less

Cytostatic action of aspirin and its effect on mitomycin C activity. A study in vitro under irradiation

NASA Astrophysics Data System (ADS)

Kammerer, Cornelia; Getoff, Nikola

2001-04-01

Experiments in vitro using E. coli bacteria (AB 1157) proved that aspirin possesses a cytostatic ability under various experimental condition (pH=7.4) in airfree, aerated as well as in media containing N 2O (converting e aq- into OH- radicals). In the last case the highest effect of aspirin was observed. The combination of aspirin with the well-known cytostaticum, mitomycin C (MMC) leads in airfree as well as in aerated media to a significant decrease of the MMC activity. However, the mixture of aspirin and MMC in the presence of N 2O causes a synergistic effect, resulting in an enhancement of the MMC activity by a factor of 1.5. Probable reaction steps are presented and discussed. Using the pulse radiolysis method the rate constants for the reactions of e aq-, H and OH- species with aspirin were also determined.

Mitomycin C induced alterations in antioxidant enzyme levels in a model insect species, Spodoptera eridania.

PubMed

Batcabe, J P; MacGill, R S; Zaman, K; Ahmad, S; Pardini, R S

1994-05-01

1. An insect species, the southern armyworm Spodoptera eridania, was used as an in vivo model to examine mitomycin C's (MMC) pro-oxidant effect reflected in alterations of antioxidant enzymes. 2. Following a 2-day exposure to 0.01 and 0.05% w/w dietary concentrations, MMC only induced superoxide dismutase activity. All other enzyme activities were not affected, indicating oxidative stress was mild. 3. Following a 5-day exposure to 0.05% w/w dietary MMC, the activities of superoxide dismutase, glutathione-S-transferase and its peroxidase activity and DT-diaphorase were induced. GR activity was not altered. The high constitutive catalase activity was also not affected. These responses of S. eridania's antioxidant enzymes are analogous to those of mammalian systems in alleviating MMC-induced oxidative stress. 4. S. eridania emerges as an appropriate non-mammalian model for initial and cost-effective screening of drug-induced oxidative stress.

Reduction of mitomycin C is catalysed by human recombinant NRH:quinone oxidoreductase 2 using reduced nicotinamide adenine dinucleotide as an electron donating co-factor

PubMed Central

Jamieson, D; Tung, A T Y; Knox, R J; Boddy, A V

2006-01-01

NRH:Quinone Oxidoreductase 2 (NQO2) has been described as having no enzymatic activity with nicotinamide adenine dinucleotide (NADH) or NADPH as electron donating cosubstrates. Mitomycin C (MMC) is both a substrate for and a mechanistic inhibitor of the NQO2 homologue NQO1. NRH:quinone oxidoreductase 2 catalysed the reduction of MMC at pH 5.8 with NADH as a co-factor. This reaction results in species that inhibit the NQO2-mediated metabolism of CB1954. In addition, MMC caused an increase in DNA cross-links in a cell line transfected to overexpress NQO2 to an extent comparable to that observed with an isogenic NQO1-expressing cell line. These data indicate that NQO2 may contribute to the metabolism of MMC to cytotoxic species. PMID:17031400

Thermal Fatigue Limitations of Continuous Fiber Metal Matrix Composites

NASA Technical Reports Server (NTRS)

Halford, Gary R.; Arya, Vinod K.

1997-01-01

The potential structural benefits of unidirectional, continuous-fiber, metal matrix composites (MMC's) are legendary. When compared to their monolithic matrices, MMC's possess superior properties such as higher stiffness and tensile strength, and lower coefficient of thermal expansion in the direction of the reinforcing fibers. As an added bonus, the MMC density will be lower if the fibers are less dense than the matrix matErial they replace. The potential has been demonstrated unequivocally both analytically and experimentally, especially at ambient temperatures. Successes prompted heavily-funded National efforts within the United States (USAF and NASA) and elsewhere to extend the promise of MMC's into the temperature regime wherein creep, stress relaxation, oxidation, and thermal fatigue damage mechanisms lurk. This is the very regime for which alternative high-temperature materials are becoming mandatory, since further enhancement of state- of-the-art monolithic alloys is rapidly approaching a point of diminishing returns.

Theoretical Noise Analysis on a Position-sensitive Metallic Magnetic Calorimeter

NASA Technical Reports Server (NTRS)

Smith, Stephen J.

2007-01-01

We report on the theoretical noise analysis for a position-sensitive Metallic Magnetic Calorimeter (MMC), consisting of MMC read-out at both ends of a large X-ray absorber. Such devices are under consideration as alternatives to other cryogenic technologies for future X-ray astronomy missions. We use a finite-element model (FEM) to numerically calculate the signal and noise response at the detector outputs and investigate the correlations between the noise measured at each MMC coupled by the absorber. We then calculate, using the optimal filter concept, the theoretical energy and position resolution across the detector and discuss the trade-offs involved in optimizing the detector design for energy resolution, position resolution and count rate. The results show, theoretically, the position-sensitive MMC concept offers impressive spectral and spatial resolving capabilities compared to pixel arrays and similar position-sensitive cryogenic technologies using Transition Edge Sensor (TES) read-out.

An Interview with Thomas W. Clawson.

ERIC Educational Resources Information Center

Juhnke, Gerald A.

2000-01-01

Presents an interview with the director of the National Board for Certified Counselors, who provides a history of the organization. He discusses his efforts in establishing unified addictions specialist credentials and offers suggestions for addiction and offender counselors seeking these credentials. He explores the pressing credentialing issues…

46 CFR 15.605 - Credentialed operators for uninspected passenger vessels.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Credentialed operators for uninspected passenger vessels. 15.605 Section 15.605 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS Manning Requirements; Uninspected Vessels § 15.605 Credentialed...

46 CFR 15.605 - Credentialed operators for uninspected passenger vessels.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Credentialed operators for uninspected passenger vessels. 15.605 Section 15.605 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS Manning Requirements; Uninspected Vessels § 15.605 Credentialed...

46 CFR 15.605 - Credentialed operators for uninspected passenger vessels.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Credentialed operators for uninspected passenger vessels. 15.605 Section 15.605 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS Manning Requirements; Uninspected Vessels § 15.605 Credentialed...

46 CFR 15.605 - Credentialed operators for uninspected passenger vessels.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Credentialed operators for uninspected passenger vessels. 15.605 Section 15.605 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS Manning Requirements; Uninspected Vessels § 15.605 Credentialed...

46 CFR 15.605 - Credentialed operators for uninspected passenger vessels.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Credentialed operators for uninspected passenger vessels. 15.605 Section 15.605 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS Manning Requirements; Uninspected Vessels § 15.605 Credentialed...

Does Medicare Managed Care reduce racial/ethnic disparities in diabetes preventive care and healthcare expenditures?

PubMed

Mahmoudi, Elham; Tarraf, Wassim; Maroukis, Brianna L; Levy, Helen G

2016-10-01

Large and persistent racial/ethnic disparities exist in diabetes care. Considering the rapid rate of growth of Medicare Managed Care (MMC) plans among minority populations, our aim was to investigate whether disparities in diabetes management and healthcare expenditures are smaller in MMC versus Medicare fee-for-service (MFFS) plans. We hypothesized that racial/ethnic disparities in diabetes care and in health expenditures would be less pronounced in MMC compared with MFFS plans. Nationally representative data from the 2006 to 2011 Medical Expenditure Panel Survey on white, African American, and Hispanic seniors with diabetes were analyzed. We examined 4 measures of diabetes care-regular foot check, eye exam, cholesterol check, and flu vaccine-and total and out-of-pocket (OOP) healthcare expenditures. We implemented the Institute of Medicine's definition of disparity, applied propensity score weighting to adjust for potential differential selection, and used a difference-in-differences generalized linear framework to estimate outcome measures. For African Americans, MMC was associated with a $1183 (P <.036) reduction and a $547 (P <.001) increase in disparities in total and OOP healthcare expenditures, respectively. For Hispanics, disparities in foot exam, flu shot, and cholesterol check decreased by 5, 10, and 7 percentage points (P <.001); additionally, disparities in total and OOP healthcare expenditures were reduced by $3588 and $276 (P <.001), respectively. MMC plans spend less on everyone, including whites. Hispanic/white disparities in diabetes management and healthcare expenditures were smaller in MMC than in MFFS plans. African American/white disparities were not consistently larger in 1 setting than the other.

Methanolic Extract of Morinda citrifolia L. (Noni) Unripe Fruit Attenuates Ethanol-Induced Conditioned Place Preferences in Mice

PubMed Central

Khan, Yasmin; Pandy, Vijayapandi

2016-01-01

Phytotherapy is an emerging field successfully utilized to treat various chronic diseases including alcohol dependence. In the present study, we examined the effect of the standardized methanolic extract of Morinda citrifolia Linn. unripe fruit (MMC), on compulsive ethanol-seeking behavior using the mouse conditioned place preference (CPP) test. CPP was established by injections of ethanol (2 g/kg, i.p.) in a 12-day conditioning schedule in mice. The effect of MMC and the reference drug, acamprosate (ACAM), on the reinforcing properties of ethanol in mice was studied by the oral administration of MMC (1, 3, and 5 g/kg) and ACAM (300 mg/kg) 60 min prior to the final CPP test postconditioning. Furthermore, CPPs weakened with repeated testing in the absence of ethanol over the next 12 days (extinction), during which the treatment groups received MMC (1, 3, and 5 g/kg, p.o.) or ACAM (300 mg/kg, p.o.). Finally, a priming injection of a low dose of ethanol (0.4 g/kg, i.p.) in the home cage (Reinstatement) was sufficient to reinstate CPPs, an effect that was challenged by the administration of MMC or ACAM. MMC (3 and 5 g/kg, p.o.) and ACAM (300 mg/kg, p.o.) significantly reversed the establishment of ethanol-induced CPPs and effectively facilitated the extinction of ethanol CPP. In light of these findings, it has been suggested that M. citrifolia unripe fruit could be utilized for novel drug development to combat alcohol dependence. PMID:27729866

Methanolic Extract of Morinda citrifolia L. (Noni) Unripe Fruit Attenuates Ethanol-Induced Conditioned Place Preferences in Mice.

PubMed

Khan, Yasmin; Pandy, Vijayapandi

2016-01-01

Phytotherapy is an emerging field successfully utilized to treat various chronic diseases including alcohol dependence. In the present study, we examined the effect of the standardized methanolic extract of Morinda citrifolia Linn. unripe fruit (MMC), on compulsive ethanol-seeking behavior using the mouse conditioned place preference (CPP) test. CPP was established by injections of ethanol (2 g/kg, i.p.) in a 12-day conditioning schedule in mice. The effect of MMC and the reference drug, acamprosate (ACAM), on the reinforcing properties of ethanol in mice was studied by the oral administration of MMC (1, 3, and 5 g/kg) and ACAM (300 mg/kg) 60 min prior to the final CPP test postconditioning. Furthermore, CPPs weakened with repeated testing in the absence of ethanol over the next 12 days (extinction), during which the treatment groups received MMC (1, 3, and 5 g/kg, p.o.) or ACAM (300 mg/kg, p.o.). Finally, a priming injection of a low dose of ethanol (0.4 g/kg, i.p.) in the home cage (Reinstatement) was sufficient to reinstate CPPs, an effect that was challenged by the administration of MMC or ACAM. MMC (3 and 5 g/kg, p.o.) and ACAM (300 mg/kg, p.o.) significantly reversed the establishment of ethanol-induced CPPs and effectively facilitated the extinction of ethanol CPP. In light of these findings, it has been suggested that M. citrifolia unripe fruit could be utilized for novel drug development to combat alcohol dependence.

Scoliosis in myelomeningocele: epidemiology, management, and functional outcome.

PubMed

Mummareddy, Nishit; Dewan, Michael C; Mercier, Michael R; Naftel, Robert P; Wellons, John C; Bonfield, Christopher M

2017-07-01

OBJECTIVE The authors aimed to provide an updated and consolidated report on the epidemiology, management, and functional outcome of cases of myelomeningocele (MMC) in patients with scoliosis. METHODS A comprehensive literature search was performed using MEDLINE, Embase, Google Scholar, and the Cochrane Database of Systematic Reviews on cases of MMC in patients with scoliosis between 1980 and 2016. The initial search yielded 670 reports. After removing duplicates and applying inclusion criteria, we included 32 full-text original articles in this study. RESULTS Pooled statistical analysis of the included articles revealed the prevalence of scoliosis in MMC patients to be 53% (95% CI 0.42-0.64). Slightly more females (56%) are affected with both MMC and scoliosis than males. Motor level appears to be a significant predictor of prevalence, but not severity, of scoliosis in MMC patients. Treatment options for these patients include tethered cord release (TCR) and fusion surgeries. Curvature improvement and stabilization after TCR may be limited to patients with milder (< 50°) curves. Meanwhile, more aggressive fusion procedures such as a combined anterior-posterior approach may result in more favorable long-term scoliosis correction, albeit with greater complication rates. Quality of life metrics including ambulatory status and sitting stability are influenced by motor level of the lesion as well as the degree of the scoliosis curvature. CONCLUSIONS Scoliosis is among the most common and challenging comorbidities from which patients with MMC suffer. Although important epidemiological and management trends are evident, larger, prospective studies are needed to discover ways to more accurately counsel and more optimally treat these patients.

Preoperative subpterygeal injection vs intraoperative mitomycin C for pterygium removal: comparison of results and complications.

PubMed

Khakshoor, Hamid; Razavi, Mohammad Etezad; Daneshvar, Ramin; Shakeri, Mohammad Taghi; Ghate, Majid Farrokh; Ghooshkhanehi, Haleh

2010-08-01

To evaluate and compare the recurrence rates and complications between 2 therapeutic methods for primary pterygium: subconjunctival injection of mitomycin C (MMC) 1 month before bare scleral excision and conjunctival rotational flap with intraoperative MMC use. Prospective, interventional, randomized clinical trial. setting: Institutional clinical trial in a tertiary, specialty eye hospital. study population and intervention: We included 82 eyes diagnosed with primary pterygium and randomly allocated them into 2 groups. Group A consisted of 36 eyes treated with subconjunctival injection of 0.02% MMC 1 month before bare scleral excision, and group B comprised 46 eyes that underwent conjunctival rotational flap with intraoperative 0.02% MMC for 2 minutes. Follow-up periods were at least 12 months (range, 12 to 18 months). main outcome measure: Recurrence and complication rate in each arm of study. During the 1-year follow-up, 2 cases of clinical recurrence in third and sixth month of follow-up occurred in group B (recurrence rate, 4.3%). In group A, there was no clinically significant recurrence, but 2 cases of hypovascularity and whitening of sclera at the site of pterygium excision was observed. There was no other serious complication. There was no statistically significant difference between groups for recurrence rate, mean age, sex, or pterygium area. Subconjunctival injection of MMC 0.02% (0.1 ml of 0.02% solution) 1 month before bare scleral excision is a quick, easy, and safe surgical procedure and is at least as effective as conjunctival rotational flap with intraoperative MMC for 2 minutes. Copyright (c) 2010 Elsevier Inc. All rights reserved.

The role of mitomycin C in preventing synechia and stenosis after endoscopic sinus surgery.

PubMed

Anand, Vijay K; Tabaee, Abtin; Kacker, Ashutosh; Newman, Jason G; Huang, Clark

2004-01-01

Synechia and stenosis formation after endoscopic sinus surgery (ESS) represents a potential source of surgical failure. Mitomycin C (MMC) has been used successfully in other fields to decrease postoperative scar formation. We hypothesize that the topical application of MMC reduces the incidence of stenosis and synechia formation after ESS. This study is a randomized, controlled, single-blinded study based in a tertiary care teaching hospital. After routine ESS, a pledget soaked in MMC (0.5%) was randomly placed into the middle meatus of one nasal cavity for 5 minutes and a pledget soaked in saline was placed in the contralateral side in each patient. A blinded observer followed the patients for any evidence of stenosis or synechia formation. The medical records of enrolled patients were reviewed for demographics, diagnosis, prior surgery, type of sinus surgery, complications, incidence of stenosis/synechia, and need for further procedures. Twenty-nine patients were included in the final analysis. The mean follow-up period was 15 months (range, 3-32 months). There were no complications in this series. Eight patients experienced 10 episodes of synechia formation and one patient experienced 1 episode of synechia formation and 1 episode of stenosis of the maxillary sinus ostium. Seven of the 12 episodes of synechia/stenosis occurred on the side of the MMC application and the remaining 5 episodes occurred on the side opposite to the MMC application. This difference was not statistically significant. The topical application of MMC did not decrease the incidence of stenosis and synechia formation after ESS.

Preoperative Subconjunctival Injection of Mitomycin C Versus Intraoperative Topical Application as an Adjunctive Treatment for Surgical Removal of Primary Pterygium

PubMed Central

Ghoneim, Ehab M.; Abd-El Ghny, Ahmed A.; Gab-Allah, Amro A.; Kamal, Mohamed Z.

2011-01-01

Purpose: To compare the efficacy of preoperative local injection of mitomycin C (MMC) to intraoperative application of MMC in the prevention of pterygium recurrence after surgical removal. Materials and Methods: Seventy eyes of 70 patients with primary pterygia were randomly allocated to two groups. The first group (Group A, 35 eyes) received 0.1 ml of 0.15 mg/ml of subconjunctival MMC injected into the head of the pterygium 24 h before surgical excision with the bare sclera technique. The second group (Group B 35 eyes) underwent surgical removal with the bare sclera technique with intraoperative application of MMC (0.15 mg/ml) over bare sclera for 3 min. The study was performed between March 2007 and December 2008, and follow up was performed for 1 year postoperatively. Differences between frequencies in both groups were compared by the Chi-square test or Fisher exact test. Differences between means in both groups were compared by Student’s t-test. P < 0.05 was considered significant. Results: The rate of pterygium recurrence was 5.70% in Group A and 8.57% in Group B at 1 year postoperatively (P>0.05). Postoperatively, scleral thinning occurred in one eye in each group that resolved by 5 months postoperatively. No serious postoperative complications occurred in either group. Conclusion: Preoperative local injection of 0.15 mg/ml MMC is as effective as intraoperative topical application of 0.15 mg/ml MMC for preventing pterygium recurrence after surgical removal. PMID:21572732

46 CFR 15.410 - Credentialed individuals for assistance towing vessels.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Credentialed individuals for assistance towing vessels. 15.410 Section 15.410 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS Manning Requirements; All Vessels § 15.410 Credentialed individuals...

Teachers for Inclusive, Diverse Urban Settings

ERIC Educational Resources Information Center

Reese, Leslie; Richards-Tutor, Cara; Hansuvadha, Nat; Pavri, Shireen; Xu, Shelley

2018-01-01

In this article, the authors discuss the creation of an Urban Dual Credential Program (UDCP) at a large, comprehensive state university in California, a program meant to prepare dually-certified teachers in general education (California Multiple Subject Credential) and special education (California Education Specialist Credential in mild/moderate…

46 CFR 15.410 - Credentialed individuals for assistance towing vessels.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Credentialed individuals for assistance towing vessels. 15.410 Section 15.410 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS Manning Requirements; All Vessels § 15.410 Credentialed individuals...

46 CFR 15.410 - Credentialed individuals for assistance towing vessels.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Credentialed individuals for assistance towing vessels. 15.410 Section 15.410 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS Manning Requirements; All Vessels § 15.410 Credentialed individuals...

46 CFR 15.410 - Credentialed individuals for assistance towing vessels.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Credentialed individuals for assistance towing vessels. 15.410 Section 15.410 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS Manning Requirements; All Vessels § 15.410 Credentialed individuals...

46 CFR 15.410 - Credentialed individuals for assistance towing vessels.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Credentialed individuals for assistance towing vessels. 15.410 Section 15.410 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS Manning Requirements; All Vessels § 15.410 Credentialed individuals...

46 CFR 169.805 - Exhibition of merchant mariner credentials.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Exhibition of merchant mariner credentials. 169.805 Section 169.805 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Operations § 169.805 Exhibition of merchant mariner credentials. Officers on any vessel...

46 CFR 169.805 - Exhibition of merchant mariner credentials.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Exhibition of merchant mariner credentials. 169.805 Section 169.805 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Operations § 169.805 Exhibition of merchant mariner credentials. Officers on any vessel...

32 CFR 767.6 - Credentials of principal investigator.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 5 2014-07-01 2014-07-01 false Credentials of principal investigator. 767.6 Section 767.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY MISCELLANEOUS... JURISDICATION OF THE DEPARTMENT OF THE NAVY Permit Guidelines § 767.6 Credentials of principal investigator. A...

32 CFR 767.6 - Credentials of principal investigator.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 5 2013-07-01 2013-07-01 false Credentials of principal investigator. 767.6 Section 767.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY MISCELLANEOUS... JURISDICATION OF THE DEPARTMENT OF THE NAVY Permit Guidelines § 767.6 Credentials of principal investigator. A...

32 CFR 767.6 - Credentials of principal investigator.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 5 2012-07-01 2012-07-01 false Credentials of principal investigator. 767.6 Section 767.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY MISCELLANEOUS... JURISDICATION OF THE DEPARTMENT OF THE NAVY Permit Guidelines § 767.6 Credentials of principal investigator. A...

32 CFR 767.6 - Credentials of principal investigator.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Credentials of principal investigator. 767.6 Section 767.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY MISCELLANEOUS... JURISDICATION OF THE DEPARTMENT OF THE NAVY Permit Guidelines § 767.6 Credentials of principal investigator. A...

32 CFR 767.6 - Credentials of principal investigator.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 5 2011-07-01 2011-07-01 false Credentials of principal investigator. 767.6 Section 767.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY MISCELLANEOUS... JURISDICATION OF THE DEPARTMENT OF THE NAVY Permit Guidelines § 767.6 Credentials of principal investigator. A...

14 CFR 121.548 - Aviation safety inspector's credentials: Admission to pilot's compartment.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Aviation safety inspector's credentials: Admission to pilot's compartment. 121.548 Section 121.548 Aeronautics and Space FEDERAL AVIATION... Operations § 121.548 Aviation safety inspector's credentials: Admission to pilot's compartment. Whenever, in...

14 CFR 121.548 - Aviation safety inspector's credentials: Admission to pilot's compartment.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Aviation safety inspector's credentials: Admission to pilot's compartment. 121.548 Section 121.548 Aeronautics and Space FEDERAL AVIATION... Operations § 121.548 Aviation safety inspector's credentials: Admission to pilot's compartment. Whenever, in...

14 CFR 121.548 - Aviation safety inspector's credentials: Admission to pilot's compartment.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Aviation safety inspector's credentials: Admission to pilot's compartment. 121.548 Section 121.548 Aeronautics and Space FEDERAL AVIATION... Operations § 121.548 Aviation safety inspector's credentials: Admission to pilot's compartment. Whenever, in...

14 CFR 121.548 - Aviation safety inspector's credentials: Admission to pilot's compartment.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Aviation safety inspector's credentials: Admission to pilot's compartment. 121.548 Section 121.548 Aeronautics and Space FEDERAL AVIATION... Operations § 121.548 Aviation safety inspector's credentials: Admission to pilot's compartment. Whenever, in...

Educational Credentialing of an Aging Workforce: Uneasy Conclusions

ERIC Educational Resources Information Center

Isopahkala-Bouret, Ulpukka

2015-01-01

This study investigates the educational attainment of an aging workforce from the perspective of educational credentialing. The research questions are defined as follows: Why are workers over age 50 attaining university degrees? How do they narratively construct the rational for pursuing well-recognized credentials in midlife? The specific focus…

Extra-Credential Experiences and Social Closure: Working-Class Students at University

ERIC Educational Resources Information Center

Lehmann, Wolfgang

2012-01-01

Human capital theorists perceive of educational expansion as beneficial to individuals, corporations and national economies, while social closure theorists have claimed that inflation of credential requirements maintains traditional status inequalities. In this paper I argue that status inequalities are not only maintained by credential inflation,…

CVISN electronic credentialing for commercial vehicles in Washington State, a case study : easier licensing and credentials processing for the motor carrier industry

DOT National Transportation Integrated Search

2004-09-01

The following case study provides an in-depth view of the deployment of Commercial Vehicle Information Systems and Networks (CVISN) Electronic Credentialing in Washington State. It describes successful practices and lessons learned in operations and ...

21 CFR 1311.110 - Requirements for obtaining an authentication credential-Individual practitioners eligible to use...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Requirements for obtaining an authentication... Prescriptions § 1311.110 Requirements for obtaining an authentication credential—Individual practitioners... credentialing office) may conduct identity proofing and authorize the issuance of the authentication credential...

46 CFR 5.903 - Application procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... REGULATIONS-PERSONNEL ACTION Issuance of New Credential or Endorsement After Revocation or Surrender § 5.903 Application procedures. (a) An application form for a new credential or endorsement may be obtained from any... for the issuance of a new credential or endorsement and should include the following: (1) A letter...

46 CFR 15.403 - When credentials for ratings are required.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false When credentials for ratings are required. 15.403 Section 15.403 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS Manning Requirements; All Vessels § 15.403 When credentials for ratings are required...

CREDENTIALISM AND THE EDUCATION SYSTEM.

ERIC Educational Resources Information Center

MILLER, S.M.

EXISTING SOCIAL AND OCCUPATIONAL STRUCTURES SHOULD BE REMADE SO THAT CREDENTIALISM DOES NOT ARBITARILY BAR NEGROES AND THE POOR FROM ECONOMIC WELL-BEING AND SOCIAL MOBILITY. GRADUATION FROM A SCHOOL SIMPLY IMPLIES THAT ONE HAS FIT INTO THE PROPER EDUCATIONAL STRAITS AND DOES NOT NECESSARILY SIGNAL QUALITY PERFORMANCE. CREDENTIALISM AND ITS…

Credentialism: Partners for Business Education. Working Papers of Planning and Development Research 90-6.

ERIC Educational Resources Information Center

Protz, Maria

This study examined the current value of credentialism, extending the findings of an earlier report, "Business Training: Content, Enrollment and Delivery." The study acknowledged the distinction between various types of credentials, but focused primarily on professional business certification and investigated the potential for TVOntario…

The Impact of Consumer Credentialism on Employee and Entrepreneur Returns to Higher Education.

ERIC Educational Resources Information Center

Tucker, Irvin B., III

1987-01-01

Examines the relative importance of education credentials in consumer perceptions of self-employed business people. Using 1980 national cross-sectional data on goods- and service-producing occupations, the regression analysis shows that highly educated entrepreneurs are not influenced by consumer credentialism. Includes 17 references. (MLH)

Teachers, Micro-Credentials, and the Performance Assessment Movement

ERIC Educational Resources Information Center

French, Dan; Berry, Barnett

2017-01-01

Micro-credentials, a new form of personalized professional development for teachers, offer a unique solution to the challenge of training school staff to design and implement performance assessments. In a relatively short period of time, micro-credentials have shown promise in enabling a more personalized, effective method of promoting teacher…

Scaling "Stackable Credentials": Implications for Implementation and Policy

ERIC Educational Resources Information Center

Ganzglass, Evelyn

2014-01-01

Postsecondary education and credentials are key to economic mobility for individuals and economic competitiveness for our nation. Although the economic return to credentials varies significantly by field of study, generally workers with higher levels of education have higher wages, work more hours, and suffer lower rates and shorter durations of…

Impact of Nuclear Laboratory Personnel Credentials & Continuing Education on Nuclear Cardiology Laboratory Quality Operations.

PubMed

Malhotra, Saurabh; Sobieraj, Diana M; Mann, April; Parker, Matthew W

2017-12-22

Background/Objectives: The specific credentials and continuing education (CME/CE) of nuclear cardiology laboratory medical and technical staff are important factors in the delivery of quality imaging services that have not been systematically evaluated. Methods: Nuclear cardiology accreditation application data from the Intersocietal Accreditation Commission (IAC) was used to characterize facilities performing myocardial perfusion imaging by setting, size, previous accreditation and credentials of the medical and technical staff. Credentials and CME/CE were compared against initial accreditation decisions (grant or delay) using multivariable logistic regression. Results: Complete data were available for 1913 nuclear cardiology laboratories from 2011-2014. Laboratories with initial positive accreditation decisions had a greater prevalence of Certification Board in Nuclear Cardiology (CBNC) certified medical directors and specialty credentialed technical directors. Certification and credentials of the medical and technical directors, respectively, staff CME/CE compliance, and assistance of a consultant with the application were positively associated with accreditation decisions. Conclusion: Nuclear cardiology laboratories directed by CBNC-certified physicians and NCT- or PET-credentialed technologists were less likely to receive delay decisions for MPI. CME/CE compliance of both the medical and technical directors was associated with accreditation decision. Medical and technical directors' years of experience were not associated with accreditation decision. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

First-principles study on the phase transitions, crystal stabilities and thermodynamic properties of TiN under high pressure

NASA Astrophysics Data System (ADS)

Sun, Xinjun; Liu, Changdong; Guo, Yongliang; Sun, Deyan; Ke, Xuezhi

2018-03-01

The structural and thermodynamic properties of titanium nitride (TiN) have been investigated by merging first-principles calculations and particle-swarm algorithm. The three phases are identified for TiN, including the B1, the P63 / mmc, and the B2 phases. A new phase of anti-TiP structure with the space group P63 / mmc has been predicted. The calculated phase transition from the B1 to the P63 / mmc occurs at 270 GPa. The vibrational, elastic, and thermodynamic properties for the three phases have been calculated and discussed.

[CME MMC: Evaluation of a continuous medical education tool by e-learning from the morbi-mortality conferences of the Burgundy].

PubMed

Serrand, M; Lefèbvre, A; Desplanches, T; Yacoub, A; Semama, D; Sagot, P

2016-10-01

The objective of this study was to validate a continuing medical education e-learning tool. The CME MMC was for all health professionals maternity Burgundy and concerned regional morbidity and mortality conferences. It was divided into steps: a pre-test for an assessment of initial knowledge, an access to the recommendations of each RMM and a post-test to assess the progress of participants. A satisfaction questionnaire was proposed after the test. The primary endpoint was the comparison of the post-test scores than the pre-test. CME MMC was opened 3 months and recorded 156 participants among 598 health professionals in Burgundy, a rate 2.4 times higher than the average participation rate at MMC the past two years. A statistically significant increase was demonstrated individually by comparing the post-test scores than the pre-test (P<0.00001). The increase was significantly higher for midwives and professionals absents at the RMM. Finally, 96.2% of participants have been satisfied by this formation. This prospective multicenter study validates our tool. CME MMC is accessible, without geographic or time restrictions, not expensive, and efficient because it proves that it can update our knowledge in obstetrics and perinatology. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Maximum Margin Clustering of Hyperspectral Data

NASA Astrophysics Data System (ADS)

Niazmardi, S.; Safari, A.; Homayouni, S.

2013-09-01

In recent decades, large margin methods such as Support Vector Machines (SVMs) are supposed to be the state-of-the-art of supervised learning methods for classification of hyperspectral data. However, the results of these algorithms mainly depend on the quality and quantity of available training data. To tackle down the problems associated with the training data, the researcher put effort into extending the capability of large margin algorithms for unsupervised learning. One of the recent proposed algorithms is Maximum Margin Clustering (MMC). The MMC is an unsupervised SVMs algorithm that simultaneously estimates both the labels and the hyperplane parameters. Nevertheless, the optimization of the MMC algorithm is a non-convex problem. Most of the existing MMC methods rely on the reformulating and the relaxing of the non-convex optimization problem as semi-definite programs (SDP), which are computationally very expensive and only can handle small data sets. Moreover, most of these algorithms are two-class classification, which cannot be used for classification of remotely sensed data. In this paper, a new MMC algorithm is used that solve the original non-convex problem using Alternative Optimization method. This algorithm is also extended for multi-class classification and its performance is evaluated. The results of the proposed algorithm show that the algorithm has acceptable results for hyperspectral data clustering.

