Integration of Riboflavin-Modified Carbon Fiber Mesh Electrode Systems in a 3D-Printed Catheter Hub.

BACKGROUND: Catheter line infection is a common complication within clinical environments, and there is a pressing need for technological options to aid in reducing the possibility of sepsis. The early identification of contamination could be pivotal in reducing cases and improving outcomes. METHOD: A sensing rationale based on a riboflavin-modified electrode system integrated within a modified 3D-printed catheter needle-free connector is proposed, which can monitor changes in pH brought about by bacterial contamination. RESULTS: Riboflavin, vitamin B2, is a biocompatible chemical that possesses a redox-active flavin core that is pH dependent. The oxidation peak potential of the adsorbed riboflavin responds linearly to changes in pH with a near-Nernstian behavior of 63 mV/pH unit and is capable of accurately monitoring the pH of an authentic IV infusate. CONCLUSIONS: The proof of principle is demonstrated with an electrode-printed hub design offering a valuable foundation from which to explore bacterial interactions within the catheter lumen with the potential of providing an early warning of contamination.

N-alkylated linear heptamethine polyenes as potent non-azole leads against Candida albicans fungal infections.

In this study, eighteen heptamethine dyes were synthesised and their antifungal activities were evaluated against three clinically relevant yeast species.. The eighteen dyes were placed within classes based on their core subunit i.e. 2,3,3-trimethylindolenine (5a-f), 1,1,2-trimethyl-1H-benzo[e]indole (6a-f), or 2-methylbenzothiazole (7a-f). The results presented herein imply that the three families of cyanine dyes, in particular compounds 5a-f, show high potential as selective scaffolds to treat C. albicans infections. This opens up the opportunity for further optimisation and investigation of this class compounds for potential antifungal treatment.

Electroanalytical properties of chlorophenol red at disposable carbon electrodes: Implications for Escherichia coli detection.

The use of coliforms and Escherichia coli as indicator species for assessing the quality of water is well established and a large variety of methods based on ß-galactosidase (B-GAL) activity, inherent to the microbes within this classification, have arisen to enable their detection and enumeration. Chlorophenol red (CPR) is widely used as a chromogenic label, but its capacity for translation to electroanalytical devices has yet to be fully explored. The CPR moiety is capable of undergoing oxidation at carbon substrates (+0.7 V) giving rise to a variety of phenolic intermediates. Electrochemical, XPS and enzymatic techniques were employed to characterise the underpinning chemistry and the intermediate identified as a 1,2-quinone derivative in which the chlorine substituent is retained. The latter was found to accumulate at the electrode and, in contrast to the parent CPR, was found to be detected at a significantly less positive potential (+0.3 V). Bacterial hydrolysis of a CPR labelled substrate was demonstrated with the 1,2-quinone oxidation product found to accumulate at the electrode and detected using square wave voltammetry. Proof of concept for the efficacy of the alternative electrode pathway was established through the detection of E.coli after an incubation time of 2.5 h with no interference from the labelled substrates.

1,8-Substituted anthraquinones, anthrones and bianthrones as potential non-azole leads against fungal infections.

The synthesis of a variety of 1,8-substituted anthraquinones, anthrones and bianthrones and their potential as antifungal agents is evaluated. Preliminary screening against Schizosaccharomyces pombe (S. pombe), a fission yeast, and Saccharomyces cerevisiae (S. cerevisiae), a budding yeast, is reported. Both these yeast species demonstrate close homologue to a number of pathogenic fungi.

Estimating the economic costs of algal blooms in the Canadian Lake Erie Basin.

