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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

Ketorolac-based analgesia improves outcomes for living kidney donors.

BACKGROUND: To reduce the morbidity of living kidney donors we introduced ketorolac-based analgesia for patients undergoing open donor nephrectomy in August 1999. There are no prior reports on the use of ketorolac for patients undergoing donor nephrectomy. METHODS: We conducted a retrospective review of all 198 consecutive patients who underwent open living donor nephrectomy between January 1998 and July 2000 at our institution. We compared patients who underwent surgery before and after introduction of ketorolac-based analgesia. RESULTS: The introduction of ketorolac-based analgesia resulted in a reduction in length of postoperative stay from 3.7+/-0.1 to 3.1+/-0.1 days (P<0.001). Patients who underwent surgery after ketorolac introduction required 58% less narcotics (P<0.001), recalled having less postoperative pain, and stopped taking pain medications sooner than patients before routine ketorolac use. Moreover, these patients drank 38% more liquids on the first postoperative day (P<0.001) and were able to resume a regular diet sooner than patients who were not managed with ketorolac. Patients who received ketorolac had a slightly lower creatinine clearance on the second postoperative day relative to patients who did not (66 vs. 72% of preoperative calculated creatinine clearance, P=0.05). However at a minimum of 3 months postoperatively, creatinine clearance did not differ between the two groups (70 vs. 73%, P=0.92). There were no differences in the rates of complications between the two groups. CONCLUSIONS: The use of ketorolac to control postoperative pain for patients undergoing open donor nephrectomy reduced morbidity and was not associated with any effect on long-term renal function or increased risk of complications. This is the first study to demonstrate the safety of using ketorolac at the time of donor nephrectomy.

Endovascular aortic aneurysm operations.

Options for the treatment of abdominal and thoracic aortic aneurysms are in a state of evolutionary change. The development and continued refinement of the endoluminal approaches has decreased the need for open aortic aneurysm surgery. Endovascular stent graft technology is an area of active research in which both the delivery systems and the endografts are undergoing continued improvement so that patients with what was previously thought to be unfavorable anatomy may be treated by these means. The design and deployment techniques of the currently available endografts, as well as those in clinical trials, are presented.

Conservatism and new technology: the impact on abdominal aortic aneurysm repair.

The last decade has represented a time of fundamental change in the treatment of abdominal aortic aneurysms (AAAs). Potentially, vascular surgeons will either acquire catheter-based skills or relinquish the care for many patients with infrarenal AAA. We investigated AAA referral patterns and method of AAA repair after the establishment of an endovascular AAA program at our institution. We conducted a retrospective review of elective AAA repairs after the initiation of an endovascular AAA program in April 1994. Six vascular surgeons performed all procedures with a clear distinction between the surgeons (n=3) who performed traditional AAA repair only and those (n=3) who managed AAAs by means of either endovascular or traditional treatment. From April 1994 through December 2000, 740 elective AAA repairs were performed. During this time the mean number of AAA repairs has been 106/year ranging from 75 to 155/year. More notable however is the steady increase in the percentage of endovascular AAA repairs from 6 per cent of all AAA repairs in 1994 to 61 per cent in 2000. During this time traditional surgeons have experienced a plateau in total AAA repairs performed per year with their number of open repairs decreasing by 36 per cent. At the same time endovascular surgeons have seen a progressive rise in total AAA cases including an increase of 200 per cent in open repairs and of 1367 per cent in endovascular repairs. Our vascular surgeons who repair AAA utilizing both endovascular and open techniques have experienced an increase in aneurysm referrals since the advent of an endovascular AAA program. Those who have not adopted endovascular skills have seen a decline in their aneurysm practice. The larger question about whether or not to embrace new technology before the availability of long-term follow-up remains unanswered.

Will claims workers dislike a computerized fraud detector?

The computerized fraud detector (CFRD) assigns suspicion scores to questionable automobile insurance claims. Evaluators pilot tested this algorithm in three offices, comparing its effects with three matched offices. Observers uncovered that in two target offices and one comparison office, Millennium 2000 (M2K) also was being installed. The study design thus became as follows: Two offices had two interventions, one office had CFRD but not M2K, another office had M2K but not CFRD, and two offices had neither. Hierarchical linear models document that offices with both new computer systems will have the most unfavorable employee attitudes toward computerized fraud detection, followed by offices with only one new system. Employees with jobs of higher rank and employees not receptive to innovation will dislike computerized fraud detection. Implementation of one computer system, CFRD or M2K, may have minor negative fixed effects on employee attitudes, but their effects on the between-office variance are inconsequential.