46 CFR 11.464 - Requirements for endorsements as master of towing vessels.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) If you hold a license or MMC endorsement as a master of steam or motor vessels of greater than 200... demonstration of skills; or (ii) Complete an approved training course. (3) Your license or MMC does not need to...

An Exploration of Virtual Study Groups Used to Prepare Candidates for a Professional Certification Exam

ERIC Educational Resources Information Center

Kayne Chaplock, Sharon

2011-01-01

Professional credentials earned through certification programs are becoming an important way to demonstrate competency within a given discipline. With the globalization of business enterprises and associations, these credentials are eagerly sought by people located throughout the world. Candidates for these credentials often study together using…

General Education Development (GED®) Credential Attainment, Externalizing Disorders, and Substance Use Disorders in Disconnected Emerging Adults

ERIC Educational Resources Information Center

Bergman, Andrea; Kong, Grace; Pope, Alice

2014-01-01

There are many benefits for emerging adults, both financial and personal, in obtaining a General Education Development (GED®) credential (Ou, 2008). However, little is known about the correlates of GED® credential attainment in "disconnected" emerging adults attending GED® programs. Our goal was to examine whether externalizing…

Why New Mathematics Teachers Do or Don't Use Practices Emphasized in Their Credential Program

ERIC Educational Resources Information Center

Gainsburg, Julie

2012-01-01

A major research concern for teacher education is the impact of university credentialing programs on K-12 teaching and the disjuncture between university-promoted practices and what teachers actually do in their classrooms. In particular, mathematics-credential programs typically promote reform-oriented methods, while mathematics teaching in the…

Commission on Teacher Credentialing Approves 8 ELL-Related Credential Options

ERIC Educational Resources Information Center

Frost, Jeff; Cadiero-Kaplan, Karen; Kuhlman, Natalie

2011-01-01

On September 30, 2010, the California Commission on Teacher Credentialing (CTC) voted unanimously to approve a set of eight recommendations for authorization to teach English language learners. These recommendations approved by the CTC had been in development for almost two years and they focused on several issues, including: (1) a specific focus…

Evaluation of field operations test 8 : electronic credentialing : New York state proof-of-concept project one stop credentialing and registration

DOT National Transportation Integrated Search

2001-09-01

The State of New York received a grant from the I-95 Corridor Coalition to develop a proof-of-concept for an electronic credentialing system for the motor carrier industry. When fully developed, the system, which is a web-based solution, will enable ...

14 CFR 135.76 - DOD Commercial Air Carrier Evaluator's Credentials: Admission to pilots compartment: Forward...

Code of Federal Regulations, 2011 CFR

2011-01-01

... Credentials: Admission to pilots compartment: Forward observer's seat. 135.76 Section 135.76 Aeronautics and... Commercial Air Carrier Evaluator's Credentials: Admission to pilots compartment: Forward observer's seat. (a.... (b) A forward observer's seat on the flight deck or forward passenger seat with headset or speaker...

14 CFR 135.76 - DOD Commercial Air Carrier Evaluator's Credentials: Admission to pilots compartment: Forward...

Code of Federal Regulations, 2010 CFR

2010-01-01

... Credentials: Admission to pilots compartment: Forward observer's seat. 135.76 Section 135.76 Aeronautics and... Commercial Air Carrier Evaluator's Credentials: Admission to pilots compartment: Forward observer's seat. (a.... (b) A forward observer's seat on the flight deck or forward passenger seat with headset or speaker...

Introducing a laparoscopic simulation training and credentialing program in gynaecology: an observational study.

PubMed

Janssens, Sarah; Beckmann, Michael; Bonney, Donna

2015-08-01

Simulation training in laparoscopic surgery has been shown to improve surgical performance. To describe the implementation of a laparoscopic simulation training and credentialing program for gynaecology registrars. A pilot program consisting of protected, supervised laparoscopic simulation time, a tailored curriculum and a credentialing process, was developed and implemented. Quantitative measures assessing simulated surgical performance were measured over the simulation training period. Laparoscopic procedures requiring credentialing were assessed for both the frequency of a registrar being the primary operator and the duration of surgery and compared to a presimulation cohort. Qualitative measures regarding quality of surgical training were assessed pre- and postsimulation. Improvements were seen in simulated surgical performance in efficiency domains. Operative time for procedures requiring credentialing was reduced by 12%. Primary operator status in the operating theatre for registrars was unchanged. Registrar assessment of training quality improved. The introduction of a laparoscopic simulation training and credentialing program resulted in improvements in simulated performance, reduced operative time and improved registrar assessment of the quality of training. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

WE-E-304-01: SBRT Credentialing: Understanding the Process From Inquiry to Approval

DOE Office of Scientific and Technical Information (OSTI.GOV)

Followill, D.

SBRT is having a dramatic impact on radiation therapy of early-stage, locally advanced cancers. A number of national protocols have been and are being developed to assess the clinical efficacy of SBRT for various anatomical sites, such as lung and spine. Physics credentialing for participating and implementation of trial protocols involve a broad spectrum of requirements from image guidance, motion management, to planning technology and dosimetric constrains. For radiation facilities that do not have extensive experiences in SBRT treatment and protocol credentialing, these complex processes of credentialing and implementation could be very challenging and, sometimes, may lead to ineffective evenmore » unsuccessful execution of these processes. In this proposal, we will provide comprehensive review of some current SBRT protocols, explain the requirements and their underline rationales, illustrate representative failed and successful experiences, related to SBRT credentialing, and discuss strategies for effective SBRT credentialing and implementation. Learning Objectives: Understand requirements and challenges of SBRT credentailing and implentation Discuss processes and strategies of effective SBRT credentailing Discuss practical considerations, potential pitfalls and solutions of SBRT implentation.« less

Complete tissue coverage achieved by scaffold-based tissue engineering in the fetal sheep model of Myelomeningocele.

PubMed

Watanabe, Miho; Li, Haiying; Kim, Aimee G; Weilerstein, Aaron; Radu, Anteneta; Davey, Marcus; Loukogeorgakis, Stavros; Sánchez, Melissa D; Sumita, Kazutaka; Morimoto, Naoki; Yamamoto, Masaya; Tabata, Yasuhiko; Flake, Alan W

2016-01-01

Myelomeningocele (MMC) is the most severe form of spina bifida, one of the most common congenital anomalies. Although open fetal surgical repair of the MMC defect has been shown to result in improved outcomes, a less invasive approach applicable earlier in gestation than the current open surgical approach between 19 and 26 weeks of gestation is desirable for further improvement of neurological symptoms, as well as reduction of maternal and fetal risks. We previously reported the therapeutic potential of a scaffold-based tissue engineering approach in a fetal rat MMC model. The objective of this study was to confirm the long-term efficacy of this approach in the surgically created fetal sheep MMC model. Gelatin-based or gelatin/collagen hybrid sponges were prepared with and without basic fibroblast growth factor (bFGF) incorporation. The defect was covered by a sponge and secured by a supporting sheet with adhesive at 100 days of gestation or the gelatin/collagen hybrid with bFGF was secured with adhesive without the sheet. Although sheets were found detached at term (140 days' gestation), both gelatin-based and gelatin/collagen hybrid sponges had integrated within the newly formed granulation tissue, resulting in complete coverage of the MMC defect. The release of bFGF from sponges resulted in enhanced formation of granulation tissue and epithelialization. There was also evidence of improved preservation of the spinal cord with less associated damage on histological analysis and reversal of hindbrain herniation. These experiments provide important proof-of-principle evidence of the efficacy of scaffold-based tissue engineered coverage for the prenatal treatment of MMC. Copyright © 2015 Elsevier Ltd. All rights reserved.

Stereochemical studies of the monocyclic agouti-related protein (103-122) Arg-Phe-Phe residues: conversion of a melanocortin-4 receptor antagonist into an agonist and results in the discovery of a potent and selective melanocortin-1 agonist.

PubMed

Joseph, Christine G; Wang, Xiang S; Scott, Joseph W; Bauzo, Rayna M; Xiang, Zhimin; Richards, Nigel G; Haskell-Luevano, Carrie

2004-12-30

The agouti-related protein (AGRP) is an endogenous antagonist of the centrally expressed melanocortin receptors. The melanocortin-4 receptor (MC4R) is involved in energy homeostasis, food intake, sexual function, and obesity. The endogenous hAGRP protein is 132 amino acids in length, possesses five disulfide bridges at the C-terminus of the molecule, and is expressed in the hypothalamus of the brain. We have previously reported that a monocyclic hAGRP(103-122) peptide is an antagonist at the melanocortin receptors expressed in the brain. Stereochemical inversion from the endogenous l- to d-isomers of single or multiple amino acid modifications in this monocyclic truncated hAGRP sequence resulted in molecules that are converted from melanocortin receptor antagonists into melanocortin receptor agonists. The Asp-Pro-Ala-Ala-Thr-Ala-Tyr-cyclo[Cys-Arg-DPhe-DPhe-Asn-Ala-Phe-Cys]-Tyr-Ala-Arg-Lys-Leu peptide resulted in a 60 nM melanocortin-1 receptor agonist that is 100-fold selective versus the mMC4R, 1000-fold selective versus the mMC3R, and ca. 180-fold selective versus the mMC5R. In attempts to identify putative ligand-receptor interactions that may be participating in the agonist induced stimulation of the MC4R, selected ligands were docked into a homology molecular model of the mMC4R. These modeling studies have putatively identified hAGRP ligand DArg111-mMC4RAsn115 (TM3) and the hAGRP DPhe113-mMC4RPhe176 (TM4) interactions as important for agonist activity.

Comparison of the visual outcomes between PRK-MMC and phakic IOL implantation in high myopic patients

PubMed Central

Hashemi, H; Miraftab, M; Asgari, S

2014-01-01

Purpose To compare the visual outcomes between PRK-MMC and phakic IOL in patients with more than 8 diopter (D) of myopia. Methods This comparative study was performed on 23 eyes under treatment with Artiflex (group A) and 23 eyes under treatment with PRK-MMC (group B). Artiflex phakic IOL (Ophtec BV) was used in group A, and the VISX STAR S4 Excimer Laser (Abbott) was used for PRK-MMC in group B. Results The safety index was 1.11±0.23 and 1.05±0.25 (P=0.100) and the efficacy index was 1.02±0.11 and 0.98±0.10 (P=0.266) in group A and B, respectively. At 1 year after surgery, the manifest refraction spherical equivalent was −0.17±1.18 and −0.25±0.18 D in group A and B, respectively (P=0.471). Mesopic CS showed no significant difference between the two groups in any spatial frequency. Total coma was 0.24±0.17 and 0.67±0.40 μm (P<0.001), spherical aberration was −0.11±0.11 and 0.41±0.18 μm (P<0.001), and RMS HOAT was 0.50±0.20 and 0.96±0.45 μm (P<0.001) in group A and B, respectively. Conclusion Phakic IOL implantation was better than PRK-MMC in the correction of high myopia in terms of visual quality, but the two methods had no difference with regard to visual acuity. Therefore, PRK-MMC can be used when the anterior chamber depth is a limiting factor in the implantation of phakic IOLs. PMID:24993326

Comparison of the visual outcomes between PRK-MMC and phakic IOL implantation in high myopic patients.

PubMed

Hashemi, H; Miraftab, M; Asgari, S

2014-09-01

To compare the visual outcomes between PRK-MMC and phakic IOL in patients with more than 8 diopter (D) of myopia. This comparative study was performed on 23 eyes under treatment with Artiflex (group A) and 23 eyes under treatment with PRK-MMC (group B). Artiflex phakic IOL (Ophtec BV) was used in group A, and the VISX STAR S4 Excimer Laser (Abbott) was used for PRK-MMC in group B. The safety index was 1.11 ± 0.23 and 1.05 ± 0.25 (P = 0.100) and the efficacy index was 1.02 ± 0.11 and 0.98 ± 0.10 (P = 0.266) in group A and B, respectively. At 1 year after surgery, the manifest refraction spherical equivalent was -0.17 ± 1.18 and -0.25 ± 0.18 D in group A and B, respectively (P = 0.471). Mesopic CS showed no significant difference between the two groups in any spatial frequency. Total coma was 0.24 ± 0.17 and 0.67 ± 0.40 μm (P < 0.001), spherical aberration was -0.11 ± 0.11 and 0.41 ± 0.18 μm (P < 0.001), and RMS HOAT was 0.50 ± 0.20 and 0.96 ± 0.45 μm (P<0.001) in group A and B, respectively. Phakic IOL implantation was better than PRK-MMC in the correction of high myopia in terms of visual quality, but the two methods had no difference with regard to visual acuity. Therefore, PRK-MMC can be used when the anterior chamber depth is a limiting factor in the implantation of phakic IOLs.

Consultant medical trainers, modernising medical careers (MMC) and the European time directive (EWTD): tensions and challenges in a changing medical education context

PubMed Central

Tsouroufli, Maria; Payne, Heather

2008-01-01

Background We analysed the learning and professional development narratives of Hospital Consultants training junior staff ('Consultant Trainers') in order to identify impediments to successful postgraduate medical training in the UK, in the context of Modernising Medical Careers (MMC) and the European Working Time Directive (EWTD). Methods Qualitative study. Learning and continuing professional development (CPD), were discussed in the context of Consultant Trainers' personal biographies, organisational culture and medical education practices. We conducted life story interviews with 20 Hospital Consultants in six NHS Trusts in Wales in 2005. Results Consultant Trainers felt that new working patterns resulting from the EWTD and MMC have changed the nature of medical education. Loss of continuity of care, reduced clinical exposure of medical trainees and loss of the popular apprenticeship model were seen as detrimental for the quality of medical training and patient care. Consultant Trainers' perceptions of medical education were embedded in a traditional medical education culture, which expected long hours' availability, personal sacrifices and learning without formal educational support and supervision. Over-reliance on apprenticeship in combination with lack of organisational support for Consultant Trainers' new responsibilities, resulting from the introduction of MMC, and lack of interest in pursuing training in teaching, supervision and assessment represent potentially significant barriers to progress. Conclusion This study identifies issues with significant implications for the implementation of MMC within the context of EWTD. Postgraduate Deaneries, NHS Trusts and the new body; NHS: Medical Education England should deal with the deficiencies of MMC and challenges of ETWD and aspire to excellence. Further research is needed to investigate the views and educational practices of Consultant Medical Trainers and medical trainees. PMID:18492261

Target drug delivery system as a new scarring modulation after glaucoma filtration surgery

PubMed Central

2011-01-01

Background Excessive wound healing following glaucoma filtration surgery is the main determinant of surgical failure, resulting from the activation of human Tenon's capsule fibroblasts (HTFs). To mitigate the excessive wound healing, the topicall use of antiproliferative agents, such as mitomycin C (MMC) and 5-fluorouracil (5-FU), has increased the surgery success rate, but the traditional administration of these agents can result in a variety of toxicities with nonspecific damage. However, modulation of the wound healing process to prevent excessive fibroblast proliferation and scar formation can play a major role in improving the outcome of surgery. Therefore, the search for alternative modes of drug delivery and new agents is needed to minimize the ocular complications and improve the success of surgery. We have shown that there is a postoperative overexpression of the LDL receptor (LDLr) in the activated HTFs may provide a novel target for drug delivery systems. Presentation of the Hypothesis We hypothesize that antifibrotic agents (MMC) encapsulated in LDLr targeting drug delivery system (LDL-MMC-chitosan nanoparticles) may be proposed in anti-scarring therapy to increase the safety and effectiveness and to reduce toxicity. Testing the Hypothesis A chitosan-based polymeric predrug of MMC was synthesized and its cytotoxicity was proved to be low. In addition, we propose hyaluronic acid film as a container to release LDL-MMC-chitosan nanoparticles gradually at subconjunctival filtering site after glaucoma filtration surgery to eliminate the LDL-MMC-chitosan nanoparticles. Implications of the Hypothesis and discussion This strategy can be applicable to anti-scarring therapy during excessive conjunctival wound healing. This hypothesis integrates advantages of the targeting drug delivery and antifibrotic agents, such as high efficiency, convenience, and lower the toxicity. PMID:21736763

Phospholipase A2 activation regulates cytotoxicity of methylmercury in vascular endothelial cells.

PubMed

Mazerik, Jessica N; Hagele, Thomas; Sherwani, Shariq; Ciapala, Valorie; Butler, Susan; Kuppusamy, M Lakshmi; Hunter, Melissa; Kuppusamy, Periannan; Marsh, Clay B; Parinandi, Narasimham L

2007-01-01

Mercury has been identified as a risk factor for cardiovascular disease among humans. Through diet, mainly fish consumption, humans are exposed to methylmercury, the biomethylated organic form of environmental mercury. As the endothelium is an important player in homeostasis of the cardiovascular system, here, the authors tested their hypothesis that methylmercury activates the lipid signaling enzyme phospholipase A(2) (PLA(2)) in vascular endothelial cells (ECs), causing upstream regulation of cytotoxicity. To test this hypothesis, the authors used bovine pulmonary artery ECs (BPAECs) cultured in monolayers, following labeling of their membrane phospholipids with [(3)H]arachidonic acid (AA). The cells were exposed to methylmercury chloride (MMC) and then the release of free AA (index of PLA(2) activity) and lactate dehydrogenase (LDH; index of cytotoxicity) were determined by liquid scintillation counting and spectrophotometry, respectively. MMC significantly activated PLA(2) in a dose-dependent (5 to 15 microM) and time-dependent (0 to 60 min) fashion. Sulfhydryl (thiol-protective) agents, calcium chelators, antioxidants, and PLA(2)-specific inhibitors attenuated the MMC-induced PLA(2) activation, suggesting the role of thiols, reactive oxygen species (ROS), and calcium in the activation of PLA(2) in BPAECs. MMC also induced the loss of thiols and increase of lipid peroxidation in BPAECs. MMC induced cytotoxicity in BPAECs as observed by the altered cell morphology and LDH leak, which was significantly attenuated by PLA(2) inhibitors. This study established that PLA(2) activation through thiols, calcium, and oxidative stress was associated with the cytotoxicity of MMC in BPAECs, drawing attention to the involvement of PLA(2) signaling in the methylmercury-induced vascular endothelial dysfunctions.

Preclinical rationale for combination of crizotinib with mitomycin C for the treatment of advanced colorectal cancer.

PubMed

Lev, Avital; Deihimi, Safoora; Shagisultanova, Elena; Xiu, Joanne; Lulla, Amriti R; Dicker, David T; El-Deiry, Wafik S

2017-09-02

Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States. We analyzed 26 MSI-High and 558 non-MSI-High CRC tumors. BRCA2 mutations were highly enriched (50%) in MSI-High CRC. Immunohistochemistry showed that BRCA2-mutated MSI-High CRC had high c-MET (64%) expression compared with BRCA-WT (17%). We hypothesized a mechanistic link between BRCA2-deficiency and c-MET overexpression and synergistic interaction between drugs that treat BRCA-deficient tumors (mitomycin C (MMC) or PARP inhibitors) and c-MET inhibitors (crizotinib). We tested CRC cell lines for sensitivity to MMC plus crizotinib or other drug combinations including PARP-inhibitors. Combined treatment of tumor cells with crizotinib and MMC led to increased apoptosis as compared with each drug alone. Additionally, combination treatment with increasing concentrations of both drugs demonstrated a synergistic anti-cancer effect (CI = 0.006-0.74). However, we found no evidence for c-MET upregulation upon effective BRCA2 knockdown in tumor cells -/+DNA damage. Although we found no mechanistic link between BRCA2 deficiency and c-MET overexpression, c-MET is frequently overexpressed in CRC and BRCA2 is mutated especially in MSI-H CRC. The combination of crizotinib with MMC appeared synergistic regardless of MSI or BRCA2 status. Using an in-vivo CRC xenograft model we found reduced tumor growth with combined crizotinib and MMC therapy (p = 0.0088). Our preclinical results support clinical testing of the combination of MMC and crizotinib in advanced CRC. Targeting cell survival mediated by c-MET in combination with targeting DNA repair may be a reasonable strategy for therapy development in CRC or other cancers.

Mitomycin C in pterygium treatment

PubMed Central

Martins, Thiago Gonçalves dos Santos; Costa, Ana Luiza Fontes de Azevedo; Alves, Milton Ruiz; Chammas, Roger; Schor, Paulo

2016-01-01

Pterygium is a benign lesion usually growing from the nasal side of the conjunctiva onto the cornea. Most cases of pterygium does not cause problem or requires specific treatment. The exact cause of pterygium is not clear yet, but some factors are pointed as causes, being the most important the long-term ultraviolet ray exposure. Pterygium surgery is usually considered when there are symptoms that do not respond to conservative treatment. Recurrence is the main complication of the surgery, and much has been done to avoid it. Mitomycin C (MMC) has been used as a fibroblast proliferation inhibitor during the surgery to reduce the chance of recurrence of the pterygium. This review describes the use of MMC as an adjunctive, the optimal dosage, the duration of administration of MMC and possible complications, when used during, after and before the surgery. Most studies suggest that increased exposure (dose or duration) of MMC is associated with a lower recurrence, but with higher risks of complications. PMID:27158622

A homozygous FANCM mutation underlies a familial case of non-syndromic primary ovarian insufficiency

PubMed Central

Caburet, Sandrine; Guigon, Celine; Mäkinen, Marika; Tanner, Laura; Hietala, Marja; Urbanska, Kaja; Bellutti, Laura; Legois, Bérangère; Bessieres, Bettina; Gougeon, Alain; Benachi, Alexandra; Livera, Gabriel; Rosselli, Filippo

2017-01-01

Primary Ovarian Insufficiency (POI) affects ~1% of women under forty. Exome sequencing of two Finnish sisters with non-syndromic POI revealed a homozygous mutation in FANCM, leading to a truncated protein (p.Gln1701*). FANCM is a DNA-damage response gene whose heterozygous mutations predispose to breast cancer. Compared to the mother's cells, the patients’ lymphocytes displayed higher levels of basal and mitomycin C (MMC)-induced chromosomal abnormalities. Their lymphoblasts were hypersensitive to MMC and MMC-induced monoubiquitination of FANCD2 was impaired. Genetic complementation of patient's cells with wild-type FANCM improved their resistance to MMC re-establishing FANCD2 monoubiquitination. FANCM was more strongly expressed in human fetal germ cells than in somatic cells. FANCM protein was preferentially expressed along the chromosomes in pachytene cells, which undergo meiotic recombination. This mutation may provoke meiotic defects leading to a depleted follicular stock, as in Fancm-/- mice. Our findings document the first Mendelian phenotype due to a biallelic FANCM mutation. PMID:29231814

Performance of hybrid nano-micro reinforced mg metal matrix composites brake calliper: simulation approach

NASA Astrophysics Data System (ADS)

Fatchurrohman, N.; Chia, S. T.

2017-10-01

Most commercial vehicles use brake calliper made of grey cast iron (GCI) which possesses heavy weight. This contributes to the total weight of the vehicle which can lead to higher fuel consumption. Another major problem is GCI calliper tends to deflect during clamping action, known as “bending of bridge”. This will result in extended pedal travel. Magnesium metal matrix composites (Mg-MMC) has a potential application in the automotive industry since it having a lower density, higher strength and very good modulus of elasticity as compared to GCI. This paper proposed initial development of hybrid Mg-MMC brake calliper. This was achieved by analyzing the performance of hybrid nano-micro reinforced Mg-MMC and comparing with the conventional GCI brake calliper. It was performed using simulation in ANSYS, a finite element analysis (FEA) software. The results show that hybrid Mg-MMC has better performance in terms of reduction the weight of the brake calliper, reduction in total deformation/deflection and better ability to withstand equivalent elastic strain.

The role of mitomycin C in surgery of the frontonasal recess: a prospective open pilot study.

PubMed

Amonoo-Kuofi, Kwame; Lund, Valerie J; Andrews, Peter; Howard, David J

2006-01-01

Mitomycin C (MMC) inhibits fibroblast proliferation. The objective of this study was to determine the efficacy of MMC in reducing frontal ostium stenosis after endoscopic sinus surgery. A prospective open pilot study was conducted in 28 patients who had undergone one or more previous surgical interventions for frontal sinusitis. MMC solution was applied to the frontal ostial region via an endoscopic or combined endoscopic and external approach. Patency of the frontal ostium was evaluated endoscopically during regular follow-up. If restenosis was observed further, endoscopic application of MMC was undertaken. There were 17 men and 11 women (mean age, 51.7 years; range, 26-86 years). Mean number of applications was 1.5 (range, 1:3). Mean follow-up was 19 months (range, 6-32 months). Patency rate was 86%. Mitomycin appears to have an important role in reducing postoperative scarring, which may obviate the need for repeated and more extensive surgery.

Effect of mitomycin C on endoscopic dacryocystorhinostomy.

PubMed

Apuhan, Tayfun; Yıldırım, Yavuz Selim; Eroglu, Faruk; Sipahier, Ali

2011-11-01

The objectives of the study were to retrospectively analyze the efficacy of intraoperative mitomycin C (MMC) in endoscopic dacryocystorhinostomy (END-DCR) and compare it with external dacryocystorhinostomy (EXT-DCR). For the comfort of the patients, the procedures were performed under general anesthesia. Intraoperatively during the END-DCR, we applied a cotton pledget soaked in a 0.5 mg/mL solution of MMC for 2.5 minutes. In each patient, a silicone tube was placed into the nasal cavity via the superior and inferior punctae and fixed in the vestibule. We retrospectively analyzed the medical records of patients who underwent END-DCR and EXT-DCR. A retrospective review was performed on the medical records of 43 patients (with a total of 49 affected cases) who were admitted to our clinics with a primary complaint of epiphora. The overall success rates were 91% in END-DCR+MMC and 71.5% in EXT-DCR. Mitomycin C, in appropriate doses, minimizes postoperative granulations and fibrosis. Adjunctive use of MMC is considered to increase the success rate of END-DCR.

The influence of microstructure on the tensile behavior of an aluminum metal matrix composite

NASA Technical Reports Server (NTRS)

Birt, Michael J.; Johnson, W. Steven

1990-01-01

The relationship between tensile properties and microstructure of a powder metallurgy aluminum alloy, 2009 was examined. The alloy was investigated both unreinforced and reinforced with 15 v/o SiC whiskers or 15 v/o SiC particulate to form a discontinuous metal matrix composite (MMC). The materials were investigated in the as-fabricated condition and in three different hot-rolled sheet thicknesses of 6.35, 3.18, and 1.8 mm. Image analysis was used to characterize the morphology of the reinforcements and their distributions within the matrix alloy. Fractographic examinations revealed that failure was associated with the presence of microstructural inhomogeneities which were related to both the matrix alloy and to the reinforcement. The results from these observations together with the matrix tensile data were used to predict the strengths and moduli of the MMC's using relatively simple models. The whisker MMC could be modeled as a short fiber composite and an attempt was made to model the particulate MMC as a dispersion/dislocation hardened alloy.

Antimutagenic and antirecombinagenic activities of noni fruit juice in somatic cells of Drosophila melanogaster.

PubMed

Franchi, Leonardo P; Guimarães, Nilza N; De Andrade, Laise R; De Andrade, Heloísa H R; Lehmann, Maurício; Dihl, Rafael R; Cunha, Kênya S

2013-01-01

Noni, a Hawaiian name for the fruit of Morinda citrifolia L., is a traditional medicinal plant from Polynesia widely used for the treatment of many diseases including arthritis, diabetes, asthma, hypertension and cancer. Here, a commercial noni juice (TNJ) was evaluated for its protective activities against the lesions induced by mitomycin C (MMC) and doxorrubicin (DXR) using the Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. Three-day-old larvae, trans-heterozygous for two genetic markers (mwh and flr3 ), were co-treated with TNJ plus MMC or DXR. We have observed a reduction in genotoxic effects of MMC and DXR caused by the juice. TNJ provoked a marked decrease in all kinds of MMC- and DXR-induced mutant spots, mainly due to its antirecombinagenic activity. The TNJ protective effects were concentration-dependent, indicating a dose-response correlation, that can be attributed to a powerful antioxidant and/or free radical scavenger ability of TNJ.

Smartphone-based secure authenticated session sharing in Internet of Personal Things

NASA Astrophysics Data System (ADS)

Krishnan, Ram; Ninglekhu, Jiwan

2015-03-01

In the context of password-based authentication, a user can only memorize limited number of usernames and passwords. They are generally referred to as user-credentials. Longer character length of passwords further adds complication in mastering them. The expansion of the Internet and our growing dependency on it, has made it almost impossible for us to handle the big pool of user-credentials. Using simple, same or similar passwords is considered a poor practice, as it can easily be compromised by password cracking tools and social engineering attacks. Therefore, a robust and painless technique to manage personal credentials for websites is desirable. In this paper, a novel technique for user-credentials management via a smart mobile device such as a smartphone in a local network is proposed. We present a secure user-credential management scheme in which user's account login (username) and password associated with websites domain name is saved into the mobile device's database using a mobile application. We develop a custom browser extension application for client and use it to import user's credentials linked with the corresponding website from the mobile device via the local Wi-Fi network connection. The browser extension imports and identifies the authentication credentials and pushes them into the target TextBox locations in the webpage, ready for the user to execute. This scheme is suitably demonstrated between two personal devices in a local network.

TH-B-12A-01: TG124 “A Guide for Establishing a Credentialing and Privileging Program for Users of Fluoroscopic Equipment in Healthcare Organizations”

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, M

Fluoroscopy credentialing and privileging programs are being instituted because of recorded patient injuries and the widespread growth in fluoroscopy use by operators whose medical education did not include formal fluoroscopy training. This lack of training is recognized as a patient safety deficiency, and medical physicists and health physicists are finding themselves responsible for helping to establish fluoroscopy credentialing programs. While physicians are very knowledgeable about clinical credentials review and the privileging process, medical physicists and health physicists are not as familiar with the process and associated requirements. To assist the qualified medical physicist (QMP) and the radiation safety officer (RSO)more » with these new responsibilities, TG 124 provides an overview of the credentialing process, guidance for policy development and incorporating trained fluoroscopy users into a facility's established process, as well as recommendations for developing and maintaining a risk-based fluoroscopy safety training program. This lecture will review the major topics addressed in TG124 and relate them to practical situations. Learning Objectives: Understand the difference between credentialing and privileging. Understand the responsibilities, interaction and coordination among key individuals and committees. Understand options for integrating the QMP and/or RSO and Radiation Safety Committee into the credentialing and privileging process. Understand issues related to implementing the fluoroscopy safety training recommendations and with verifying and documenting successful completion.« less

The Efficacy of Multicultural Education Training in Teacher-Credentialing Programs: A Descriptive Case Study

ERIC Educational Resources Information Center

Delk, Tricia

2017-01-01

The purpose of the qualitative descriptive embedded single case study research was to explore how multicultural curriculum and instruction in a teacher-credentialing program prepared pre-service teachers to work with diverse students. The problem was the inadequacy on the part of teacher-credentialing programs to train pre-service teachers to make…

Micro-Credentials for Impact: Holding Professional Learning to High Standards

ERIC Educational Resources Information Center

Crow, Tracy

2017-01-01

This paper seeks to chart a course for leveraging a micro-credentialing system to enable more educators to achieve the potential of professional learning. The paper uses the Standards for Professional Learning as a frame to provide guidance to everyone involved in micro-credentials to ensure that learners experience the research-based elements of…

Elements of Success: How Type of Secondary Education Credential Helps Predict Enlistee Attrition

ERIC Educational Resources Information Center

Burkhauser, Susan; Hanser, Lawrence M.; Hardison, Chaitra M.