Over the past two decades there has been a re-emergence of regular harmful algal blooms in Lake Erie due to increasing phosphorus loading, mainly from non-point agricultural sources. The Canadian and United States governments have jointly agreed to reduce phosphorus loadings to the lake in order to control the extent and severity of the blooms. Citizens on both sides of the border face a number of economic costs, both market and non-market, as a result of the blooms. This study values these costs for the Canadian portion of the Lake Erie basin economy using standard economic approaches that are widely applied within the world of cost-benefit analysis. The results suggest that algal blooms will impose equivalent annual costs equal to $272 million in 2015 prices over a 30-year period if left unchecked. The largest market costs will be imposed on the tourism industry ($110 million in equivalent annual costs) and the largest non-market costs will be borne by recreational users and those who place inherent value on the lake's quality ($115 million in equivalent annual costs). Management action to reduce phosphorus loadings is found to be justified on economic grounds if the 30-year net present value of the reduction program is less than $1294 million (2015 Canadian dollars).

Sensor systems for bacterial reactors: A new flavin-phenol composite film for the in situ voltammetric measurement of pH.

Monitoring pH within microbial reactors has become an important requirement across a host of applications ranging from the production of functional foods (probiotics) to biofuel cell systems. An inexpensive and scalable composite sensor capable of monitoring the pH within the demanding environments posed by microbial reactors has been developed. A custom designed flavin derivative bearing an electropolymerisable phenol monomer was used to create a redox film sensitive to pH but free from the interferences that can impede conventional pH systems. The film was integrated within a composite carbon-fibre-polymer laminate and was shown to exhibit Nernstian behaviour (55 mV/pH) with minimal drift and robust enough to operate within batch reactors.

Development of a structured diabetes self-management education program specific to the cultural and ethnic population of New Zealand.

AIM: To develop and pilot a diabetes self-management education (DSME) program specific to the needs of New Zealanders with type 2 diabetes mellitus (T2DM). METHODS: There were two parts in the present study. The first was the development of the program. This involved a literature review, consultation with end-user groups and drafting the content of the program. In the second part, the program was tested and modified according to feedback provided by both participants and facilitators. RESULTS: The present study achieved its primary goal of developing, piloting and modifying a DSME program specific to the New Zealand population. The DSME program was developed using concepts and content of international DSME programs. The content and concept was extensively tested via discussion groups with 71 individuals with T2DM and practice nurses to ensure the program met the unique cultural needs of New Zealanders with T2DM. Twenty-seven participants with T2DM were recruited into the pilot, of which 13 attended four of six sessions. Feedback from participants, observing nurses and facilitators was incorporated into the final program. CONCLUSIONS: DSME programs are an effective vehicle for providing individuals with T2DM the initial information and support to start self-managing their diabetes. However, to ensure DSME programs help individuals with the highest rates of diabetes and diabetes-related complications, it is important end-users participate in the development of the program. This DSME program now requires longitudinal trial to determine if in the New Zealand context it is able generate the same improvements in both clinical and qualitative outcomes as seen in similar international programs.

Using Computerized Physician Order Entry to Ensure Appropriate Vaccination of Patients with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a disorder in which an aberrant immune response in a genetically susceptible host, with influences from environmental factors, leads to intestinal inflammation. Vaccines against influenza and pneumococcal pneumonia are indicated for all patients with IBD, while vaccines such as hepatitis A and B, human papillomavirus, and meningococcal meningitis are only indicated for patients with specific risk factor profiles. Some vaccines are contraindicated for patients receiving immunosuppressive medications; typically, these are live or live attenuated vaccines such as measles-mumps-rubella, varicella zoster, and herpes zoster. Given the importance of ensuring patients with IBD are properly vaccinated, we designed a quality improvement project to determine the perceived barriers to ordering these vaccines and to make the process easier. METHODS: At the outset of the study, providers in our gastroenterology department who treat patients with IBD received a survey about vaccinations. Based on the preintervention survey responses, we created an order panel in our electronic medical record (Epic Systems Corporation) to facilitate vaccination ordering. This order panel prompted physicians to order the vaccinations and informed them of contraindications. At the end of the 2-month implementation period, we distributed a second survey to assess the utility of the order panel. RESULTS: Respondents generally agreed that the Epic SmartSet order panel made vaccinations easier to order, ensured physician confidence in ordering vaccinations, was helpful for use in practice, made the clinic more efficient, and reminded physicians which vaccinations are contraindicated because of immunosuppression. Respondents were divided regarding whether a greater number of patients with IBD were actually receiving vaccinations after the order panel was implemented. CONCLUSION: We used the order entry function in Epic to facilitate vaccination ordering for patients with IBD. Our results indicate that the order panel we built made ordering vaccinations easier and more efficient compared to the previous process. We hope this order panel promotes improved patient care and becomes a future area of study for how Epic and other electronic health records may be used.

