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2. Cold stored platelets in the management of bleeding: is it about bioenergetics?

Author

George, CE, Saunders, CV, Morrison, A, Scorer, T, Jones, S, Dempsey-Hibbert, N, George, CE, Saunders, CV, Morrison, A, Scorer, T, Jones, S, and Dempsey-Hibbert, N

Abstract

When platelet concentrates (PCs) were first introduced in the 1960s as a blood component therapy, they were stored in the cold. As platelet transfusion became more important for the treatment of chemotherapy-induced thrombocytopenia, research into ways to increase supply intensified. During the late 1960s/early 1970s, it was demonstrated through radioactive labeling of platelets that room temperature platelets (RTP) had superior post-transfusion recovery and survival compared with cold-stored platelets (CSP). This led to a universal switch to room temperature storage, despite CSP demonstrating superior hemostatic effectiveness upon being transfused. There has been a global resurgence in studies into CSP over the last two decades, with an increase in the use of PC to treat acute bleeding within hospital and pre-hospital care. CSP demonstrate many benefits over RTP, including longer shelf life, decreased bacterial risk and easier logistics for transport, making PC accessible in areas where they have not previously been, such as the battlefield. In addition, CSP are reported to have greater hemostatic function than RTP and are thus potentially better for the treatment of bleeding. This review describes the history of CSP, the functional and metabolic assays used to assess the platelet storage lesion in PC and the current research, benefits and limitations of CSP. We also discuss whether the application of new technology for studying mitochondrial and glycolytic function in PC could provide enhanced understanding of platelet metabolism during storage and thus contribute to the continued improvements in the manufacturing and storage of PC.

Published
2023

3. Low-cost, facile droplet modification of screen-printed arrays for internally validated electrochemical detection of serum procalcitonin

Author

Roberto de Oliveira, P, Crapnell, RD, Garcia-Miranda Ferrari, A, Wuamprakhon, P, Hurst, NJ, Dempsey-Hibbert, N, Sawangphruk, M, Janegitz, BC, Banks, CE, Roberto de Oliveira, P, Crapnell, RD, Garcia-Miranda Ferrari, A, Wuamprakhon, P, Hurst, NJ, Dempsey-Hibbert, N, Sawangphruk, M, Janegitz, BC, and Banks, CE

Abstract

This manuscript presents the design and facile production of screen-printed arrays (SPAs) for the internally validated determination of raised levels of serum procalcitonin (PCT). The screen-printing methodology produced SPAs with six individual working electrodes that exhibit an inter-array reproducibility of 3.64% and 5.51% for the electrochemically active surface area and heterogenous electrochemical rate constant respectively. The SPAs were modified with antibodies specific for the detection of PCT through a facile methodology, where each stage simply uses droplets incubated on the surface, allowing for their mass-production. This platform was used for the detection of PCT, achieving a linear dynamic range between 1 and 10 ng mL−1 with a sensor sensitivity of 1.35 × 10−10 NIC%/ng mL−1. The SPA produced an intra- and inter-day %RSD of 4.00 and 5.05%, with a material cost of £1.14. Internally validated human serum results (3 sample measurements, 3 control) for raised levels of PCT (>2 ng mL−1) were obtained, with no interference effects seen from CRP and IL-6. This SPA platform has the potential to offer clinicians vital information to rapidly begin treatment for “query sepsis” patients while awaiting results from more lengthy remote laboratory testing methods. Analytical ranges tested make this an ideal approach for rapid testing in specific patient populations (such as neonates or critically ill patients) in which PCT ranges are inherently wider. Due to the facile modification methods, we predict this could be used for various analytes on a single array, or the array increased further to maintain the internal validation of the system.

Published
2023

4. The Effect of Human Blood Plasma Conditioning Films on Platelet Transfusion Bag Surface Properties

Author

Wilson-Nieuwenhuis, J, Dempsey-Hibbert, N, Liauw, CM, Whitehead, KA, Wilson-Nieuwenhuis, J, Dempsey-Hibbert, N, Liauw, CM, and Whitehead, KA

Abstract

Transfusion-associated bacterial infections continue to occur which may be due to the formation of bacterial biofilms on the inner surface of the blood bag. Plasticized poly (vinyl chloride) (p-PVC) platelet storage bags in three surface roughness states (rough, smooth and flattened) were used to determine the effect that a conditioning film (CF) of human plasma had on surface properties and its interaction with Staphylococcus epidermidis and Serratia marcescens. SEM and optical profilometry determined changes in surface roughness, whilst EDX and ATR-FTIR determined surface chemistry. The physicochemistry of the surfaces and bacteria was assessed using contact angle measurements and MATH assays respectively. When applied to a rougher surface, the CF reduced the surface topography, masked certain surface chemistry features and made the surfaces more hydrophilic. The CF reduced the adhesion of the bacteria to most of the hydrocarbons. When human plasma was combined with bacteria, most of the physicochemical properties changed similarly to those of human plasma alone, with the most significant changes observed after 24 h especially with Ser. marcescens. The results demonstrated that the presence of human plasma had a significant effect on the surface properties of the platelet bags and also on microbial interactions with the bag surface.

Published
2022

6. Estrogen deficiency – a central paradigm in age-related impaired healing?

Author

El Mohtadi, M, Whitehead, K, Dempsey-Hibbert, N, Belboul, A, Ashworth, J, El Mohtadi, M, Whitehead, K, Dempsey-Hibbert, N, Belboul, A, and Ashworth, J

Abstract

Wound healing is a dynamic biological process achieved through four sequential, overlapping phases; hemostasis, inflammation, tissue proliferation and remodeling. For effective wound healing, all four phases must occur in the appropriate order and time frame. It is well accepted that the wound healing process becomes disrupted in the elderly, increasing the propensity of non-healing wound states that can lead to substantial patient morbidity and an enormous financial burden on healthcare systems. Estrogen deprivation in the elderly has been identified as the key driver of age-related delayed wound healing in both genders, with topical and systemic estrogen replacement reversing the detrimental effects of aging on wound repair. Evidence suggests estrogen deprivation may contribute to the development of chronic wound healing states in the elderly but research in this area is somewhat limited, warranting further investigations. Moreover, although the beneficial effects of estrogen on cutaneous healing have been widely explored, the development of estrogen-based treatments to enhance wound repair in the elderly have yet to be widely exploited. This review explores the critical role of estrogen in reversing age-related impaired healing and evaluates the prospect of developing more focused novel therapeutic strategies that enhance wound repair in the elderly via activation of specific estrogen signaling pathways in regenerating tissues, whilst leaving non-target tissues largely unaffected.

Published
2021

7. Differential engulfment of staphylococcus aureus and pseudomonas aeruginosa by monocyte-derived macrophages is associated with altered phagocyte biochemistry and morphology

Author

Mohtadi, ME, Pilkington, L, Liauw, CM, Ashworth, JJ, Dempsey-Hibbert, N, Belboul, A, Whitehead, KA, Mohtadi, ME, Pilkington, L, Liauw, CM, Ashworth, JJ, Dempsey-Hibbert, N, Belboul, A, and Whitehead, KA

Abstract

© 2020, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved. Knowledge of changes in macrophages following bacterial engulfment is limited. U937-derived macrophages were incubated with Staphylococcus aureus or Pseudomonas aeruginosa. Morphological and biochemical changes in macrophages following host-pathogen interactions were visualized using Scanning Electron Microscopy (SEM) and Fourier-Transform Infrared Spectroscopy (FTIR) respectively. Principal Component Analysis (PCA) was used to assess the variability in the FTIR spectra. Following host-pathogen interactions, survival of S. aureus was significantly lower than P. aeruginosa (P<0.05) and cellular morphology of macrophages was different after incubation with S. aureus compared to P. aeruginosa. Following incubation with S. aureus macrophages were more globular and amorphous in shape whereas long linear pseudopodia were observed following incubation with P. aeruginosa. Distinct FTIR spectra were identified in macrophages post interaction with the different bacteria and PCA analysis demonstrated distinct biochemical differences in the phagocytes following engulfment of the bacteria, with > 99 % of variability in the FTIR spectra explained by the first two principal components. These findings demonstrated that there were clear morphological and biochemical changes in macrophages following engulfment of two different bacterial types suggesting that the biochemical components of the bacterial cell wall influenced the biochemical characteristics and hence the morphology of macrophages in distinct ways.