2014-01-01

The U.S. military services have traditionally used a tiering system, including education credentials such as high school diplomas, in combination with Armed Forces Qualification Test (AFQT) scores to help gauge the likelihood of a recruit persevering through his or her first term of service. But what about less traditional credentials, such as…

How to Tackle the Credentials Puzzle

ERIC Educational Resources Information Center

Jenkins, Rob

2008-01-01

In this article, the author discusses the issue of credentials in reply to one of the correspondents who is confused about the credentials she needs to teach at a community college. Generally speaking, to teach in programs that award associate of arts or associate of science degrees--i.e., to teach at a community college--faculty members are…

Adult Training and Education: Results from the National Household Education Surveys Program of 2016. First Look. NCES 2017-103

ERIC Educational Resources Information Center

Cronen, Stephanie; McQuiggan, Meghan; Isenberg, Emily

2017-01-01

This report presents data on adults' training and education in the United States as of 2016. The report focuses on nondegree credentials and work experience programs. Nondegree credentials include two types of work credentials--certifications and licenses--and postsecondary educational certificates. A certification is an occupational credential…

Employers, Low-Income Young Adults, and Postsecondary Credentials: A Practical Typology for Business, Education, and Community Leaders

ERIC Educational Resources Information Center

Bozell, Maureen R.; Goldberg, Melissa

2009-01-01

This report investigates a number of education and training programs involving employers in efforts to help disadvantaged young adults attain post-secondary credentials leading to career track employment. For the purposes of this report, the authors define credentials to mean credit and non-credit industry-recognized certifications, associate…

Degree and Nondegree Credentials Held by Labor Force Participants. Data Point. NCES 2018-057

ERIC Educational Resources Information Center

Cronen, Stephanie; Isenberg, Emily

2018-01-01

A common approach to describing the credentials required for occupations is to cite whether workers hold an educational degree beyond a high school diploma--that is, whether they hold a postsecondary degree. Using a postsecondary degree as a measure of occupational credentialing, 45 percent of labor force participants (adults who are working or…

"A Degree Is a Part of the Puzzle, but Only a Piece." Understanding How Employers Determine the Value of Academic Credentials

ERIC Educational Resources Information Center

Kaspari, Brenda Anderson

2017-01-01

With the skyrocketing costs of higher education and the increased scrutiny of how educational institutions prepare graduates for the workplace, this dissertation explored how the "outsiders," or employers, view and determine the value of academic credentials. Using the premise of credentialism, this grounded theory, qualitative study…

Familial polyposis coli: no evidence for increased sensitivity to mitomycin C.

PubMed Central

Mazzullo, H A; Attwood, J; Delhanty, J D

1988-01-01

Spontaneous chromosome instability is well established for the dominantly inherited cancer prone condition, familial polyposis coli (FPC), but conflicting results have been obtained regarding sensitivity to mitomycin C (MMC). We have investigated cell survival in fibroblasts and the induction of sister chromatid exchanges and chromosome damage in lymphocytes and fibroblasts after MMC treatment. We can find no evidence for a differential response of FPC cells as measured by any of these parameters, although individual FPC fibroblast cultures did show an enhanced chromosomal response. Overall, the FPC mutation does not appear to result in defective DNA repair in response to MMC. PMID:2835481

Fabrication of Metallic Magnetic Calorimeter for Radionuclide Analysis

NASA Astrophysics Data System (ADS)

Yoon, W. S.; Kim, G. B.; Lee, H. J.; Lee, J. Y.; Lee, J. H.; Jang, Y. S.; Lee, S. J.; Lee, M. K.; Kim, Y. H.

2014-09-01

We present a detailed report on the fabrication process of a metallic magnetic calorimeter (MMC). The MMC is configured in a planar geometry with a meander-shaped pickup coil covered with a Au:Er temperature sensor layer. The meander coil is used to apply a magnetic field to magnetize the erbium ions and to measure the magnetization change of the spin system. The MMC is designed to have a large area (1 mm) and 3 m thickness Au:Er layer, which is suited for large metal absorbers with a few nJ/K heat capacity in radionuclide analysis applications. The completed devices are used in alpha and Q spectrometries.

Certification, Accreditation, and Credentialing for 503A Compounding Pharmacies.

PubMed

Pritchett, Jon; McCrory, Gary; Kraemer, Cheri; Jensen, Brenda; Allen, Loyd V

2018-01-01

The terms certification, accreditation, and credentialing are often used interchangeably when they apply to compounding-pharmacy qualifications, but they are not synonymous. The reasons for obtaining each, the requirements for each, and the benefits of each differ. Achieving such distinctions can negatively or positively affect the status of a pharmacy among peers and prescribers as well as a pharmacy's relationships with third-party payors. Changes in the third-party payor industry evolve constantly and, we suggest, will continue to do so. Compounding pharmacists must be aware of those changes to help ensure success in a highly competitive marketplace. To our knowledge at the time of this writing, there is no certification program for compounding pharmacists, although pharmacy technicians can achieve certification and may be required to do so by the state in which they practice (a topic beyond the scope of this article). For that reason, we primarily address accreditation and credentialing for 503A compounding pharmacies. In this article, the evolution of the third-party payment system for compounds is reviewed; the definitions of certification, accreditation, and credentialing are examined; and the benefits and recognition of obtaining accredited or credentialed status are discussed. Suggestions for selecting an appropriate agency that offers accreditation or credentialing, preparing for and undergoing an onsite survey, responding to findings, and maintaining a pharmacy practice that enables a successful survey outcome are presented. The personal experience of author CK during accreditation and credentialing is discussed, as is the role of a consultant (author BJ) in helping compounders prepare for the survey process. A list of agencies that offer accreditation and credentialing for compounding pharmacies is included for easy reference. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Expecting the Unexpected: Towards Robust Credential Infrastructure

NASA Astrophysics Data System (ADS)

Xu, Shouhuai; Yung, Moti

Cryptographic credential infrastructures, such as Public key infrastructure (PKI), allow the building of trust relationships in electronic society and electronic commerce. At the center of credential infrastructures is the methodology of digital signatures. However, methods that assure that credentials and signed messages possess trustworthiness and longevity are not well understood, nor are they adequately addressed in both literature and practice. We believe that, as a basic engineering principle, these properties have to be built into the credential infrastructure rather than be treated as an after-thought since they are crucial to the long term success of this notion. In this paper we present a step in the direction of dealing with these issues. Specifically, we present the basic engineering reasoning as well as a model that helps understand (somewhat formally) the trustworthiness and longevity of digital signatures, and then we give basic mechanisms that help improve these notions.

From Legion to Avaki: The Persistence of Vision

DTIC Science & Technology

2006-01-01

person, but what component, is requesting an action. 5.3.1 Authentication Users authenticate themselves to a Legion grid with the login paradigm...password supplied during login is compared to the password in the state of the authentication object in order to permit or deny subsequent access to...In either case, the credential is protected by the security of the underlying operating system. Although login is the most commonly used method

Autophagy-deficient breast cancer shows early tumor recurrence and escape from dormancy

PubMed Central

Aqbi, Hussein F.; Tyutyunyk-Massey, Liliya; Keim, Rebecca C.; Butler, Savannah E.; Thekkudan, Theresa; Joshi, Supriya; Smith, Timothy M.; Bandyopadhyay, Dipankar; Idowu, Michael O.; Bear, Harry D.; Payne, Kyle K.; Gewirtz, David A.; Manjili, Masoud H.

2018-01-01

Breast cancer patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu-overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting response to immunotherapy. We explored two strategies: 1) transient blockade of autophagy with chloroquine (CQ), which blocks fusion of autophagosomes and lysosomes during ADR treatment, and 2) permanent inhibition of autophagy by a stable knockdown of ATG5 (ATG5KD), which inhibits the formation of autophagosomes in MMC during and after ADR treatment. We found that while CQ prolonged tumor dormancy, but that stable knockdown of autophagy resulted in early escape from dormancy and recurrence. Interestingly, ATG5KD MMC contained an increased frequency of ADR-induced polyploid-like cells and rendered MMC resistant to immunotherapy. On the other hand, a transient blockade of autophagy did not affect the sensitivity of MMC to immunotherapy. Our observations suggest that while chemotherapy-induced autophagy may facilitate tumor relapse, cell-intrinsic autophagy delays tumor relapse, in part, by inhibiting the formation of polyploid-like tumor dormancy. PMID:29774126

Mission Management Computer and Sequencing Hardware for RLV-TD HEX-01 Mission

NASA Astrophysics Data System (ADS)

Gupta, Sukrat; Raj, Remya; Mathew, Asha Mary; Koshy, Anna Priya; Paramasivam, R.; Mookiah, T.

2017-12-01

Reusable Launch Vehicle-Technology Demonstrator Hypersonic Experiment (RLV-TD HEX-01) mission posed some unique challenges in the design and development of avionics hardware. This work presents the details of mission critical avionics hardware mainly Mission Management Computer (MMC) and sequencing hardware. The Navigation, Guidance and Control (NGC) chain for RLV-TD is dual redundant with cross-strapped Remote Terminals (RTs) interfaced through MIL-STD-1553B bus. MMC is Bus Controller on the 1553 bus, which does the function of GPS aided navigation, guidance, digital autopilot and sequencing for the RLV-TD launch vehicle in different periodicities (10, 20, 500 ms). Digital autopilot execution in MMC with a periodicity of 10 ms (in ascent phase) is introduced for the first time and successfully demonstrated in the flight. MMC is built around Intel i960 processor and has inbuilt fault tolerance features like ECC for memories. Fault Detection and Isolation schemes are implemented to isolate the failed MMC. The sequencing hardware comprises Stage Processing System (SPS) and Command Execution Module (CEM). SPS is `RT' on the 1553 bus which receives the sequencing and control related commands from MMCs and posts to downstream modules after proper error handling for final execution. SPS is designed as a high reliability system by incorporating various fault tolerance and fault detection features. CEM is a relay based module for sequence command execution.

Mitomycin C: a promising agent for the treatment of canine corneal scarring

PubMed Central

Gupta, Rangan; Yarnall, Benjamin W.; Giuliano, Elizabeth A.; Kanwar, Jagat R.; Buss, Dylan G.; Mohan, Rajiv R.

2012-01-01

Objective To evaluate the safety and efficacy of mitomycin C (MMC) in prevention of canine corneal scarring. Methods With an in vitro approach using healthy canine corneas, cultures of primary canine corneal fibroblasts or myofibroblasts were generated. Primary canine corneal fibroblasts were obtained by growing corneal buttons in minimal essential medium supplemented with 10% fetal bovine serum. Canine corneal myofibroblasts were produced by growing cultures in serum-free medium containing transforming growth factor β1 (1 ng/mL). Trypan blue assay and phase-contrast microscopy were used to evaluate the toxicity of three doses of MMC (0.002%, 0.02% and 0.04%). Real-time PCR, immunoblot, and immunocytochemistry techniques were used to determine MMC efficacy to inhibit markers of canine corneal scarring. Results A single 2-min treatment of 0.02% or less MMC did not alter canine corneal fibroblast or keratocyte phenotype, viability, or growth. The 0.02% dose substantially reduced myofibroblast formation (up to 67%; P < 0.001), as measured by the change in RNA and protein expression of fibrosis biomarkers (α-smooth muscle actin and F-actin). Conclusion This in vitro study suggests that a single 2-min 0.02% MMC treatment to the canine corneal keratocytes is safe and may be useful in decreasing canine corneal fibrous metaplasia. In vivo studies are warranted. PMID:21929607

In vitro assessment of the antimicrobial susceptibility of caprine isolates of Mycoplasma mycoides subsp. capri.

PubMed

Paterna, A; Tatay-Dualde, J; Amores, J; Prats-van der Ham, M; Sánchez, A; de la Fe, C; Contreras, A; Corrales, J C; Gómez-Martín, Á

2016-08-01

The minimum inhibitory concentration (MIC) and minimum mycoplasmacidal concentration (MMC) of 17 antimicrobials against 41 Spanish caprine isolates of Mycoplasma mycoides subsp. capri (Mmc) obtained from different specimens (milk, external auricular canal and semen) were determined using a liquid microdilution method. For half of the isolates, the MIC was also estimated for seven of the antimicrobials using an epsilometric test (ET), in order to compare both methods and assess the validity of ET. Mutations in genes gyrA, gyrB, parC and parE conferring fluoroquinolone resistance, which have been recently described in Mmc, were investigated using PCR. The anatomical origin of the isolate had no effect on its antimicrobial susceptibility. Moxifloxacin and doxycycline had the lowest MIC values. The rest of the fluoroquinolones studied (except norfloxacin), together with tylosin and clindamycin, also had low MIC values, although the MMC obtained for clindamycin was higher than for the other antimicrobials. For all the aminoglycosides, spiramycin and erythromycin, a notable level of resistance was observed. The ET was in close agreement with broth microdilution at low MICs, but not at intermediate or high MICs. The analysis of the genomic sequences revealed the presence of an amino acid substitution in codon 83 of the gene gyrA, which has not been described previously in Mmc. Copyright © 2016 Elsevier Ltd. All rights reserved.

Middle region of FancM interacts with Mhf and Rmi1 in silkworms, a species lacking the Fanconi anaemia (FA) core complex.

PubMed

Sugahara, R; Mon, H; Lee, J M; Kusakabe, T

2014-04-01

The Fanconi anaemia (FA) pathway is responsible for interstrand crosslink (ICL) repair. Among the FA core complex components, FANCM is believed to act as a damage sensor for the ICL-blocked replication fork and also as a molecular platform for FA core complex assembly and interaction with Bloom's syndrome (BS) complex that is thought to play an important role in the processing of DNA structures such as stalled replication forks. In the present study, we found that in silkworms, Bombyx mori, a species lacking the major FA core complex components (FANCA, B, C, E, F, and G), FancM is required for FancD2 monoubiquitination and cell proliferation in the presence of mitomycin C (MMC). Silkworm FancM (BmFancM) was phosphorylated in the middle regions, and the modification was associated with its subcellular localization. In addition, BmFancM interacted with Mhf1, a histone-fold protein, and Rmi1, a subunit of the BS complex, in the different regions. The interaction region containing at least these two protein-binding domains played an essential role in FancM-dependent resistance to MMC. Our results suggest that BmFancM also acts as a platform for recruitment of both the FA protein and the BS protein, although the silkworm genome seems to lose FAAP24, a FancM-binding partner protein in mammals. © 2013 The Royal Entomological Society.

Multiphoton Imaging of Rabbit Cornea Treated with Mitomycin C after Photorefractive Keratectomy

NASA Astrophysics Data System (ADS)

Hsueh, Chiu-Mei; Lo, Wen; Wang, Tsung-Jen; Hu, Fung-Rong; Dong, Chen-Yuan

2007-07-01

In this work we use multiphoton microscopy to observe the post surgery structure variation of rabbit cornea after photorefractive keratectomy (PRK). In addition, we added mitomycin C (MMC) to the post surgery rabbit cornea in order to investigate the effect of MMC treatment on the postoperative regeneration.

Spartan Auxiliary Mount Panel (SPAM): A Metal Matrix Composite Honeycomb Panel for Space Flight Use

NASA Technical Reports Server (NTRS)

Segal, Kenneth N.; Stevens, Edward J.

1998-01-01

This presentation focus on the use of metal matrix composite (MMC) material option in spaceflight hardware applications. It addresses the important questions and issues such as: what is SPAM; why the use of MMC; design requirements and flexibility; qualification testing; and flight concerns.

Region, Locality Characteristics, High School Tracking and Equality in Access to Educational Credentials: The Case of Palestinian Arab Communities in Israel.

ERIC Educational Resources Information Center

Mazawi, Andre Elias

1998-01-01

Examines the effects of regional, locality, and high school characteristics on access opportunities to educational credentials of Palestinian Arab students in Israel. Reveals that while tracking patterns are affected by high school variables at the community level, access to educational credentials is determined by community-level, socioeconomic…

Type of High-School Credentials and Older Age ADL and IADL Limitations: Is the GED Credential Equivalent to a Diploma?

ERIC Educational Resources Information Center

Liu, Sze Yan; Chavan, Niraj R.; Glymour, M. Maria

2013-01-01

Purpose: Educational attainment is a robust predictor of disability in elderly Americans: older adults with high-school (HS) diplomas have substantially lower disability than individuals who did not complete HS. General Educational Development (GED) diplomas now comprise almost 20% of new HS credentials issued annually in the United States but it…

The Perceived Influence of Industry-Sponsored Credentials on the Recruitment Process in the Information Technology Industry: Employer and Employee Perspectives

ERIC Educational Resources Information Center

Bartlett, Kenneth R.; Horwitz, Sujin K.; Ipe, Minu; Liu, Yuwen

2005-01-01

The increase in the number of industry-sponsored credential programs raises many questions for career and technical education. This study investigated the perceived influence of industry-sponsored credentials on the recruitment process in the information technology (IT) field. Influence is examined from the perspective of Human Resource (HR)…

What Is a Bilingual School Psychologist? A National Survey of the Credentialing Bodies of School Psychologists: Implications for the Assessment of Bilinguals

ERIC Educational Resources Information Center

Sotelo-Dynega, Marlene

2015-01-01

The present study explored the credentialing practices for bilingual school psychologists in the United States. Credentialing agencies of school psychologists, mostly State Departments of Education, across the 50 states and the District of Columbia were contacted via telephone by trained graduate student research assistants. Only two of the…

The Earnings of Community College Graduates in California. A CAPSEE Working Paper

ERIC Educational Resources Information Center

Bahr, Peter Riley

2016-01-01

In this study, I draw on longitudinal data for 1.1 million students in California to estimate the effects of community college credentials on students' earnings, as compared with students who are not awarded a credential. In contrast to much of the recent work on this subject, which assumed that the effects of credentials on students' earnings are…

Potential Relationships of Community College Faculty Credentials and Measures of Instructional Effectiveness: Student Survey of Instruction and Grades

ERIC Educational Resources Information Center

Willis, Marc

2017-01-01

The purpose of this research was to determine what, if any, relationship existed when considering instructor credentials in relation to student surveys of instruction (SSOI), instructor credentials in relation to grade distribution, and the relationship between SSOI and grade distribution. The case study college is a two-year rural institution in…

Stackable Credentials: Do They Have Labor Market Value? CCRC Working Paper No. 97

ERIC Educational Resources Information Center

Bailey, Thomas; Belfield, Clive R.

2017-01-01

Stackable credentials--sequential postsecondary awards that allow individuals to progress on a career path--have been suggested as a way to enhance the labor market prospects of middle-skill workers. Yet, thus far, little evidence has been provided on the economic value of these credentials. Here, we report a series of estimates on the association…

Evaluating Evidence-Based Nutrition Support Practice Among Healthcare Professionals With and Without the Certified Nutrition Support Clinician Credential.

PubMed

Brody, Rebecca; Hise, Mary; Marcus, Andrea Fleisch; Harvey-Banchik, Lillian; Matarese, Laura E

2016-01-01

The National Board of Nutrition Support Certification credentials healthcare professionals and certifies that holders of the Certified Nutrition Support Clinician (CNSC) credential have specialized knowledge of safe and effective nutrition support therapy. The purpose of this pilot study was to survey healthcare professionals affiliated with the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) regarding their approaches to nutrition support practice using a complex patient case scenario in accordance with established clinical guidelines. An electronic survey was emailed to individuals affiliated with A.S.P.E.N. Eight multiple-choice knowledge questions addressed evidence-based nutrition support practice issues for a patient with progressing pancreatitis. Demographic and clinical characteristic data were collected. Of 48,093 email invitations sent, 4455 (9.1%) responded and met inclusion criteria. Most respondents were dietitians (70.8%) and in nutrition support practice for 10.3 years, and 29.3% held the CNSC credential. Respondents with the CNSC credential answered 6.18 questions correctly compared with 4.56 for non-CNSC respondents (P < .001). For all 8 questions, CNSC respondents were significantly more likely to choose the correct answer compared with non-CNSC respondents (P < .001). Professionals with the CNSC credential scored significantly higher on a complex case-based knowledge assessment of guideline recommendations for the nutrition support treatment of pancreatitis compared with those without a credential. © 2015 American Society for Parenteral and Enteral Nutrition.

Connect the Credentials: A New Effort Aims to Change the Nation's Fragmented Credentialing System

ERIC Educational Resources Information Center

Pierce, Dennis

2016-01-01

Over the past 30 years, the number of industry certificates awarded by colleges and universities has surged more than 800 percent, according to Lumina Foundation. At the same time, new forms of credentials--such as badges--also have emerged. And while there are more than 4,000 organizations granting certifications in the U.S., fewer than 10…

Every Student Counts. The State We're in: 2016-2017. A Report on Public Education in Illinois

ERIC Educational Resources Information Center

Advance Illinois, 2016

2016-01-01

Illinois has set an ambitious target: 60% of working adults will hold a college degree or credential by 2025, as research suggests that at least 60% of jobs will require some type of educational credential past high school. Today, only 50% of the state's working adults hold college credentials. This report takes a snapshot of Illinois state's…

Accessibility and utilization patterns of a mobile medical clinic among vulnerable populations.

PubMed

Gibson, Britton A; Ghosh, Debarchana; Morano, Jamie P; Altice, Frederick L

2014-07-01

We mapped mobile medical clinic (MMC) clients for spatial distribution of their self-reported locations and travel behaviors to better understand health-seeking and utilization patterns of medically vulnerable populations in Connecticut. Contrary to distance decay literature, we found that a small but significant proportion of clients was traveling substantial distances to receive repeat care at the MMC. Of 8404 total clients, 90.2% lived within 5 miles of a MMC site, yet mean utilization was highest (5.3 visits per client) among those living 11-20 miles of MMCs, primarily for those with substance use disorders. Of clients making >20 visits, 15.0% traveled >10 miles, suggesting that a significant minority of clients traveled to MMC sites because of their need-specific healthcare services, which are not only free but available at an acceptable and accommodating environment. The findings of this study contribute to the important research on healthcare utilization among vulnerable population by focusing on broader dimensions of accessibility in a setting where both mobile and fixed healthcare services coexist. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fatigue testing and damage development in continuous fiber reinforced metal matrix composites

NASA Technical Reports Server (NTRS)

Johnson, W. S.

1988-01-01

A general overview of the fatigue behavior of metal matrix composites (MMC) is presented. The first objective is to present experimental procedures and techniques for conducting a meaningful fatigue test to detect and quantify fatigue damage in MMC. These techniques include interpretation of stress-strain responses, acid etching of the matrix, edge replicas of the specimen under load, radiography, and micrographs of the failure surfaces. In addition, the paper will show how stiffness loss in continuous fiber reinforced metal matrix composites can be a useful parameter for detecting fatigue damage initiation and accumulation. Second, numerous examples of how fatigue damage can initiate and grow in various MMC are given. Depending on the relative fatigue behavior of the fiber and matrix, and the interface properties, the failure modes of MMC can be grouped into four categories: (1) matrix dominated, (2) fiber dominated, (3) self-similar damage growth, and (4) fiber/matrix interfacial failures. These four types of damage will be discussed and illustrated by examples with the emphasis on the fatigue of unnotched laminates.

Studies on mechanical properties of aluminium 6061 reinforced with titanium and E glass fibre metal matrix hybrid composites

NASA Astrophysics Data System (ADS)

Kumar, B. N. Ravi; Vidyasagar, H. N.; Shivanand, H. K.

2018-04-01

2Development of the mmc with fibers and filler materials as a replacement material for some engineering purpose such as automobiles, aerospace are indispensable. Therefore, the studies related to hybrid mmc's of Al6061 were noted in this paper. In this work, Al6061 reinforced with E glass fibers and micro Titanium particles. Hybrid composites was prepared by very feasible and commercially used technique Stir casting and by varying composition of Al6061, Titanium and E-glass fibre. Experiments were done by varying weight fraction of Titanium (0%, 1%, 3% and 5%) and E glass fibre (0%, 1%, 3% and 5%). Wire EDM were used to prepare the specimens required for tensile and hardness according to standards and tests conducted. The proportion of elements which are present the mmc's are identified by EDAX. Optical microscopy were conducted by SU3500 machine Scanning Electron Microscope and Microstructure shows the distribution of reinforced Ti particles and E glass fibres. The characterization of Al6061 hybrid mmc's is having significant impact on the mechanical properties.

Fatigue testing and damage development in continuous fiber reinforced metal matrix composites

NASA Technical Reports Server (NTRS)

Johnson, W. S.

1989-01-01

A general overview of the fatigue behavior of metal matrix composites (MMC) is presented. The first objective is to present experimental procedures and techniques for conducting a meaningful fatigue test to detect and quantify fatigue damage in MMC. These techniques include interpretation of stress-strain responses, acid etching of the matrix, edge replicas of the specimen under load, radiography, and micrographs of the failure surfaces. In addition, the paper will show how stiffness loss in continuous fiber reinforced metal matrix composites can be a useful parameter for detecting fatigue damage initiation and accumulation. Second, numerous examples of how fatigue damage can initiate and grow in various MMC are given. Depending on the relative fatigue behavior of the fiber and matrix, and the interface properties, the failure modes of MMC can be grouped into four categories: (1) matrix dominated, (2) fiber dominated, (3) self-similar damage growth, and (4) fiber/matrix interfacial failures. These four types of damage will be discussed and illustrated by examples with the emphasis on the fatigue of unnotched laminates.

Genome-Wide Mutational Signature of the Chemotherapeutic Agent Mitomycin C in Caenorhabditis elegans.

PubMed

Tam, Annie S; Chu, Jeffrey S C; Rose, Ann M

2015-11-12

Cancer therapy largely depends on chemotherapeutic agents that generate DNA lesions. However, our understanding of the nature of the resulting lesions as well as the mutational profiles of these chemotherapeutic agents is limited. Among these lesions, DNA interstrand crosslinks are among the more toxic types of DNA damage. Here, we have characterized the mutational spectrum of the commonly used DNA interstrand crosslinking agent mitomycin C (MMC). Using a combination of genetic mapping, whole genome sequencing, and genomic analysis, we have identified and confirmed several genomic lesions linked to MMC-induced DNA damage in Caenorhabditis elegans. Our data indicate that MMC predominantly causes deletions, with a 5'-CpG-3' sequence context prevalent in the deleted regions of DNA. Furthermore, we identified microhomology flanking the deletion junctions, indicative of DNA repair via nonhomologous end joining. Based on these results, we propose a general repair mechanism that is likely to be involved in the biological response to this highly toxic agent. In conclusion, the systematic study we have described provides insight into potential sequence specificity of MMC with DNA. Copyright © 2016 Tam et al.

Influence of thermal residual stress on behaviour of metal matrix composites reinforced with particles

NASA Astrophysics Data System (ADS)

Guzmán, R. E.; Hernández Arroyo, E.

2016-02-01

The properties of a metallic matrix composites materials (MMC's) reinforced with particles can be affected by different events occurring within the material in a manufacturing process. The existence of residual stresses resulting from the manufacturing process of these materials (MMC's) can markedly differentiate the curves obtained in tensile tests obtained from compression tests. One of the themes developed in this work is the influence of residual stresses on the mechanical behaviour of these materials. The objective of this research work presented is numerically estimate the thermal residual stresses using a unit cell model for the Mg ZC71 alloy reinforced with SiC particles with volume fraction of 12% (hot-forging technology). The MMC's microstructure is represented as a three dimensional prismatic cube-shaped with a cylindrical reinforcing particle located in the centre of the prism. These cell models are widely used in predicting stress/strain behaviour of MMC's materials, in this analysis the uniaxial stress/strain response of the composite can be obtained through the calculation using the commercial finite-element code.

Fatal intoxication with 3-methyl-N-methylcathinone (3-MMC) and 5-(2-aminopropyl)benzofuran (5-APB).

PubMed

Adamowicz, Piotr; Zuba, Dariusz; Byrska, Bogumiła

2014-12-01

The emergence of a large number of new psychoactive substances (NPSs) in recent years poses a serious problem to clinical and forensic toxicologists. Here we report a patient who administrated ca. 500mg of 3-MMC (3-methyl-N-methylcathinone) and 400mg of 5-APB (5-(2-aminopropyl)benzofuran) in combination with 80g of ethyl alcohol. The clinical manifestations included agitation, seizures, hypertension, tachycardia, hyperthermia and bradycardia. The patient did not recover and died around 4h after the use of drugs. The cause of death was acute cardiovascular collapse that occurred following mixed intoxication with NPSs and alcohol. Toxicological analysis of post-mortem blood revealed 3-MMC and 5-APB in concentrations of 1.6μg/mL and 5.6μg/mL, respectively. Moreover, the serum alcohol concentration was 1.4g/L in ante-mortem sample collected 1h after admission to the hospital. This is the first report on blood concentration of 3-MMC and 5-APB in fatal intoxication. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Dark-Fermentative Biological Hydrogen Production from Mixed Biowastes Using Defined Mixed Cultures.

PubMed

Patel, Sanjay K S; Lee, Jung-Kul; Kalia, Vipin C

2017-06-01

Biological hydrogen (H 2 ) production from the biowastes is widely recognized as a suitable alternative approach to utilize low cost feed instead of costly individual sugars. In the present investigation, pure and mixed biowastes were fermented by defined sets of mixed cultures for hydrolysis and H 2 production. Under batch conditions, up to 65, 67 and 70 L H 2 /kg total solids (2%, TS) were evolved from apple pomace (AP), onion peels (OP) and potato peels (PP) using a combination of hydrolytic mixed culture (MHC5) and mixed microbial cultures (MMC4 or MMC6), respectively. Among the different combinations of mixed biowastes including AP, OP, PP and pea-shells, the combination of OP and PP exhibited maximum H 2 production of 73 and 84 L/kg TS with MMC4 and MMC6, respectively. This study suggested that H 2 production can be effectively regulated by using defined sets of mixed cultures for hydrolysis and H 2 production from pure and mixed biowastes as feed even under unsterile conditions.

Tocolysis for in utero Surgery: Atosiban Performs Distinctly Better than Magnesium Sulfate.