Volcanology. The Yellowstone magmatic system from the mantle plume to the upper crust.

The Yellowstone supervolcano is one of the largest active continental silicic volcanic fields in the world. An understanding of its properties is key to enhancing our knowledge of volcanic mechanisms and corresponding risk. Using a joint local and teleseismic earthquake P-wave seismic inversion, we revealed a basaltic lower-crustal magma body that provides a magmatic link between the Yellowstone mantle plume and the previously imaged upper-crustal magma reservoir. This lower-crustal magma body has a volume of 46,000 cubic kilometers, ~4.5 times that of the upper-crustal magma reservoir, and contains a melt fraction of ~2%. These estimates are critical to understanding the evolution of bimodal basaltic-rhyolitic volcanism, explaining the magnitude of CO2 discharge, and constraining dynamic models of the magmatic system for volcanic hazard assessment.

N-alkylated 2,3,3-trimethylindolenines and 2-methylbenzothiazoles. Potential lead compounds in the fight against Saccharomyces cerevisiae infections.

The synthesis of a variety of N-alkylated 2,3,3-trimethylindolenines and 2-methylbenzothiazoles is reported herein. Their potential as antifungal agents is evaluated by preliminary screening against Saccharomyces cerevisiae (S. cerevisiae), Schizosaccharomyces pombe (S. pombe), and Candida albicans (C. albicans). Statistical analyses illustrate a strong relationship between chain length and growth inhibition for S. cerevisiae and S. pombe (p < 0.0001 in every case). Of particular interest is the activity of both sets of compounds against S. cerevisiae, as this is emerging as an opportunistic pathogen, especially in immunosuppressed and immunocompromised patients. Bioassays were set up to compare the efficacy of our range of N-alkylated compounds against classic antifungal agents; Amphotericin B and Thiabendazole.

Smart bandages--a colourful approach to early stage infection detection & control in wound care.

With the recent increase in bacterial resistance to conventional antibiotics, the early-stage detection and control of infection has become imperative in the fight against opportunistic pathogens in healthcare. The traditional ß-lactam wonder-drugs (e.g. penicillin and cephalosporins), are rendered inactive due to enzymatic hydrolysis by bacterial ß-lactamase enzymes as a bacterial defence mechanism. However, this deactivation mechanism produces different responses in the two aforementioned drugs - with the cephalosporins showing a molecular rearrangement mechanism which could be utilised for prodrug delivery. This unique mechanism could mean that inactive forms of cephalosporin antibiotics, once used as chemotherapeutics in oncology, could once again be used in the fight against disease as sensors to detect and treat bacterial colonisation. Therefore, we hypothesize that cephalosporin-dye bandages might provide an effective method to visually detect, and subsequently control, the early stages of an infection using photoantimicrobial chemotherapy (PACT).

Approaching intelligent infection diagnostics: Carbon fibre sensor for electrochemical pyocyanin detection.

Pyocyanin is produced by Ps. aeruginosa as a result of quorum sensing during wound colonisation increasing bacterial virulence and damaging host physiology, both of which contribute to an increased risk of infection. The use of carbon fibre tow as an electrochemical sensing matrix for assessing pyocyanin production is evaluated. Prototype sensor assemblies have been developed and response characteristics towards pyocyanin are detailed. The sensitive and linear quantification of pyocyanin is presented (r(2)=0.998) across the biomedically relevant concentration range (1-100 microM). Precise electrochemical measurements of pyocyanin by square wave voltammetry are established using carbon fibre assemblies (coefficient of variance=1.2 and 1.4% for 10 and 50 microM pyocyanin, respectively). Further testing of the sensors in bacterial cultures shows the ability to monitor pyocyanin production by Ps. aeruginosa in agreement with the chloroform-acid/photometric method and in the presence of other bacterially derived pigments and metabolites. The proposed small and inexpensive sensor assembly is suggested for use in monitoring Ps. aeruginosa growth.