Published
2020

8. Acknowledgement to reviewers of social sciences in 2019

Author

Abbas, A., Abel, G., Abreu, A., Adam, A., Adamek, M., Adiletta, G., Adusei-asante, K.A., Romeo, M.D.M., Alderson, A., Alfaro, E., Aliverti, A., Almeida, Fernando, Álvarez-gonzález, L.I., Amelina, A., Anand, C., Anderson, G., Andreasson, J., Ang, I., Aragon, J., Arcidiacono, C., Arcuri, S., Assante, D., Atukeren, E., Avery, H., Ayeb-karlsson, S., Azadi, H., Bachman, R., Bader, M., Badulescu, A., Bahmanteymouri, E., Baines, S., Baker, T., Baker‐beall, C., Bañón, L., Bar‐am, N., Barbier‐greenland, K., Barnett, R., Barragán‐escandón, A., Barreto, A.M., Barrett, E., Bartkowski, J., Bartram, R., Bartzas, G., Bates, D., Baviera‐puig, A., Bayley, A., Beazley, H., Beer, C., Behr, H., Beier, G., Belford, N., Bencivenga, R., Benli, A.E., Benton‐short, L., Berei, J.M., Berbel‐pineda, E., Bernstein, Berntzen, E.R., Bertella, L., Birney, G., Bittle, M., Black, S., Rivero, L.B., Blattner, J.J., Blok, C., Blount, A., Boas, Y., Bockarie, I., Bockerman, A., Bodén, P., Bönisch‐brednich, L., Bontje, B., Bontje, M., Borsellino, V., Bostan, I., Bowl, M., Bowman, B., Bracci, E., Bracken, C.M., Bradley, H., Brereton, P., Brewer, J., Bridge, D., Brooks, S., Brown, Andrijana, Brzoska, M., Brzozowski, W., Buckley, G., Buente, W., Bullaro, G.R., Burke, M.D., Burlacu, S., Busu, M., Butler, S., Byrne, J., Cabral, L., Cai, Y., Cajias, M., Calin, A.C., Callegari, C., Camarero, M., Campbell-figuerola, H., Campbell, J.R., Cannito, M., Canonico, E., Canosa, A., Carabelli, G., Carlbom, A., Carlone, T., Caron, R., Carpenter, A., Caruso, G., Casais, B., Castro, M.P., Cava, M.-J., Čeněk, J., Cerchione, R., Certomà, C., Chan, E., Charles, D., Charlwood, A., Chatzifotiou, S., Chell, K., Chen, L., Chen, Q., Chen, W.-J., Ching, L., Christensen, J., Ciasullo, M.V., Cimermanová, I., Činčera, J., Cipollina, M., Clutterbuck, R., Cochrane, B., Collin, K., Conley, R., Connell, H., Connelly, J., Connelly, L., Connelly, R., Conti, D., Conversi, D., Conway, G., Cooper, S., Cope, M., Corsini, F., Cristian, P., Crohn, H.M., Croog, R.C., Salazar, T., Csiszár, C., D’auria, I., D’souza, A., D’souza, N., Dabija, D.-C., Dagg, J., Dalby, S., DaleDalsgård, B., Dʹamato, A.L., Daniel, D., Dant, L., Dantas, C., Darwin, H., Dashper, K., David, M.E., De Flippo, D., De, A., Edi, M., Velázquez, E.D.C., Velázquez, F., Del Vecchio, P., Delatolla, A., Delgado, P., Delgado‐romero, E., Delrosso, J., Desimone, J., Detlefsen, L., Devaney, C., Díaz, L.M., Didham, R., Diogo, E., Dirakis, A., Doberneck, D., Doidge, M.D., Molero, G., Dombrowski, P.J., Doñate, C., Đorđević, Martín, Reis, P.G.R., Doucek, P., Dundes, L., Dvouletý, O., Dybo, T., Eastman, J., Eckhardt, J., Economou, A., Edler, D., Edu, U., Ekblom, P.E., Khaled, D., Ellis, C., Elsabry, E., Erceg, A., Erokhin, V., Ertz, M., Everitt, J., Evers, A., Falcone, P.M.F., Cabana, P., Fawcett, B., Fearnley, B., Featherstone, M., Ferreira, M., Ferreira, P., Fetner, T., Fisher, J., Fisher, R., Fitzpatrick, T., Flanagan, C., Fogarty, E.A., Fonchingong, C.C., Fontana, M., Fook, J., Foreman, A.M., Foster‐mcgregor, N., Fox, S., Franco, J.A., Franklin, A.L., Friedrich, T., Fromm, I., Fu, N., Fucà, R., Fukuda, Y., Fusco, G., Gabriela, D., Galan, D., Gamo, A., Galiano, J., Garcia, A., García, M.E.A., García‐germán, S., García‐machado, J.J., García‐ruiz, C.R., Gavini, M., Gazzano, A., Gebhardt, M., Gerson, S., Gherghina, Ş.C., Gibbs, P., Gilhooly, D., Gill, F., Gill, N., Gil‐lopez, A.J., Ginès Fabrellas, A., Giuffrida, N., Giuliani, G., Goddard, J., Godderis, R., Goh, C.S., Gomes, O., Goncharuk, A.G., Canche, M.G., Pérez, I.G., Valero, G., González, R.C.L., Gonzalez‐benson, O., Gonzalez‐feliu, J., González‐lópez, M., Gozdziak, E., Granx, B., Gran, R., Gray, S.L., Grbes, A., Grondys, K., Grugan, S., Guenther, J., Guijarro, F., Gurko, T., Haas, L.L., Hagellx, A., Hagell, H., Hallgrímsdóttir, H., Hamada, T., Hanf, J., Hannouf, M., Hao, F., Harman, G., Harris, K.L., Harris, R., Harrison, N.H., Healy, G., Healy, K., Heikkilä, E., Hellmich, C., Henig, J., Henninger, C.E., Heo, W., Herman, C., Herrero‐diz, P., Heyman, J., Hibbert, N., Hillman, A.L., Hillman, B., Hine, B., Hino, K., Hinten, M., Hipp, L., Hoang, D., Holleran, D., Hollin, I., Holm, M., Holmes, C., Hook, G., Hoornweg, D., Hopper, L., Hossain, M., Hoxhaj, R., Hu, B., Huang, Y., Huarita, E., Hudec, O., Humbert, A.L., Hung, M.-C., Hunt, A., Husu, L., IanoleIbáñez‐gonzález, R., Ibáñez‐gonzález, M.J., Ide, T., Ijaz, Muhammad Fazal, Impicciatore, R., Ingwersen, M., Ioannides, D., Iseppi, L., Islam, M.M., Jaakkola, M., Jagger, S., Jagosh, J., Jenkin, G., Joelsson, T., Johansen, R.E.B., Johnsen, H.C., Garmann Jona, G., Jones, T., Judit, O., Kalalahti, M., Kang, M., Kantamaneni, K., Kaplan, L., Kapsalis, V., Karbowski, A., Katsoni, V., Kavish, D.R., Kawamura, H., Keilman, N.W., Kelly, J., Kenneth, H., Kepaptsoglou, K., Kevin, D., Kewley, S., Kim, J.-C., Kim, K.-Y., Kim, S., Kimengsi, J.N., Klein, J., Kleine, M., Klemes, J.I.R.I., Klepp, S., Klinkenberg, L.E.F., Knight, L., Knowles, J., Koerner, S., Konsolakis, K., Konstantinov, V., Kopkin, N.K., Kordova, S., Kosinski, E., Kostelka, F., Kot, S., Kotter, R., Kramers, A., Krienert, J.L., Kubon, M., Kuffer, M., Kungolos, A., Kuttner, P., Kużelewska, E., Ladd, A.E., Lammi, M., Landrum, J., Lange, B., Languilaire, T.D., Lantz, J.-C., Laudal, B., Laurentsyeva, T., Lavizzari, N., Lavoie, A., Feuvre, J.L., Leakey, N., Lee, R., Lee, A., Lee, E., Lee, J., Lentner, J.-H., Lenz‐taguchi, C., Leong, H., Levac, W.S., Lewin, L., Lewinson, E., Li, T., Li, F., Li, G., Li, M., Liczmańska‐kopcewicz, Y., Lillard, K., Linková, C., Links, M., Lipinski, P., Storto, J.L., Lochtman, C., Lockwood, K., Loh, A., Lomonaco‐benzing, V., Łopaciuk‐gonczaryk, R., López, B., lópez, D., Lorenzini, J., Löther, A., Loughnan, C., Love, T., Lucas, M.L., Ubago, J., Lukić, J., Lumley‐sapanski, A., Macedo, I., Macfarlane, S., Machimbarrena, J.M., Magda, R., Magrane, D., Maier, D., Majić, S., Majumdar, S., Makarovič, M., Malekigorji, M., Mallick, B., Malone, D., Mandić, D., Maniou, T., Mannell, J.M., Barbutiu, S., Marczak, M., Markvica, K.M., Aragón, M.D.M., Martín, J.S.M., Pereira, A., Marzal‐felici, J., Mason, F., Mather, J., Matijosaitiene, I., MatthewsMattisson, R., Mattisson, C., Matuszak, Ł., Matuzeviciute, K., Mauerer, G., Mayer, A., McCaig, C., McClearn, D., McKee, S.C., McKendry, S., McMahon, M., McReynolds, P., Medina‐vicent, M., Medyna, G., Mees, H., Meil, G., Meringolo, P., Miciuła, I., Milczarek‐andrzejewska, D., Miles, P., Milivojević, S., Miller, G., Minello, A., Miron, D., Mironeasa, S., Misra, J., Mitchell, T., Moldovan, O., Molero, P.P., Møllersen, S., Momsen, J.H., Moniz, A.B., Morea, D., Moreau, M.