PubMed

Ochsenbein-Kölble, Nicole; Krähenmann, Franziska; Hüsler, Margret; Meuli, Martin; Moehrlen, Ueli; Mazzone, Lucca; Biro, Peter; Zimmermann, Roland

2017-08-17

To compare tocolysis with magnesium sulfate versus atosiban regarding the occurrence of short-term preterm labor and maternal side effects during and after open fetal myelomeningocele (MMC) repair. A prospective nonrandomized cohort study was performed including 30 fetal MMC cases. The first 15 cases (group 1) received magnesium sulfate according to the MOMS protocol. In the following 15 cases (group 2), magnesium sulfate was substituted by atosiban. Chorioamniotic membrane separation (CMS), premature prelabor rupture of the fetal membranes (PPROM), preterm delivery <3 weeks after fetal MMC repair, and maternal complications due to the tocolytic medication were the major endpoints. In both groups, one CMS but no PPROM was diagnosed <3 weeks after fetal MMC repair. One patient of group 2 delivered <3 weeks after fetal MMC repair because of an intraoperative placental abruption at 25 weeks. All women of group 1 showed an electrolyte imbalance during magnesium sulfate administration. One woman of group 1 developed several episodes of a third-degree atrioventricular block within the first 3 days after fetal surgery. Lethargy was found in all women during magnesium sulfate therapy. No maternal side effects were found under atosiban. The use of atosiban resulted in an almost identical short-term uterine outcome without any serious maternal complications as seen when magnesium sulfate was given. Thus, the authors suggest using atosiban instead of magnesium sulfate in the context of open fetal surgery. © 2017 S. Karger AG, Basel.

Conjunctival autografting combined with low-dose mitomycin C for prevention of primary pterygium recurrence.

PubMed

Frucht-Pery, Joseph; Raiskup, Frederic; Ilsar, Michael; Landau, David; Orucov, Faik; Solomon, Abraham

2006-06-01

To compare the clinical outcome of pterygium surgery combining intraoperative mitomycin C (MMC) with a free conjunctival autograft, with three other methods of pterygium surgery, including intraoperative MMC alone, conjunctival autograft alone, and bare sclera without adjunctive treatment. Interventional, randomized and in part nonrandomized, prospective, comparative study. setting: A university medical center department of ophthalmology. One hundred and twenty patients underwent pterygium excision surgery. These patients were divided into four treatment groups. In group 1 (30 patients), MMC, 0.2 mg/ml, was applied for three minutes. In group 2 (30 patients), conjunctival autografting was performed. Group 3 (30 patients) received sodium chloride 0.9% only, and group 4 (30 patients) underwent conjunctival autografting combined with one minute application of MMC, 0.2 mg/ml. Recurrence rates and complications. Pterygium recurred in two patients (6.6%) in group 1, in four patients (13.3%) in group 2, in 14 patients (46.6%) in group 3, and in none of the patients in group 4. chi(2) analysis revealed a significantly lower recurrence rate in group 4 compared with group 2 (P = .038) and with group 3 (P < .0001). Epithelialization of the wounds was complete within 14 days of surgery. No complications were demonstrated in any of the study groups except for one case of minor melting of the flap in group 4. This study indicates that pterygium excision with a free conjunctival autograft combined with intraoperative low-dose MMC is a safe and effective technique in pterygium surgery.

Morbidity and Mortality Conference: Its Purpose Reclaimed and Grounded in Theory.

PubMed

Gregor, Alexander; Taylor, David

2016-01-01

The morbidity and mortality conference (MMC) remains a central activity within the departments of our academic healthcare institutions. It is deeply rooted in the premise that we can learn from our mistakes, thereby improving the care we provide. Recent advances in our understanding of medical error and quality improvement have challenged the value of traditional models of MMC. As a result the purpose of MMC has become clouded and ill-defined: Is it an educational conference that promotes mastery of clinical acumen, or is it a venue to drive quality improvement by addressing systems-based issues in delivering care? Or can it serve both purposes? Review of the history of MMC, the literature, and critical application of education theory demonstrates the source of the confusion and the challenges in viewing it through the exclusive lens of either education or quality improvement. Application of experiential learning theory helps resolve this discord showing how the conference facilitates the development of clinical mastery while informing quality improvement programs about important and relevant systems-based issues. Building on this, we present a model for MMC involving five essential elements: case-based involving an adverse patient event, anonymity for participants, expert guided critical analysis, reframing understanding of the case presentation and related systems-based factors, and projection to practice change. This model builds on previously described models, is grounded in the literature, and helps clarify its role from both the educational and the quality improvement perspectives.

Ex-PRESS outcomes using mitomycin-C, Ologen alone, Ologen with 5-fluorouracil.

PubMed

Menda, Shivali A; Lowry, Eugene A; Porco, Travis C; Stamper, Robert L; Rubin, Michel R; Han, Ying

2015-06-01

To compare the complication rate and effectiveness of mitomycin C (MMC), Ologen alone, and Ologen with 5-fluorouracil (5-FU) as adjunctives with Ex-PRESS mini shunt for medically uncontrolled glaucoma. Retrospective comparative study of 59 Ex-PRESS mini shunt trabeculectomy operations coupled with Ologen implantation alone, transient MMC application or Ologen implantation with 5-FU as adjunctive treatment. Eight eyes (7 patients) received Ologen alone, 37 eyes (34 patients) received MMC, and 14 eyes (14 patients) received Ologen with 5-FU as adjunctive therapy. Baseline characteristics, adjunctive used during operation, along with outcomes including intraocular pressure (IOP), number of anti-hypertensive drops, visual acuity, and complications were documented and compared. The primary outcome was IOP at 12 months. Variables were compared with r × c Fisher tests. The Ologen only group had a significantly higher IOP at 12 months (20.5 ± 10.23 mmHg) compared with Ologen combined with 5-FU (12.2 ± 1.47 mmHg) or MMC (13.8 ± 4.37 mmHg) (p = 0.015, linear mixed model). The Ologen only cohort also had a higher re-operation rate (p = 0.01, Fisher's Exact Test) and higher rate of bleb leak (p = 0.02, Fisher's Exact Test). Visual acuity was similar among all three groups. 5-FU with Ologen is as effective as MMC in maintaining IOP following Ex-PRESS shunt surgery at 1 year. However, Ologen alone may not be as effective as the other two adjunctive agents.

N-succinyl-chitosan as a drug carrier: water-insoluble and water-soluble conjugates.

PubMed

Kato, Yoshinori; Onishi, Hiraku; Machida, Yoshiharu

2004-02-01

N-succinyl-chitosan (Suc-Chi) has favourable properties as a drug carrier such as biocompatibility, low toxicity and long-term retention in the body. It was long retained in the systemic circulation after intravenous administration, and the plasma half-lives of Suc-Chi (MW: 3.4 x 10(5); succinylation degree: 0.81 mol/sugar unit; deacetylation degree: 1.0 mol/sugar unit) were ca. 100.3h in normal mice and 43 h in Sarcoma 180-bearing mice. The biodistribution of Suc-Chi into other tissues was trace apart from the prostate and lymph nodes. The maximum tolerable dose for the intraperitoneal injection of Suc-Chi to mice was greater than 2 g/kg. The water-insoluble and water-soluble conjugates could be prepared using a water-soluble carbodiimide and mitomycin C (MMC) or using an activated ester of glutaric MMC. In vitro release characteristics of these conjugates showed similar patterns, i.e. a pH-dependent manner, except that water-insoluble conjugates showed a slightly slower release of MMC than water-soluble ones. The conjugates of MMC with Suc-Chi showed good antitumour activities against various tumours such as murine leukaemias (L1210 and P388), B16 melanoma, Sarcoma 180 solid tumour, a murine liver metastatic tumour (M5076) and a murine hepatic cell carcinoma (MH134). This review summarizes the utilization of Suc-Chi as a drug carrier for macromolecular conjugates of MMC and the therapeutic efficacy of the conjugates against various tumours.

Genotoxic and Antigenotoxic Assessment of Chios Mastic Oil by the In Vitro Micronucleus Test on Human Lymphocytes and the In Vivo Wing Somatic Test on Drosophila.

PubMed

Vlastos, Dimitris; Drosopoulou, Elena; Efthimiou, Ioanna; Gavriilidis, Maximos; Panagaki, Dimitra; Mpatziou, Krystalenia; Kalamara, Paraskevi; Mademtzoglou, Despoina; Mavragani-Tsipidou, Penelope

2015-01-01

Chios mastic oil (CMO), the essential oil derived from Pistacia lentiscus (L.) var. chia (Duham), has generated considerable interest because of its antimicrobial, anticancer, antioxidant and other beneficial properties. In the present study, the potential genotoxic activity of CMO as well as its antigenotoxic properties against the mutagenic agent mitomycin-C (MMC) were evaluated by employing the in vitro Cytokinesis Block MicroNucleus (CBMN) assay and the in vivo Somatic Mutation And Recombination Test (SMART). In the in vitro experiments, lymphocytes were treated with 0.01, 0.05 and 0.10% (v/v) of CMO with or without 0.05 μg/ml MMC, while in the in vivo assay Drosophila larvae were fed with 0.05, 0.10, 0.50 and 1.00% (v/v) of CMO with or without 2.50 μg/ml MMC. CMO did not significantly increase the frequency of micronuclei (MN) or total wing spots, indicating lack of mutagenic or recombinogenic activity. However, the in vitro analysis suggested cytotoxic activity of CMO. The simultaneous administration of MMC with CMO did not alter considerably the frequencies of MMC-induced MN and wing spots showing that CMO doesn't exert antigenotoxic or antirecombinogenic action. Therefore, CMO could be considered as a safe product in terms of genotoxic potential. Even though it could not afford any protection against DNA damage, at least under our experimental conditions, its cytotoxic potential could be of interest.

Early Evidence from California on Transitions to a Reformed Health Insurance System for Persons Living With HIV/AIDS

PubMed Central

Leibowitz, Arleen A.; Lester, Robbie; Curtis, Philip G.; Farrell, Kevin; Fox, Aaron; Klipp, Luke H.; Wise, Jason

2014-01-01

Background Many uninsured people living with HIV/AIDS (PLWHA) will obtain managed health insurance coverage when the Affordable Care Act (ACA) is implemented in January 2014. Since 2011, California has transitioned PLWHA to Medicaid managed care (MMC) and to the Low Income Health Program (LIHP). Objectives To draw lessons for the ACA implementation from the transitions into MMC and the LIHP. Methods Surveys about clients and services provided before and after the transition to MMC and the LIHP were sent to 43 HIV service providers. Usable responses were obtained from 18 (42%). Results Although total client loads were similar in the pre- (January 2011) and post- transition periods (June 2012), many clients transitioned from fee-for-service (FFS) Medicaid to MMC. Over this period, responding agencies served 43.5% fewer PLWHA in FFS Medicaid while the share of PLWHA covered by MMC rose from 16.9% to 55.5%. Managed care covered a smaller number of services than either FFS Medicaid or Ryan White sites. Ryan White providers reported that 53% of the clients they served in January 2011 had transitioned to the LIHPs. Nonetheless, they continued to provide services to many of these clients and Ryan White cases loads did not decline. Conclusions PLWHA enrolled in Medicaid managed care continue to depend on Ryan White sites to supply the full range of services that will allow them to take full advantage of increased access to care under ACA. PMID:24126449

Vibration-Induced Motor Responses of Infants With and Without Myelomeningocele

PubMed Central

Teulier, Caroline; Smith, Beth A.; Kim, Byungji; Beutler, Benjamin D.; Martin, Bernard J.; Ulrich, Beverly D.

2012-01-01

Background The severity of myelomeningocele (MMC) stems both from a loss of neurons due to neural tube defect and a loss of function in viable neurons due to reduced movement experience during the first year after birth. In young infants with MMC, the challenge is to reinforce excitability and voluntary control of all available neurons. Muscle vibration paired with voluntary movement may increase motoneuron excitability and contribute to improvements in neural organization, responsiveness, and control. Objectives This study examined whether infants with or without MMC respond to vibration by altering their step or stance behavior when supported upright on a treadmill. Design This was a cross-sectional study. Methods Twenty-four 2- to 10-month-old infants, 12 with typical development (TD) and 12 with MMC (lumbar and sacral lesions), were tested. Infants were supported upright with their feet in contact with a stationary or moving treadmill during 30-second trials. Rhythmic alternating vibrations were applied to the right and left rectus femoris muscles, the lateral gastrocnemius muscle, or the sole of the foot. Two cameras and behavior coding were used to determine step count, step type, and motor response to vibration onset. Results Step count decreased and swing duration increased in infants with TD during vibration of the sole of the foot on a moving treadmill (FT-M trials). Across all groups the percentage of single steps increased during vibration of the lateral gastrocnemius muscle on a moving treadmill. Infants with MMC and younger infants with TD responded to onset of vibration with leg straightening during rectus femoris muscle stimulation and by stepping during FT-M trials more often than older infants with TD. Conclusions Vibration seems a viable option for increasing motor responsiveness in infants with MMC. Follow-up studies are needed to identify optimal methods of administering vibration to maximize step and stance behavior in infants. PMID:22228610

In utero repair of myelomeningocele: experimental pathophysiology, initial clinical experience, and outcomes.

PubMed

Farmer, Diana L; von Koch, Cornelia S; Peacock, Warwick J; Danielpour, Moise; Gupta, Nalin; Lee, Hanmin; Harrison, Michael R

2003-08-01

Experimental work raises the possibility that in utero repair of myelomeningocele (MMC) may improve lower extremity, bladder, and bowel function, ameliorate the Arnold-Chiari malformation, and decrease the need for postnatal shunting. We previously developed fetal lamb models to create and reverse lower extremity damage and the Arnold-Chiari malformation in utero. We then applied our extensive experience with fetal surgery, including fetal endoscopic (fetoscopic) surgical manipulation, to develop techniques for MMC repair. A tertiary referral center. All patients treated between 1998 and 2002 for a prenatally diagnosed MMC. Either fetoscopic MMC repair, fetoscopic patch repair, or limited maternal hysterotomy and microsurgical 3-layered fetal MMC repair was performed. Gestational age at delivery, survival, neurologic outcome, and need for ventricular shunting at 1 year. Complete fetoscopic repair was accomplished in 1 fetus. Two other fetuses underwent partial fetoscopic procedures. The remaining 10 patients underwent limited maternal hysterotomy and microsurgical 3-layered fetal MMC repair. Four of 13 patients died, and the mean gestational age at delivery of 11 fetuses born alive was 31 weeks. Five of 9 required ventricular shunting by age 1 year. In 2 patients, lower extremity function improved by more than 2 vertebral levels compared with prenatal ultrasonography. Five of 10 patients who lived longer than 3 weeks required postnatal wound revision within 7 days after birth. Fetoscopic repair, although feasible, does not yet yield optimal surgical results. Open surgical repair before 22 weeks' gestation is physiologically sound and technically feasible. One third of patients appear to be spared the need for a shunt at age 1 year, but improvement in distal neurologic function is less clear. Additionally, fetal mortality is associated with this procedure. Our results complement the data published by groups at Children's Hospital of Philadelphia, in Pennsylvania, and Vanderbilt University, Nashville, Tenn. A National Institutes of Health-sponsored prospective randomized trial is now underway at these 3 centers to compare fetal repair with postnatal repair.

Flow cytometric characterization of the response of Fanconi's anemia cells to mitomycin C treatment.

PubMed

Kaiser, T N; Lojewski, A; Dougherty, C; Juergens, L; Sahar, E; Latt, S A

1982-03-01

DNA flow histogram analysis, using 33342 Hoechst as a stain, has been used to detect the effect of the potentially bifunctional alkylating agent, mitomycin C (MMC) on dermal fibroblasts from patients with Fanconi's anemia (FA), a hereditary human disease characterized by pancytopenia, hypersensitivity to DNA-crosslinking agents, congenital abnormalities and a predisposition for neoplasia. At 24 or 48 hr after a 2-hr exposure to 0.05 or 0.10 micrograms/ml MMC, (3)HdT incorporation was reduced to a greater extent in FA cells than in normal cells. Cells sorted from the last half of S phase showed a slightly greater inhibition of (3)HdT incorporation than did those sorted from the first half of S. Fanconi's anemia cells exhibited a marked accumulation in the G(2) + M peak of flow histograms following exposure to MMC. Twenty-four hr after treatment with .0.5 micrograms/ml MMC, the G(2) + M fraction of FA cells (eight lines) increased to more than 0.5 from a control value of approximately 0.02. Both normals (six lines) and heterozygotes (eight lines) showed, on the average, much less of a G(2) + M increment than did FA cells, even after exposure to 0.1 micrograms/ml MMC. Examination of cells sorted from the G(2) + M peak revealed that MMC-treated FA cells were blocked prior to mitosis. To determine whether the response of FA cells was specific for bifunctional alkylating agent, cells were also treated with ethylmethanesulfonate, a monofunctional agent. Twenty-four hours after exposure to 0.25 or 0.5 mg/ml ethylmethanesulfonate, FA and normal cells showed similar, small increases in the G(2) + M peak. The results suggest the utility of flow cytometry in the diagnostic evaluation of fibroblasts from patients suspected of having Fanconi's anemia.

A randomized trial of adjuvant endocrine therapy, chemotherapy, and chemoendocrine therapy for operable breast cancer stratified by estrogen receptors.

PubMed

Nomura, Y; Tashiro, H; Hisamatsu, K; Shinozuka, K

1988-06-01

Based on estrogen receptor (ER) status and menopausal status, operable breast cancer (International Union Against Cancer [UICC] Stage I, II, and III) patients were randomized for adjuvant endocrine therapy, chemotherapy, and chemoendocrine therapy, and the effects on the disease-free survival (DFS) and overall survival (OS) were compared. Adjuvant endocrine therapy was composed of tamoxifen (TAM) 20 mg/day orally for 2 years in postmenopausal patients. In premenopausal patients, oophorectomy (OVEX) was done before TAM administration. In the chemotherapy arm, the patients were given 0.06 mg/kg of body weight of mitomycin C (MMC) intravenously (IV) and then an oral administration of cyclophosphamide (CPA) 100 mg/body orally in an administration of a 3-month period and a 3-month intermission. This 6-month schedule was repeated four times in 2 years. As the chemoendocrine therapy arm, TAM with MMC + CPA chemotherapy was added. The patients were randomized according to ER and menopausal status. Estrogen receptor-positive (ER+) cancer patients were randomized to three arms: TAM +/- OVEX, MMC + CPA, or MMC + CPA + TAM. For estrogen receptor-negative (ER-) patients, there were two arms: MMC + CPA, or MMC + TAM. The study started in September 1978, and 692 patients entered until the end of 1984 were evaluated. The median follow-up was about 46 months. Totally, a 9.8% rate (68/692) of recurrence was noted, a 7.5% rate (52/692) of mortality. There were no significant differences in DFS or OS among the treatment arms in ER+ or ER- patients. There was significant differences in adverse effects such as bone marrow suppression, gastrointestinal disturbances, cystitis, hair loss between endocrine therapy and chemotherapy or chemoendocrine therapy groups. In this preliminary study, it was concluded that because of less adverse effects of endocrine therapy, it seems rational to select the operable breast cancer patients by the presence or absence of ER, namely, endocrine therapy for ER+ and chemotherapy for ER- cancer patients.

Femtosecond-Assisted LASIK Versus PRK: Comparison of 6-Month Visual Acuity and Quality Outcome for High Myopia.

PubMed

Hashemi, Hassan; Miraftab, Mohammad; Ghaffari, Reza; Asgari, Soheila

2016-11-01

To compare the results of femtosecond-assisted laser in situ keratomileusis (femto-LASIK) and photorefractive keratectomy with mitomycin C (PRK-MMC) for the correction of myopia more than 7.0 diopters (D). In this comparative nonrandomized trial, 60 eyes (30 eyes in each group) were enrolled. Patients were tested for uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction spherical equivalent, ocular and corneal aberrations, and contrast sensitivity (CS) before surgery and at 3 and 6 months postoperatively. Mean preoperative myopia was -8.65±1.51 and -8.04±1.70 D in the femto-LASIK and PRK-MMC groups, respectively (P=0.149). Intergroup differences in baseline indices were not statistically significant. At 6 months after surgery, UDVA showed an improving trend, but it was better in the femto-LASIK group (P=0.026). CDVA in the two groups remained similarly unchanged (P=0.170). For the femto-LASIK and PRK-MMC groups, the safety indices were 1.01±0.05 and 1.01±0.14 (P=0.949), respectively, and the efficacy indices were 0.99±0.07 and 0.93±0.22 (P=0.192), respectively. Comparing CS, only CS18 showed a significantly greater decrease in the femto-LASIK group compared with the PRK-MMC group (P=0.016). Intergroup differences were not statistically significant in other spatial frequencies. Changes in the ocular and corneal higher order aberrations were not statistically different between the two groups except ocular coma, which increased in the femto-LASIK group (P=0.041). Femto-LASIK improves UDVA better than PRK-MMC in high myopia. However, because of increased coma, the quality of vision is reduced. In other words, visual acuity outcome is better with femto-LASIK and visual quality outcome is better with PRK-MMC.

Astaxanthin down-regulates Rad51 expression via inactivation of AKT kinase to enhance mitomycin C-induced cytotoxicity in human non-small cell lung cancer cells.

PubMed

Ko, Jen-Chung; Chen, Jyh-Cheng; Wang, Tai-Jing; Zheng, Hao-Yu; Chen, Wen-Ching; Chang, Po-Yuan; Lin, Yun-Wei

2016-04-01

Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects, including anti-inflammatory and anti-cancer properties. However, the molecular mechanism of astaxanthin-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination, and studies show that chemo-resistant carcinomas exhibit high levels of Rad51 expression. In this study, astaxanthin treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1703. Astaxanthin treatment (2.5-20 μM) decreased Rad51 expression and phospho-AKT(Ser473) protein level in a time and dose-dependent manner. Furthermore, expression of constitutively active AKT (AKT-CA) vector rescued the decreased Rad51 mRNA and protein levels in astaxanthin-treated NSCLC cells. Combined treatment with phosphatidylinositol 3-kinase (PI3K) inhibitors (LY294002 or wortmannin) further decreased the Rad51 expression in astaxanthin-exposed A549 and H1703 cells. Knockdown of Rad51 expression by transfection with si-Rad51 RNA or cotreatment with LY294002 further enhanced the cytotoxicity and cell growth inhibition of astaxanthin. Additionally, mitomycin C (MMC) as an anti-tumor antibiotic is widely used in clinical NSCLC chemotherapy. Combination of MMC and astaxanthin synergistically resulted in cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced phospho-AKT(Ser473) level and Rad51 expression. Overexpression of AKT-CA or Flag-tagged Rad51 reversed the astaxanthin and MMC-induced synergistic cytotoxicity. In contrast, pretreatment with LY294002 further decreased the cell viability in astaxanthin and MMC co-treated cells. In conclusion, astaxanthin enhances MMC-induced cytotoxicity by decreasing Rad51 expression and AKT activation. These findings may provide rationale to combine astaxanthin with MMC for the treatment of NSCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

Mitomycin-C- or Cisplatin-Based Chemoradiotherapy for Anal Canal Carcinoma: Long-Term Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olivatto, Luis O., E-mail: olivatto@inca.gov.b; Cabral, Vania; Rosa, Arthur

2011-02-01

Purpose: To evaluate the long-term efficacy of concurrent radiotherapy with mitomycin-C (MMC)-based or cisplatin (CP)-based combinations in a cohort of patients with locally advanced anal canal carcinoma. Methods and Materials: Between 1988 and 2000, 179 patients with locally advanced anal canal carcinoma were treated at the Instituto Nacional de Cancer with two cycles of chemotherapy during Weeks 1 and 5 of radiotherapy. 5-Fluorouracil (750 mg/m{sup 2} 120-hour infusion or 1,000 mg/m{sup 2} 96-hour infusion) plus CP (100 mg/m{sup 2}) on the first day of each cycle or MMC (10-15 mg/m{sup 2}) on the first day of Cycle 1 was administeredmore » concurrent with radiotherapy (total dose, 55-59.4 Gy). Of the 179 patients, 60% were included from a randomized trial initiated at the Instituto Nacional de Cancer in 1991 that compared concurrent chemoradiotherapy with MMC vs. CP. Results: The median follow-up for the whole chemoradiotherapy group was 83 months. The median patient age was 58 years, 57% had Stage T3-T4 tumors, and 35% had N-positive disease. The 5-year cumulative colostomy rate was not significantly different between the CP group (22%) and MMC group (29%; p = .28). The actuarial 10-year overall survival and disease-free survival rate for the CP group was 54% and 49% and for the MMC group was 52% and 53%, respectively (p = .32 and p = .92, respectively). On multivariate analysis, male gender (p = .042) and advanced Stage T3-T4 disease (p <.0001) were statistically significant for worse disease-free survival. Stage T3-T4 (p = .039) and N+ (p = .039) disease remained independently significant for overall survival. Conclusion: Long-term follow-up has confirmed the good results of chemoradiotherapy with CP plus 5-fluorouracil, which seem to provide results equivalent to those with MMC plus 5-fluorouracil.« less

Intraoperative Injection vs Sponge-applied Mitomycin C during Trabeculectomy: One-year Study.

PubMed

S Khouri, Albert; Huang, Grace; Y Huang, Linda

2017-01-01

To determine the safety and efficacy of intraoperative injection of mitomycin C (MMC) against conventional sponge-applied MMC during trabeculectomy. This study was a retrospective, comparative case series. Thirty eyes with primary open-angle glaucoma underwent consecutive trabeculectomies with MMC injection (injection group), and thirty eyes with sponge-applied MMC were as controls (sponge group). Data were collected preoperatively and postoperatively at 1 day, 1 week, 1 month, 3 months, 6 months, and 1 year after surgery. Demographic data, applanation intraocular pressure (IOP), best-corrected visual acuity (VA), number of glaucoma medications, postoperative interventions, postoperative complications, and number of visits within 3 months were recorded. In order to stratify data, proportion of eyes achieving >30% IOP reduction from baseline with or without glaucoma medications was calculated and defined as surgical success. Mean IOP reduction at 1 year was significant in both the injection and sponge groups from baseline (46.8 and 37.8% respectively). The injection group had overall lower postoperative IOP and comparable complete treatment success, defined as achieving >30% IOP reduction without glaucoma medications (p = 0.941). The number of postoperative visits within 3 months and the proportion of eyes needing 5-fluorouracil (5-FU) intervention were significantly lower in the injection group (p = 0.03, p = 0.04 respectively). Injection of MMC was as safe and effective as sponge application with comparable estimated complete treatment success, less need for visits within 3 months, and 5-FU intervention. Surgeons may consider intraopera-tive injection of MMC in appropriate patient cohorts given comparable safety and efficacy and several advantages over traditional sponge application. Further study in a prospective, larger, long-term manner is necessary to assess this modality. How to cite this article: Khouri AS, Huang G, Huang LY. Intraoperative Injection vs Sponge-applied Mitomycin C during Trabeculectomy: One-year Study. J Curr Glaucoma Pract 2017;11(3):101-106.

Locoregional mitomycin C injection for esophageal stricture after endoscopic submucosal dissection.

PubMed

Machida, H; Tominaga, K; Minamino, H; Sugimori, S; Okazaki, H; Yamagami, H; Tanigawa, T; Watanabe, K; Watanabe, T; Fujiwara, Y; Arakawa, T

2012-06-01

This prospective study aimed to evaluate the feasibility and safety of locoregional mitomycin C (MMC) injection to treat refractory esophageal strictures after endoscopic submucosal dissection (ESD) for superficial esophageal carcinoma. Patients with dysphagia and strictures that were refractory to repeated endoscopic balloon dilation (EBD) were eligible. After EBD, MMC was injected into the dilated site. Between June 2009 and August 2010, five patients were recruited. The treatment was performed once in two patients and twice in three patients with recurrent dysphagia or restenosis. In all patients, passing a standard endoscope through the site was easy and the dysphagia grade improved (grade 3→1 in 3 patients, grade 4→2 in 2 patients). No serious complications were noted. During the observation period of 4.8 months, neither recurrent dysphagia nor re-stricture appeared in any of the patients. The combination of locoregional MMC injections and EBD is feasible and safe for the treatment of esophageal strictures after ESD.Recently, endoscopic submucosal dissection (ESD) has been developed and accepted as a new endoscopic treatment for gastrointestinal tumors. ESD is a promising treatment for superficial esophageal carcinoma (SEC), and it has a reliable en bloc resection rate. However, the application of ESD for widespread lesions is challenging because of the high risk of the development of severe strictures, which lead to a low quality of life after ESD. Although endoscopic balloon dilation (EBD) is effective for benign strictures, it needs to be performed frequently until the dysphagia disappears 1. Mitomycin C (MMC), which is a chemotherapeutic agent derived from some Streptomyces species 2, reduces scar formation when topically applied to a surgical lesion. MMC has been applied to treat strictures in a variety of anatomical locations, including a variety of organs 3. The aim of this study was to prospectively evaluate both the feasibility and the safety of locoregional MMC injection therapy in patients with refractory esophageal strictures after ESD for SEC. © Georg Thieme Verlag KG Stuttgart · New York.

Topical infliximab for the suppression of wound healing following experimental glaucoma filtration surgery

PubMed Central

Turgut, Burak; Eren, Kenan; Akın, Mehmet Mustafa; Demir, Tamer; Kobat, Sabiha

2014-01-01

Background The purpose of this work was to look into the effects of infliximab on wound healing in experimental glaucoma filtration surgery and to compare the antifibrotic effects of this agent to that of mitomycin-C (MMC). Methods Twenty-eight male New Zealand White rabbits were randomly assigned to four groups, each including seven rabbits: control group, sham group, MMC group, and infliximab group. The rabbits in the control group were not operated on and did not receive any treatment. The rabbits in the sham group underwent trabeculectomy and had one drop of saline instilled four times a day for 14 days. The rabbits in the MMC treatment group underwent trabeculectomy, and a sponge soaked in 0.4 mg/mL MMC was applied intraoperatively to the scleral surgical site for three minutes. The rabbits in the infliximab treatment group underwent trabeculectomy and one drop of 10 mg/mL infliximab was instilled four times a day for 14 days after surgery. On day 14 of the experiment, the operated and control eyes were enucleated and histologically and immunohistochemically analyzed. Results The mean fibroblast and mononuclear cell (MNC) numbers and the mean immunostaining intensities of transforming growth factor-β (TGF-β), fibroblast growth factor-β (FGF-β), and platelet-derived growth factor (PDGF) in the sham group were higher than those of the control group (P<0.01). The mean fibroblast and MNC numbers and the mean immunostaining intensities of TGF-β, FGF-β, and PDGF in the MMC and infliximab groups were statistically significantly lower than those of the sham group (P<0.01). The mean fibroblast and MNC numbers and the mean TGF-β, FGF-β, and PDGF immunostaining intensities of the MMC and infliximab groups were similar (P>0.05). Conclusion Our study suggests that topical infliximab effectively suppresses the subconjunctival wound healing response after experimental glaucoma filtration surgery, reducing the MNC and fibroblast numbers and immunostaining intensities of TGF-β, FGF-β, and PDGF. PMID:24851041

Practice-based learning and improvement: a two-year experience with the reporting of morbidity and mortality cases by general surgery residents.