Comparison of accuracy of 14-, 18- and 20-G needles in ex-vivo renal mass biopsy: a prospective, blinded study.

OBJECTIVE: To prospectively determine the accuracy of 14-, 18- and 20-G core needle biopsies to render the appropriate histological diagnosis of solid, enhancing renal masses, using a controlled, ex-vivo biopsy technique. PATIENTS AND METHODS: From March 2007 to September 2007, 31 patients undergoing partial or radical nephrectomy were randomly selected for biopsy. After extirpative surgery, three ex-vivo biopsies were taken from each lesion with 14-, 18- and 20-G biopsy needles. One experienced genitourinary pathologist, unaware of patient identifiers and final pathology results, determined the biopsy histology and tumour grade, based on standard haematoxylin and eosin (H&E) techniques and immunohistochemistry. RESULTS: The final pathological evaluation classified 21 masses (68%) as clear cell renal cell carcinoma (RCC), three (10%) as papillary RCC, three (10%) as chromophobe RCC, three (10%) as oncocytoma and one (3%) as a benign lymphoid infiltrate. The biopsy histology correlated with the final pathology in 29/31 cases (94%) with the 14-G, 30/31 cases (97%) with the 18-G and 25/31 cases (81%) with the 20-G needles. In two cases chromophobe RCC was misdiagnosed with oncocytoma, and vice versa. CONCLUSION: In this study a minimum of an 18-G biopsy needle was the most accurate in determining the histological diagnosis. Clear cell and papillary RCCs were accurately diagnosed on biopsy using an 18-G, whereas oncocytoma and chromophobe RCC were difficult to differentiate using standard H&E techniques and immunohistochemistry.

Intraoperative thrombus embolization during nephrectomy and tumor thrombectomy: critical analysis of the University of California-Los Angeles experience.

PURPOSE: Vascular invasion commonly occurs in renal cell carcinoma and intraoperative thrombus embolization is a known complication of tumor thrombectomy. We reviewed our experience with this complication to determine frequency, mortality, common factors and management strategies. MATERIALS AND METHODS: We retrospectively reviewed a prospective database of cases of open nephrectomy/tumor thrombectomy performed from 1989 to 2008. All cases were reviewed to identify clinicopathological variables, the thrombus extent and intraoperative complications. All cases with events were reviewed to identify preoperative pulmonary embolism, preoperative imaging, thrombus extent, presentation, management and outcome. RESULTS: A total of 282 cases of venous tumor thrombus were identified. Tumor thrombus level was 0 in 133 cases (47.2%), I to II in 85 (30.1%), III in 27 (9.6%) and IV in 29 (10.3%). Thrombus embolization was identified in 5 patients (1.8%). The incidence in level 0 vs I to IV was 0 of 133 cases (0%) vs 5 of 149 (3.4%), which was statistically significant (p = 0.04). Three patients (60%) died of the event. A review of recent series demonstrated a 1.49% incidence with 75% mortality. CONCLUSIONS: Intraoperative thrombus embolization is rare but when it occurs, mortality is extremely high. Strict attention to surgical principles is necessary to decrease risk. Extension into the vena cava, preoperative pulmonary embolism and a bland thrombus component may indicate increased risk. Adjunct procedures, such as preoperative filters and endoluminal occlusive balloons, may be justified in patients at high risk. Even with prompt recognition and embolectomy survival is rare.

Bromide-sulfur interchange: ion chromatographic determination of total reduced thiol levels in plasma.