-P., Morgan, D.L., Morgan, H., Moscatelli, S., Mostowska, M., Mousavi, A., Mousavi, S., Mrugalska, B., Muinos, G., Mukungu, K., Mukuni, J., Murakami, D., Muresan, I.C., Murib, Z., Muro, A., Mustafa, G., Nackerud, L., Nalmpantis, D., Napal, M., Närvi, J., Naser, M., Nash, V., Navarre‐jackson, L., Navarro, R., Nazarczuk, D., Neale, J., Necula, J., Němec, S., Neven, D., Nevgi, A., Newbold, A., Newton, G., New, A., Niakšu, O., Niiniluoto, I., Nkogo, J.C., Nobre, S., Nunn, P., Oakes, R., Obrad, C., Oke, A., Okorie, O., Oncioiu, I., Ormsbee, F., Ortega‐sánchez, D., Osgood, J., Osorio, C., Oswald, J., Otis, M.D., Ouassini, A., Oxford, S., Page, T., Paixão, M.J., De Pajares, E.M., Palmesr, E., Palos‐sánchez, P., Pamučar, Dragan, Pan, H., Panek, J., Pankowska, M., Papadakis, S., Papafilippou, V.P., Medina, R., Park, C.S., Partalidou, M., Passantino, A., Passini, S., Paul, S., Pavliuk, R., Pearce, P., Pease, K., Pentaris, P., Perez, V.W., Pérez‐armendáriz, C., Perez‐vaisvidovsky, N., Perez‐y‐perez, M., Perry, N., Prtchu, D., Peterson, D.A.M., Alexandru‐ionut, Petrykowski, Petrykowski, P., Phillips, L., Pickard, S., Pickel, A., Pieke, F., Piekut, A., Pierce, S., Pierrakis, Y., Piguet, E., Pleace, N., Połom, M., Polsa, P., Ponticorvo, M., Pookulangara, S., Pope, J., Popoli, P., Postigo, J.C., Price‐Wolf, J., Prior, S., Privitera, D., Prud’homme, C., Prosser, J., Prus, P., Puiu, S., Purcell, R., Pyrialakou, D., Quam‐wickham, N., Quarmby, T., Quinlan, K.M., Quinn, A., Quinn, R., Raciti, M., Radicić, D., Rahimi, B., Ramlo, S., Randle, H., Ratajczak, M., Raymond, T., Recio‐menéndez, M., Reese, L.A., Regner, T., Reichman, J., WReim, iebke, R., Pastor, A.M., Rexhepi, G., Reyes‐menendez, A., Reynaud, C., Ribeiro‐soriano, D., Ricci, S., Ridaura, G., Rita, C., Roberts, M., Roberts, G., Roberts, K., Rockerbie, D., Rodger, J.A., Rodin, G., Rodrigues, D.R., Martín, J.A., Rodríguez, C.F., Rodriguez‐modroño, P., Romero‐rodríguez, L.M., Rončáková, T., Roper, I., Rorie, M.R., Marzán, C.F., Rose, G., Rose, M., Rosen, R., Roth, R., Roubík, H., Roumpos, C., Rowbottom, D., Roy, J., Ruban, D., Rubira‐garcía, R., Ruiperez‐valiente, J.A., Ruiz, R., Ruiz‐real, J.L., Russell, B., Russo, K., Sabol, W., Safonte, F., Salin, M., Salom‐carrasco, J.S., Sánchez, L.D., Sanghera, Santos, B.S., Silva, D., Sanz, F., Sanz‐altamira, B., Sarapura, S., Sari, D., Satybaldieva, E., Saura, J.R., Sayed, N., Scandurra, C., Schartner, A., Schellekens, J., Schenk‐hoppé, K.R., Scherer, L., Schewe, J.A., Schewe, R., Schiller, N.G., Schmidt, E.-M., Schneickert, C., Schneider, J., Scott, H., Scott, P., Seibel, K., Seidler, R., Seifert, S.S., Puyuelo, M.S., Azevedo, P.S., Lopez, A.E.S., Raamkumar, A.S., Blundo, D., Severo, M., Shakya, K.M., Shapiro, A., Shaw, I.F., Shaw, T.V., Shea, B., Shearer, H., Sheldon, S., Shell‐duncan, B., Shepherd, S., Sheridan, L., Siemienska, R., Sillup, G.P., Simeon, J.C., Simonelli, A., Skilodimou, H.D., Škrinjarić, T., Slater, G., Smardon, R., Smith, J., Smoląg, K., Snauwaert, D.T., Soanes‐white, T., Sobocińska, M., Sohaib, O., Soldatić, K., Sorainen, G.T., Soldatos, A., Sørensen, N.N., Spanu, S., Stadlober, E., Stafford, F., Ștefănescu‐mihăilă, R.O., Stefanini, A., Štefko, R., Steglich, E., Steirer, G., Stephenson, M.O., Stoecker, R., Stoffelen, A., Strang, A., Suppa, D., Sutton, J., Svobodová, L., Swigon, M., Synnott, J., Sytsma, V., Tabe, T., Tajeddini, K., Tang, S., Taylor, B., Taylor, C., Teignier, M., Teixeira, C., Tempelaar, D., Ter Avest, K.H., Ter Horst, E., Testa, M.R., Thakur, N., Thiamwong, L., Thijsen, A., Thomas, B.A., Thompson, C., Thompson, D., Tisdall, K., Toft, Mancini, Torell, A., Toscano‐hernández, G., Tregua, A.E., Triandafyllidou, M., Tseloni, A., Seloni, A., Tsikouras, P., Tsogas, G., Twamley, K., Tyler, D.U., Haque, A., Underwood, M., Urbański, M., Uribe‐toril, J., Vaezipour, A., Van Hove, L.V., Huylenbroeck, G., Van Nuland, S., Vanner, C., Vázquez‐cano, E., Veen, E., Veintimilla, S.G.-A., Veković, M., Velija, P., Venco, E.M., Verticelli, A., Vicente, P.V., Estiarte, C., Višnjić, A., Visvizi, A., Vlasblom, J.D., Volsche, S.V., Fintel, D., Von Keyserlingk, L., Vranješević, J., Walter, K.V., Wandosell, G., Wang, Y., Wasileski, G., Wastl‐walter, D., Weaving, C., Weenik, D., Wehr, K., Wei, X., Wharton, A., White, G., Whitehouse, H., Whitley, C.T., Whitman, L., Wiersma‐mosley, J.D., Wilcke, H., Wilkes, R., Williams, L., Williamson, R.D., Wimalasena, L., Wiseman, A., Wołek, M., Wright, E.Q., Wroblewski, A., Wyile, A.S., Wynn, C., Xu, X., Xue, B., Yang, J., Yoe, T.M., Young, M., Younus, M., Yu, T.-F., Yuan, Q., Zadra, C., Zaharijević, A., Zajda, J., Zander, K., Zbuchea, A., Zelin, A., Zhang, C., Zippel, K., Zitricky, V., Živanović, P., Zou, L., Zufferey, C., Zuhdi, M., Zumeta, W.M., Abbas, A., Abel, G., Abreu, A., Adam, A., Adamek, M., Adiletta, G., Adusei-asante, K.A., Romeo, M.D.M., Alderson, A., Alfaro, E., Aliverti, A., Almeida, Fernando, Álvarez-gonzález, L.I., Amelina, A., Anand, C., Anderson, G., Andreasson, J., Ang, I., Aragon, J., Arcidiacono, C., Arcuri, S., Assante, D., Atukeren, E., Avery, H., Ayeb-karlsson, S., Azadi, H., Bachman, R., Bader, M., Badulescu, A., Bahmanteymouri, E., Baines, S., Baker, T., Baker‐beall, C., Bañón, L., Bar‐am, N., Barbier‐greenland, K., Barnett, R., Barragán‐escandón, A., Barreto, A.M., Barrett, E., Bartkowski, J., Bartram, R., Bartzas, G., Bates, D., Baviera‐puig, A., Bayley, A., Beazley, H., Beer, C., Behr, H., Beier, G., Belford, N., Bencivenga, R., Benli, A.E., Benton‐short, L., Berei, J.M., Berbel‐pineda, E., Bernstein, Berntzen, E.R., Bertella, L., Birney, G., Bittle, M., Black, S., Rivero, L.B., Blattner, J.J., Blok, C., Blount, A., Boas, Y., Bockarie, I., Bockerman, A., Bodén, P., Bönisch‐brednich, L., Bontje, B., Bontje, M., Borsellino, V., Bostan, I., Bowl, M., Bowman, B., Bracci, E., Bracken, C.M., Bradley, H., Brereton, P., Brewer, J., Bridge, D., Brooks, S., Brown, Andrijana, Brzoska, M., Brzozowski, W., Buckley, G., Buente, W., Bullaro, G.R., Burke, M.D., Burlacu, S., Busu, M., Butler, S., Byrne, J., Cabral, L., Cai, Y., Cajias, M., Calin, A.C., Callegari, C., Camarero, M., Campbell-figuerola, H., Campbell, J.R., Cannito, M., Canonico, E., Canosa, A., Carabelli, G., Carlbom, A., Carlone, T., Caron, R., Carpenter, A., Caruso, G., Casais, B., Castro, M.P., Cava, M.-J., Čeněk, J., Cerchione, R., Certomà, C., Chan, E., Charles, D., Charlwood, A., Chatzifotiou, S., Chell, K., Chen, L., Chen, Q., Chen, W.-J., Ching, L., Christensen, J., Ciasullo, M.V., Cimermanová, I., Činčera, J., Cipollina, M., Clutterbuck, R., Cochrane, B., Collin, K., Conley, R., Connell, H., Connelly, J., Connelly, L., Connelly, R., Conti, D., Conversi, D., Conway, G., Cooper, S., Cope, M., Corsini, F., Cristian, P., Crohn, H.M., Croog, R.C., Salazar, T., Csiszár, C., D’auria, I., D’souza, A., D’souza, N., Dabija, D.-C., Dagg, J., Dalby, S., DaleDalsgård, B., Dʹamato, A.L., Daniel, D., Dant, L., Dantas, C., Darwin, H., Dashper, K., David, M.E., De Flippo, D., De, A., Edi, M., Velázquez, E.D.C., Velázquez, F., Del Vecchio, P., Delatolla, A., Delgado, P., Delgado‐romero, E., Delrosso, J., Desimone, J., Detlefsen, L., Devaney, C., Díaz, L.M., Didham, R., Diogo, E., Dirakis, A., Doberneck, D., Doidge, M.D., Molero, G., Dombrowski, P.J., Doñate, C., Đorđević, Martín, Reis, P.G.R., Doucek, P., Dundes, L., Dvouletý, O., Dybo, T., Eastman, J., Eckhardt, J., Economou, A., Edler, D., Edu, U., Ekblom, P.E., Khaled, D., Ellis, C., Elsabry, E., Erceg, A., Erokhin, V., Ertz, M., Everitt, J., Evers, A., Falcone, P.M.F., Cabana, P., Fawcett, B., Fearnley, B., Featherstone, M., Ferreira, M., Ferreira, P., Fetner, T., Fisher, J., Fisher, R., Fitzpatrick, T., Flanagan, C., Fogarty, E.A., Fonchingong, C.C., Fontana, M., Fook, J., Foreman, A.M., Foster‐mcgregor, N., Fox, S., Franco, J.A., Franklin, A.L., Friedrich, T., Fromm, I., Fu, N., Fucà, R., Fukuda, Y., Fusco, G., Gabriela, D., Galan, D., Gamo, A., Galiano, J., Garcia, A., García, M.E.A., García‐germán, S., García‐machado, J.J., García‐ruiz, C.R., Gavini, M., Gazzano, A., Gebhardt, M., Gerson, S., Gherghina, Ş.C., Gibbs, P., Gilhooly, D., Gill, F., Gill, N., Gil‐lopez, A.J., Ginès Fabrellas, A., Giuffrida, N., Giuliani, G., Goddard, J., Godderis, R., Goh, C.S., Gomes, O., Goncharuk, A.G., Canche, M.G., Pérez, I.G., Valero, G., González, R.C.L., Gonzalez‐benson, O., Gonzalez‐feliu, J., González‐lópez, M., Gozdziak, E., Granx, B., Gran, R., Gray, S.L., Grbes, A., Grondys, K., Grugan, S., Guenther, J., Guijarro, F., Gurko, T., Haas, L.L., Hagellx, A., Hagell, H., Hallgrímsdóttir, H., Hamada, T., Hanf, J., Hannouf, M., Hao, F., Harman, G., Harris, K.L., Harris, R., Harrison, N.H., Healy, G., Healy, K., Heikkilä, E., Hellmich, C., Henig, J., Henninger, C.E., Heo, W., Herman, C., Herrero‐diz, P., Heyman, J., Hibbert, N., Hillman, A.L., Hillman, B., Hine, B., Hino, K., Hinten, M., Hipp, L., Hoang, D., Holleran, D., Hollin, I., Holm, M., Holmes, C., Hook, G., Hoornweg, D., Hopper, L., Hossain, M., Hoxhaj, R., Hu, B., Huang, Y., Huarita, E., Hudec, O., Humbert, A.L., Hung, M.