PubMed

Falcone, John L; Lee, Kenneth K W; Billiar, Timothy R; Hamad, Giselle G

2012-01-01

The Accreditation Council for Graduate Medical Education (ACGME) core competency of practice-based learning and improvement can be assessed with surgical Morbidity and Mortality Conference (MMC). We aim to describe the MMC reporting patterns of general surgery residents, describe the adverse event rate for patients and compare that with existing published rates, and describe the nature of our institutional adverse events. We hypothesize that reporting patterns and incidence rates will remain constant over time. In this retrospective cohort study, archived MMC case lists were evaluated from January 1, 2009 to December 31, 2010. The reporting patterns of the residents, the adverse event ratios, and the specific categories of adverse events were described over the academic years. χ(2) and Fisher's exact tests were used to compare across academic years, using an α = 0.05. There were 85 surgical MMC case lists evaluated. Services achieved a reporting rate above 80% (p < 0.001). The most consistent reporting was done by postgraduate year (PGY) 5 level chief residents for all services (p > 0.05). Out of 11,368 patients evaluated from complete MMC submissions, 289 patients had an adverse event reported (2.5%). This was lower than published reporting rates for patient adverse event rates (p < 0.001). Adverse event rates were consistent for residents at the postgraduate year 2, 4, and 5 levels for all services (p > 0.05). Over 2 years, 522 adverse events were reported for 461 patients. A majority of adverse events were from death (24.1%), hematologic and/or vascular events (16.7%), and gastrointestinal system events (16.1%). Surgery resident MMC reporting patterns and adverse event rates are generally stable over time. This study shows which adverse event cases are important for chief residents to report. Copyright © 2012 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Employer Perceptions of Associate Degrees in Local Labor Markets: A Case Study of the Employment of Information Technology Technicians in Detroit and Seattle. CCRC Working Paper No. 39

ERIC Educational Resources Information Center

Van Noy, Michelle; Jacobs, James

2012-01-01

While promoting postsecondary credential completion is a national priority intended to help graduates secure good jobs, the value of credentials in the labor market from the perspective of employers is not well understood. Specifically, more attention is needed to understand how credentials align with employer needs. Through in-depth interviews…

Transfected MDCK cell line with enhanced expression of CYP3A4 and P-glycoprotein as a model to study their role in drug transport and metabolism.

PubMed

Kwatra, Deep; Budda, Balasubramanyam; Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K

2012-07-02

The aim of this study was to characterize and utilize MDCK cell line expressing CYP3A4 and P-glycoprotein as an in vitro model for evaluating drug-herb and drug-drug of abuse interactions. MDCK cell line simultaneously expressing P-gp and CYP3A4 (MMC) was developed and characterized by using expression and activity studies. Cellular transport study of 200 μM cortisol was performed to determine their combined activity. The study was carried across MDCK-WT, MDCK-MDR1 and MMC cell lines. Similar studies were also carried out in the presence of 50 μM naringin and 3 μM morphine. Samples were analyzed by HPLC for drug and its CYP3A4 metabolite. PCR, qPCR and Western blot studies confirmed the enhanced expression of the proteins in the transfected cells. The Vivid CYP3A4 assay and ketoconazole inhibition studies further confirmed the presence of active protein. Apical to basal transport of cortisol was found to be 10- and 3-fold lower in MMC as compared to MDCK-WT and MDCK-MDR1 respectively. Higher amount of metabolite was formed in MMC than in MDCK-WT, indicating enhanced expression of CYP3A4. Highest cortisol metabolite formation was observed in MMC cell line due to the combined activities of CYP3A4 and P-gp. Transport of cortisol increased 5-fold in the presence of naringin in MMC and doubled in MDCK-MDR1. Cortisol transport in MMC was significantly lower than that in MDCK-WT in the presence of naringin. The permeability increased 3-fold in the presence of morphine, which is a weaker inhibitor of CYP3A4. Formation of 6β-hydroxy cortisol was found to decrease in the presence of morphine and naringin. This new model cell line with its enhanced CYP3A4 and P-gp levels in addition to short culture time can serve as an invaluable model to study drug-drug interactions. This cell line can also be used to study the combined contribution of efflux transporter and metabolizing enzymes toward drug-drug interactions.

TRANSFECTED MDCK CELL LINE WITH ENHANCED EXPRESSION OF CYP3A4 AND P-GLYCOPROTEIN AS A MODEL TO STUDY THEIR ROLE IN DRUG TRANSPORT AND METABOLISM

PubMed Central

Kwatra, Deep; Budda, Balasubramanyam; Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K.

2012-01-01

The aim of this study was to characterize and utilize MDCK cell line expressing CYP3A4 and P-glycoprotein as an in vitro model for evaluating drug-herb and drug-drugs of abuse interactions. MDCK cell line simultaneously expressing P-gp and CYP3A4 (MMC) was developed and characterized by using expression and activity studies. Cellular transport study of 200 μM cortisol was performed to determine their combined activity. The study was carried across MDCK-WT, MDCK-MDR1 and MMC cell lines. Similar studies were also carried out in the presence of 50 μM naringin and 3 μM morphine. Samples were analyzed by HPLC for drug and its CYP3A4 metabolite. PCR, qPCR and western blot studies confirmed the enhanced expression of the proteins in the transfected cells. The vivid CYP3A4 assay and ketoconazole inhibition studies further confirmed the presence of active protein. Apical to basal transport of cortisol was found to be ten and three fold lower in MMC as compared to WT and MDCKMDR1 respectively. Higher amount of metabolite was formed in MMC than in MDCK-WT indicating enhanced expression of CYP3A4. Highest cortisol metabolite formation was observed in MMC cell line due to the combined metabolic activities of CYP3A4 and P-gp. Transport of cortisol increased fivefold in presence of naringin in MMC and doubled in MDCKMDR1. Cortisol transport in MMC was significantly lower than that in WT in presence of naringin. The permeability increased three fold in presence of morphine which is a weaker inhibitor of CYP3A4. Formation of 6β-hydroxy cortisol was found to decrease in presence of morphine and naringin. This new model cell line with its enhanced CYP3A4 and P-gp levels in addition to short culture time can serve as an invaluable model to study drug-drug interactions. This cell line can also be used to study the combined contribution of efflux transporter and metabolizing enzymes towards drug-drug interactions. PMID:22676443

Structure-activity relationships of the melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH(2) at the mouse melanocortin receptors: part 2 modifications at the Phe position.

PubMed

Holder, Jerry Ryan; Bauzo, Rayna M; Xiang, Zhimin; Haskell-Luevano, Carrie

2002-07-04

The melanocortin pathway is an important participant in skin pigmentation, steroidogenesis, obesity, energy homeostasis and exocrine gland function. The centrally located melanocortin-3 and melanocortin-4 receptors (MC3R, MC4R) are involved in the metabolic and food intake aspects of energy homeostasis and are stimulated by melanocortin agonists such as alpha-melanocyte stimulation hormone (alpha-MSH). The melanocortin agonists contain the putative message sequence "His-Phe-Arg-Trp," and it has been well-documented that inversion of chirality of the Phe to DPhe results in a dramatic increase in melanocortin receptor potency. Herein, we report a tetrapeptide library, based upon the template Ac-His-DPhe-Arg-Trp-NH(2), consisting of 26 members that have been modified at the DPhe(7) position (alpha-MSH numbering) and pharmacologically characterized for agonist and antagonist activity at the mouse melanocortin receptors MC1R, MC3R, MC4R, and MC5R. The most notable results of this study include the identification of the tetrapeptide Ac-His-(pI)DPhe-Arg-Trp-NH(2) that is a full nanomolar agonist at the mMC1 and mMC5 receptors, a mMC3R partial agonist with potent antagonist activity (pA(2) = 7.25, K(i) = 56 nM) and, but unexpectedly, is a potent agonist at the mMC4R (EC(50) = 25 nM). This ligand possesses novel melanocortin receptor pharmacology, as compared to previously reported peptides, and is potentially useful for in vivo studies to differentiate MC3R vs MC4R physiological roles in animal models, such as primates, where "knockout" animals are not viable options. The DNal(2') substitution for DPhe resulted in a mMC3R partial agonist with antagonist activity (pA(2) = 6.5, K(i) = 295 nM) and a mMC4R (pA(2) = 7.8, K(i) = 17 nM) antagonist possessing 60- and 425-fold decreased potency, respectively, as compared with SHU9119 at these receptors. Examination of this DNal(2')-containing tetrapeptide at the F254S and F259S mutant mMC4Rs resulted in agonist activity of this mMC4R tetrapeptide antagonist, similar to that observed for the SHU9119 peptide, supporting our previously proposed hypothesis that the Phe 254 and 259 transmembrane six receptor residues are important for differentiating melanocortin sequence-based MC4R antagonists vs the agouti-related protein (AGRP) sequence-based antagonists.

Pediatric PRK (PhotoRefractive Keratectomy) with Mitomycin C (MCC) for Persistent Anisometropic Amblyopia. A Case Report.

PubMed

Crawford, Courtney M; Frazier, Travis C; Torres, Mark F; Arnold, Robert W; Mazzoli, Robert A; Raymond, William R

2012-01-01

To evaluate the safety and efficacy of photorefractive keratectomy (PRK) with Mitomycin C (MMC) for the treatment of severe pediatric anisometropia and amblyopia resistant to more conservative treatment modalities. A 3 year-old-child, who at 18 months old underwent unilateral diode laser treatment for threshold ROP, developed 11 diopters of anisometropic myopia and secondary dense amblyopia of the Right Eye. Only after all conservative treatment options failed was he treated with PRK and MMC. Principal outcome measures included cycloplegic refraction, the amount of refractive correction, degree of corneal haze and change in visual acuity. On presentation: BCVA: 20/CF OD; 20/30 OS. CRNS: -11.50 diopters sphere OD; -0.50 diopters sphere OS. Unilateral PRK followed by application of MMC (0.2 mg/ml) for 1 min was performed under general anesthesia. Three-month postoperative findings include: VA: 20/30 OD; 20/25 OS. CRNS: +0.25 diopters sphere OD. At one year, the BCVA remained equal at the 20/30 level despite mild myopic regression OD. CRNS OD at one year was -1.25 +050 x 116. No corneal haze was appreciated. In this child, treatment with PRK and MMC safely reduced the anisometropia thus facilitating his visual rehabilitation. While encouraging, further study is required to verify the longer term results of this single case. To evaluate the safety and efficacy of photorefractive keratectomy (PRK) with Mitomycin C (MMC) for the treatment of severe pediatric anisometropia and amblyopia resistant to more conservative treatment modalities. A 3 year-old-child, who at 18 months old underwent unilateral diode laser treatment for threshold ROP, developed 11 diopters of anisometropic myopia and secondary dense amblyopia of the Right Eye. Only after all conservative treatment options failed was he treated with PRK and MMC. Principal outcome measures included cycloplegic refraction, the amount of refractive correction, degree of corneal haze and change in visual acuity. On presentation: BCVA: 20/CF OD; 20/30 OS. CRNS: -11.50 diopters sphere OD; -0.50 diopters sphere OS. Unilateral PRK followed by application of MMC (0.2 mg/ml) for 1 min was performed under general anesthesia. Three-month postoperative findings include: VA: 20/30 OD; 20/25 OS. CRNS: +0.25 diopters sphere OD. At one year, the BCVA remained equal at the 20/30 level despite mild myopic regression OD. CRNS OD at one year was -1.25 +050 x 116. No corneal haze was appreciated. In this child, treatment with PRK and MMC safely reduced the anisometropia thus facilitating his visual rehabilitation. While encouraging, further study is required to verify the longer term results of this single case.

Private credentialing of health care personnel: an antitrust perspective. Part Two.

PubMed

Havighurst, C C; King, N M

1983-01-01

Having argued in Part One against extensive judicial or regulatory interference with private personnel credentialing in the health care field, this Article now shifts its focus to emphasize the anticompetitive hazards inherent in credentialing as practiced by professional interests. Competitor-sponsored credentialing is shown to be a vital part of a larger cartel strategy to curb competition by standardizing personnel and services and controlling the flow of information to health care consumers. Instead of altering the conclusions reached in Part One, however, Part Two sets forth a new and hitherto unexplored agenda for antitrust enforcement, one that the authors believe will increase the quantity and quality of information available to consumers and offer a fairer competitive environment to individuals and groups disadvantaged by the denial of desirable credentials. The specific targets singled out for antitrust scrutiny are (1) the practice of "grandfathering," by which new candidates for credentials are required to meet tougher requirements than were met by existing credential holders; (2) agreements to standardize educational programs if they go beyond setting and applying accrediting standards and impair the freedom of institutions to decide independently whether to offer unaccredited training; (3) agreements by which independent certifying or accrediting bodies limit the nature or scope of competition among themselves; and (4) mergers and joint ventures in credentialing and accrediting. The legal theory supporting antitrust attacks in the latter two categories is strengthened by the apparently original insight that commercial information and opinion are themselves articles of commerce such that agreements and combinations restricting their nature and output can be characterized as restraints of trade. Among the many self-regulatory institutions in the health care field whose operation or sponsorship is called into question by the analysis herein are the leading medical specialty boards, the Liaison Committee on Medical Education, various accrediting and certifying bodies in the allied health occupations, and the Joint Commission on Accreditation of Hospitals.

Aerodynamic characteristics of several launch configurations utilizing the Titan 3 L booster and MMC DTO-7 Orbiter

NASA Technical Reports Server (NTRS)

Michna, D. J.

1972-01-01

The .00429 scale model Titan 3 booster was mated with the DTO-7 space shuttle orbiter with drop tanks and tested for aerodynamic performance in a 14 x 14 inch trisonic wind tunnel. Six component aerodynamic force and moment data were measured on several variations of the above component in a launch configuration over a Mach number range from 0.6 to 3.48. Angle of attack ranged from -12 deg to 12 deg at 0 deg and -6 deg sideslip angle and sideslip angle ranged from -12 deg to 12 deg at 0 deg angle of attack. Date are presented in plotted form in both the stability and body axis system.

Credentialing Requirements: A Summary of the Thirty-One Professions Supervised by the Board of Regents and Administered by the New York State Education Department.

ERIC Educational Resources Information Center

New York State Education Dept., Albany.

The basic requirements for credentialing in 31 professions supervised by the Board of Regents and administered by the New York State Department of Education are listed. Not every requirement is cited, and a more detailed statement of the credentialing requirements for these professions may be found in Title VIII of the Education Law and in the…

Veterans’ Health Care: Improved Oversight of Community Care Physicians Credentials Needed

DTIC Science & Technology

2016-09-01

Physicians’ Credentials Needed What GAO Found GAO found that the Department of Veterans Affairs’ (VA) contractors —Health Net Federal Services (Health...program, but were deficient in doing so under another program. Based on GAO’s review of selected physicians, GAO found that the contractors almost...program consistent with the requirements of the contract. In contrast, the contractors did not always verify credentials of the physicians in the

Making more matrix: enhancing the deposition of dermal-epidermal junction components in vitro and accelerating organotypic skin culture development, using macromolecular crowding.

PubMed

Benny, Paula; Badowski, Cedric; Lane, E Birgitte; Raghunath, Michael

2015-01-01

Skin is one of the most accessible tissues for experimental biomedical sciences, and cultured skin cells represent one of the longest-running clinical applications of stem cell therapy. However, culture-generated skin mimetic multicellular structures are still limited in their application by the time taken to develop these constructs in vitro and by their incomplete differentiation. The development of a functional dermal-epidermal junction (DEJ) is one of the most sought after aspects of cultured skin, and one of the hardest to recreate in vitro. At the DEJ, dermal fibroblasts and epidermal keratinocytes interact to form an interlinked basement membrane of extracellular matrix (ECM), which forms as a concerted action of both keratinocytes and fibroblasts. Successful formation of this basement membrane is essential for take and stability of cultured skin autografts. We studied interactive matrix production by monocultures and cocultures of primary human keratinocytes and fibroblasts in an attempt to improve the efficiency of basement membrane production in culture using mixed macromolecular crowding (mMMC); resulting ECM were enriched with the deposition of collagens I, IV, fibronectin, and laminin 332 (laminin 5) and also in collagen VII, the anchoring fibril component. Our in vitro data point to fibroblasts, rather than keratinocytes, as the major cellular contributors of the DEJ. Not only did we find more collagen VII production and deposition by fibroblasts in comparison to keratinocytes, but also observed that decellularized fibroblast ECM stimulated the production and deposition of collagen VII by keratinocytes, over and above that of keratinocyte monocultures. In confrontation cultures, keratinocytes and fibroblasts showed spontaneous segregation and demarcation of cell boundaries by DEJ protein deposition. Finally, mMMC was used in a classical organotypic coculture protocol with keratinocytes seeded over fibroblast-containing collagen gels. Applied during the submerged phase, mMMC was sufficient to accelerate the emergence of collagen VII along the de novo DEJ, together with stronger transglutaminase activity in the neoepidermis. Our findings corroborate the role of fibroblasts as important players in producing collagen VII and inducing collagen VII deposition in the DEJ, and that macromolecular crowding leads to organotypic epidermal differentiation in tissue culture in a significantly condensed time frame.

Medicaid Managed Care Structures and Care Coordination.

PubMed

Gilchrist-Scott, Douglas H; Feinstein, James A; Agrawal, Rishi

2017-09-01

Child enrollment in Medicaid managed care (MMC) has expanded dramatically, primarily through state mandates. Care coordination is a key metric in MMC evaluation because it drives much of the proposed cost savings and may be associated with improved health outcomes and utilization. We evaluated the relationships between enrollment in 2 MMC structures, primary care case management (PCCM) and health maintenance organization (HMO) and access to and receipt of care coordination by children. Using data from the 2011/2012 National Survey of Children's Health and the Medicaid Statistical Information System state data mart, we conducted a retrospective, cross-sectional analysis of the relationships between fee-for-service, PCCM or HMO enrollment, and access to and receipt of care coordination. State-level univariate analyses and individual and state multilevel multivariable analyses evaluated correlations between MMC enrollment and care coordination, controlling for demographic characteristics and state financing levels. In univariate and multilevel multivariable analyses, the PCCM penetration rate was significantly associated with increased access to care coordination (adjusted odds ratio: 1.23, P = .034) and receipt of care coordination (adjusted odds ratio: 1.37, P = .02). The HMO penetration rate was significantly associated with lower access to care coordination (adjusted odds ratio: 0.85, P = .05) and receipt of care coordination (adjusted odds ratio: 0.71, P < .001). Fee-for-service served as the referent. State utilization of MMC varied widely. These data suggest that care coordination may be more effective in PCCM than HMO structures. States should consider care coordination outcomes when structuring their Medicaid programs. Copyright © 2017 by the American Academy of Pediatrics.

Genotoxic and Antigenotoxic Assessment of Chios Mastic Oil by the In Vitro Micronucleus Test on Human Lymphocytes and the In Vivo Wing Somatic Test on Drosophila

PubMed Central

Vlastos, Dimitris; Drosopoulou, Elena; Efthimiou, Ioanna; Gavriilidis, Maximos; Panagaki, Dimitra; Mpatziou, Krystalenia; Kalamara, Paraskevi; Mademtzoglou, Despoina; Mavragani-Tsipidou, Penelope

2015-01-01

Chios mastic oil (CMO), the essential oil derived from Pistacia lentiscus (L.) var. chia (Duham), has generated considerable interest because of its antimicrobial, anticancer, antioxidant and other beneficial properties. In the present study, the potential genotoxic activity of CMO as well as its antigenotoxic properties against the mutagenic agent mitomycin-C (MMC) were evaluated by employing the in vitro Cytokinesis Block MicroNucleus (CBMN) assay and the in vivo Somatic Mutation And Recombination Test (SMART). In the in vitro experiments, lymphocytes were treated with 0.01, 0.05 and 0.10% (v/v) of CMO with or without 0.05 μg/ml MMC, while in the in vivo assay Drosophila larvae were fed with 0.05, 0.10, 0.50 and 1.00% (v/v) of CMO with or without 2.50 μg/ml MMC. CMO did not significantly increase the frequency of micronuclei (MN) or total wing spots, indicating lack of mutagenic or recombinogenic activity. However, the in vitro analysis suggested cytotoxic activity of CMO. The simultaneous administration of MMC with CMO did not alter considerably the frequencies of MMC-induced MN and wing spots showing that CMO doesn’t exert antigenotoxic or antirecombinogenic action. Therefore, CMO could be considered as a safe product in terms of genotoxic potential. Even though it could not afford any protection against DNA damage, at least under our experimental conditions, its cytotoxic potential could be of interest. PMID:26110900

Motion capture for human motion measuring by using single camera with triangle markers

NASA Astrophysics Data System (ADS)

Takahashi, Hidenori; Tanaka, Takayuki; Kaneko, Shun'ichi

2005-12-01

This study aims to realize a motion capture for measuring 3D human motions by using single camera. Although motion capture by using multiple cameras is widely used in sports field, medical field, engineering field and so on, optical motion capture method with one camera is not established. In this paper, the authors achieved a 3D motion capture by using one camera, named as Mono-MoCap (MMC), on the basis of two calibration methods and triangle markers which each length of side is given. The camera calibration methods made 3D coordinates transformation parameter and a lens distortion parameter with Modified DLT method. The triangle markers enabled to calculate a coordinate value of a depth direction on a camera coordinate. Experiments of 3D position measurement by using the MMC on a measurement space of cubic 2 m on each side show an average error of measurement of a center of gravity of a triangle marker was less than 2 mm. As compared with conventional motion capture method by using multiple cameras, the MMC has enough accuracy for 3D measurement. Also, by putting a triangle marker on each human joint, the MMC was able to capture a walking motion, a standing-up motion and a bending and stretching motion. In addition, a method using a triangle marker together with conventional spherical markers was proposed. Finally, a method to estimate a position of a marker by measuring the velocity of the marker was proposed in order to improve the accuracy of MMC.

The effect of paclitaxel on conjunctival wound healing: a pilot study.

PubMed

Koz, Ozlem Gurbuz; Ozhuy, Serife; Tezel, Gaye Guler; Karaman, Nazmiye; Unlu, Nursen; Yarangumeli, Alper; Kural, Gulcan

2007-01-01

To compare the effects of mitomycin C (MMC) and paclitaxel entrapped within Carbopol 980 hydrogel (CH) on conjunctival wound healing. Twenty rabbits were randomized into 2 groups. In group 1, limbal-based conjunctival flaps were created in both eyes. In this stage, eyes were randomized for 4 different processes. In process 1, a dry cellulose sponge soaked with 0.2 mg/mL of MMC was applied to the scleral surface. A cellulose sponge soaked with balanced saline solution was applied in the same manner in process 2. In process 3, paclitaxel 1 mg/mL entrapped within CH was placed between the conjunctiva and sclera. In process 4, CH without paclitaxel was applied in the same manner. The conjunctiva was then sutured. All procedures were applied in the same manner in both eyes of animals in group 2. Eyes from group 1 were sampled at the seventh day, and the sampling was also carried out in group 2 on day 14. The inflammatory response and fibrosis were evaluated with light microscopy. Among 4 different processes, lower cell counts and fibrosis scores were found in eyes treated with MMC and paclitaxel compared with balanced saline solution and CH groups (P<0.05). There was no difference between eyes treated with MMC and paclitaxel in terms of these histopathologic parameters (P>0.05). Paclitaxel was shown to provide MMC-like antifibrotic effects during conjunctival wound healing, particularly when delivered with CH and might be a promising alternative as an adjunctive antimetabolite in glaucoma filtration surgery.

[Therapeutic effect of mitomycin C in the immediate postoperative period in patients with intermediate-risk non-muscle-invasive bladder tumors].

PubMed

Jalón Monzón, A; Fernández Gómez, J M; Escaf Barmadah, S; Alvarez Múgica, M; Martín Benito, J L; Regadera Sejas, F J

2008-10-01

Approximately 70-85% of transitional bladder cell carcinomas are non-muscle-invasive. After an initial surgery, around 60-90% will have a recurrence, being the highest risk period the first two years. Urothelium instability could be the main reason for recurrence in mid grade tumours, reason why a single dose of a chemotherapy after transurethral resection of the bladder (TURB) might be insufficient. That is why a deferred therapy in occasions associated with maintenance is recommended. A prospective, controlled and randomized study was performed. We included non-muscle-invasive mid risk bladder tumours. All patients had initially a TURB performed and were randomized to receive a single dose of mitomycin C (MMC), in the immediate postoperative period. A total of 105 patients were included. Mean follow-up was 22, 70 +/- 8, 15 months. MMC was administered to 53 patients. Of these 66, 0% had no recurrence and 34.0% had a non-muscle-invasive recurrence. Of the 52 patients in the non MMC group, 53.8% had no recurrence and 44.2% had a non-muscle-invasive recurrence and only 1 patient had a muscle-invasive progression. We did not find significantly differences in time to recurrence in mid risk tumours when using immediate postoperative single dose of MMC or deferred therapy. There was only one case of myelosuppression. In mid risk non-muscle-invasive tumors, some studies suggest that early intravesical instillation of chemotherapy reduces the risk of recurrence after TURB. We could not show significantly differences when comparing postoperatorive MMC versus traditional deferred instillations.

Current and future directions in Medi-Cal chronic disease care management: a view from the top.

PubMed

Goldman, L Elizabeth; Handley, Margaret; Rundall, Thomas G; Schillinger, Dean

2007-05-01

To determine the extent to which Medicaid managed care (MMC) organizations are engaged in chronic disease care management (CDCM), tailor CDCM for diverse populations, or plan to expand CDCM. Web-based survey of 23 eligible California MMC health plan executives in fall 2005. Frequency distributions of survey responses. Nineteen (83%) of 23 executives responded, representing 2.5 million beneficiaries. Eighteen (95%) MMC plans reported implementing 1 or more elements of CDCM. Although plans used a wide range of CDCM strategies to reach performance goals, most implemented provider awareness activities such as offering guidelines or disease-specific feedback to physician groups. More than half of the plans reported interest in expanding CDCM to include more active interventions such as disease registries, pay for performance, telephone counseling to patients, and other self-management support programs. Few plans reported tailoring their CDCM to vulnerable member populations such as those with limited literacy or limited English proficiency. Executives reported that insufficient financial resources at the plan level, lack of organizational leadership and commitment in physician organizations, and limited information technology in physician offices were barriers to CDCM expansion. California MMC health plans reported substantial interest in CDCM and a desire to increase CDCM. Representatives reported intentions to expand to strategies that more directly engage providers and patients. To ensure that the growing number of vulnerable enrollees with chronic disease receive high-quality care, policy efforts should focus on enabling MMC health plans to more consistently implement and target population-based strategies such as CDCM.

Melanomacrophages in three species of free-ranging sharks from the northwestern Atlantic, the blue shark Prionacae glauca (L.), the shortfin mako, Isurus oxyrhinchus Rafinesque, and the thresher, Alopias vulpinus (Bonnaterre).

PubMed

Borucinska, J D; Kotran, K; Shackett, M; Barker, T

2009-10-01

The melanomacrophage aggregates or cells (MMC) are commonly used as biomarkers of exposure to pollution in fish, albeit their numbers and morphological characteristics can be influenced not only by environmental toxins but also by a range of physiological parameters and pathological conditions. Accordingly, before we can use MMC as biomarkers in any fish species, their normal, 'background' characteristics have to be established in apparently healthy fish. The knowledge of MMC in sharks is minimal. The aim of this study was to characterize MMC from 51 free-ranging, large pelagic sharks from the northwestern Atlantic, including shortfin mako, Isurus oxyrhinchus, thresher, Alopias vulpinus and blue shark, Prionacae glauca. The rationale of this study was twofold. First, because, sharks have life histories predisposing them to the accumulation of environmental toxins they constitute good sentinel species of the health of the global marine ecosystem. Second, because many shark populations are in decline or threatened by extinction, we need to expand our understanding of their health status in order to develop appropriate protective measures. All sharks were collected by sports fishing gear between June and August in 2007. Their health condition was assessed by necropsy, morphometrics, and by microscopic examination of gonads, livers, spleens and kidneys. Routine, haematoxylin and eosin and/or Pearl's reagent-stained paraffin embedded sections were studied by light microscopy. Our results provide the first data on the morphometric and morphological characteristics of MMC in viscera of apparently healthy free-ranging sharks from the northwestern Atlantic.

Evaluation of differential representative values between Chinese hamster cells and human lymphocytes in mitomycin C-induced cytogenetic assays and caspase-3 activity.

PubMed

Liao, Pei-Hu; Lin, Ruey-Hseng; Yang, Ming-Ling; Li, Yi-Ching; Kuan, Yu-Hsiang

2012-03-01

Chinese hamster ovary (CHO) cells, its lung fibroblasts (V79), and human lymphocytes are routinely used in in vitro cytogenetic assays, which include micronuclei (MN), sister chromatid exchange (SCE), and chromosome aberration (CA) assays. Mitomycin C (MMC), a DNA cross-link alkylating agent, is both an anticancer medicine and a carcinogen. To study the differential representative values of cell types in MMC-treated cytogenetic assays and its upstream factor, cysteine aspartic acid-specific protease (caspase)-3. Among the chosen cell types, lymphocytes expressed the highest sensitivity in all three MMC-induced assays, whereas CHO and V79 showed varied sensitivity in different assays. In MN assay, the sensitivity of CHO is higher than or equal to V79; in SCE assay, the sensitivity of CHO is the same as V79; and in CA assay, the sensitivity of CHO is higher than V79. In-depth analysis of CA revealed that in chromatid breaks and dicentrics formation, lymphocyte was the most sensitive of all and CHO was more sensitive than V79; and in acentrics and interchanges formation, lymphocyte was much more sensitive than the others. Furthermore, we found caspase-3 activity plays an important role in MMC-induced cytogenetic assays, with MMC-induced caspase-3 activity resulting in more sensitivity in lymphocytes than in CHO and V79. Based on these findings, lymphocyte will make a suitable predictive or representative control reference in cytogenetic assays and caspase-3 activity with its high specificity, positive predictive value, and sensitivity.

Tyrosine Kinase Inhibitor, Vatalanib, Inhibits Proliferation and Migration of Human Pterygial Fibroblasts.

PubMed

Kim, Hong Kyu; Choi, Ji-Young; Park, Sang Min; Rho, Chang Rae; Cho, Kyong Jin; Jo, Sangmee Ahn

2017-09-01

Vatalanib is a small-molecule tyrosine kinase inhibitor. We investigated the effects of vatalanib on the proliferation and migration of cultured human pterygial fibroblasts (HPFs). Pterygium tissues were obtained after pterygium excision surgery and subjected to primary culture. HPFs were treated with vatalanib at various concentrations. Mitomycin C (MMC) was used as a positive control. Cell proliferation and migration assays were used to investigate the effects of vatalanib. Cell death was measured using flow cytometry analysis. Western blot analysis was performed to identify signaling molecules associated with the response to vatalanib. Vatalanib inhibited both proliferation and migration of HPFs in a dose-dependent manner. Cell proliferation was significantly suppressed by vatalanib (10 and 100 μM) and MMC (0.004% and 0.04%) treatments. Migration assays revealed significant HPF delay when treated with vatalanib (1, 10, and 100 μM) and MMC (0.004% and 0.04%) compared with that in a negative control. Cell death analysis showed that high concentrations of vatalanib (100 μM) and MMC (0.004% and 0.04%) decreased cell numbers. Western blot analysis of vatalanib-treated cells showed vascular endothelial growth factor and transforming growth factor-β significantly reduced, but there was no alteration in p53 protein levels in HPFs. These results indicate that vatalanib significantly suppressed the proliferation and migration of HPFs by decreasing vascular endothelial growth factor and transforming growth factor-β. Vatalanib showed less toxicity than that of MMC. Based on these results, vatalanib may potentially serve as a new adjuvant treatment after pterygium excision surgery.

Fraudulent Credentials. Joint Hearing before the Subcommittee on Health and Long-Term Care and the Subcommittee on Housing and Consumer Interests of the Select Committee on Aging. House of Representatives, Ninety-Ninth Congress, First Session.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Select Committee on Aging.

