Adhesion of microorganisms to bovine submaxillary mucin coatings: effect of coating deposition conditions

The adhesion of Staphylococcus epidermidis, Escherichia coli, and Candida albicans on mucin coatings has been evaluated to explore the feasibility of the coating to increase the infection resistance of biomaterials. Coatings of bovine submaxillary mucin (BSM) were deposited on a base layer consisting of a poly(acrylic acid-b-methyl methacrylate) (PAA-b-PMMA) diblock copolymer. This bi-layer system exploits the mucoadhesive interactions of the PAA block to aid the adhesion of mucin to the substrate, whereas the PMMA block prevents the coating's dissolution in aqueous environments. The thickness of the mucin coating was adjusted by varying the pH of the solution from which it was deposited. Thin mucin coatings decreased the numbers of bacteria but increased the numbers of C. albicans adhering to the copolymer and control surfaces. Increasing the mucin film thickness resulted in a further lowering of the number density of adhering S. epidermidis cells, but it did not affect the number density of E. coli. In contrast, the C. albicans number densities increased with an increased mucin thickness

Therapeutics discovery: from bench to first in-human trials*

The 'Therapeutics discovery: From bench to first in-human trials' conference, held at the King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), Kingdom of Saudi Arabia (KSA) from October 10-12, 2017, provided a unique opportunity for experts worldwide to discuss advances in drug discovery and development, focusing on phase I clinical trials. It was the first event of its kind to be hosted at the new research center, which was constructed to boost drug discovery and development in the KSA in collaboration with institutions, such as the Academic Drug Discovery Consortium in the United States of America (USA), Structural Genomics Consortium of the University of Oxford in the United Kingdom (UK), and Institute of Materia Medica of the Chinese Academy of Medical Sciences in China. The program was divided into two parts. A pre-symposium day took place on October 10, during which courses were conducted on clinical trials, preclinical drug discovery, molecular biology and nanofiber research. The attendees had the opportunity for one-to-one meetings with international experts to exchange information and foster collaborations. In the second part of the conference, which took place on October 11 and 12, the clinical trials pipeline, design and recruitment of volunteers, and economic impact of clinical trials were discussed. The Saudi Food and Drug Administration presented the regulations governing clinical trials in the KSA. The process of preclinical drug discovery from small molecules, cellular and immunologic therapies, and approaches to identifying new targets were also presented. The recommendation of the conference was that researchers in the KSA must invest more fund, talents and infrastructure to lead the region in phase I clinical trials and preclinical drug discovery. Diseases affecting the local population, such as Middle East Respiratory Syndrome and resistant bacterial infections, represent the optimal starting point

Analyse von Risikofaktoren für Funktionseinschränkungen nach Therapie des Oropharynxkarzinoms

Mit den verbesserten Therapiemöglichkeiten gewinnen die funktionellen Outcomes bei der Behandlung des Oropharynxkarzinoms zunehmend an Bedeutung. Nichtsdestotrotz gibt es derzeit einen Mangel an prädiktiven Modellen, welche die funktionellen Outcomes betrachten und im Rahmen von Risikostratifikationsmodellen quantifizieren. Die vorliegende retrospektive monozentrische Kohortenstudie untersuchte in einem Patientenkollektiv von n=489 prädiktive Faktoren für die Tracheostomie- und die PEG-Notwendigkeit, sowie für das Überleben nach der Therapie des Oropharynxkarzinoms. Hierfür extrahierten wir eine Reihe an potentiell relevanten Studienvariablen aus unserem Patienteninformationssystem und wendeten logistische Regressionsmodelle, einen CHAID (Chi-Quadrat Automatic Interaction Detection) Algorithmus und COX-Regressionsmodelle an, um den Zusammenhang dieser unabhängigen Studienvariablen mit den Variablen „PEGNotwendigkeit“, „Tracheostomie-Notwendigkeit“ und das Überleben zu untersuchen. Unsere Ergebnisse zeigten, dass das männliche Geschlecht (p=0.030) und die Durchführung einer sanierenden Operation (p<0.001) mit einer geringeren Wahrscheinlichkeit für das Auftreten einer PEG-Notwendigkeit in unserer Kohorte assoziiert waren, während die Tracheostomie-Notwendigkeit mit einer höheren Wahrscheinlichkeit für das Auftreten einer PEG-Notwendigkeit in unserer Kohorte assoziiert war (p<0.001). Die Analyse der Variable „HPV-Status“ als Prädiktor für die PEG-Notwendigkeit wies zwar auf eine niedrigere Wahrscheinlichkeit der PEGNotwendigkeit bei HPV-positiven Patienten hin, dieses Ergebnis verfehlte jedoch das Signifikanzniveau knapp (p=0.073). Weiterhin zeigten unsere Ergebnisse, dass der transorale OP-Zugang mit einer geringeren Wahrscheinlichkeit für das Auftreten einer Tracheostomie-Notwendigkeit assoziiert waren (p<0.001), während die PEG-Notwendigkeit (p<0.001) und eine sanierende OP (p<0.001) mit einer höheren Wahrscheinlichkeit für das Auftreten einer Tracheostomie-Notwendigkeit assoziiert war. Die Analyse der Variable „HPV-Status“ als Prädiktor für die Tracheostomie- Notwendigkeit wies zwar auf eine niedrigere Wahrscheinlichkeit der Tracheostomie-Notwendigkeit bei HPV-positiven Patienten hin, aber auch dieses Ergebnis verfehlte das Signifikanzniveau knapp (p=0.471). Auch hier zeigten andere Studienvariablen keine signifikanten Assoziationen mit der Tracheostomie-Notwendigkeit. Unsere Überlebenszeitanalyse zeigte, dass das Überleben von Patienten mit einer PEG-Notwendigkeit signifikant geringer ist (2.00 ± 0.190 Jahre) als das von den Patienten ohne PEG (7.33 ± 0.774 Jahre) (p<0.001). Gleicherweise zeigte die Überlebenszeitanalyse, dass das Überleben von Patienten mit Tracheostomie-Notwendigkeit signifikant geringer ist (2.00 ± 0.23 Jahre) als für Patienten, die tracheotomiert werden mussten (6.16 ± 0.58 Jahre) (p<0.001). In unserer Studie waren als signifikant relevante prädiktive Faktoren für das Überleben ein höheres Alter (p<0.001), alle anderen Lokalisationen im Vergleich zu der Vorderwand-Lokalisation (p=0.001 - 0.041), ein höheres T-Stadium (p=0.003), ein höheres UICC Stadium (p<0.001) und ein höheres ECOG (p=0.02), die mit einer höheren Wahrscheinlichkeit für das Auftreten eines Events (Tod) assoziiert waren. Eine sanierende OP (p<0.001) und ein HPV-positiver Status (p<0.001) waren mit einer geringeren Wahrscheinlichkeit für das Auftreten eines Events (Tod) assoziiert. Weitere Studien sind erforderlich, um das Vorhersagemodell prospektiv zu analysieren und die Reproduzierbarkeit dieser Ergebnisse zu prüfen