-C., Hunt, A., Husu, L., IanoleIbáñez‐gonzález, R., Ibáñez‐gonzález, M.J., Ide, T., Ijaz, Muhammad Fazal, Impicciatore, R., Ingwersen, M., Ioannides, D., Iseppi, L., Islam, M.M., Jaakkola, M., Jagger, S., Jagosh, J., Jenkin, G., Joelsson, T., Johansen, R.E.B., Johnsen, H.C., Garmann Jona, G., Jones, T., Judit, O., Kalalahti, M., Kang, M., Kantamaneni, K., Kaplan, L., Kapsalis, V., Karbowski, A., Katsoni, V., Kavish, D.R., Kawamura, H., Keilman, N.W., Kelly, J., Kenneth, H., Kepaptsoglou, K., Kevin, D., Kewley, S., Kim, J.-C., Kim, K.-Y., Kim, S., Kimengsi, J.N., Klein, J., Kleine, M., Klemes, J.I.R.I., Klepp, S., Klinkenberg, L.E.F., Knight, L., Knowles, J., Koerner, S., Konsolakis, K., Konstantinov, V., Kopkin, N.K., Kordova, S., Kosinski, E., Kostelka, F., Kot, S., Kotter, R., Kramers, A., Krienert, J.L., Kubon, M., Kuffer, M., Kungolos, A., Kuttner, P., Kużelewska, E., Ladd, A.E., Lammi, M., Landrum, J., Lange, B., Languilaire, T.D., Lantz, J.-C., Laudal, B., Laurentsyeva, T., Lavizzari, N., Lavoie, A., Feuvre, J.L., Leakey, N., Lee, R., Lee, A., Lee, E., Lee, J., Lentner, J.-H., Lenz‐taguchi, C., Leong, H., Levac, W.S., Lewin, L., Lewinson, E., Li, T., Li, F., Li, G., Li, M., Liczmańska‐kopcewicz, Y., Lillard, K., Linková, C., Links, M., Lipinski, P., Storto, J.L., Lochtman, C., Lockwood, K., Loh, A., Lomonaco‐benzing, V., Łopaciuk‐gonczaryk, R., López, B., lópez, D., Lorenzini, J., Löther, A., Loughnan, C., Love, T., Lucas, M.L., Ubago, J., Lukić, J., Lumley‐sapanski, A., Macedo, I., Macfarlane, S., Machimbarrena, J.M., Magda, R., Magrane, D., Maier, D., Majić, S., Majumdar, S., Makarovič, M., Malekigorji, M., Mallick, B., Malone, D., Mandić, D., Maniou, T., Mannell, J.M., Barbutiu, S., Marczak, M., Markvica, K.M., Aragón, M.D.M., Martín, J.S.M., Pereira, A., Marzal‐felici, J., Mason, F., Mather, J., Matijosaitiene, I., MatthewsMattisson, R., Mattisson, C., Matuszak, Ł., Matuzeviciute, K., Mauerer, G., Mayer, A., McCaig, C., McClearn, D., McKee, S.C., McKendry, S., McMahon, M., McReynolds, P., Medina‐vicent, M., Medyna, G., Mees, H., Meil, G., Meringolo, P., Miciuła, I., Milczarek‐andrzejewska, D., Miles, P., Milivojević, S., Miller, G., Minello, A., Miron, D., Mironeasa, S., Misra, J., Mitchell, T., Moldovan, O., Molero, P.P., Møllersen, S., Momsen, J.H., Moniz, A.B., Morea, D., Moreau, M.-P., Morgan, D.L., Morgan, H., Moscatelli, S., Mostowska, M., Mousavi, A., Mousavi, S., Mrugalska, B., Muinos, G., Mukungu, K., Mukuni, J., Murakami, D., Muresan, I.C., Murib, Z., Muro, A., Mustafa, G., Nackerud, L., Nalmpantis, D., Napal, M., Närvi, J., Naser, M., Nash, V., Navarre‐jackson, L., Navarro, R., Nazarczuk, D., Neale, J., Necula, J., Němec, S., Neven, D., Nevgi, A., Newbold, A., Newton, G., New, A., Niakšu, O., Niiniluoto, I., Nkogo, J.C., Nobre, S., Nunn, P., Oakes, R., Obrad, C., Oke, A., Okorie, O., Oncioiu, I., Ormsbee, F., Ortega‐sánchez, D., Osgood, J., Osorio, C., Oswald, J., Otis, M.D., Ouassini, A., Oxford, S., Page, T., Paixão, M.J., De Pajares, E.M., Palmesr, E., Palos‐sánchez, P., Pamučar, Dragan, Pan, H., Panek, J., Pankowska, M., Papadakis, S., Papafilippou, V.P., Medina, R., Park, C.S., Partalidou, M., Passantino, A., Passini, S., Paul, S., Pavliuk, R., Pearce, P., Pease, K., Pentaris, P., Perez, V.W., Pérez‐armendáriz, C., Perez‐vaisvidovsky, N., Perez‐y‐perez, M., Perry, N., Prtchu, D., Peterson, D.A.M., Alexandru‐ionut, Petrykowski, Petrykowski, P., Phillips, L., Pickard, S., Pickel, A., Pieke, F., Piekut, A., Pierce, S., Pierrakis, Y., Piguet, E., Pleace, N., Połom, M., Polsa, P., Ponticorvo, M., Pookulangara, S., Pope, J., Popoli, P., Postigo, J.C., Price‐Wolf, J., Prior, S., Privitera, D., Prud’homme, C., Prosser, J., Prus, P., Puiu, S., Purcell, R., Pyrialakou, D., Quam‐wickham, N., Quarmby, T., Quinlan, K.M., Quinn, A., Quinn, R., Raciti, M., Radicić, D., Rahimi, B., Ramlo, S., Randle, H., Ratajczak, M., Raymond, T., Recio‐menéndez, M., Reese, L.A., Regner, T., Reichman, J., WReim, iebke, R., Pastor, A.M., Rexhepi, G., Reyes‐menendez, A., Reynaud, C., Ribeiro‐soriano, D., Ricci, S., Ridaura, G., Rita, C., Roberts, M., Roberts, G., Roberts, K., Rockerbie, D., Rodger, J.A., Rodin, G., Rodrigues, D.R., Martín, J.A., Rodríguez, C.F., Rodriguez‐modroño, P., Romero‐rodríguez, L.M., Rončáková, T., Roper, I., Rorie, M.R., Marzán, C.F., Rose, G., Rose, M., Rosen, R., Roth, R., Roubík, H., Roumpos, C., Rowbottom, D., Roy, J., Ruban, D., Rubira‐garcía, R., Ruiperez‐valiente, J.A., Ruiz, R., Ruiz‐real, J.L., Russell, B., Russo, K., Sabol, W., Safonte, F., Salin, M., Salom‐carrasco, J.S., Sánchez, L.D., Sanghera, Santos, B.S., Silva, D., Sanz, F., Sanz‐altamira, B., Sarapura, S., Sari, D., Satybaldieva, E., Saura, J.R., Sayed, N., Scandurra, C., Schartner, A., Schellekens, J., Schenk‐hoppé, K.R., Scherer, L., Schewe, J.A., Schewe, R., Schiller, N.G., Schmidt, E.-M., Schneickert, C., Schneider, J., Scott, H., Scott, P., Seibel, K., Seidler, R., Seifert, S.S., Puyuelo, M.S., Azevedo, P.S., Lopez, A.E.S., Raamkumar, A.S., Blundo, D., Severo, M., Shakya, K.M., Shapiro, A., Shaw, I.F., Shaw, T.V., Shea, B., Shearer, H., Sheldon, S., Shell‐duncan, B., Shepherd, S., Sheridan, L., Siemienska, R., Sillup, G.P., Simeon, J.C., Simonelli, A., Skilodimou, H.D., Škrinjarić, T., Slater, G., Smardon, R., Smith, J., Smoląg, K., Snauwaert, D.T., Soanes‐white, T., Sobocińska, M., Sohaib, O., Soldatić, K., Sorainen, G.T., Soldatos, A., Sørensen, N.N., Spanu, S., Stadlober, E., Stafford, F., Ștefănescu‐mihăilă, R.O., Stefanini, A., Štefko, R., Steglich, E., Steirer, G., Stephenson, M.O., Stoecker, R., Stoffelen, A., Strang, A., Suppa, D., Sutton, J., Svobodová, L., Swigon, M., Synnott, J., Sytsma, V., Tabe, T., Tajeddini, K., Tang, S., Taylor, B., Taylor, C., Teignier, M., Teixeira, C., Tempelaar, D., Ter Avest, K.H., Ter Horst, E., Testa, M.R., Thakur, N., Thiamwong, L., Thijsen, A., Thomas, B.A., Thompson, C., Thompson, D., Tisdall, K., Toft, Mancini, Torell, A., Toscano‐hernández, G., Tregua, A.E., Triandafyllidou, M., Tseloni, A., Seloni, A., Tsikouras, P., Tsogas, G., Twamley, K., Tyler, D.U., Haque, A., Underwood, M., Urbański, M., Uribe‐toril, J., Vaezipour, A., Van Hove, L.V., Huylenbroeck, G., Van Nuland, S., Vanner, C., Vázquez‐cano, E., Veen, E., Veintimilla, S.G.-A., Veković, M., Velija, P., Venco, E.M., Verticelli, A., Vicente, P.V., Estiarte, C., Višnjić, A., Visvizi, A., Vlasblom, J.D., Volsche, S.V., Fintel, D., Von Keyserlingk, L., Vranješević, J., Walter, K.V., Wandosell, G., Wang, Y., Wasileski, G., Wastl‐walter, D., Weaving, C., Weenik, D., Wehr, K., Wei, X., Wharton, A., White, G., Whitehouse, H., Whitley, C.T., Whitman, L., Wiersma‐mosley, J.D., Wilcke, H., Wilkes, R., Williams, L., Williamson, R.D., Wimalasena, L., Wiseman, A., Wołek, M., Wright, E.Q., Wroblewski, A., Wyile, A.S., Wynn, C., Xu, X., Xue, B., Yang, J., Yoe, T.M., Young, M., Younus, M., Yu, T.-F., Yuan, Q., Zadra, C., Zaharijević, A., Zajda, J., Zander, K., Zbuchea, A., Zelin, A., Zhang, C., Zippel, K., Zitricky, V., Živanović, P., Zou, L., Zufferey, C., Zuhdi, M., and Zumeta, W.M.