Hearings on the promotion and purchase of fraudulent credentials are presented, along with the results of an inquiry conducted by a Subcommittee of the Select Committee on Aging of the House of Representatives. Cases of persons who obtained fraudulent credentials and/or illegally practiced a profession are described. Testimony from state licensing…

Credentialing high school psychology teachers.

PubMed

Weaver, Kenneth A

2014-09-01

The National Standards for High School Psychology Curricula (American Psychological Association, 2013b) require a teacher with considerable psychology content knowledge to teach high school psychology courses effectively. In this study, I examined the initial teaching credential requirements for high school psychology teachers in the 50 states plus the District of Columbia. Thirty-four states (the District of Columbia is included as a state) require the social studies credential to teach high school psychology. An analysis of the items on standardized tests used by states to validate the content knowledge required to teach social studies indicates little or no presence of psychology, a reflection of psychology's meager presence in the social studies teacher preparation curricula. Thus, new teachers with the social studies teaching credential are not prepared to teach high school psychology according to the National Standards. Approval of The College, Career, and Civic Life (C3) Framework for Social Studies State Standards: Guidance for Enhancing the Rigor of K-12 Civics, Economics, Geography, and History (National Council for the Social Studies, 2013) presents an opportunity to advocate for establishing a psychology credential in the 34 states. (c) 2014 APA, all rights reserved.

WE-E-304-00: Implementing SBRT Protocols

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2015-06-15

SBRT is having a dramatic impact on radiation therapy of early-stage, locally advanced cancers. A number of national protocols have been and are being developed to assess the clinical efficacy of SBRT for various anatomical sites, such as lung and spine. Physics credentialing for participating and implementation of trial protocols involve a broad spectrum of requirements from image guidance, motion management, to planning technology and dosimetric constrains. For radiation facilities that do not have extensive experiences in SBRT treatment and protocol credentialing, these complex processes of credentialing and implementation could be very challenging and, sometimes, may lead to ineffective evenmore » unsuccessful execution of these processes. In this proposal, we will provide comprehensive review of some current SBRT protocols, explain the requirements and their underline rationales, illustrate representative failed and successful experiences, related to SBRT credentialing, and discuss strategies for effective SBRT credentialing and implementation. Learning Objectives: Understand requirements and challenges of SBRT credentailing and implentation Discuss processes and strategies of effective SBRT credentailing Discuss practical considerations, potential pitfalls and solutions of SBRT implentation.« less

WE-E-304-02: Implementing SBRT Protocols: A NRG CIRO Perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Y.

2015-06-15

SBRT is having a dramatic impact on radiation therapy of early-stage, locally advanced cancers. A number of national protocols have been and are being developed to assess the clinical efficacy of SBRT for various anatomical sites, such as lung and spine. Physics credentialing for participating and implementation of trial protocols involve a broad spectrum of requirements from image guidance, motion management, to planning technology and dosimetric constrains. For radiation facilities that do not have extensive experiences in SBRT treatment and protocol credentialing, these complex processes of credentialing and implementation could be very challenging and, sometimes, may lead to ineffective evenmore » unsuccessful execution of these processes. In this proposal, we will provide comprehensive review of some current SBRT protocols, explain the requirements and their underline rationales, illustrate representative failed and successful experiences, related to SBRT credentialing, and discuss strategies for effective SBRT credentialing and implementation. Learning Objectives: Understand requirements and challenges of SBRT credentailing and implentation Discuss processes and strategies of effective SBRT credentailing Discuss practical considerations, potential pitfalls and solutions of SBRT implentation.« less

Operationa1 Logistics 2010.

DTIC Science & Technology

1997-04-02

movements control center (MCC) which is co-located with a material management center (MMC) forming a distribution management center (DMC). The MMC...missions by a section in Support Operations called the Distribution Management Center (DMC)29. The DMC executes the distribution management (also...restructured organizations are the formula for making theater distribution a reality and the locus of these changes is the Distribution Management Center

Theoretical Estimation of the Processes While Using Casting Methods of Obtaining MMC

NASA Astrophysics Data System (ADS)

Popov, V.

2017-08-01

It is a well-known problem that silicone carbide particles are poorly wetted by aluminum melt, which is a main limiting factor for wide use of metal matrix composites within linear technologies. This paper seeks to find a theoretical explanation of this problem. As result, paper recommends to use solid methods for preparation of MMC with nanoreinforcements.

Instructional Climates in Preschool Children Who Are At-Risk. Part II: Perceived Physical Competence

ERIC Educational Resources Information Center

Robinson, Leah E.; Rudisill, Mary E.; Goodway, Jacqueline D.

2009-01-01

In Part II of this study, we examined the effect of two 9-week instructional climates (low-autonomy [LA] and mastery motivational climate [MMC]) on perceived physical competence (PPC) in preschoolers (N = 117). Participants were randomly assigned to an LA, MMC, or comparison group. PPC was assessed by a pretest, posttest, and retention test with…

Instructional Climates in Preschool Children Who Are At-Risk. Part I: Object-Control Skill Development

ERIC Educational Resources Information Center

Robinson, Leah E.; Goodway, Jacqueline D.

2009-01-01

Part I of this study examined the effect of two 9-week instructional climates (low autonomy [LA] and mastery motivational climate [MMC]) on object-control (OC) skill development in preschoolers (N = 117). Participants were randomly assigned to an LA, MMC, or comparison group. OC skills were assessed at pretest, posttest, and retention test with…

Mechanisms and FEM Simulation of Chip Formation in Orthogonal Cutting In-Situ TiB₂/7050Al MMC.

PubMed

Xiong, Yifeng; Wang, Wenhu; Jiang, Ruisong; Lin, Kunyang; Shao, Mingwei

2018-04-15

The in-situ TiB₂/7050Al composite is a new kind of Al-based metal matrix composite (MMC) with super properties, such as low density, improved strength, and wear resistance. This paper, for a deep insight into its cutting performance, involves a study of the chip formation process and finite element simulation during orthogonal cutting in-situ TiB₂/7050Al MMC. With chips, material properties, cutting forces, and tool geometry parameters, the Johnson-Cook (J-C) constitutive equation of in-situ TiB₂/7050Al composite was established. Then, the cutting simulation model was established by applying the Abaqus-Explicit method, and the serrated chip, shear plane, strain rate, and temperature were analyzed. The experimental and simulation results showed that the obtained material's constitutive equation was of high reliability, and the saw-tooth chips occurred commonly under either low or high cutting speed and small or large feed rate. From result analysis, it was found that the mechanisms of chip formation included plastic deformation, adiabatic shear, shearing slip, and crack extension. In addition, it was found that the existence of small, hard particles reduced the ductility of the MMC and resulted in segmental chips.

Cough response and uptake of mercury by Brook trout, Salvelinus fontinalis, exposed to mercuric compounds at different hydrogen-ion concentrations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drummond, R.A.; Olson, G.F.; Battermna, A.R.

1974-01-01

The lowest concentration of methylmercuric chloride (MMC) and mercuric chloride added to Lake Superior water that caused a significant increase in cough frequency in Brook trout was 3 micrograms Hg/liter. Cough frequency is a good short-term indicator of the long-term effects of MMC. The response can be used to predict the safe concentration of mercuric chloride since the long-term effects of the compound are not known. Increases in cough frequency were proportional to the concentration (from 3 to 12 micrograms Hg/liter) of both compounds at pH 7.5. The fish were more responsive to MMC when the pH of the testmore » water was lowered to 6.0; response to mercuric chloride was not changed by lowered pH. Fish exposed to MMC at pH 6.0 contained more total mercury in their gills and red blood cells than fish tested at pH 9.0. The uptake of mercury by brook trout exposed to mercuric chloride did not differ significantly at pH 6.0 and 9.0.« less

Mitomycin C, 5-fluorouracil, and cyclosporin A prevent epidural fibrosis in an experimental laminectomy model.

PubMed

Yildiz, Kartal Hakan; Gezen, Ferruh; Is, Merih; Cukur, Selma; Dosoglu, Murat

2007-09-01

This study examined the preventive effects of the local application of mitomycin C (MMC), 5-fluorouracil (5-FU), and cyclosporine A (CsA) in minimizing spinal epidural fibrosis in a rat laminectomy model. Thirty-two 2-year-old male Wistar albino rats, each weighing 400 +/- 50 g, were divided into four equal groups: sham, MMC, 5-FU, and CsA. Each rat underwent laminectomy at the L5-L6 lumbar level. Cotton pads (4 x 4 mm2) soaked with MMC (0.5 mg/ml), 5-FU (5 ml/mg), or CsA (5 mg/ml) were placed on the exposed dura for 5 min. Thirty days after surgery, the rats were killed and the epidural fibrosis, fibroblast density, inflammatory cell density, and arachnoid fibrosis were quantified. The epidural and arachnoid fibroses were reduced significantly in the treatment groups compared to the sham group. Fibroblast cell density and inflammatory cell density were decreased significantly in the MMC and 5-FU groups, but were similar in the sham and CsA groups. The decreased rate of epidural fibrosis was promising. Further studies in humans are needed to determine the short- and long-term complications of the agents used here.

Cost Models for MMC Manufacturing Processes

NASA Technical Reports Server (NTRS)

Elzey, Dana M.; Wadley, Haydn N. G.

1996-01-01

Processes for the manufacture of advanced metal matrix composites are rapidly approaching maturity in the research laboratory and there is growing interest in their transition to industrial production. However, research conducted to date has almost exclusively focused on overcoming the technical barriers to producing high-quality material and little attention has been given to the economical feasibility of these laboratory approaches and process cost issues. A quantitative cost modeling (QCM) approach was developed to address these issues. QCM are cost analysis tools based on predictive process models relating process conditions to the attributes of the final product. An important attribute, of the QCM approach is the ability to predict the sensitivity of material production costs to product quality and to quantitatively explore trade-offs between cost and quality. Applications of the cost models allow more efficient direction of future MMC process technology development and a more accurate assessment of MMC market potential. Cost models were developed for two state-of-the art metal matrix composite (MMC) manufacturing processes: tape casting and plasma spray deposition. Quality and Cost models are presented for both processes and the resulting predicted quality-cost curves are presented and discussed.

First 60 fetal in-utero myelomeningocele repairs at Saint Louis Fetal Care Institute in the post-MOMS trial era: hydrocephalus treatment outcomes (endoscopic third ventriculostomy versus ventriculo-peritoneal shunt).

PubMed

Elbabaa, Samer K; Gildehaus, Anne M; Pierson, Matthew J; Albers, J Andrew; Vlastos, Emanuel J

2017-07-01

The published results of the Management of Myelomeningocele Study (MOMS) trial in 2011 showed improved outcomes (reduced need for shunting, decreased incidence of Chiari II malformation, and improved scores of mental development and motor function) in the fetal prenatal repair group compared to the postnatal group. Historically, endoscopic third ventriculostomy (ETV) remains as a controversial hydrocephalus treatment option with high failure rates in pediatric patients with a history of myelomeningocele (MMC). We report hydrocephalus treatment outcomes in the fetal in-utero myelomeningocele repair patients who underwent repair at our Saint Louis Fetal Care Institute following the MOMS trial. We looked carefully at ETV outcomes in this patient population and we identified risk factors for failure. At our Saint Louis Fetal Care Institute, we followed the maternal and fetal inclusion and exclusion criteria used by the MOMS trial. The records of our first 60 fetal MMC repairs performed at our institute between 2011 and 2017 were examined. We retrospectively reviewed the charts, prenatal fetal magnetic resonance imaging (MRI) and ultrasound (US) imaging findings, postnatal brain MRI, and Bayley neurodevelopment testing results for infants and children who underwent surgical treatment of symptomatic hydrocephalus (VP shunt versus ETV). Multiple variables possibly related to ETV failure were considered for identifying risk factors for ETV failure. Between May 2011 and March 2017, 60 pregnant female patients underwent the prenatal MMC repair for their fetuses between 20 and 26 weeks' gestational age (GA) utilizing the standard hysterotomy for exposure of the fetus, and microsurgical repair of the MMC defect. All MMC defects underwent successful in-utero repair, with subsequent progression of the pregnancy. At the time of this study, 58 babies have been born, 56 are alive since there were 2 mortalities in the neonatal period due to prematurity. One patient was excluded given lack of consent for research purposes. From the remaining 55 patient included in this study, a total of 30 infants and toddlers underwent treatment of hydrocephalus (ETV and VPS groups). Twenty-five patients underwent ETV (24 primary ETV and 1 after shunt failure). Nineteen patients underwent shunt placements (6 primary/13 after ETV failure). Mean GA at time of MMC repair for the ETV group was 24 + 6/7 weeks (range 22 + 4/7 to 25 + 6/7). Mean follow up for patients who had a successful ETV was 17.25 months (range 4-57 months). Bayley neurodevelopmental testing results were examined pre- and post-ETV. Overall ETV success rate was 11/24 (45.8%) at the time of this study. The total number of patients who underwent shunt placement was 19/55 (34.5%), while shunting rate was 40% in the MOMS trial. Using a simple logistic regression analysis to identify predictors of ETV failure, ETV age ≤6 months and gestational age ≥23 weeks at repair of myelomeningocele were significant predictors for ETV failure while in-utero ventricular stability ≤4 mm and in-utero ventricular size post-repair ≤15.5 mm were significant predictors for ETV success. None of the listed variables independently predicted classification into ETV success versus ETV failure groups when entered into multiple logistic regression analysis. ETV, as an alternative to initial shunting, may continue to show promising results for treating fetal MMC repair patient population who present with symptomatic hydrocephalus during infancy and early childhood. Although our overall CSF diversion rate (ETV and VPS groups) in our fetal MMC group is higher than the MOMS trial, our shunting rate is lower given our higher incidence of patients with successful ETV. To our knowledge, this is the largest reported ETV series in patients who underwent fetal MMC repair. ETV deserves a closer look in the setting of improved hindbrain herniation in fetal in-utero MMC repair patients. In our series, young age (less than 6 months) and late GA at time of fetal MMC repair (after 23 weeks GA) were predictors for ETV failure, while in-utero stability of ventricular size (less than 4 mm) and in-utero ventricular size post-repair ≤15.5 mm were predictors for ETV success. Larger series and potential prospective randomized studies are required for further evaluation of risk factors for ETV failure in the fetal MMC patient population.

Preventing Unofficial Information Propagation

NASA Astrophysics Data System (ADS)

Le, Zhengyi; Ouyang, Yi; Xu, Yurong; Ford, James; Makedon, Fillia

Digital copies are susceptible to theft and vulnerable to leakage, copying, or manipulation. When someone (or some group), who has stolen, leaked, copied, or manipulated digital documents propagates the documents over the Internet and/or distributes those through physical distribution channels many challenges arise which document holders must overcome in order to mitigate the impact to their privacy or business. This paper focuses on the propagation problem of digital credentials, which may contain sensitive information about a credential holder. Existing work such as access control policies and the Platform for Privacy Preferences (P3P) assumes that qualified or certified credential viewers are honest and reliable. The proposed approach in this paper uses short-lived credentials based on reverse forward secure signatures to remove this assumption and mitigate the damage caused by a dishonest or honest but compromised viewer.

On the sensitivity of TG-119 and IROC credentialing to TPS commissioning errors.

PubMed

McVicker, Drew; Yin, Fang-Fang; Adamson, Justus D

2016-01-08

We investigate the sensitivity of IMRT commissioning using the TG-119 C-shape phantom and credentialing with the IROC head and neck phantom to treatment planning system commissioning errors. We introduced errors into the various aspects of the commissioning process for a 6X photon energy modeled using the analytical anisotropic algorithm within a commercial treatment planning system. Errors were implemented into the various components of the dose calculation algorithm including primary photons, secondary photons, electron contamination, and MLC parameters. For each error we evaluated the probability that it could be committed unknowingly during the dose algorithm commissioning stage, and the probability of it being identified during the verification stage. The clinical impact of each commissioning error was evaluated using representative IMRT plans including low and intermediate risk prostate, head and neck, mesothelioma, and scalp; the sensitivity of the TG-119 and IROC phantoms was evaluated by comparing dosimetric changes to the dose planes where film measurements occur and change in point doses where dosimeter measurements occur. No commissioning errors were found to have both a low probability of detection and high clinical severity. When errors do occur, the IROC credentialing and TG 119 commissioning criteria are generally effective at detecting them; however, for the IROC phantom, OAR point-dose measurements are the most sensitive despite being currently excluded from IROC analysis. Point-dose measurements with an absolute dose constraint were the most effective at detecting errors, while film analysis using a gamma comparison and the IROC film distance to agreement criteria were less effective at detecting the specific commissioning errors implemented here.

Muscle Activation Patterns in Infants with Myelomeningocele Stepping on a Treadmill

PubMed Central

Sansom, Jennifer K.; Teulier, Caroline; Smith, Beth A.; Moerchen, Victoria; Muraszko, Karin; Ulrich, Beverly D.

2013-01-01

Purpose To characterize how infants with myelomeningocele (MMC) activate lower limb muscles over the first year of life, without practice, while stepping on a motorized treadmill. Methods Twelve infants with MMC were tested longitudinally at 1, 6, 12 months. Electromyography (EMG) was used to collect data from the tibialis anterior (TA), lateral gastrocnemius (LG), rectus femoris (RF), biceps femoris (BF). Results Across the first year, infants showed no EMG activity for ~50% of the stride cycle w/poor rhythmicity and timing of muscles, when activated. Single muscle activation predominated; agonist-antagonist co-activation was low. Probability of individual muscle activity across the stride decreased w/age. Conclusions Infants with MMC show high variability in timing and duration of muscle activity, few complex combinations, and very little change over time. PMID:23685739

Thermal and mechanical behavior of metal matrix and ceramic matrix composites

NASA Technical Reports Server (NTRS)

Kennedy, John M. (Editor); Moeller, Helen H. (Editor); Johnson, W. S. (Editor)

1990-01-01

The present conference discusses local stresses in metal-matrix composites (MMCs) subjected to thermal and mechanical loads, the computational simulation of high-temperature MMCs' cyclic behavior, an analysis of a ceramic-matrix composite (CMC) flexure specimen, and a plasticity analysis of fibrous composite laminates under thermomechanical loads. Also discussed are a comparison of methods for determining the fiber-matrix interface frictional stresses of CMCs, the monotonic and cyclic behavior of an SiC/calcium aluminosilicate CMC, the mechanical and thermal properties of an SiC particle-reinforced Al alloy MMC, the temperature-dependent tensile and shear response of a graphite-reinforced 6061 Al-alloy MMC, the fiber/matrix interface bonding strength of MMCs, and fatigue crack growth in an Al2O3 short fiber-reinforced Al-2Mg matrix MMC.

Isothermal fatigue mechanisms in Ti-based metal matrix composites

NASA Technical Reports Server (NTRS)

Majumdar, Bhaskar S.; Newaz, Golam M.

1993-01-01

Stress-controlled isothermal fatigue experiments were performed at room temperature (RT) and 548 C (in argon) on (0)8 SCS6/Ti 15-3 metal matrix composites (MMC's) with 15 and 41 volume percent SCS6 (SiC) fibers. The primary objectives were to evaluate the mechanical responses, and to obtain a clear understanding of the damage mechanisms leading to failure of the MMC's. The mechanical data indicated that strain ranges attained fairly constant values in the stress-controlled experiments at both RT and 538 C, and remained so for more than 85 percent of life. The fatigue data for MMC's with different volume fraction fibers showed that MMC life was controlled by the imposed strain range rather than the stress range. At RT, and at low and intermediate strain ranges, the dominant fatigue mechanism was matrix fatigue, and this was confirmed metallurgically from fractographic evidence as well as from observations of channel type dislocation structures in the matrix of fatigued MMC specimens. Reaction-zone cracks acted as important crack initiating sites at RT, with their role being to facilitate slip band formation and consequent matrix crack initiation through classical fatigue mechanisms. MMC life agreed with matrix life at the lower strain ranges, but was smaller than matrix life at higher strain ranges. Unlike the case of monotonic deformation, debonding damage was another major damage mechanism during fatigue at RT, and it increased for higher strain ranges. At high strain ranges at RT, fractography and metallography showed an absence of matrix cracks, but long lengths of debonds in the outer layers of the SCS6 fibers. Such debonding and consequent rubbing during fatigue is believed to have caused fiber damage and their failure at high strain ranges. Thus, whereas life was matrix dominated at low and intermediate strain ranges, it was fiber dominated at high strain ranges. At 538 C, the mean stain constantly increased (ratchetting) with the number of cycles. At high strain ranges, such ratchetting led to overload failure of the fibers, and debonding of the type at RT was very small. At intermediate strain ranges, fractography showed large areas of matrix cracks. However, in spite of this matrix dominated mechanism, the MMC life at elevated temperatures was significantly less than the matrix fatigue life at all strain ranges. The reason for this difference is still unclear, although metallographic and fractographic evidences suggest that internal crack initiation sites at Mo-ribbons and reaction-zone cracks may have played a critical role, with the former tending to dominate.

Enabling Interoperable and Selective Data Sharing among Social Networking Sites

NASA Astrophysics Data System (ADS)

Shin, Dongwan; Lopes, Rodrigo

With the widespread use of social networking (SN) sites and even introduction of a social component in non-social oriented services, there is a growing concern over user privacy in general, how to handle and share user profiles across SN sites in particular. Although there have been several proprietary or open source-based approaches to unifying the creation of third party applications, the availability and retrieval of user profile information are still limited to the site where the third party application is run, mostly devoid of the support for data interoperability. In this paper we propose an approach to enabling interopearable and selective data sharing among SN sites. To support selective data sharing, we discuss an authenticated dictionary (ADT)-based credential which enables a user to share only a subset of her information certified by external SN sites with applications running on an SN site. For interoperable data sharing, we propose an extension to the OpenSocial API so that it can provide an open source-based framework for allowing the ADT-based credential to be used seamlessly among different SN sites.

Has the Shift to Managed Care Reduced Medicaid Expenditures? Evidence from State and Local-Level Mandates

ERIC Educational Resources Information Center

Duggan, Mark; Hayford, Tamara

2013-01-01

From 1991 to 2009, the fraction of Medicaid recipients enrolled in HMOs and other forms of Medicaid managed care (MMC) increased from 11 percent to 71 percent. This increase was largely driven by state and local mandates that required most Medicaid recipients to enroll in an MMC plan. Theoretically, it is ambiguous whether the shift from…

Re-establishing safer medical-circumcision-integrated initiation ceremonies for HIV prevention in a rural setting in Papua New Guinea. A multi-method acceptability study

PubMed Central

MacLaren, David; Baigry, Maggie; Trowalle, Emil; Muller, Reinhold; Vallely, Andrew; Gesch, Patrick; Hombhanje, Francis; McBride, William John

2017-01-01

Background Efforts to stem the spread of Human Immunodeficiency Virus (HIV) in Papua New Guinea (PNG) are hampered by multiple interrelated factors including limited health services, extreme diversities in culture and language and highly prevalent gender inequity, domestic violence and poverty. In the rural district of Yangoru-Saussia, a revival of previously ceased male initiation ceremonies (MICs) is being considered for a comprehensive approach to HIV prevention. In this study, we explore the local acceptability of this undertaking including replacing traditional penile cutting practices with medical male circumcision (MMC). Methods A multi-method study comprising three phases. Phase one, focus group discussions with male elders to explore locally appropriate approaches to HIV prevention; Phase two, interviews and a cross-sectional survey with community men and women to assess views on MICs that include MMC for HIV prevention; Phase three, interviews with cultural leaders and a cross sectional survey to assess the acceptability of replacing traditional penile bleeding with MMC. Results Cultural leaders expressed that re-establishing MICs was locally appropriate for HIV prevention given the focus on character building and cultural preservation. Most surveyed participants (81.5%) supported re-establishing MICs and 92.2% supported adapting MICs with MMC. Changes to penile bleeding emerged as a contentious and contested issue given its cultural significance in symbolizing initiates’ transition from childhood to adulthood. Participants were concerned about potential clash with modern education, introduced religious beliefs and limited government support in leadership and funding. Conclusions Most people in this study in Yangoru-Saussia support re-establishing MICs and replacing traditional penile bleeding with MMC. This culturally-sensitive alignment of MMC (and HIV prevention) with revived MICs responds to a national health priority in PNG and acts as an example of providing culturally-sensitive male circumcision for HIV prevention recommended by WHO/UNAIDS. However, the implementation of this undertaking will require considerable effort, especially when modern pursuits in education and religion must be factored and when there is expectation for local authorities to lead and provide funding. PMID:29117244

Preparation of an antitumor and antivirus agent: chemical modification of α-MMC and MAP30 from Momordica Charantia L. with covalent conjugation of polyethyelene glycol.

PubMed

Meng, Yao; Liu, Shuangfeng; Li, Juan; Meng, Yanfa; Zhao, Xiaojun

2012-01-01

Alpha-momorcharin (α-MMC) and momordica anti-HIV protein (MAP30) derived from Momordica charantia L. have been confirmed to possess antitumor and antivirus activities due to their RNA-N-glycosidase activity. However, strong immunogenicity and short plasma half-life limit their clinical application. To solve this problem, the two proteins were modified with (mPEG)(2)-Lys-NHS (20 kDa). In this article, a novel purification strategy for the two main type I ribosome-inactivating proteins (RIPs), α-MMC and MAP30, was successfully developed for laboratory-scale preparation. Using this dramatic method, 200 mg of α-MMC and about 120 mg of MAP30 was obtained in only one purification process from 200 g of Momordica charantia seeds. The homogeneity and some other properties of the two proteins were assessed by gradient SDS-PAGE, electrospray ionization quadruple mass spectrometry, and N-terminal sequence analysis as well as Western blot. Two polyethylene glycol (PEG)ylated proteins were synthesized and purified. Homogeneous mono-, di-, or tri-PEGylated proteins were characterized by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The analysis of antitumor and antivirus activities indicated that the serial PEGylated RIPs preserved moderate activities on JAR choriocarcinoma cells and herpes simplex virus-1. Furthermore, both PEGylated proteins showed about 60%-70% antitumor and antivirus activities, and at the same time decreased 50%-70% immunogenicity when compared with their unmodified counterparts. α-MMC and MAP30 obtained from this novel purification strategy can meet the requirement of a large amount of samples for research. Their chemical modification can solve the problem of strong immunogenicity and meanwhile preserve moderate activities. All these findings suggest the potential application of PEGylated α-MMC and PEGylated MAP30 as antitumor and antivirus agents. According to these results, PEGylated RIPs can be constructed with nanomaterials to be a targeting drug that can further decrease immunogenicity and side effects. Through nanotechnology we can make them low-release drugs, which can further prolong their half-life period in the human body.

Preliminary results of antiscarring therapy in the prevention of postendoscopic esophageal mucosectomy strictures

PubMed Central

Wu, Yuhsin; Schomisch, Steve J.; Cipriano, Cassandra; Chak, Amitabh; Lash, Richard H.; Ponsky, Jeffrey L.

2015-01-01

Background Esophageal endoscopic submucosal dissection (ESD) is an effective minimally invasive therapy for early esophageal cancer and high-grade Barrett dysplasia. However, esophageal stricture formation after circumferential or large ESD has limited its wide adoption. Mitomycin C (MMC), halofuginone (Hal), and transforming growth factor β3 (TGF-β3) exhibits antiscarring effects that may prevent post-ESD stricture formation. Methods Using endoscopic mucosectomy (EEM) technique, an 8- to 10-cm-long circumferential esophageal mucosal segment was excised in a porcine model. The site was either untreated (control, n = 6) or received 40 evenly distributed injections of antiscarring agent immediately and at weeks 1 and 2. High and low doses were used: MMC 5 mg (n = 2), 0.5 mg (n = 2); Hal 5 mg (n = 2), 1.5 mg (n = 2), 0.5 mg (n = 2); TGF-β3 2 μg (n = 2), 0.5 μg (n = 2). The degree of stricture formation was determined by the percentage reduction of the esophageal lumen on weekly fluoroscopic examination. Animals were euthanized when strictures exceeded 80 % or the animals were unable to maintain weight. Results The control group had a luminal diameter reduction of 78.2 ± 10.9 % by 2 weeks and were euthanized by week 3. Compared at 2 weeks, the Hal group showed a decrease in mean stricture formation (68.4 % low dose, 57.7 % high dose), while both TGF-β3 dosage groups showed no significant change (65.3 % low dose, 76.2 % high dose). MMC was most effective in stricture prevention (53.6 % low dose, 35 % high dose). Of concern, the esophageal wall treated with high-dose MMC appeared to be necrotic and eventually led to perforation. In contrast, low dose MMC, TGF-β3 and Hal treated areas appeared re-epithelialized and healthy. Conclusions Preliminary data on MMC and Hal demonstrated promise in reducing esophageal stricture formation after EEM. More animal data are needed to perform adequate statistical analysis in order to determine overall efficacy of antiscarring therapy. PMID:24100858

Internal Urethrotomy With Intralesional Mitomycin C: An Effective Option for Endoscopic Management of Recurrent Bulbar and Bulbomembranous Urethral Strictures.

PubMed

Farrell, M Ryan; Lawrenz, Cedric W; Levine, Laurence A

2017-12-01

To describe our experience with direct visual internal urethrotomy (DVIU) and mitomycin C (MMC) for recurrent bulbar and bulbomembranous urethral strictures of radiation and non-radiation-induced etiologies. We reviewed our database of consecutive patients presenting to our tertiary care institution with recurrent bulbar and bulbomembranous urethral strictures who underwent DVIU with MMC from 2011 to 2016. Patients were stratified by radiation-induced strictures (RIS) vs non-RIS. Cold-knife incisions were made at 12-, 3-, and 9-o'clock positions followed by intralesional injection of 10 mL MMC (0.4 mg/mL) in 0.2-0.4 mL aliquots and 1 month of postoperative daily clean intermittent catheterization (CIC). All 44 patients (RIS n = 18, non-RIS n = 26) failed prior endoscopic management or urethroplasty. Median stricture length was 2.0 cm (interquartile range [IQR] 1.0-2.5). Over a median follow-up of 25.8 months (IQR 12.9-47.2), 75.0% of patients (33/44) required no additional surgical intervention (RIS 12/18, 66.7%; non-RIS 21/26, 80.8%). Median time to stricture recurrence among those who recurred was 10.7 months (IQR 3.9-17.6; RIS 9.4 months, IQR 3.5-17.6; non-RIS 11.2 months, IQR 8.0-25.6). Four patients (RIS n = 2, non-RIS n = 2) elected to undergo urethroplasty for recurrence. A second DVIU with MMC was performed in the remaining recurrences (n = 7) with no further surgical intervention required in 37 of 40 of patients (92.5%) overall (RIS 14/16, 87.5%; non-RIS 23/24, 95.8%). No long-term complications were attributable to MMC. DVIU with MMC and short-term CIC for recurrent, short, bulbar and bulbomembranous urethral strictures is a safe endoscopic modality with promising early results. This approach may be useful for patients who are suboptimal candidates for open reconstruction. Copyright © 2017 Elsevier Inc. All rights reserved.

Anxiolytic- and antidepressant-like activities of a methanolic extract of Morinda citrifolia Linn. (noni) fruit in mice: Involvement of benzodiazepine-GABAAergic, serotonergic and adrenergic systems.