Developing and characterising mucin films and evaluating them as a bacteria resistant coating.

Mucin is a naturally occurring polymer that belongs to the glycoprotein family. It is an amphiphilic molecule made of two main parts: a hydrophobic protein backbone and hydrophilic carbohydrate side chains. As a result of this structure, it can adsorb on many types of surfaces to create a hydrophilic, lubricating layer. Mucin has been shown in recent studies to have the potential to suppress the adhesion of bacteria. The aim of this study is to develop a uniform mucin coating resistant to bacterial adhesion. In developing a coating technique, we created a multi-layer system consisting of a poly(acrylic acid) (PAA) copolymer as a base layer and a mucin layer on top, as this exploits the mucoadhesion interactions between PAA and mucin in bonding to the base. The mucin coatings created were then evaluated against the adhesion of microorganisms, including two species of bacteria (Staphylococcus epidermidis and Escherichia coli) and one species of yeast (Candida albicans) known to be problematic for patients inserted with urinary catheters. This study develops as the following: oExperimental work was conducted on the creation of the mucin coating using poly(aciylic acid)-b-poly(methyl methacrylate) as a base coating and poly(methyl methacrylate) and silicon as controls. The effect of pH was used as a means to control the mucin layer thickness, where a thicker mucin layer was adsorbed on the copolymer from acidic mucin solutions than neutral and basic mucin solutions. Roughness and surface energy measurements revealed smoother and more hydrophilic surfaces created from the thicker mucin layers. oInfrared spectroscopic ellipsometiy was used to study the interfacial bonding between the copolymer layer and the adsorbed mucin layer. This study showed that at pH 3 more hydrogen bonds were created between PAA-b-PMMA and mucin. It also showed conformational changes in the protein backbone of mucin at lower pH. oIn evaluating the adhesion of microorganisms on the mucin coating, through direct counting, we saw a decrease in bacterial adhesion after mucin coating compared to the bare surfaces but no effect on the adhesion of yeast cells. Increasing the mucin coating thickness further reduced the numbers of Staphylococcus epidermidis but not Escherichia coli

Planning And Evaluation Of Special Event Transportation Systems With Application To The Hajj.

PhDCivil engineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/180794/2/7804662.pd

Developing and characterising mucin films and evaluating them as a bacteria resistant coating.

Mucin is a naturally occurring polymer that belongs to the glycoprotein family. It is an amphiphilic molecule made of two main parts: a hydrophobic protein backbone and hydrophilic carbohydrate side chains. As a result of this structure, it can adsorb on many types of surfaces to create a hydrophilic, lubricating layer. Mucin has been shown in recent studies to have the potential to suppress the adhesion of bacteria. The aim of this study is to develop a uniform mucin coating resistant to bacterial adhesion. In developing a coating technique, we created a multi-layer system consisting of a poly(acrylic acid) (PAA) copolymer as a base layer and a mucin layer on top, as this exploits the mucoadhesion interactions between PAA and mucin in bonding to the base. The mucin coatings created were then evaluated against the adhesion of microorganisms, including two species of bacteria (Staphylococcus epidermidis and Escherichia coli) and one species of yeast (Candida albicans) known to be problematic for patients inserted with urinary catheters. This study develops as the following: oExperimental work was conducted on the creation of the mucin coating using poly(aciylic acid)-b-poly(methyl methacrylate) as a base coating and poly(methyl methacrylate) and silicon as controls. The effect of pH was used as a means to control the mucin layer thickness, where a thicker mucin layer was adsorbed on the copolymer from acidic mucin solutions than neutral and basic mucin solutions. Roughness and surface energy measurements revealed smoother and more hydrophilic surfaces created from the thicker mucin layers. oInfrared spectroscopic ellipsometiy was used to study the interfacial bonding between the copolymer layer and the adsorbed mucin layer. This study showed that at pH 3 more hydrogen bonds were created between PAA-b-PMMA and mucin. It also showed conformational changes in the protein backbone of mucin at lower pH. oIn evaluating the adhesion of microorganisms on the mucin coating, through direct counting, we saw a decrease in bacterial adhesion after mucin coating compared to the bare surfaces but no effect on the adhesion of yeast cells. Increasing the mucin coating thickness further reduced the numbers of Staphylococcus epidermidis but not Escherichia coli