Published
2020

10. The effects of blood conditioning films on the antimicrobial and retention properties of zirconium-nitride silver surfaces

Author

Slate, AJ, Wickens, D, Wilson-Nieuwenhuis, J, Dempsey-Hibbert, N, West, G, Kelly, P, Verran, J, Banks, CE, Whitehead, KA, Slate, AJ, Wickens, D, Wilson-Nieuwenhuis, J, Dempsey-Hibbert, N, West, G, Kelly, P, Verran, J, Banks, CE, and Whitehead, KA

Abstract

External bone fixation devices provide support and rehabilitation for severely damaged/broken bones, however, this invasive procedure is prone to infection. Zirconium nitride/silver (Ti-ZrN/Ag) coatings were characterised for surface topography, chemical composition, physicochemistry and antimicrobial efficacy (against Staphylococcus aureus and Staphylococcus epidermidis), in the presence of a blood conditioning film. The conditioning film altered the width of the microtopography of the surfaces however, the depth of the features remained relatively constant. The conditioning film also altered the coatings from hydrophobic to hydrophilic/partially hydrophilic surfaces. Following the MATH assay, the presence of a conditioning film reduced affinity towards the hydrocarbons for both microorganisms. The addition of a blood conditioning film reduced the antimicrobial efficacy of the Ti-ZrN/Ag coatings but also reduced the number of retained bacteria. This study suggests that the presence of a pre-defined blood conditioning film may result in surfaces with anti-adhesive properties, potentially leading to a reduction in bacterial retention. This, combined with the antimicrobial efficacy of the coatings, could reduce the risk of infection on biomaterial surfaces.

Published
2019

11. Effectiveness of titanium nitride silver coatings against Staphylococcus spp. in the presence of BSA and whole blood conditioning agents

Author

Saubade, FJ, Hughes, S, Wickens, DJ, Wilson-Nieuwenhuis, J, Dempsey-Hibbert, N, Crowther, G, West, G, Kelly, P, Banks, CE, Whitehead, KA, Saubade, FJ, Hughes, S, Wickens, DJ, Wilson-Nieuwenhuis, J, Dempsey-Hibbert, N, Crowther, G, West, G, Kelly, P, Banks, CE, and Whitehead, KA

Abstract

Implanted medical devices are at risk of developing an infection at the surgical site. Once a medical implant is inserted, it initially becomes coated by a conditioning film, followed by bacterial retention. In the present study, medical grade stainless steel substrata were coated with titanium nitride (TiN) or titanium nitride/silver (TiN/14.94 at.%Ag or TiN/19.04 at.%Ag). Surface analysis determined that with increased silver concentration, silver nanoparticles were heterogeneously distributed throughout the coatings. The effect of bovine serum albumin or whole blood conditioning agents on the antimicrobial activity and microbial retention were determined using Staphylococcus aureus or Staphylococcus epidermidis. The presence of the conditioning agents reduced the antimicrobial effect of the surfaces against S. aureus. When the cells and conditioning agents were applied together, a reduction in bacterial retention and conditioning film was observed. These results suggest that the impact of conditioning agents should be considered since conditioning films may reduce bacterial retention but may also decrease the antimicrobial properties of the surface coatings.

Published
2019

12. Antimicrobial Strategies and Economic Considerations for Polymeric Medical Implants

Author

Grennhalgh, R, Dempsey-Hibbert, N, and Vagg-Whitehead, Kathryn

Abstract

Healthcare acquired infections (HAI's) are a worldwide problem that can be exacerbated by surgery and the implantation of polymeric medical devices. The use of polymer based medical devices which incorporate antimicrobial strategies are now becoming an increasingly routine way of trying to prevent the potential for reduce chronic infection and device failure. There are a wide range of potential antimicrobial agents currently being incorporated into such polymers. However, it is difficult to determine which antimicrobial agent provides the greatest infection control. The economics of replacing current methods with impregnated polymer materials further complicates matters. It has been suggested that the use of a holistic system wide approach should to be developed around the implantation of medical devices which minimises the potential risk of infection. However, the use of such different approaches is still being developed. The control of such infections is important for individual patient health and the economic implications for healthcare services.

Published
2018

16. Effectiveness of titanium nitride silver coatings against Staphylococcus spp. in the presence of BSA and whole blood conditioning agents

Author

Saubade, FJ, Hughes, S, Wickens, DJ, Wilson-Nieuwenhuis, J, Dempsey-Hibbert, N, Crowther, G, West, G, Kelly, P, Banks, CE, Whitehead, KA, Saubade, FJ, Hughes, S, Wickens, DJ, Wilson-Nieuwenhuis, J, Dempsey-Hibbert, N, Crowther, G, West, G, Kelly, P, Banks, CE, and Whitehead, KA

Abstract

Implanted medical devices are at risk of developing an infection at the surgical site. Once a medical implant is inserted, it initially becomes coated by a conditioning film, followed by bacterial retention. In the present study, medical grade stainless steel substrata were coated with titanium nitride (TiN) or titanium nitride/silver (TiN/14.94 at.%Ag or TiN/19.04 at.%Ag). Surface analysis determined that with increased silver concentration, silver nanoparticles were heterogeneously distributed throughout the coatings. The effect of bovine serum albumin or whole blood conditioning agents on the antimicrobial activity and microbial retention were determined using Staphylococcus aureus or Staphylococcus epidermidis. The presence of the conditioning agents reduced the antimicrobial effect of the surfaces against S. aureus. When the cells and conditioning agents were applied together, a reduction in bacterial retention and conditioning film was observed. These results suggest that the impact of conditioning agents should be considered since conditioning films may reduce bacterial retention but may also decrease the antimicrobial properties of the surface coatings.

Published
2018

18. Antimicrobial synergy of cationic grafted poly(para-phenylene ethynylene) and poly(para-phenylene vinylene) compounds with UV or metal ions against Enterococcus faecium

Author

McBrearty, J, Barker, D, Damavandi, M, Wilson-Nieuwenhuis, J, Pilkington, LI, Dempsey-Hibbert, N, Slate, AJ, Vagg-Whitehead, KA, McBrearty, J, Barker, D, Damavandi, M, Wilson-Nieuwenhuis, J, Pilkington, LI, Dempsey-Hibbert, N, Slate, AJ, and Vagg-Whitehead, KA

Abstract

The rise in multidrug resistant bacteria is an area of growing concern and it is essential to identify new biocidal agents. Cationic grafted compounds were investigated for their antimicrobial properties using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests. Synergy testing was carried out using the compounds in the presence of ultraviolet (UV). Fractional inhibitory concentration (FIC) and fractional bactericidal concentration (FBC) tests were carried out using the cationic molecules in conjunction with metal ion solutions of gold, silver, palladium, platinum, rhodium, titanium, tin, vanadium and molybdenum. Individually, the cationic compounds containing quaternary amines, polyphenylene vinylene (PPV) with long polyacrylate grafts (PPV-g-PMETAC (HMw)), polyphenylene ethylene (PPE) with long polyacrylate grafts (PPE-g-PMETAC (HMw)), polyphenylene vinylene (PPV) with short polyacrylate grafts (PPV-g-PMETAC (LMw)) and polyphenylene ethylene (PPE) with short polyacrylate grafts (PPE-gPMETAC (LMw)) were effective against Enterococcus faecium. The most successful compound under UV was PPV-g-PMETAC (HMw). Following the FICs, palladium and rhodium ion solutions caused a synergistic reaction with all four tested compounds. The presence of conjugated bonds in the cationic molecules increased its antimicrobial activity. These results suggest that the chemical backbone of the compounds, alongside the chain lengths and chain attachment affect the antimicrobial efficacy of a compound. These factors should be taken into consideration when formulating new biocidal combinations.