PubMed

Narasingam, Megala; Vijeepallam, Kamini; Mohamed, Zahurin; Pandy, Vijayapandi

2017-12-01

This study presents anxiolytic- and antidepressant-like effects of a methanolic extract of Morinda citrifolia Linn. (noni) fruit (MMC) in well-established mouse models of anxiety and depression. The administration of MMC (1 g/kg, p.o.) and diazepam (1 mg/kg, i.p.) significantly attenuated anxiety-like behaviour in mice by increasing the percentage of time spent and number of entries in the open arms in the elevated plus maze (EPM), and significantly enhanced the exploration in the light box in the light/dark test (LDT). The pre-treatment with flumazenil (6 mg/kg, i.p.) or bicuculline (3 mg/kg, i.p.) or WAY 100635 (1 mg/kg, i.p.) antagonized the anxiolytic-like effect elicited by MMC (1 g/kg, p.o.). These results suggest the possible involvement of benzodiazepine-GABA A ergic and serotonergic mechanisms in the anxiolytic-like effect of noni fruit. Meanwhile, in the antidepressant study, the administration of MMC (0.5 and 0.75 g/kg, p.o.) and desipramine (30 mg/kg, i.p.) significantly reduced the duration of immobility in the tail suspension test (TST). Furthermore, pre-treatment of mice with 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA; 100 mg/kg, i.p., an inhibitor of serotonin synthesis) for four consecutive days or a single dose of WAY 100635 (1 mg/kg, i.p., 5HT 1A receptor antagonist) or α-methyl-DL-tyrosine (AMPT; 100 mg/kg, i.p., an inhibitor of noradrenaline synthesis) significantly reversed the anti-immobility effect of MMC (0.5 g/kg, p.o.) in TST by indicating the specific involvement of the serotonergic and noradrenergic systems in the antidepressant-like effect of noni fruit. Taken together, these findings suggest that MMC has both anxiolytic- and antidepressant-like activities to be resorted as a valuable alternative therapy for comorbid anxiety and depressive conditions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Fractal-like kinetics of intracellular enzymatic reactions: a chemical framework of endotoxin tolerance and a possible non-specific contribution of macromolecular crowding to cross-tolerance.

PubMed

Vasilescu, Catalin; Olteanu, Mircea; Flondor, Paul; Calin, George A

2013-09-14

The response to endotoxin (LPS), and subsequent signal transduction lead to the production of cytokines such as tumor necrosis factor-α (TNF-α) by innate immune cells. Cells or organisms pretreated with endotoxin enter into a transient state of hyporesponsiveness, referred to as endotoxin tolerance (ET) which represents a particular case of negative preconditioning. Despite recent progress in understanding the molecular basis of ET, there is no consensus yet on the primary mechanism responsible for ET and for the more complex cases of cross tolerance. In this study, we examined the consequences of the macromolecular crowding (MMC) and of fractal-like kinetics (FLK) of intracellular enzymatic reactions on the LPS signaling machinery. We hypothesized that this particular type of enzyme kinetics may explain the development of ET phenomenon. Our aim in the present study was to characterize the chemical kinetics framework in ET and determine whether fractal-like kinetics explains, at least in part, ET. We developed an ordinary differential equations (ODE) mathematical model that took into account the links between the MMC and the LPS signaling machinery leading to ET. We proposed that the intracellular fractal environment (MMC) contributes to ET and developed two mathematical models of enzyme kinetics: one based on Kopelman's fractal-like kinetics framework and the other based on Savageau's power law model. Kopelman's model provides a good image of the potential influence of a fractal intracellular environment (MMC) on ET. The Savageau power law model also partially explains ET. The computer simulations supported the hypothesis that MMC and FLK may play a role in ET. The model highlights the links between the organization of the intracellular environment, MMC and the LPS signaling machinery leading to ET. Our FLK-based model does not minimize the role of the numerous negative regulatory factors. It simply draws attention to the fact that macromolecular crowding can contribute significantly to the induction of ET by imposing geometric constrains and a particular chemical kinetic for the intracellular reactions.

Re-establishing safer medical-circumcision-integrated initiation ceremonies for HIV prevention in a rural setting in Papua New Guinea. A multi-method acceptability study.

PubMed

Manineng, Clement Morris; MacLaren, David; Baigry, Maggie; Trowalle, Emil; Muller, Reinhold; Vallely, Andrew; Gesch, Patrick; Hombhanje, Francis; McBride, William John

2017-01-01

Efforts to stem the spread of Human Immunodeficiency Virus (HIV) in Papua New Guinea (PNG) are hampered by multiple interrelated factors including limited health services, extreme diversities in culture and language and highly prevalent gender inequity, domestic violence and poverty. In the rural district of Yangoru-Saussia, a revival of previously ceased male initiation ceremonies (MICs) is being considered for a comprehensive approach to HIV prevention. In this study, we explore the local acceptability of this undertaking including replacing traditional penile cutting practices with medical male circumcision (MMC). A multi-method study comprising three phases. Phase one, focus group discussions with male elders to explore locally appropriate approaches to HIV prevention; Phase two, interviews and a cross-sectional survey with community men and women to assess views on MICs that include MMC for HIV prevention; Phase three, interviews with cultural leaders and a cross sectional survey to assess the acceptability of replacing traditional penile bleeding with MMC. Cultural leaders expressed that re-establishing MICs was locally appropriate for HIV prevention given the focus on character building and cultural preservation. Most surveyed participants (81.5%) supported re-establishing MICs and 92.2% supported adapting MICs with MMC. Changes to penile bleeding emerged as a contentious and contested issue given its cultural significance in symbolizing initiates' transition from childhood to adulthood. Participants were concerned about potential clash with modern education, introduced religious beliefs and limited government support in leadership and funding. Most people in this study in Yangoru-Saussia support re-establishing MICs and replacing traditional penile bleeding with MMC. This culturally-sensitive alignment of MMC (and HIV prevention) with revived MICs responds to a national health priority in PNG and acts as an example of providing culturally-sensitive male circumcision for HIV prevention recommended by WHO/UNAIDS. However, the implementation of this undertaking will require considerable effort, especially when modern pursuits in education and religion must be factored and when there is expectation for local authorities to lead and provide funding.

Preparation of an antitumor and antivirus agent: chemical modification of α-MMC and MAP30 from Momordica Charantia L. with covalent conjugation of polyethyelene glycol

PubMed Central

Meng, Yao; Liu, Shuangfeng; Li, Juan; Meng, Yanfa; Zhao, Xiaojun

2012-01-01

Background Alpha-momorcharin (α-MMC) and momordica anti-HIV protein (MAP30) derived from Momordica charantia L. have been confirmed to possess antitumor and antivirus activities due to their RNA-N-glycosidase activity. However, strong immunogenicity and short plasma half-life limit their clinical application. To solve this problem, the two proteins were modified with (mPEG)2-Lys-NHS (20 kDa). Methodology/principal findings In this article, a novel purification strategy for the two main type I ribosome-inactivating proteins (RIPs), α-MMC and MAP30, was successfully developed for laboratory-scale preparation. Using this dramatic method, 200 mg of α-MMC and about 120 mg of MAP30 was obtained in only one purification process from 200 g of Momordica charantia seeds. The homogeneity and some other properties of the two proteins were assessed by gradient SDS-PAGE, electrospray ionization quadruple mass spectrometry, and N-terminal sequence analysis as well as Western blot. Two polyethylene glycol (PEG)ylated proteins were synthesized and purified. Homogeneous mono-, di-, or tri-PEGylated proteins were characterized by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The analysis of antitumor and antivirus activities indicated that the serial PEGylated RIPs preserved moderate activities on JAR choriocarcinoma cells and herpes simplex virus-1. Furthermore, both PEGylated proteins showed about 60%–70% antitumor and antivirus activities, and at the same time decreased 50%–70% immunogenicity when compared with their unmodified counterparts. Conclusion/significance α-MMC and MAP30 obtained from this novel purification strategy can meet the requirement of a large amount of samples for research. Their chemical modification can solve the problem of strong immunogenicity and meanwhile preserve moderate activities. All these findings suggest the potential application of PEGylated α-MMC and PEGylated MAP30 as antitumor and antivirus agents. According to these results, PEGylated RIPs can be constructed with nanomaterials to be a targeting drug that can further decrease immunogenicity and side effects. Through nanotechnology we can make them low-release drugs, which can further prolong their half-life period in the human body. PMID:22802682

Experimental and numerical investigation on cladding of corrosion-erosion resistant materials by a high power direct diode laser

NASA Astrophysics Data System (ADS)

Farahmand, Parisa

In oil and gas industry, soil particles, crude oil, natural gas, particle-laden liquids, and seawater can carry various highly aggressive elements, which accelerate the material degradation of component surfaces by combination of slurry erosion, corrosion, and wear mechanisms. This material degradation results into the loss of mechanical properties such as strength, ductility, and impact strength; leading to detachment, delamination, cracking, and ultimately premature failure of components. Since the failure of high valued equipment needs considerable cost and time to be repaired or replaced, minimizing the tribological failure of equipment under aggressive environment has been gaining increased interest. It is widely recognized that effective management of degradation mechanisms will contribute towards the optimization of maintenance, monitoring, and inspection costs. The hardfacing techniques have been widely used to enhance the resistance of surfaces against degradation mechanisms. Applying a surface coating improves wear and corrosion resistance and ensures reliability and long-term performance of coated parts. A protective layer or barrier on the components avoids the direct mechanical and chemical contacts of tool surfaces with process media and will reduce the material loss and ultimately its failure. Laser cladding as an advanced hardfacing technique has been widely used for industrial applications in order to develop a protective coating with desired material properties. During the laser cladding, coating material is fused into the base material by means of a laser beam in order to rebuild a damaged part's surface or to enhance its surface function. In the hardfacing techniques such as atmospheric plasma spraying (APS), high velocity oxygen-fuel (HVOF), and laser cladding, mixing of coating materials with underneath surface has to be minimized in order to utilize the properties of the coating material most effectively. In this regard, laser cladding offers advantages due to creating coating layers with superior properties in terms of purity, homogeneity, low dilution, hardness, bonding, and microstructure. In the development of modern materials for hardfacing applications, the functionality is often improved by combining materials with different properties into composites. Metal Matrix Composite (MMC) coating is a composite material with two constituent parts, i.e., matrix and the reinforcement. This class of composites are addressing improved mechanical properties such as stiffness, strength, toughness, and tribological and chemical resistance. Fabrication of MMCs is to achieve a combination of properties not achievable by any of the materials acting alone. MMCs have attracted significant attention for decades due to their combination of wear-resistivity, corrosion-resistivity, thermal, electrical and magnetic properties. Presently, there is a strong emphasis on the development of advanced functional coatings for corrosion, erosion, and wear protection for different industrial applications. In this research, a laser cladding system equipped with a high power direct diode laser associated with gas driven metal powder delivery system was used to develop advanced MMC coatings. The high power direct diode laser used in this study offers wider beam spot, shorter wavelength and uniform power distribution. These properties make the cladding set-up ideal for coating due to fewer cladding tracks, lower operation cost, higher laser absorption, and improved coating qualities. In order to prevent crack propagation, porosity, and uniform dispersion of carbides in MMC coating, cladding procedure was assisted by an induction heater as a second heat source. The developed defect free MMC coatings were combined with nano-size particles of WC, rare earth (RE) element (La2O3), and Mo as a refractory metal to enhance mechanical properties, chemical composition, and subsequently improve the tribological performance of the coatings. The resistance of developed MMC coatings were examined under highly accelerated slurry erosion, corrosion, and wear as the most frequently encountered failure modes of mechanical components. The microstructure, mechanical properties, and the level of induced residual stress on the coating after cladding procedure are closely related to cladding process variables. Study about the effect of processing parameters on clad quality and experienced thermal history and thermally-induced stress evolution requires both theoretical and experimental understanding of the associated physical phenomena. Numerical modeling offers a cost-efficient way to better understand the related complex physics in laser cladding process. It helps to reveal the effects and significance of each processing parameters on the desired characteristics of clad parts. Successful numerical simulation can provide unique insight into complex laser cladding process, efficiently calculate the complex procedure, and help to obtain coating parts with quality integrity. Therefore, current study develops a three-dimensional (3D) transient and uncoupled thermo-elastic-plastic model to study thermal history, molten pool evolution, thermally induced residual stress, and the effect of utilizing an induction heater as a second heat source on the mechanical properties and microstructural properties of final cladded coating.

Measurement and Simulation of Thermal Conductivity of Hafnium-Aluminum Thermal Neutron Absorber Material

DOE PAGES

Guillen, Donna Post; Harris, William H.

2016-05-11

A metal matrix composite (MMC) material comprised of hafnium aluminide (Al3Hf) intermetallic particles in an aluminum matrix has been identified as a promising material for fast-flux irradiation testing applications. This material can filter thermal neutrons while simultaneously providing high rates of conductive cooling for experiment capsules. Our purpose is to investigate effects of Hf-Al material composition and neutron irradiation on thermophysical properties, which were measured before and after irradiation. When performing differential scanning calorimetry (DSC) on the irradiated specimens, a large exotherm corresponding to material annealment was observed. Thus, a test procedure was developed to perform DSC and laser flashmore » analysis (LFA) to obtain the specific heat and thermal diffusivity of pre- and post-annealment specimens. This paper presents the thermal properties for three states of the MMC material: (1) unirradiated, (2) as-irradiated, and (3) irradiated and annealed. Microstructure-property relationships were obtained for the thermal conductivity. These relationships are useful for designing components from this material to operate in irradiation environments. Furthermore, the ability of this material to effectively conduct heat as a function of temperature, volume fraction Al 3Hf, radiation damage and annealing is assessed using the MOOSE suite of computational tools.« less

The strength of metal matrix composites

NASA Astrophysics Data System (ADS)

Baxter, William J.

1992-11-01

There is intensive interest in metal matrix composites (MMCs) for automotive components, and the first production applications in Japan use discontinuous fibers as the reinforcements. These fibers are randomly oriented, resulting in an MMC with isotropic properties. However, there are conflicting reports on the tensile strengths attainable. In some cases, the strength increases with increasing volume fraction (V f) of fibers, while in other cases, there is little or no benefit. A simple method is proposed to calculate the strength of this type of MMC. It is shown that the fibers oriented perpendicular to the stress direction play a key role, and the strength depends upon the strength of the interfacial bond. Upper and lower limits of the composite strength are calculated. If the bond strength is larger than the matrix strength, the composite strength has a maximum value which increases with V f. If the bond strength is weaker than the matrix, the composite strength has a minimum value which is either weakly dependent or even independent of V f. These calculations are in good agreement with examples taken from the literature of aluminum composites reinforced with either A12O3, graphite, or SiC. The strength of the matrix alloy is shown to be a very important parameter: weak alloys are easily strengthened, while in certain cases, strong alloys may be weakened.

Nobody Sells Gold for the Price of Silver: Dishonesty, Uncertainty and the Underground Economy

NASA Astrophysics Data System (ADS)

Herley, Cormac; Florêncio, Dinei

The underground economy has attracted a lot of attention recently as a key component of cybercrime. In particular the IRC markets for stolen identities, phishing kits, botnets, and cybercrime related services have been extensively studied. It is suggested that sophisticated underground markets show great specialization and maturity. There are complex divisions of labor and service offerings for every need. Stolen credentials are traded in bulk for pennies on the dollar. It is suggested that large sums move on these markets.

West Virginia hospital preparedness: vision for the future.

PubMed

Rose, D William; Shorr, Terry; Veazey, Amy Johnson

2006-01-01

The ability of hospitals to respond to individuals who have been chemically contaminated or victims of biologic warfare has been limited. This article reviews the current state of readiness of West Virginia hospitals and how new requirements have resulted in better preparedness for future events. Increased isolation capacity, hospital decontamination units and stockpiling of medications, forward deployment of chemical antidotes, electronic disease surveillance, and advanced credentialing of medical personnel are all key components in the overall plan for the state's preparedness.

Leveraging Commercially Issued Multi-Factor Identification Credentials

NASA Technical Reports Server (NTRS)

Baldridge, Tim W.

2010-01-01

This slide presentation reviews the Identity, Credential and Access Management (ICAM) system. This system is a complete system of identity management, access to desktops and applications, use of smartcards, and building access throughout NASA.

American Academy of Cosmetic Dentistry

MedlinePlus

... Library Subscriptions Midline Clinical Newsletter Newsroom Credentialing Guides Surveys & Research Give Back a Smile About AACD Charitable Foundation ... Library Subscriptions Midline Clinical Newsletter Newsroom Credentialing Guides Surveys & Research Give Back a Smile About AACD Charitable Foundation ...

28 CFR 544.73 - Program participation.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) shall be deemed to be making satisfactory progress toward earning a GED credential or high school... program until the inmate earns a GED credential or high school diploma. At these meetings, the inmate may...

28 CFR 544.73 - Program participation.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) shall be deemed to be making satisfactory progress toward earning a GED credential or high school... program until the inmate earns a GED credential or high school diploma. At these meetings, the inmate may...

28 CFR 544.73 - Program participation.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) shall be deemed to be making satisfactory progress toward earning a GED credential or high school... program until the inmate earns a GED credential or high school diploma. At these meetings, the inmate may...

28 CFR 544.73 - Program participation.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) shall be deemed to be making satisfactory progress toward earning a GED credential or high school... program until the inmate earns a GED credential or high school diploma. At these meetings, the inmate may...

Adjunctive Mitomycin C or Amniotic Membrane Transplantation for Ahmed Glaucoma Valve Implantation: A Randomized Clinical Trial.

PubMed

Yazdani, Shahin; Mahboobipour, Hassan; Pakravan, Mohammad; Doozandeh, Azadeh; Ghahari, Elham

2016-05-01

To determine whether adjunctive mitomycin C (MMC) or amniotic membrane transplantation (AMT) improve the outcomes of Ahmed glaucoma valve (AGV) implantation. This double-blind, stratified, 3-armed randomized clinical trial includes 75 eyes of 75 patients aged 7 to 75 years with refractory glaucoma. Eligible subjects underwent stratified block randomization; eyes were first stratified to surgery in the superior or inferior quadrants based on feasibility; in each subgroup, eyes were randomly assigned to the study arms using random blocks: conventional AGV implantation (group A, 25 eyes), AGV with MMC (group B, 25 eyes), and AGV with AMT (group C, 25 eyes). The 3 study groups were comparable regarding baseline characteristics and mean follow-up (P=0.288). A total of 68 patients including 23 eyes in group A, 25 eyes in group B, and 20 eyes group C completed the follow-up period and were analyzed. Intraocular pressure was lower in the MMC group only 3 weeks postoperatively (P=0.04) but comparable at other time intervals. Overall success rate was comparable in the 3 groups at 12 months (P=0.217). The number of eyes requiring medications (P=0.30), time to initiation of medications (P=0.13), and number of medications (P=0.22) were comparable. Hypertensive phase was slightly but insignificantly more common with standard surgery (82%) as compared with MMC-augmented (60%) and AMT-augmented (70%) procedures (P=0.23). Complications were comparable over 1 year (P=0.28). Although adjunctive MMC and AMT were safe during AGV implantation, they did not influence success rates or intraocular pressure outcomes. Complications, including hypertensive phase, were also comparable.

Increasing dwell time of mitomycin C in the upper tract with a reverse thermosensitive polymer.

PubMed

Wang, Agnes J; Goldsmith, Zachariah G; Neisius, Andreas; Astroza, Gaston M; Oredein-McCoy, Olugbemisola; Iqbal, Muhammad W; Simmons, W Neal; Madden, John F; Preminger, Glenn M; Inman, Brant A; Lipkin, Michael E; Ferrandino, Michael N

2013-03-01

Abstract Background and Purpose: Topical chemotherapy for urothelial cancer is dependent on adequate contact time of the chemotherapeutic agent with the urothelium. To date, there has not been a reliable method of maintaining this contact for renal or ureteral urothelial carcinoma. We evaluated the safety and feasibility of using a reverse thermosensitive polymer to improve dwell times of mitomycin C (MMC) in the upper tract. Using a porcine model, four animals were treated ureteroscopically with both upper urinary tracts receiving MMC mixed with iodinated contrast. One additional animal received MMC percutaneously. The treatment side had ureteral outflow blocked with a reverse thermosensitive polymer plug. MMC dwell time was monitored fluoroscopically and intrarenal pressures measured. Two animals were euthanized immediately, and three animals were euthanized 5 days afterward. In control kidneys, drainage occurred at a mean of 5.3±0.58 minutes. Intrarenal pressures stayed fairly stable: 9.7±14.0 cm H20. In treatment kidneys, dwell time was extended to 60 minutes, when the polymer was washed out. Intrarenal pressures in the treatment kidneys peaked at 75.0±14.7 cm H20 and reached steady state at 60 cm H20. Pressures normalized after washout of the polymer with cool saline. Average washout time was 11.8±9.6 minutes. No histopathologic differences were seen between the control and treatment kidneys, or with immediate compared with delayed euthanasia. A reverse thermosensitive polymer can retain MMC in the upper urinary tract and appears to be safe from our examination of intrarenal pressures and histopathology. This technique may improve the efficacy of topical chemotherapy in the management of upper tract urothelial carcinoma.

Optimization of intrinsic and extrinsic tendon healing through controllable water-soluble mitomycin-C release from electrospun fibers by mediating adhesion-related gene expression.

PubMed

Zhao, Xin; Jiang, Shichao; Liu, Shen; Chen, Shuai; Lin, Zhi Yuan William; Pan, Guoqing; He, Fan; Li, Fengfeng; Fan, Cunyi; Cui, Wenguo

2015-08-01

To balance intrinsic and extrinsic healing during tendon repair is challenging in tendon surgery. We hypothesized that by mediating apoptotic gene and collagen synthesis of exogenous fibroblasts, the adhesion formation induced by extrinsic healing could be inhibited. With the maintenance of intrinsic healing, the tendon could be healed with proper function with no adhesion. In this study, we loaded hydrophilic mitomycin-C (MMC) into hyaluronan (HA) hydrosols, which were then encapsulated in poly(L-lactic acid) (PLLA) fibers by micro-sol electrospinning. This strategy successfully provided a controlled release of MMC to inhibit adhesion formations with no detrimental effect on intrinsic healing. We found that micro-sol electrospinning was an effective and facile approach to incorporate and control hydrophilic drug release from hydrophobic polyester fibers. MMC exhibited an initially rapid, and gradually steadier release during 40 days, and the release rates could be tuned by its concentration. In vitro studies revealed that low concentrations of MMC could inhibit fibroblast adhesion and proliferation. When lacerate tendons were healed using the MMC-HA loaded PLLA fibers in vivo, they exhibited comparable mechanical strength to the naturally healed tendons but with no significant presence of adhesion formation. We further identified the up-regulation of apoptotic protein Bax expression and down-regulation of proteins Bcl2, collage I, collagen III and α-SMA during the healing process associated with minimum adhesion formations. This approach presented here leverages new advances in drug delivery and nanotechnology and offers a promising strategy to balance intrinsic and extrinsic tendon healing through modulating genes associated with fibroblast apoptosis and collagen synthesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immunization Coverage and Medicaid Managed Care in New Mexico: A Multimethod Assessment

PubMed Central

Schillaci, Michael A.; Waitzkin, Howard; Carson, E. Ann; López, Cynthia M.; Boehm, Deborah A.; López, Leslie A.; Mahoney, Sheila F.

2004-01-01

BACKGROUND We wanted to examine the association between Medicaid managed care (MMC) and changing immunization coverage in New Mexico, a predominantly rural, poor, and multiethnic state. METHODS As part of a multimethod assessment of MMC, we studied trends in quantitative data from the National Immunization Survey (NIS) using temporal plots, Fisher’s exact test, and the Cochran-Armitage trend test. To help explain changes in immunization rates in relation to MMC, we analyzed qualitative data gathered through ethnographic observations at safety net institutions: income support (welfare) offices, community health centers, hospital emergency departments, private physicians’ offices, mental health institutions, managed care organizations, and agencies of state government. RESULTS Immunization coverage decreased significantly after implementation of MMC, from 80% in 1996 to 73% in 2001 for the 4:3:1 vaccination series (Fisher’s exact test, P = .031). New Mexico dropped in rank among states from 30th for this vaccination series in 1996 to 50th in 2001. A significant decreasing trend (Cochran-Armitage P = .025) in coverage occurred between 1996 and 2001. Findings from the ethnographic study revealed conditions that might have contributed to decreased immunization coverage: (1) reduced funding for immunizations at public health clinics, and difficulties in gaining access to MMC providers; (2) informal referrals from managed care organizations and contracting physicians to community health centers and state-run public health clinics; and (3) increased workloads and delays at community health centers, linked partly to these informal referrals for immunizations. CONCLUSIONS Medicaid reform in New Mexico did not improve immunization coverage, which declined significantly to among the lowest in the nation. Reduced funding for public health clinics and informal referrals may have contributed to this decline. These observations show how unanticipated and adverse consequences can result from policy interventions in complex insurance systems. PMID:15053278

Mitomycin C, ceramide, and 5-fluorouracil inhibit corneal haze and apoptosis after PRK.

PubMed

Kim, Tae-im; Lee, Sun Young; Pak, Jhang Ho; Tchah, Hungwon; Kook, Michael S

2006-01-01

To investigate the effects of mitomycin C (MMC), ceramide, and 5-fluororacil (5-FU) on haze after photorefractive keratectomy (PRK) and exposure to ultraviolet B (UVB) radiation. The right eyes of 42 New Zealand white rabbits were treated with PRK to correct -10 diopter with a 5-mm optical zone. Sponges soaked in 0.02% MMC, 10 or 40 micromol/L ceramide, or 0.5% 5-FU were applied to the right eyes of 6 rabbits each, and a tarsorrhaphy was performed. Eight weeks after complete healing, topical 0.02% MMC or 0.5% 5-FU was applied twice daily to the right eyes of 6 rabbits that had previously received PRK but no topical medication. The control group of 6 rabbits was treated only with PRK. Three weeks after PRK, all the laser-treated eyes were exposed to 100 mJ/cm UVB radiation. Corneal haze was assessed biomicroscopically every 2 weeks using the Fantes scale. Eyes were enucleated 2, 7, and 13 weeks after PRK, and tissue specimens were stained with hematoxylin and eosin and with Apostain. Corneal haze was observed in all rabbits after PRK and was aggravated by UVB irradiation. When applied immediately after PRK, MMC induced corneal opacity and apoptosis of keratocytes, but, at later times, this reagent significantly suppressed opacity, Apostain-positive keratocytes and reactivation of keratocytes, even after UVB irradiation. In contrast, ceramide and 5-FU suppressed corneal opacity after PRK, but this effect was not sustained after UVB irradiation. MMC is a potent inhibitor of haze induced by PRK and UVB irradiation. Throughout the process of corneal wound healing, the severity of apoptosis and reactivation of keratocytes was closely correlated with haze formation.

Sex-specific effects of cytotoxic chemotherapy agents cyclophospha-mide and mitomycin C on gene expression, oxidative DNA damage, and epigenetic alterations in the prefrontal cortex and hippocampus – an aging connection

PubMed Central

Kovalchuk, Anna; Rodriguez-Juarez, Rocio; Ilnytskyy, Yaroslav; Byeon, Boseon; Shpyleva, Svitlana; Melnyk, Stepan; Pogribny, Igor; Kolb, Bryan; Kovalchuk, Olga

2016-01-01

Recent research shows that chemotherapy agents can be more toxic to healthy brain cells than to the target cancer cells. They cause a range of side effects, including memory loss and cognitive dysfunction that can persist long after the completion of treatment. This condition is known as chemo brain. The molecular and cellular mechanisms of chemo brain remain obscure. Here, we analyzed the effects of two cytotoxic chemotherapy drugs—cyclophosphamide (CPP) and mitomycin C (MMC) - on transcriptomic and epigenetic changes in the murine prefrontal cortex (PFC) and hippocampal regions. We for the first time showed that CPP and MMC treatments led to profound sex- and brain region-specific alterations in gene expression profiles. Gene expression changes were most prominent in the PFC tissues of female mice 3 weeks after MMC treatment, and the gene expression response was much greater for MCC than CPP exposure. MMC exposure resulted in oxidative DNA damage, evidenced by accumulation of 8-oxo-2′-deoxyguanosine (8-oxodG) and a decrease in the level of 8-oxodG repair protein OGG1 in the PFC of female animals 3 weeks after treatment. MMC treatment decreased global DNA methylation and increased DNA hydroxymethylation in the PFC tissues of female mice. The majority of the changes induced by chemotherapy in the PFC tissues of female mice resembled those that occur during the brain's aging processes. Therefore, our study suggests a link between chemotherapy-induced chemo brain and brain aging, and provides an important roadmap for future analysis. PMID:27032448

Standardized Solution for Management Controller for MTCA.4

NASA Astrophysics Data System (ADS)

Makowski, D.; Fenner, M.; Ludwig, F.; Mavrič, U.; Mielczarek, A.; Napieralski, A.; Perek, P.; Schlarb, H.

2015-06-01

The Micro Telecommunications Computing Architecture (MTCA) standard is a modern platform that is gaining popularity in the area of High Energy Physics (HEP) experiments. The standard provides extensive management, monitoring and diagnostics functionalities. The hardware control and monitoring is based on the Intelligent Platform Management Interface (IPMI), that was initially developed for supervision of complex computers operation. The original IPMI specification was extended to support functions required by the MTCA specification. The Module Management Controller (MMC) is required on each Advanced Mezzanine Card (AMC) installed in MTCA chassis. The Rear Transition Modules (RTMs) have to be equipped with RTM Management Controllers (RMCs) which is required by the MTCA.4 subsidiary specification. The commercially available implementations of MMC and RMC are expensive and do not provide the complete functionality that is required by specific HEP applications. Therefore, many research centers and commercial companies work on their own implementation of AMC and RTM controllers. The available implementations suffer because of lack of common approach and interoperability problems. Since both Lodz University of Technology (TUL) and Deutsches Elektronen-Synchrotron (DESY) have long-term experience in developing ATCA and MTCA hardware, the authors decided to develop a unified solution of management controller fully compliant with AMC and MTCA.4 standards. The MMC v1.00 solution is dedicated for management of AMC and RTM modules. The MMC v1.00 is based on Atmel ATxmega MCUs and can be fully customized by the user or used as a drop-in-module without any modifications. The paper discusses the functionality of the MMC v1.00 solution. The implementation was verified with developed evaluation kits for AMC and RTM cards.

Unfolding of a model protein on ion exchange and mixed mode chromatography surfaces.

PubMed

Gospodarek, Adrian M; Hiser, Diana E; O'Connell, John P; Fernandez, Erik J

2014-08-15

Recent studies with proteins indicate that conformational changes and aggregation can occur during ion exchange chromatography (IEC). Such behavior is not usually expected, but could lead to decreased yield and product degradation from both IEC and multi mode chromatography (MMC) that has ligands of both hydrophobic and charged functionalities. In this study, we used hydrogen exchange mass spectrometry to investigate unfolding of the model protein BSA on IEC and MMC surfaces under different solution conditions at 25°C. Increased solvent exposure, indicating greater unfolding relative to that in solution, was found for protein adsorbed on cationic IEC and MMC surfaces in the pH range of 3.0 to 4.5, where BSA has decreased stability in solution. There was no effect of anionic surfaces at pH values in the range from 6.0 to 9.0. Differences of solvent exposure of whole molecules when adsorbed and in solution suggest that adsorbed BSA unfolds at lower pH values and may show aggregation, depending upon pH and the surface type. Measurements on digested peptides showed that classifications of stability can be made for various regions; these are generally retained as pH is changed. When salt was added to MMC systems, where electrostatic interactions would be minimized, less solvent exposure was seen, implying that it is the cationic moieties, rather than the hydrophobic ligands, which cause greater surface unfolding at low salt concentrations. These results suggest that proteins of lower stability may exhibit unfolding and aggregation during IEC and MMC separations, as they can with hydrophobic interaction chromatography. Copyright © 2014 Elsevier B.V. All rights reserved.