Plasma thiol concentration has long been recognised as a potential indicator for assessing the severity of oxidative stress processes within physiological systems. While such measurements are normally restricted to research studies, this communication has sought to develop and characterise a novel approach through which this parameter could be exploited within routine clinical settings. The protocol is based on the rapid derivatisation of reduced thiol functionalities (protein and monomolecular moieties) through the homogenous reaction of a naphthoquinone bromide derivative. Bromide released in the reaction can be easily quantified through ion chromatography (Isocractic Dionex DX-120 incorporating an IonPac AS14 anion exchange column and a 25 microL sample loop with conductivity detector. Mobile phase consisted sodium carbonate/bicarbonate (3.5 mM/1 mM) at a flow rate of 1.5 mL/min). Method selectivity and sensitivity has been critically evaluated. The technique covers the range 15 microM-3.5 mM PSH with a detection limit of 9 microM PSH and analysis time of 5 min. The efficacy of the approach for the analysis of human plasma from five volunteers was assessed (ranging from 49 to 72 microM with an intra assay variation of less than 5% in all cases). The responses were validated through comparison with the standard Ellman colorimetric technique.

Rapid assessment of the latent hazard posed by dissolved mercaptans within aqueous effluent.

The presence of mercaptans (RSH) can usually be detected by their inherent noxious odour but there is a need to quantify the concentration within effluent and hence allow an assessment of the latent hazard to be made prior to disposal. The versatility of using naphthoquinone as a rapid derivatising agent through which to trap such species has been evaluated. The quinone moiety provides a label that can be quantified using colorimetric, electrochemical and chromatographic means and offers a significant advantage over conventional thiol labelling agents. The analytical characteristics of each approach have been investigated and the selectivity, sensitivity and applicability of the reaction system critically assessed for a range of model compounds. The naphthoquinone system has a detection limit in the low micromolar range with little interference from other components common to discharge water with 96% recovery of mercaptopropionate. The reaction to sulfide (HS-) has also been assessed and a disparity in response between the detection methods observed and a possible reaction pathway outlined.

Accelerated uplift and magmatic intrusion of the Yellowstone caldera, 2004 to 2006.

The Yellowstone caldera began a rapid episode of ground uplift in mid-2004, revealed by Global Positioning System and interferometric synthetic aperture radar measurements, at rates up to 7 centimeters per year, which is over three times faster than previously observed inflation rates. Source modeling of the deformation data suggests an expanding volcanic sill of approximately 1200 square kilometers at a 10-kilometer depth beneath the caldera, coincident with the top of a seismically imaged crustal magma chamber. The modeled rate of source volume increase is 0.1 cubic kilometer per year, similar to the amount of magma intrusion required to supply the observed high heat flow of the caldera. This evidence suggests magma recharge as the main mechanism for the accelerated uplift, although pressurization of magmatic fluids cannot be ruled out.

A chromatographic tool for preparing combinatorial quinone-thiol conjugate libraries.

Quinones are well established as key players in the production of reactive oxygen species within cellular environments. Many factors govern their cytotoxicity but most studies have been restricted to a few, core, derivatives. A new strategy for the in situ production of quinone derivatives has been developed such that libraries of diverse functionality can be rapidly created without recourse to extensive synthetic procedures. The approach relies upon nucleophilic addition by reduced thiol derivatives to the quinone core within a pre-culture assay mixture and provides a generic strategy that exploits the large reservoir of commercial thiols currently available. A readily accessible chromatographic method has been developed that allows the derivatisation process to be easily monitored and the purity of the resulting one pot preparation to be assessed. The viability of the combinatorial approach has been fully validated through comparison with a range of quinone-S-conjugates prepared using conventional bench synthesis. The latter have been fully characterised.

Metabolic mimics: thiol responsive drug release.

A new approach to the design of selective release interfaces is assessed in which a hydrophobic component is functionalised with a receptor reactive toward reduced thiol peptides-principally glutathione. The assembly has been characterised using electrochemical techniques and its ability to form a coherent, water insoluble coating is demonstrated. The subsequent reaction with glutathione creates a supramolecular conjugate that exploits the hydrophilic nature of the amino acid chain as a route through which the protective coating can be eroded and hence the underlying substrate exposed. The efficacy of the release process has been critically assessed with a view to establishing the action and selectivity of the trigger mechanism.