Published
2018

19. Antimicrobial activity of Ti-ZrN/Ag coatings for use in biomaterial applications

Author

Slate, A, Wickens, D, El Mohtadi, M, Dempsey-Hibbert, N, West, G, Banks, C, Vagg-Whitehead, KA, Slate, A, Wickens, D, El Mohtadi, M, Dempsey-Hibbert, N, West, G, Banks, C, and Vagg-Whitehead, KA

Abstract

Severely broken bones often require external bone fixation pins to provide support but they can become infected. In order to reduce such infections, novel solutions are required. Titanium zirconium nitride (Ti-ZrN) and Ti-ZrN silver (Ti-ZrN/Ag) coatings were deposited onto stainless steel. Surface microtopography demonstrated that on the silver containing surfaces, Sa and Sv values demonstrated similar trends whilst the Ra, average height and RMS value and Sp values increased with increasing silver concentration. On the Ti-ZrN/Ag coatings, surface hydrophobicity followed the same trend as the Sa and Sv values. An increase in dead Staphylococcus aureus and Staphylococcus epidermidis cells was observed on the coatings with a higher silver concentration. Using CTC staining, a significant increase in S. aureus respiration on the silver containing surfaces was observed in comparison to the stainless steel control whilst against S. epidermidis, no significant difference in viable cells was observed across the surfaces. Cytotoxicity testing revealed that the TiZrN coatings, both with and without varying silver concentrations, did not possess a detrimental effect to a human monocyte cell line U937. This work demonstrated that such coatings have the potential to reduce the viability of bacteria that result in pin tract infections.

Published
2018

20. Thieno[2,3-b]pyridine derivatives are potent anti-platelet drugs, inhibiting platelet activation, aggregation and showing synergy with aspirin

Author

Binsaleh, NK, Wigley, CA, Vagg-Whitehead, Kathryn, van Rensburg, M, Reynisson, J, Pilkington, LI, Barker, D, Jones, Sarah, Dempsey-Hibbert, N, Binsaleh, NK, Wigley, CA, Vagg-Whitehead, Kathryn, van Rensburg, M, Reynisson, J, Pilkington, LI, Barker, D, Jones, Sarah, and Dempsey-Hibbert, N

Abstract

Drugs which inhibit platelet function are commonly used to prevent blood clot formation in patients with Acute Coronary Syndromes (ACS) or those at risk of stroke. The thieno[3,2-c]pyridine class of therapeutic agents, of which clopidogrel is the most commonly used, target the P2Y12 receptor, and are often used in combination with acetylsalicylic acid (ASA). Six thieno[2,3-b]pyridine were assessed for in vitro anti-platelet activity; all derivatives showed effects on both platelet activation and aggregation, and showed synergy with ASA. Some compounds demonstrated greater activity when compared to clopidogrel. These compounds, therefore, represent potential novel P2Y12 inhibitors for improved treatment for patients.

Published
2018

21. Poly(para-Phenylene Ethynylene) (PPE)- and Poly(para-Phenylene Vinylene) (PPV)-Poly[(2-(Methacryloyloxy)Ethyl) Trimethylammonium Chloride] (PMETAC) Graft Copolymers Exhibit Selective Antimicrobial Activity

Author

Damavandi, M, Pilkington, L, Whitehead, KA, Wilson-Nieuwenhuis, J, McBrearty, J, Dempsey-Hibbert, N, Travas-Sejdic, J, Barker, D, Damavandi, M, Pilkington, L, Whitehead, KA, Wilson-Nieuwenhuis, J, McBrearty, J, Dempsey-Hibbert, N, Travas-Sejdic, J, and Barker, D

Abstract

Antimicrobial resistance is becoming a global health concern; as such, the need for new effective treatments and preventive measures is increasing. Poly(para-phenylene ethynylene) (PPE)- and poly(para-phenylene vinylene) (PPV)-poly[(2-(methacryloyloxy)ethyl) trimethylammonium chloride] (PMETAC) graft copolymers were tested against a range of clinically and industrially relevant bacteria and results showed many of these conjugated polyelectrolytes (CPE’s) to be active. Of all of the compounds tested, PPE-g-PMETAC (low molecular weight, LMW) had greatest antimicrobial activity, especially against Enterococcus faecium, Methicillin resistant Staphylococcus aureus (MRSA), Escherichia coli and Acinetobacter baumannii.

Published
2018

23. Poly(para-Phenylene Ethynylene) (PPE)- and Poly(para-Phenylene Vinylene) (PPV)-Poly[(2-(Methacryloyloxy)Ethyl) Trimethylammonium Chloride] (PMETAC) Graft Copolymers Exhibit Selective Antimicrobial Activity

Author

Damavandi, M, Pilkington, L, Whitehead, KA, Wilson-Nieuwenhuis, J, McBrearty, J, Travas-Sejdic, J, Barker, D, Dempsey-Hibbert, N, Damavandi, M, Pilkington, L, Whitehead, KA, Wilson-Nieuwenhuis, J, McBrearty, J, Travas-Sejdic, J, Barker, D, and Dempsey-Hibbert, N

Abstract

Antimicrobial resistance is becoming a global health concern; as such, the need for new effective treatments and preventive measures is increasing. Poly(para-phenylene ethynylene) (PPE)- and poly(para-phenylene vinylene) (PPV)-poly[(2-(methacryloyloxy)ethyl) trimethylammonium chloride] (PMETAC) graft copolymers were tested against a range of clinically and industrially relevant bacteria and results showed many of these conjugated polyelectrolytes (CPE’s) to be active. Of all of the compounds tested, PPE-g-PMETAC (low molecular weight, LMW) had greatest antimicrobial activity, especially against Enterococcus faecium, Methicillin resistant Staphylococcus aureus (MRSA), Escherichia coli and Acinetobacter baumannii.

Published
2017

24. Surface modification of platelet concentrate bags to reduce biofilm formation and transfusion sepsis.

Author

Wilson-Nieuwenhuis, JST, Dempsey-Hibbert, N, Liauw, CM, Whitehead, KA, Wilson-Nieuwenhuis, JST, Dempsey-Hibbert, N, Liauw, CM, and Whitehead, KA

Abstract

Bacterial contamination of blood products poses a major risk in transfusion medicine, including transfusions involving platelet products. Although testing systems are in place for routine screening of platelet units, the formation of bacterial biofilms in such units may decrease the likelihood that bacteria will be detected. This work determined the surface properties of p-PVC platelet concentrate bags and investigated how these characteristics influenced biofilm formation. Serratia marcescens and Staphylococcus epidermidis, two species commonly implicated in platelet contamination, were used to study biofilm growth. The platelet concentrate bags were physically flattened to determine if reducing the surface roughness altered biofilm formation. The results demonstrated that the flattening process of the platelet bags affected the chemistry of the surface and reduced the surface hydrophobicity. Flattening of the surfaces resulted in a reduction in biofilm formation for both species after 5 days, with S. marcescens demonstrating a greater reduction. However, there was no significant difference between the smooth and flat surfaces following 7 days’ incubation for S. marcescens and no significant differences between any of the surfaces following 7 days’ incubation for S. epidermidis. The results suggest that flattening the p-PVC surfaces may limit potential biofilm 2 formation for the current duration of platelet storage time of 5 days. It is hoped that this work will enhance the understanding of how surface properties influence the development of microbial biofilms in platelet concentrate bags in order to devise a solution to discourage biofilm formation.

Published
2017

32. Chemoselective bond activation by unidirectional and asynchronous PCET using ketone photoredox catalysts.

Author

Sun R, Ruccolo S, Nascimento DL, Qin Y, Hibbert N, and Nocera DG

Abstract

The triplet excited states of ketones are found to effect selective H-atom abstraction from strong amide N-H bonds in the presence of weaker C-H bonds through a proton-coupled electron transfer (PCET) pathway. This chemoselectivity, which results from differences in ionization energies (IEs) between functional groups rather than bond dissociation energies (BDEs) arises from the asynchronicity between electron and proton transfer in the PCET process. We show how this strategy may be leveraged to achieve the intramolecular anti-Markovnikov hydroamidation of alkenes to form lactams using camphorquinone as an inexpensive and sustainable photocatalyst., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Published
2023
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33. The effect of iron deficiency on quality of life outcomes after surgery for obstructive sleep apnoea.

Author

Reynolds Z, Hibbert N, Stevenson P, and Vijayasekaran S

Subjects
Adenoidectomy, Child, Humans, Iron, Polysomnography, Quality of Life, Iron Deficiencies, Sleep Apnea, Obstructive epidemiology, Sleep Apnea, Obstructive surgery, Tonsillectomy
Abstract

Aim: This study aimed to assess the effect of iron deficiency on parent-reported changes in quality of life (QOL) among children receiving an adenotonsillectomy for paediatric obstructive sleep apnoea (OSA)., Methods: This was a retrospective review study that recruited children under 16 years of age undergoing an adenotonsillectomy, adenoidectomy, or tonsillectomy for clinically diagnosed paediatric OSA between June 2020 and January 2021 inclusive, in Western Australia. The main outcome measures for this study were changes in QOL by age group and iron status, defined by an absolute change of more than 3 points on OSA-18 survey domains., Results: About 249 participants had iron studies performed on perioperative blood samples drawn at operation and completed both pre-operative and post-operative OSA-18 QOL questionnaires at initial consultation and 8-12 weeks post-surgery, respectively. 41.8% were iron deficient, 53.8% were borderline iron deficient and 4.4% had normal iron levels. Following surgery, a decrease was observed for all OSA-18 score domains in post-operation scores compared to pre-operation scores in both iron-deficient and borderline iron-deficient cohorts. 'Daytime Problems' in the <2 years group, within the iron-deficient cohort, was the only domain that found to be non-superior (i.e. 'not better') following surgery., Conclusions: Following adenotonsillectomy, patients with paediatric OSA reported significant improvements in QOL regardless of their iron status. Those undergoing an adenotonsillectomy for paediatric OSA had a high prevalence of iron deficiency at operation, especially those under 6 years of age., (© 2022 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Published
2022
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34. A simplified diagnostic pathway for the differential diagnosis of iron deficiency anaemia and anaemia of chronic disease.