The effect of geometrical presentation of multimodal cation-exchange ligands on selective recognition of hydrophobic regions on protein surfaces.

PubMed

Woo, James; Parimal, Siddharth; Brown, Matthew R; Heden, Ryan; Cramer, Steven M

2015-09-18

The effects of spatial organization of hydrophobic and charged moieties on multimodal (MM) cation-exchange ligands were examined by studying protein retention behavior on two commercial chromatographic media, Capto™ MMC and Nuvia™ cPrime™. Proteins with extended regions of surface-exposed aliphatic residues were found to have enhanced retention on the Capto MMC system as compared to the Nuvia cPrime resin. The results further indicated that while the Nuvia cPrime ligand had a strong preference for interactions with aromatic groups, the Capto MMC ligand appeared to interact with both aliphatic and aromatic clusters on the protein surfaces. These observations were formalized into a new set of protein surface property descriptors, which quantified the local distribution of electrostatic and hydrophobic potentials as well as distinguishing between aromatic and aliphatic properties. Using these descriptors, high-performing quantitative structure-activity relationship (QSAR) models (R(2)>0.88) were generated for both the Capto MMC and Nuvia cPrime datasets at pH 5 and pH 6. Descriptors of electrostatic properties were generally common across the four models; however both Capto MMC models included descriptors that quantified regions of aliphatic-based hydrophobicity in addition to aromatic descriptors. Retention was generally reduced by lowering the ligand densities on both MM resins. Notably, elution order was largely unaffected by the change in surface density, but smaller and more aliphatic proteins tended to be more affected by this drop in ligand density. This suggests that modulating the exposure, shape and density of the hydrophobic moieties in multimodal chromatographic systems can alter the preference for surface exposed aliphatic or aromatic residues, thus providing an additional dimension for modulating the selectivity of MM protein separation systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Visual Internal Urethrotomy With Intralesional Mitomycin C and Short-term Clean Intermittent Catheterization for the Management of Recurrent Urethral Strictures and Bladder Neck Contractures.

PubMed

Farrell, Michael R; Sherer, Benjamin A; Levine, Laurence A

2015-06-01

To evaluate our longitudinal experience using visual internal urethrotomy (VIU) with intralesional mitomycin C (MMC) and short-term clean intermittent catheterization (CIC) for urethral strictures and bladder neck contractures (BNC) after failure of endoscopic management. This case series involved review of our prospectively developed database of all men who underwent VIU with MMC and CIC in a standardized fashion for urethral stricture or BNC between 2010 and 2013 at our tertiary care medical center. Etiology was identified as radiation-induced stricture (RIS) or non-RIS and analyzed by stricture location. Cold knife incisions were made in a tri or quadrant fashion followed by intralesional injection of MMC and 1 month of once daily CIC. All 37 patients previously underwent at least 1 intervention for urethral stricture or BNC before VIU with MMC and CIC. Mean stricture length was 2.0 cm (range, 1-6 cm; standard deviation, 1.0 cm). Over the median follow-up period of 23 months (range, 12-39 months), 75.7% of patients required no additional surgical intervention (RIS, 54.5%; non-RIS, 84.6%; P = .051). In those that did recur, median time to stricture recurrence was 8 months (range, 2-28 months). One patient with recurrence required urethroplasty. VIU with MMC followed by short-term CIC provides a minimally invasive and widely available tool to manage complex recurrent urethral strictures (<3 cm) and BNC without significant morbidity. This approach may be most attractive for patients who are poor candidates for open surgery. Copyright © 2015 Elsevier Inc. All rights reserved.

Heated naringin mitigate the genotoxicity effect of Mitomycin C in BALB/c mice through enhancing the antioxidant status.

PubMed

Maatouk, Mouna; Mustapha, Nadia; Mokdad-Bzeouich, Imen; Chaaban, Hind; Ioannou, Irina; Ghedira, Kamel; Ghoul, Mohamed; Chekir-Ghedira, Leila

2018-01-01

A major problem with cancer chemotherapy is its severe toxic effects on non-target tissues. Assessment of natural products for their protective effect against anticancer drugs induced toxicity is gaining importance in cancer biology. The aim of the present study was to evaluate the effect of native and thermal treated naringin on the protective effect against mitomycin C (MMC) induced genotoxicity. The genotoxicity in liver kidney and brain cells isolated from Balb/C mice were evaluated by performing the comet assay. Antioxidant and lipid peroxidation assays were carried out to understand the protective effects of these compounds. The comet assay showed that heated and native naringin were not genotoxic at the tested dose (40 mg/kg b.w) on liver, kidney and brain cells. A significant decrease in DNA damages was observed, at the tested doses (20 mg/kg b.w and 40 mg/kg b.w) suggesting a protective role of these molecules against the genotoxicity induced by mitomycin C on liver, kidney and brain cells. Moreover, administration of MMC (6 mg/kg b.w.) altered the activities of glutathione peroxidase and superoxide dismutase accompanied by a significant increase of lipid peroxidation. Pretreatment of mouse with heated and native naringin before MMC administration significantly raised the glutathione peroxidase and superoxide dismutase activities followed by a reduced MMC-induced lipid peroxidation. Our study demonstrated that heat treatment of naringin preserve activities of native naringin. The genoprotective properties of heated and native naringin against MMC could be attributed to its antioxidant activities and its inhibitory effect on lipid peroxidation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

September 11, 2001. A CEO's story.

PubMed

Greenberg, Jeffrey W

2002-10-01

On the day of the terrorist attacks on New York's World Trade Center, 1,779 employees of Marsh & McLennan Companies had office space in the twin towers, and another 129 were visiting that day. From his office at MMC headquarters in midtown, CEO Jeffrey Greenberg watched in horror as the second plane hit. By the time the towers fell, he had gathered a team of his colleagues to begin to outline how the company would respond. In this first-person account, Greenberg relates what it was like to manage through the unimaginable. The needs of MMC's people, and the families of employees who perished, took top priority. In the midst of chaos and unforeseeable problems, Greenberg and his colleagues improvised ways of communicating and assembled a broad-based program of support. Help appeared from all sides, from people of various ranks, titles, and functional expertise within MMC as well as past chairmen, outside directors, and retired executives. An emergency communications center was immediately set up at MMC headquarters and became a centralized location for messages and information and a memorial to colleagues lost in the attacks. The company arranged for grief counselors and established a family assistance center and a Family Relationship Management Program for those who had lost MMC employees. It has also provided families with access to long-term psychological and financial counseling. At the same time, Greenberg offers lessons about leadership, company culture, and adaptability. He and his colleagues held responsibility for a business beset by operational destruction and financial losses and facing dramatically changed market conditions. Their resolve was not simply to keep it on course but to come back stronger than ever.

Googling Service Boundaries for Endovascular Clot Retrieval Hub Hospitals in a Metropolitan Setting: Proof-of-Concept Study.

PubMed

Phan, Thanh G; Beare, Richard; Chen, Jian; Clissold, Benjamin; Ly, John; Singhal, Shaloo; Ma, Henry; Srikanth, Velandai

2017-05-01

There is great interest in how endovascular clot retrieval hubs provide services to a population. We applied a computational method to objectively generate service boundaries for such endovascular clot retrieval hubs, defined by traveling time to hub. Stroke incidence data merged with population census to estimate numbers of stroke in metropolitan Melbourne, Australia. Traveling time from randomly generated addresses to 4 endovascular clot retrieval-capable hubs (Royal Melbourne Hospital [RMH], Monash Medical Center [MMC], Alfred Hospital [ALF], and Austin Hospital [AUS]) estimated using Google Map application program interface. Boundary maps generated based on traveling time at various times of day for combinations of hubs. In a 2-hub model, catchment was best distributed when RMH was paired with MMC (model 1a, RMH 1765 km 2 and MMC 1164 km 2 ) or with AUS (model 1c, RMH 1244 km 2 and AUS 1685 km 2 ), with no statistical difference between models ( P =0.20). Catchment was poorly distributed when RMH was paired with ALF (model 1b, RMH 2252 km 2 and ALF 676 km 2 ), significantly different from both models 1a and 1c (both P <0.05). Model 1a had the greatest proportion of patients arriving within ideal time of 30 minutes followed by model 1c ( P <0.001). In a 3-hub model, the combination of RMH, MMC, and AUS was superior to that of RMH, MMC, and ALF in catchment distribution and travel time. The method was also successfully applied to the city of Adelaide demonstrating wider applicability. We provide proof of concept for a novel computational method to objectively designate service boundaries for endovascular clot retrieval hubs. © 2017 American Heart Association, Inc.

Integrin α5β1 Inhibition by CLT-28643 Reduces Postoperative Wound Healing in a Mouse Model of Glaucoma Filtration Surgery.

PubMed

Van Bergen, Tine; Zahn, Grit; Caldirola, Patrizia; Fsadni, Mario; Caram-Lelham, Ninus; Vandewalle, Evelien; Moons, Lieve; Stalmans, Ingeborg

2016-11-01

To evaluate the therapeutic potential of the small molecule integrin α5β1 inhibitor, CLT-28643, to improve the filtering surgery outcome in a mouse model. Different dose regimens and administration routes of the inhibitor were compared with mitomycin C (MMC), the gold standard in clin ical practice. The efficacy of CLT-28643 on surgical outcome was studied in a mouse model for filtering surgery (n = 40 eyes from 20 mice per group). Single and repeated subconjunctival (SCJ) injections (1 or 2 μg) and topical eye drops (10 μg) of the integrin inhibitor were compared with 2-minute administration of MMC 0.02%. Bleb size, survival, and signs of toxicity were examined until 28 days after surgery. Immunohistochemical analysis of angiogenesis, inflammation, collagen deposition, and integrin α5β1 expression were performed on postoperative days 3, 8, 14, and 28. A masked observer performed all the assessments. Immunostaining showed that integrin α5β1 was highly expressed in the bleb at early time-points after surgery and that CLT-28643 inhibited this upregulation. Efficacy was shown to be dose-dependent for the integrin inhibitor CLT-28643 for bleb area and survival, and the wound healing process. While 2-μg single injection of CLT-28643 improved bleb characteristics in a similar way as 10-μg administered by eye drops and MMC, repeated injections of 2 μg showed superior efficacy compared to MMC, with no corneal toxicity. Administration of the integrin α5β1 inhibitor CLT-28643 has therapeutic potential as an adjunct to glaucoma surgery, possibly with a superior efficacy and tolerability compared with MMC when used at the optimal dose.

Proteomic profiling of an undefined microbial consortium cultured in fermented dairy manure: Methods development.

PubMed

Hanson, Andrea J; Paszczynski, Andrzej J; Coats, Erik R

2016-03-01

The production of polyhydroxyalkanoates (PHA; bioplastics) from waste or surplus feedstocks using mixed microbial consortia (MMC) and aerobic dynamic feeding (ADF) is a growing field within mixed culture biotechnology. This study aimed to optimize a 2DE workflow to investigate the proteome dynamics of an MMC synthesizing PHA from fermented dairy manure. To mitigate the challenges posed to effective 2DE by this complex sample matrix, the bacterial biomass was purified using Accudenz gradient centrifugation (AGC) before protein extraction. The optimized 2DE method yielded high-quality gels suitable for quantitative comparative analysis and subsequent protein identification by LC-MS/MS. The optimized 2DE method could be adapted to other proteomic investigations involving MMC in complex organic or environmental matrices. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Magnetic Microcalorimeter (MMC) Gamma Detectors with Ultra-High Energy Resolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Friedrich, Stephen

The goal of this LCP is to develop ultra-high resolution gamma detectors based on magnetic microcalorimeters (MMCs) for accurate non-destructive analysis (NDA) of nuclear materials. For highest energy resolution, we will introduce erbium-doped silver (Ag:Er) as a novel sensor material, and implement several geometry and design changes to improve the signal-to-noise ratio. The detector sensitivity will be increased by developing arrays of 32 Ag:Er pixels read out by 16 SQUID preamplifiers, and by developing a cryogenic Compton veto to reduce the spectral background. Since best MMC performance requires detector operation at ~10 mK, we will purchase a dilution refrigerator withmore » a base temperature <10 mK and adapt it for MMC operation. The detector performance will be tested with radioactive sources of interest to the safeguards community.« less

Cytostatica efficiency enhancement by vitamins C, E and β-carotene under irradiation. State of the art

NASA Astrophysics Data System (ADS)

Getoff, Nikola

2001-01-01

A review is presented on the enhancement of MMC (mitomycin C) efficiency by the vitamins C, E and β-carotene using E. coil bacteria (AB 1157) and leukemia cells (HL 60) as a model for experiments in vitro. New and previously published spectroscopic and kinetic data of transients obtained by pulse radiolysis of MMC and the above mentioned vitamins were also discussed. Based on all these results a possible cascade electron transfer process from vit. C→ vit. E→ β-car.→MMC or oxidants in the living cells is presented. By vit. C deficiency a cell mutation might occur, possibly leading to appearance of cancer. The presented radiation chemical and radiation biological characteristic data are of importance as a basis for the development of an improved chemo-radiation therapy of cancer.

21 CFR 1311.105 - Requirements for obtaining an authentication credential-Individual practitioners.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Office of Technology Strategy/Division of Identity Management to conduct identity proofing that meets the... assurance level or above. (b) The practitioner must submit identity proofing information to the credential...

Redefining commercial vehicle permitting and credentialing violations.

DOT National Transportation Integrated Search

2015-08-01

The objective of this study was to analyze enforcement and adjudication of common commercial vehicle tax, credentialing, and safety offenses. This study examined violations of the International Fuel Tax Agreement and the Kentucky Intrastate Tax, Kent...

Credentialism among Graduate Students.

ERIC Educational Resources Information Center

Stodt, Martha McGinty; Thielens, Wagner, Jr.

1985-01-01

An exploratory study of students entering four elite fields found that most sought both credentials and competence. Stiff competition within chosen occupations led the majority of students to seek every advantage that graduate education could provide. (Author/MLW)

Mechanisms and FEM Simulation of Chip Formation in Orthogonal Cutting In-Situ TiB2/7050Al MMC

PubMed Central

Wang, Wenhu; Jiang, Ruisong; Lin, Kunyang; Shao, Mingwei

2018-01-01

The in-situ TiB2/7050Al composite is a new kind of Al-based metal matrix composite (MMC) with super properties, such as low density, improved strength, and wear resistance. This paper, for a deep insight into its cutting performance, involves a study of the chip formation process and finite element simulation during orthogonal cutting in-situ TiB2/7050Al MMC. With chips, material properties, cutting forces, and tool geometry parameters, the Johnson–Cook (J–C) constitutive equation of in-situ TiB2/7050Al composite was established. Then, the cutting simulation model was established by applying the Abaqus–Explicit method, and the serrated chip, shear plane, strain rate, and temperature were analyzed. The experimental and simulation results showed that the obtained material’s constitutive equation was of high reliability, and the saw-tooth chips occurred commonly under either low or high cutting speed and small or large feed rate. From result analysis, it was found that the mechanisms of chip formation included plastic deformation, adiabatic shear, shearing slip, and crack extension. In addition, it was found that the existence of small, hard particles reduced the ductility of the MMC and resulted in segmental chips. PMID:29662047

The Covariance Adjustment Approaches for Combining Incomparable Cox Regressions Caused by Unbalanced Covariates Adjustment: A Multivariate Meta-Analysis Study.

PubMed

Dehesh, Tania; Zare, Najaf; Ayatollahi, Seyyed Mohammad Taghi

2015-01-01

Univariate meta-analysis (UM) procedure, as a technique that provides a single overall result, has become increasingly popular. Neglecting the existence of other concomitant covariates in the models leads to loss of treatment efficiency. Our aim was proposing four new approximation approaches for the covariance matrix of the coefficients, which is not readily available for the multivariate generalized least square (MGLS) method as a multivariate meta-analysis approach. We evaluated the efficiency of four new approaches including zero correlation (ZC), common correlation (CC), estimated correlation (EC), and multivariate multilevel correlation (MMC) on the estimation bias, mean square error (MSE), and 95% probability coverage of the confidence interval (CI) in the synthesis of Cox proportional hazard models coefficients in a simulation study. Comparing the results of the simulation study on the MSE, bias, and CI of the estimated coefficients indicated that MMC approach was the most accurate procedure compared to EC, CC, and ZC procedures. The precision ranking of the four approaches according to all above settings was MMC ≥ EC ≥ CC ≥ ZC. This study highlights advantages of MGLS meta-analysis on UM approach. The results suggested the use of MMC procedure to overcome the lack of information for having a complete covariance matrix of the coefficients.

Structure-Activity Relationships of Peptides Incorporating a Bioactive Reverse-Turn Heterocycle at the Melanocortin Receptors: Identification of a 5,800-fold Mouse Melanocortin-3 Receptor (mMC3R) Selective Antagonist/Partial Agonist versus the Mouse Melanocortin-4 Receptor (mMC4R)

PubMed Central

Singh, Anamika; Dirain, Marvin; Witek, Rachel; Rocca, James R.; Edison, Arthur S; Haskell-Luevano, Carrie

2013-01-01

The melanocortin-3 (MC3) and melanocortin-4 (MC4) receptors regulate energy homeostasis, food intake, and associated physiological conditions. The MC4R has been studied extensively. Less is known about specific physiological roles of the MC3R. A major obstacle to this lack of knowledge is attributed to a limited number of identified MC3R selective ligands. We previously reported a spatial scanning approach of a 10-membered thioether-heterocycle ring incorporated into a chimeric peptide template that identified a lead nM MC4R ligand. Based upon those results, 17 compounds were designed and synthesized that focused upon modification in the pharmacophore domain. Notable results include the identification of a 0.13 nM potent 5800-fold mMC3R selective antagonist/slight partial agonist versus a 760 nM mMC4R full agonist (ligand 11). Biophysical experiments (2D 1H NMR and computer assisted molecular modeling) of this ligand resulted in the identification of an inverse γ-turn secondary structure in the ligand pharmacophore domain. PMID:23432160

Synthesis of a Fluorescently Labeled 68Ga-DOTA-TOC Analog for Somatostatin Receptor Targeting.

PubMed

Ghosh, Sukhen C; Hernandez Vargas, Servando; Rodriguez, Melissa; Kossatz, Susanne; Voss, Julie; Carmon, Kendra S; Reiner, Thomas; Schonbrunn, Agnes; Azhdarinia, Ali

2017-07-13

Fluorescently labeled imaging agents can identify surgical margins in real-time to help achieve complete resections and minimize the likelihood of local recurrence. However, photon attenuation limits fluorescence-based imaging to superficial lesions or lesions that are a few millimeters beneath the tissue surface. Contrast agents that are dual-labeled with a radionuclide and fluorescent dye can overcome this limitation and combine quantitative, whole-body nuclear imaging with intraoperative fluorescence imaging. Using a multimodality chelation (MMC) scaffold, IRDye 800CW was conjugated to the clinically used somatostatin analog, 68 Ga-DOTA-TOC, to produce the dual-labeled analog, 68 Ga-MMC(IRDye 800CW)-TOC, with high yield and specific activity. In vitro pharmacological assays demonstrated retention of receptor-targeting properties for the dual-labeled compound with robust internalization that was somatostatin receptor (SSTR) 2-mediated. Biodistribution studies in mice identified the kidneys as the primary excretion route for 68 Ga-MMC(IRDye 800CW)-TOC, along with clearance via the reticuloendothelial system. Higher uptake was observed in most tissues compared to 68 Ga-DOTA-TOC but decreased as a function of time. The combination of excellent specificity for SSTR2-expressing cells and suitable biodistribution indicate potential application of 68 Ga-MMC(IRDye 800CW)-TOC for intraoperative detection of SSTR2-expressing tumors.

A simple method to assess in vivo proliferation in lung vasculature with EdU: the case of MMC-induced PVOD in rat.

PubMed

Fabrice, Antigny; Benoît, Ranchoux; Valérie, Nadeau; Lau, Edmund; Sébastien, Bonnet; Frédéric, Perros

2015-01-01

5-Ethynyl-2'-deoxyuridine (EdU) incorporation is becoming the gold standard method for in vitro and in vivo visualization of proliferating cells. The small size of the fluorescent azides used for detection results in a high degree of specimen penetration. It can be used to easily detect DNA replication in large tissue samples or organ explants with low proliferation and turnover of cells formerly believed to be in a "terminal" state of differentiation. Here we describe a protocol for the localization and identification of proliferating cells in quiescent or injured pulmonary vasculature, in a model of pulmonary veno-occlusive disease (PVOD). PVOD is an uncommon form of pulmonary hypertension characterized by progressive obstruction of small pulmonary veins. We previously reported that mitomycin-C (MMC) therapy is associated with PVOD in human. We demonstrated that MMC can induce PVOD in rats, which currently represents the sole animal model that recapitulates human PVOD lesions. Using the EdU assay, we demonstrated that MMC-exposed lungs displayed areas of exuberant microvascular endothelial cell proliferation which mimics pulmonary capillary hemangiomatosis, one of the pathologic hallmarks of human PVOD. In vivo pulmonary cell proliferation measurement represents an interesting methodology to investigate the potential efficacy of therapies aimed at normalizing pathologic angioproliferation.

Genetic algorithm with maximum-minimum crossover (GA-MMC) applied in optimization of radiation pattern control of phased-array radars for rocket tracking systems.

PubMed

Silva, Leonardo W T; Barros, Vitor F; Silva, Sandro G

2014-08-18

In launching operations, Rocket Tracking Systems (RTS) process the trajectory data obtained by radar sensors. In order to improve functionality and maintenance, radars can be upgraded by replacing antennas with parabolic reflectors (PRs) with phased arrays (PAs). These arrays enable the electronic control of the radiation pattern by adjusting the signal supplied to each radiating element. However, in projects of phased array radars (PARs), the modeling of the problem is subject to various combinations of excitation signals producing a complex optimization problem. In this case, it is possible to calculate the problem solutions with optimization methods such as genetic algorithms (GAs). For this, the Genetic Algorithm with Maximum-Minimum Crossover (GA-MMC) method was developed to control the radiation pattern of PAs. The GA-MMC uses a reconfigurable algorithm with multiple objectives, differentiated coding and a new crossover genetic operator. This operator has a different approach from the conventional one, because it performs the crossover of the fittest individuals with the least fit individuals in order to enhance the genetic diversity. Thus, GA-MMC was successful in more than 90% of the tests for each application, increased the fitness of the final population by more than 20% and reduced the premature convergence.

Mitomycin C, 5-fluorouracil, and cyclosporin A prevent epidural fibrosis in an experimental laminectomy model

PubMed Central

Yildiz, Kartal Hakan; Gezen, Ferruh; Cukur, Selma; Dosoglu, Murat

2007-01-01

This study examined the preventive effects of the local application of mitomycin C (MMC), 5-fluorouracil (5-FU), and cyclosporine A (CsA) in minimizing spinal epidural fibrosis in a rat laminectomy model. Thirty-two 2-year-old male Wistar albino rats, each weighing 400 ± 50 g, were divided into four equal groups: sham, MMC, 5-FU, and CsA. Each rat underwent laminectomy at the L5–L6 lumbar level. Cotton pads (4 × 4 mm2) soaked with MMC (0.5 mg/ml), 5-FU (5 ml/mg), or CsA (5 mg/ml) were placed on the exposed dura for 5 min. Thirty days after surgery, the rats were killed and the epidural fibrosis, fibroblast density, inflammatory cell density, and arachnoid fibrosis were quantified. The epidural and arachnoid fibroses were reduced significantly in the treatment groups compared to the sham group. Fibroblast cell density and inflammatory cell density were decreased significantly in the MMC and 5-FU groups, but were similar in the sham and CsA groups. The decreased rate of epidural fibrosis was promising. Further studies in humans are needed to determine the short- and long-term complications of the agents used here. PMID:17387523

Genetic Algorithm with Maximum-Minimum Crossover (GA-MMC) Applied in Optimization of Radiation Pattern Control of Phased-Array Radars for Rocket Tracking Systems

PubMed Central

Silva, Leonardo W. T.; Barros, Vitor F.; Silva, Sandro G.

2014-01-01

In launching operations, Rocket Tracking Systems (RTS) process the trajectory data obtained by radar sensors. In order to improve functionality and maintenance, radars can be upgraded by replacing antennas with parabolic reflectors (PRs) with phased arrays (PAs). These arrays enable the electronic control of the radiation pattern by adjusting the signal supplied to each radiating element. However, in projects of phased array radars (PARs), the modeling of the problem is subject to various combinations of excitation signals producing a complex optimization problem. In this case, it is possible to calculate the problem solutions with optimization methods such as genetic algorithms (GAs). For this, the Genetic Algorithm with Maximum-Minimum Crossover (GA-MMC) method was developed to control the radiation pattern of PAs. The GA-MMC uses a reconfigurable algorithm with multiple objectives, differentiated coding and a new crossover genetic operator. This operator has a different approach from the conventional one, because it performs the crossover of the fittest individuals with the least fit individuals in order to enhance the genetic diversity. Thus, GA-MMC was successful in more than 90% of the tests for each application, increased the fitness of the final population by more than 20% and reduced the premature convergence. PMID:25196013

School Counselors and Student Assessment

ERIC Educational Resources Information Center

Blacher, Joan H.; Murray-Ward, Mildred; Uellendahl, Gail E.

2005-01-01

National school counselor certification examinations and state credentialing standards require knowledge of and skill development in assessment (California Commission on Teacher Credentialing [CCTC], 2001; National Board for Certified Counselors, 1998). And, professional associations have specified assessment competencies (American School…

46 CFR 15.720 - Use of non-U.S.-credentialed personnel.

Code of Federal Regulations, 2014 CFR

2014-10-01

... MANNING REQUIREMENTS Limitations and Qualifying Factors § 15.720 Use of non-U.S.-credentialed personnel... outside the jurisdiction of the United States, in order to meet manning requirements, may use non-U.S...

28 CFR 544.74 - Work assignment limitations.

Code of Federal Regulations, 2014 CFR

2014-07-01

... program. (2) An inmate ordinarily must show prior attainment of a GED credential or high school diploma in... attainment of a GED credential or high school diploma to be promoted above the minimum pay level or grade in...

28 CFR 544.74 - Work assignment limitations.

Code of Federal Regulations, 2011 CFR

2011-07-01

... program. (2) An inmate ordinarily must show prior attainment of a GED credential or high school diploma in... attainment of a GED credential or high school diploma to be promoted above the minimum pay level or grade in...

28 CFR 544.74 - Work assignment limitations.

Code of Federal Regulations, 2012 CFR

2012-07-01

... program. (2) An inmate ordinarily must show prior attainment of a GED credential or high school diploma in... attainment of a GED credential or high school diploma to be promoted above the minimum pay level or grade in...

28 CFR 544.74 - Work assignment limitations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... program. (2) An inmate ordinarily must show prior attainment of a GED credential or high school diploma in... attainment of a GED credential or high school diploma to be promoted above the minimum pay level or grade in...

Audited credential delegation: a usable security solution for the virtual physiological human toolkit.

PubMed

Haidar, Ali N; Zasada, Stefan J; Coveney, Peter V; Abdallah, Ali E; Beckles, Bruce; Jones, Mike A S

2011-06-06

We present applications of audited credential delegation (ACD), a usable security solution for authentication, authorization and auditing in distributed virtual physiological human (VPH) project environments that removes the use of digital certificates from end-users' experience. Current security solutions are based on public key infrastructure (PKI). While PKI offers strong security for VPH projects, it suffers from serious usability shortcomings in terms of end-user acquisition and management of credentials which deter scientists from exploiting distributed VPH environments. By contrast, ACD supports the use of local credentials. Currently, a local ACD username-password combination can be used to access grid-based resources while Shibboleth support is underway. Moreover, ACD provides seamless and secure access to shared patient data, tools and infrastructure, thus supporting the provision of personalized medicine for patients, scientists and clinicians participating in e-health projects from a local to the widest international scale.

Audited credential delegation: a usable security solution for the virtual physiological human toolkit

PubMed Central

Haidar, Ali N.; Zasada, Stefan J.; Coveney, Peter V.; Abdallah, Ali E.; Beckles, Bruce; Jones, Mike A. S.

2011-01-01

We present applications of audited credential delegation (ACD), a usable security solution for authentication, authorization and auditing in distributed virtual physiological human (VPH) project environments that removes the use of digital certificates from end-users' experience. Current security solutions are based on public key infrastructure (PKI). While PKI offers strong security for VPH projects, it suffers from serious usability shortcomings in terms of end-user acquisition and management of credentials which deter scientists from exploiting distributed VPH environments. By contrast, ACD supports the use of local credentials. Currently, a local ACD username–password combination can be used to access grid-based resources while Shibboleth support is underway. Moreover, ACD provides seamless and secure access to shared patient data, tools and infrastructure, thus supporting the provision of personalized medicine for patients, scientists and clinicians participating in e-health projects from a local to the widest international scale. PMID:22670214

Reasons identified for seeking the American Physical Therapy Association-Credentialed Clinical Instructor Program (CCIP) in Florida.

PubMed

Musolino, Gina M; van Duijn, Jacqueline; Noonan, Ann C; Eargle, Linda K; Gray, Debra L

2013-01-01

The American Physical Therapy Association's (APTA) Strategic Plan strives to increase the number of APTA credentialed clinical instructors. Available to all health care providers, as of 2012, there were 39,851 credentialed clinical instructors. Study purposes were threefold: to determine participants' a. reasons to attend the APTA Credentialed Clinical Instructor Program (CCIP); b. pre-CCIP learning goals; and c. related post-CCIP learning outcomes. This IRB-approved study was completed with informed consent procedures followed. APTA CCIP credentialed trainers (n=5) developed a survey and pilot tested for face and content validity. The instrument included demographics, forced choice and open-ended questions. The pre/post survey was administered to 301 participants of 21 Florida APTA CCIP courses with 5 trainers from 2009-2011. Quantitative survey data were collated, tabulated, and summarized comparing pre/post data. Narrative data was analyzed for codes and themes, synthesized, re-contextualized and triangulated by trainers then cross-compared with APTA CCIP objectives and trainer expertise. The qualitative insights were presented with resulting primary themes and subthemes. Results informed the study purposes with a clear determination of the reasons participants attend the APTA CCIP, the pre-course goals and post learning outcomes. Participants overwhelmingly recommend the APTA CCIP and most receive support from employers with geographic course location being a prime reason for course selection. Precourse learning goals included 5 over-arching themes, with few sub-themes; while post learning outcomes generated 12 specific themes with numerous subthemes. APTA CCIP-credentialed clinical instructors are achieving numerous learning outcomes immediately applicable for clinical education.

33 CFR 160.310 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

....310 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND... credential; (5) Transportation Worker Identification Credential (TWIC) issued by the Transportation Security... authority of the government of a country that has ratified the International Labour Organization Seafarers...