Author

Svenson N, Bailey J, Durairaj S, and Dempsey-Hibbert N

Subjects
Anemia blood, Anemia, Iron-Deficiency blood, Anemia, Iron-Deficiency etiology, Biomarkers, Chronic Disease, Critical Pathways, Diagnosis, Differential, Diagnostic Tests, Routine standards, Disease Management, Disease Susceptibility, Erythrocyte Indices, Humans, ROC Curve, Anemia diagnosis, Anemia etiology, Anemia, Iron-Deficiency diagnosis, Diagnostic Tests, Routine methods
Abstract

Introduction: Iron deficiency anaemia (IDA) and anaemia of chronic disease (ACD) are common causes of anaemia with similar clinical and laboratory features. IDA is caused by low iron stores while ACD is due to iron-restricted erythropoiesis occurring in inflammatory states. Differential diagnosis requires analysis of multiple biochemical and haematological parameters. IDA can occur simultaneously to ACD (mixed aetiology). It is essential that true iron deficiency is identified, as these patients will require iron therapy. This preliminary study investigated whether hepcidin, the master regulator of iron homeostasis, in conjunction with reticulocyte haemoglobin equivalent (RetHe) has the potential to differentiate IDA from ACD, and to exclude IDA in patients with mixed aetiology., Methods: Hepcidin concentration (measured using a commercially available ELISA method), RetHe, and iron parameters along with C-reactive protein (CRP) were analysed in 77 Gastroenterology patients with anaemia in a secondary care setting., Results: Receiver operator characteristic (ROC) analysis showed that hepcidin at an optimal cut-off concentration of <6ng/ml could identify IDA with a sensitivity and specificity of 88.9% and 90.6% respectively and could distinguish ACD from IDA with both a sensitivity and specificity of 100% at a cut-off of >46ng/ml. Identifying true IDA in mixed aetiology patients could be achieved by RetHe analysis and applying an optimal cut-off of <30pg., Conclusion: Hepcidin, in conjunction with RetHe, offers a new simplified diagnostic pathway for differential diagnosis of IDA and ACD, thereby reducing the diagnostic turnaround time and allowing appropriate treatment of patients with a true iron deficiency., (© 2021 The Authors. International Journal of Laboratory Hematology published by John Wiley & Sons Ltd.)

Published
2021
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35. Factors Involved in the onset of infection following bacterially contaminated platelet transfusions.

Author

Wilson-Nieuwenhuis J, El-Mohtadi M, Edwards K, Whitehead K, and Dempsey-Hibbert N

Subjects
Bacterial Infections pathology, Humans, Bacterial Infections etiology, Platelet Transfusion adverse effects
Abstract

Transfusion of platelet concentrates (PCs) is associated with several adverse patient reactions, the most common of which are febrile non-hemolytic transfusion reactions (FNHTRs) and transfusion-associated bacterial-infection/transfusion-associated sepsis (T-ABI/TA-S). Diagnosis of T-ABI/T-AS requires a positive blood culture (BC) result from the transfusion recipient and also a positive identification of bacterial contamination within a test aliquot of the transfused PC. In a significant number of cases, clinical symptoms post-transfusion are reported by the clinician, yet the BCs from the patient and/or PC are negative. The topic of 'missed bacterial detection' has therefore been the focus of several primary research studies and review articles, suggesting that biofilm formation in the blood bag and the presence of viable but non-culturable (VBNC) pathogens are the major causes of this missed detection. However, platelets are emerging as key players in early host responses to infection and as such, the aforementioned biofilm formation could elicit 'platelet priming', which could lead to significant immunological reactions in the host, in the absence of planktonic bacteria in the host bloodstream. This review reflects on what is known about missed detection and relates this to the emerging understanding of the effect of bacterial contamination on the platelets themselves and the significant role played by platelets in exacerbation of an immune response to infection within the transfusion setting.

Published
2021
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36. Estrogen deficiency - a central paradigm in age-related impaired healing?

Author

El Mohtadi M, Whitehead K, Dempsey-Hibbert N, Belboul A, and Ashworth J

Abstract

Wound healing is a dynamic biological process achieved through four sequential, overlapping phases; hemostasis, inflammation, tissue proliferation and remodeling. For effective wound healing, all four phases must occur in the appropriate order and time frame. It is well accepted that the wound healing process becomes disrupted in the elderly, increasing the propensity of non-healing wound states that can lead to substantial patient morbidity and an enormous financial burden on healthcare systems. Estrogen deprivation in the elderly has been identified as the key driver of age-related delayed wound healing in both genders, with topical and systemic estrogen replacement reversing the detrimental effects of aging on wound repair. Evidence suggests estrogen deprivation may contribute to the development of chronic wound healing states in the elderly but research in this area is somewhat limited, warranting further investigations. Moreover, although the beneficial effects of estrogen on cutaneous healing have been widely explored, the development of estrogen-based treatments to enhance wound repair in the elderly have yet to be widely exploited. This review explores the critical role of estrogen in reversing age-related impaired healing and evaluates the prospect of developing more focused novel therapeutic strategies that enhance wound repair in the elderly via activation of specific estrogen signaling pathways in regenerating tissues, whilst leaving non-target tissues largely unaffected., (Copyright © 2021 El Mohtadi et al.)

Published
2021
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37. Differential engulfment of Staphylococcus aureus and Pseudomonas aeruginosa by monocyte-derived macrophages is associated with altered phagocyte biochemistry and morphology.

Author

El Mohtadi M, Pilkington L, Liauw CM, Ashworth JJ, Dempsey-Hibbert N, Belboul A, and Whitehead KA

Abstract

Knowledge of changes in macrophages following bacterial engulfment is limited. U937-derived macrophages were incubated with Staphylococcus aureus or Pseudomonas aeruginosa . Morphological and biochemical changes in macrophages following host-pathogen interactions were visualized using Scanning Electron Microscopy (SEM) and Fourier-Transform Infrared Spectroscopy (FTIR) respectively. Principal Component Analysis (PCA) was used to assess the variability in the FTIR spectra. Following host-pathogen interactions, survival of S. aureus was significantly lower than P. aeruginosa (P<0.05) and cellular morphology of macrophages was different after incubation with S. aureus compared to P. aeruginosa. Following incubation with S. aureus macrophages were more globular and amorphous in shape whereas long linear pseudopodia were observed following incubation with P. aeruginosa. Distinct FTIR spectra were identified in macrophages post interaction with the different bacteria and PCA analysis demonstrated distinct biochemical differences in the phagocytes following engulfment of the bacteria, with > 99 % of variability in the FTIR spectra explained by the first two principal components. These findings demonstrated that there were clear morphological and biochemical changes in macrophages following engulfment of two different bacterial types suggesting that the biochemical components of the bacterial cell wall influenced the biochemical characteristics and hence the morphology of macrophages in distinct ways., (Copyright © 2020 El Mohtadi et al.)

Published
2020
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38. Transnationalism and care of migrant families during pregnancy, postpartum and early-childhood: an integrative review.

Author

Merry L, Villadsen SF, Sicard V, and Lewis-Hibbert N

Subjects
Australia, Canada, Child, Europe, Female, Humans, Internationality, New Zealand, Postpartum Period, Pregnancy, Prenatal Care, Primary Health Care, Culturally Competent Care methods, Delivery of Health Care methods, Family, Maternal Health Services, Transients and Migrants
Abstract

Background: Migrant families' transnational ties (i.e., connections to their countries of origin) may contribute to their hardships and/or may be a source of resiliency. A care approach that addresses these transnational ties may foster a positive identity and give coherence to experiences. We conducted an integrative review to determine what is known about transnational ties and the care of migrant families during pregnancy, postpartum and early childhood., Methods: We searched 15 databases to identify literature reporting on a health or social program, service, or care experience of migrant families during pregnancy up to age five in a Western country (i.e., Canada, US, Australia, New Zealand or a European country). Information regarding if and how the service/program/care considered transnational ties, and care-providers' perceptions of transnational ties, was extracted, analyzed and synthesized according to transnational 'ways of belonging' and 'ways of being'., Results: Over 34,000 records were screened; 69 articles were included. Care, programs and services examined included prenatal interventions (a mhealth app, courses, videos, and specialized antenatal care), doula support, maternity care, support groups, primary healthcare and psycho-social early intervention and early childhood programs. The results show that transnational ties in terms of 'ways of belonging' (cultural, religious and linguistic identity) are acknowledged and addressed in care, although important gaps remain. Regarding 'ways of being', including emotional, social, and economic ties with children and other family members, receipt of advice and support from family, and use of health services abroad, there is very little evidence that these are acknowledged and addressed by care-providers. Perceptions of 'ways of belonging' appear to be mixed, with some care-providers being open to and willing to adapt care to accommodate religious, cultural and linguistic differences, while others are not. How care-providers perceive the social, emotional and economic ties and/or the use of services back home, remains relatively unknown., Conclusion: Significant knowledge gaps remain regarding care-providers' perceptions of transnational 'ways of being' and whether and how they take them into account, which may affect their relationships with migrant families and/or the effectiveness of their interventions. Continued efforts are needed to ensure care is culturally safe for migrants.

Published
2020
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39. Exploring the putative interactions between chronic kidney disease and chronic periodontitis.

Author

Hickey NA, Shalamanova L, Whitehead KA, Dempsey-Hibbert N, van der Gast C, and Taylor RL

Subjects
Bacteremia microbiology, Bacteria metabolism, Chronic Periodontitis microbiology, Comorbidity, Humans, Inflammation pathology, Renal Insufficiency, Chronic microbiology, Risk Factors, Chronic Periodontitis pathology, Mouth Mucosa microbiology, Renal Insufficiency, Chronic pathology
Abstract

Chronic kidney disease (CKD) and chronic periodontitis (CP) are both common diseases, which are found disproportionately comorbid with each other and have been reported to have a detrimental effect on the progression of each respective disease. They have an overlap in risk factors and both are a source of systemic inflammation along with a wide selection of immunological and non-specific effects that can affect the body over the lifespan of the conditions. Previous studies have investigated the directionality of the relationship between these two diseases; however, there is a lack of literature that has examined how these diseases may be interacting at the localized and systemic level. This review discusses how oral microorganisms have the ability to translocate and have distal effects and provides evidence for microbial involvement in a systemic disease. Furthermore, it summarizes the reported local and systemic effects of CKD and CP and discusses how the interaction of these effects may be responsible for directionality associations reported.

Published
2020
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40. The effects of blood conditioning films on the antimicrobial and retention properties of zirconium-nitride silver surfaces.

Author

Slate AJ, Wickens D, Wilson-Nieuwenhuis J, Dempsey-Hibbert N, West G, Kelly P, Verran J, Banks CE, and Whitehead KA

Subjects
Anti-Bacterial Agents pharmacology, Bacterial Adhesion drug effects, Bone-Implant Interface microbiology, Coated Materials, Biocompatible pharmacology, Colony Count, Microbial, External Fixators microbiology, Extracellular Space chemistry, Humans, Microscopy, Atomic Force, Silver chemistry, Silver pharmacology, Staphylococcal Infections prevention & control, Staphylococcus aureus growth & development, Staphylococcus epidermidis growth & development, Surface Properties, Titanium chemistry, Titanium pharmacology, Zirconium pharmacology, Anti-Bacterial Agents chemistry, Blood Cells chemistry, Coated Materials, Biocompatible chemistry, Plasma chemistry, Staphylococcus aureus drug effects, Staphylococcus epidermidis drug effects, Zirconium chemistry
Abstract

External bone fixation devices provide support and rehabilitation for severely damaged/broken bones, however, this invasive procedure is prone to infection. Zirconium nitride/silver (Ti-ZrN/Ag) coatings were characterised for surface topography, chemical composition, physicochemistry and antimicrobial efficacy (against Staphylococcus aureus and Staphylococcus epidermidis), in the presence of a blood conditioning film. The conditioning film altered the width of the microtopography of the surfaces however, the depth of the features remained relatively constant. The conditioning film also altered the coatings from hydrophobic to hydrophilic/partially hydrophilic surfaces. Following the MATH assay, the presence of a conditioning film reduced affinity towards the hydrocarbons for both microorganisms. The addition of a blood conditioning film reduced the antimicrobial efficacy of the Ti-ZrN/Ag coatings but also reduced the number of retained bacteria. This study suggests that the presence of a pre-defined blood conditioning film may result in surfaces with anti-adhesive properties, potentially leading to a reduction in bacterial retention. This, combined with the antimicrobial efficacy of the coatings, could reduce the risk of infection on biomaterial surfaces., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2019
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41. Antimicrobial synergy of cationic grafted poly( para -phenylene ethynylene) and poly( para -phenylene vinylene) compounds with UV or metal ions against Enterococcus faecium .

Author

McBrearty J, Barker D, Damavandi M, Wilson-Nieuwenhuis J, Pilkington LI, Dempsey-Hibbert N, Slate AJ, and Whitehead KA

Abstract

The rise in multidrug resistant bacteria is an area of growing concern and it is essential to identify new biocidal agents. Cationic grafted compounds were investigated for their antimicrobial properties using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests. Synergy testing was carried out using the compounds in the presence of ultraviolet (UV). Fractional inhibitory concentration (FIC) and fractional bactericidal concentration (FBC) tests were carried out using the cationic molecules in conjunction with metal ion solutions of gold, silver, palladium, platinum, rhodium, titanium, tin, vanadium and molybdenum. Individually, the cationic compounds containing quaternary amines, polyphenylene vinylene (PPV) with long polyacrylate grafts (PPV- g -PMETAC (HMw)), polyphenylene ethylene (PPE) with long polyacrylate grafts (PPE- g -PMETAC (HMw)), polyphenylene vinylene (PPV) with short polyacrylate grafts (PPV- g -PMETAC (LMw)) and polyphenylene ethylene (PPE) with short polyacrylate grafts (PPE- g -PMETAC (LMw)) were effective against Enterococcus faecium . The most successful compound under UV was PPV- g -PMETAC (HMw). Following the FICs, palladium and rhodium ion solutions caused a synergistic reaction with all four tested compounds. The presence of conjugated bonds in the cationic molecules increased its antimicrobial activity. These results suggest that the chemical backbone of the compounds, alongside the chain lengths and chain attachment affect the antimicrobial efficacy of a compound. These factors should be taken into consideration when formulating new biocidal combinations., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Published
2018
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43. Antimicrobial activity of Ti-ZrN/Ag coatings for use in biomaterial applications.

Author

Slate AJ, Wickens DJ, El Mohtadi M, Dempsey-Hibbert N, West G, Banks CE, and Whitehead KA

Subjects
Cell Survival drug effects, Humans, Monocytes drug effects, Stainless Steel chemistry, Staphylococcus aureus drug effects, Staphylococcus aureus physiology, Staphylococcus epidermidis drug effects, Staphylococcus epidermidis physiology, U937 Cells, Anti-Infective Agents pharmacology, Coated Materials, Biocompatible chemistry, Microbial Viability drug effects, Silver pharmacology, Titanium pharmacology, Zirconium pharmacology
Abstract

Severely broken bones often require external bone fixation pins to provide support but they can become infected. In order to reduce such infections, novel solutions are required. Titanium zirconium nitride (Ti-ZrN) and Ti-ZrN silver (Ti-ZrN/Ag) coatings were deposited onto stainless steel. Surface microtopography demonstrated that on the silver containing surfaces, S a and S v values demonstrated similar trends whilst the R a , average height and RMS value and S p values increased with increasing silver concentration. On the Ti-ZrN/Ag coatings, surface hydrophobicity followed the same trend as the S a and S v values. An increase in dead Staphylococcus aureus and Staphylococcus epidermidis cells was observed on the coatings with a higher silver concentration. Using CTC staining, a significant increase in S. aureus respiration on the silver containing surfaces was observed in comparison to the stainless steel control whilst against S. epidermidis, no significant difference in viable cells was observed across the surfaces. Cytotoxicity testing revealed that the TiZrN coatings, both with and without varying silver concentrations, did not possess a detrimental effect to a human monocyte cell line U937. This work demonstrated that such coatings have the potential to reduce the viability of bacteria that result in pin tract infections.

Published
2018
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44. Surface modification of platelet concentrate bags to reduce biofilm formation and transfusion sepsis.

Author

Wilson-Nieuwenhuis JST, Dempsey-Hibbert N, Liauw CM, and Whitehead KA

Subjects
Bacterial Adhesion, Hydrophobic and Hydrophilic Interactions, Platelet Transfusion adverse effects, Product Packaging standards, Sepsis etiology, Surface Properties, Time Factors, Biofilms growth & development, Blood Platelets microbiology, Product Packaging methods, Sepsis microbiology, Serratia marcescens physiology, Staphylococcus epidermidis physiology
Abstract

Bacterial contamination of blood products poses a major risk in transfusion medicine, including transfusions involving platelet products. Although testing systems are in place for routine screening of platelet units, the formation of bacterial biofilms in such units may decrease the likelihood that bacteria will be detected. This work determined the surface properties of p-PVC platelet concentrate bags and investigated how these characteristics influenced biofilm formation. Serratia marcescens and Staphylococcus epidermidis, two species commonly implicated in platelet contamination, were used to study biofilm growth. The platelet concentrate bags were physically flattened to determine if reducing the surface roughness altered biofilm formation. The results demonstrated that the flattening process of the platelet bags affected the chemistry of the surface and reduced the surface hydrophobicity. Flattening of the surfaces resulted in a reduction in biofilm formation for both species after 5 days, with S. marcescens demonstrating a greater reduction. However, there was no significant difference between the smooth and flat surfaces following 7 days' incubation for S. marcescens and no significant differences between any of the surfaces following 7 days' incubation for S. epidermidis. The results suggest that flattening the p-PVC surfaces may limit potential biofilm formation for the current duration of platelet storage time of 5 days. It is hoped that this work will enhance the understanding of how surface properties influence the development of microbial biofilms in platelet concentrate bags in order to devise a solution to discourage biofilm formation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Published
2017
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45. Transcription Analysis of the Myometrium of Labouring and Non-Labouring Women.

Author

Sharp GC, Hutchinson JL, Hibbert N, Freeman TC, Saunders PT, and Norman JE

Subjects
Cluster Analysis, Computational Biology methods, Female, Gene Expression Regulation, High-Throughput Nucleotide Sequencing, Humans, Pregnancy, Reproducibility of Results, Gene Expression Profiling, Labor, Obstetric genetics, Myometrium metabolism, Transcriptome
Abstract

An incomplete understanding of the molecular mechanisms that initiate normal human labour at term seriously hampers the development of effective ways to predict, prevent and treat disorders such as preterm labour. Appropriate analysis of large microarray experiments that compare gene expression in non-labouring and labouring gestational tissues is necessary to help bridge these gaps in our knowledge. In this work, gene expression in 48 (22 labouring, 26 non-labouring) lower-segment myometrial samples collected at Caesarean section were analysed using Illumina HT-12 v4.0 BeadChips. Normalised data were compared between labouring and non-labouring groups using traditional statistical methods and a novel network graph approach. We sought technical validation with quantitative real-time PCR, and biological replication through inverse variance-weighted meta-analysis with published microarray data. We have extended the list of genes suggested to be associated with labour: Compared to non-labouring samples, labouring samples showed apparent higher expression at 960 probes (949 genes) and apparent lower expression at 801 probes (789 genes) (absolute fold change ≥1.2, rank product percentage of false positive value (RP-PFP) <0.05). Although half of the women in the labouring group had received pharmaceutical treatment to induce or augment labour, sensitivity analysis suggested that this did not confound our results. In agreement with previous studies, functional analysis suggested that labour was characterised by an increase in the expression of inflammatory genes and network analysis suggested a strong neutrophil signature. Our analysis also suggested that labour is characterised by a decrease in the expression of muscle-specific processes, which has not been explicitly discussed previously. We validated these findings through the first formal meta-analysis of raw data from previous experiments and we hypothesise that this represents a change in the composition of myometrial tissue at labour. Further work will be necessary to reveal whether these results are solely due to leukocyte infiltration into the myometrium as a mechanism initiating labour, or in addition whether they also represent gene changes in the myocytes themselves. We have made all our data available at www.ebi.ac.uk/arrayexpress/ (accession number E-MTAB-3136) to facilitate progression of this work.

Published
2016
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