Dhvar5 antimicrobial peptide (AMP) chemoselective covalent immobilization results on higher antiadherence effect than simple physical adsorption

Bacterial colonization and subsequent biofilm formation is still one of the major problems associated with medical devices. Antimicrobial peptides (AMP) immobilization onto biomaterials surface is a promising strategy to avoid bacterial colonization. However, a correct peptide orientation and exposure from the surface is essential to maintain AMP antimicrobial activity. This work aims to evaluate the effect of the immobilization on antibacterial activity of Dhvar5 (LLLFLLKKRKKRKY), an AMP with a head-to-tail amphipathicity. Dhvar5 was linked to thin chitosan coatings in i) a controlled orientation and exposure, testing covalent immobilization of its N- or C-terminus and using spacers with different lengths and flexibilities or in ii) a random orientation by physical adsorption. Chitosan coating was chosen due to its antimicrobial properties and readiness to be functionalized. Surface characterization demonstrated the chemoselective immobilization of the peptide with different spacers in a similar concentration (∼2 ng/cm2). Efficacy assays demonstrated that covalent immobilization of Dhvar5 exposing its cationic end, improves the chitosan coating antimicrobial effect by decreasing Methicillin-resistant Staphylococcus aureus (MRSA) colonization. This effect was enhanced when longer spacers were used independently of their flexibility. In opposite, immobilized Dhvar5 exposing its hydrophobic end has no effect on bacterial adhesion to chitosan, and when adsorbed in a random orientation even induces bacterial adhesion to chitosan coating.This work was financed by FEDER funds through the Programa Operacional Factores de Competitividade (COMPETE) and by Portuguese funds through FCT (Fundacao para a Ciencia e a Tecnologia) in the framework of the projects: PTDC/CTM/101484/2008; PEst-C/SAU/LA0002/2013; Pest-C/QUI/UI0081/2013. Fabiola Costa acknowledges FCT for the PhD grant SFRH/BD/72471/2010

Microwave plasma chemical vapour deposition diamond nucleation on ferrous substrates with Ti and Cr interlayers

Diamond-coated steel is considered an important issue in synthetic diamond technology due to the great economical importance of enhancing the wear resistance and surface hardness of commercial Fe-based alloys. However, direct diamond coating by chemical vapour deposition (CVD) is rather problematic-adhesion and growth are seriously affected. The use of interlayers is a common approach to minimise these problems. This work reports an investigation on the establishment of good nucleation and growth conditions of diamond films by microwave plasma CVD (MPCVD) on ferrous substrates coated with Ti and Cr interlayers. Commercial grade ferrous substrates were pre-coated with commercial interlayers by sputtering (Ti, Cr) and electroplating (Cr) techniques. Steel substrates led to better results than iron cast substrates. The best films were obtained on Ti pre-coated steel substrate. The results on Cr interlayers pointed to the advantage of electroplating over the physical vapour deposition (PVD) sputtering. From the two selected parameter sets for diamond deposition, the one using lower power level conducted to the best results. Initial roughness and growth parameters were found to counteract on the uniformity of the diamond films. The morphology was studied by scanning electron microscopy (SEM), the roughness was estimated by profilometry, while diamond quality and stress state were evaluated by mu-Raman spectroscopy. (C) 2002 Elsevier Science B.V. All rights reserved

Effect of intraperitioneally administered hydrolyzed whey protein on blood pressure and renal sodium handling in awake spontaneously hypertensive rats

The present study evaluated the acute effect of the intraperitoneal. (ip) administration of a whey protein hydrolysate (WPH) on systolic arterial blood pressure (SBP) and renal sodium handling by conscious spontaneously hypertensive rats (SHR). The ip administration of WPH in a volume of 1 ml dose-dependently lowered the SBP in SHR 2 h after administration at doses of 0.5 g/kg (0.15 M NaCl: 188.5 +/- 9.3 mmHg vs WPH: 176.6 +/- 4.9 mmHg, N = 8, P = 0.001) and 1.0 g/kg (0.15 M NaCl: 188.5 9.3 mmHg vs WPH: 163.8 +/- 5.9 mmHg, N = 8, P = 0.0018). Creatinine clearance decreased significantly (P = 0.0084) in the WPH-treated group (326 +/- 67 mu L min(-1) 100 g body weight(-1)) compared to 0.15 M NaCl-treated (890 26 mu L min(-1) 100 g body weight(-1)) and captopril-treated (903 +/- 72 mu L min(-1) 100 g body weight(-1)) rats. The ip administration of 1.0 g WPH/kg also decreased fractional sodium excretion to 0.021 +/- 0.019% compared to 0.126 +/- 0.041 and 0.66 +/- 0.015% in 0.15 M NaCl and captopril-treated rats, respectively (P = 0.033). Similarly, the fractional potassium excretion in WPH-treated rats (0.25 +/- 0.05%) was significantly lower (P = 0.0063) than in control (0.91 +/- 0.15%) and captopril-treated rats (1.24 +/- 0.30%), respectively. The present study shows a decreased SBP in SHR after the administration of WPH associated with a rise in tubule sodium reabsorption despite an angiotensin I-converting enzyme (ACE)-inhibiting in vitro activity (IC50 = 0.68 mg/mL). The present findings suggest a pathway involving ACE inhibition but measurements of plasma ACE activity and angiotensin Id levels are needed to support this suggestion.38121817182

Agreement and accuracy using the FIGO, ACOG and NICE cardiotocography interpretation guidelines.

INTRODUCTION: One of the limitations reported with cardiotocography (CTG) is the modest interobserver agreement observed in tracing interpretation. This study compared agreement, reliability and accuracy of CTG interpretation using the FIGO, ACOG and NICE guidelines. MATERIAL AND METHODS: A total of 151 tracings was evaluated by 27 clinicians from three centers where FIGO, ACOG and NICE guidelines were routinely used. Interobserver agreement was evaluated using the proportions of agreement (PA) and reliability with the kappa (k) statistic. The accuracy of tracings classified as "pathological/category III" was assessed for prediction of newborn acidemia. For all measures, 95% confidence intervals (95%CI) were calculated RESULTS: CTG classifications were more distributed with FIGO (9%, 52%, 39%) and NICE (30%, 33%, 37%) than with ACOG (13%, 81%, 6%). The category with the highest agreement was ACOG category II (PA=0.73 95%CI 0.70-76), and the ones with the lowest agreement were ACOG categories I and III. Reliability was significantly higher with FIGO (k=0.37, 95%CI 0.31-0.43), and NICE (k=0.33, 95%CI 0.28-0.39) than with ACOG (k= 0.15, 95%CI 0.10-0.21), however all represent only slight/fair reliability. FIGO and NICE showed a trend towards higher sensitivities in prediction of newborn acidemia (89% and 97% respectively) than ACOG (32%,), but the latter achieved a significantly higher specificity (95%) CONCLUSIONS: With ACOG guidelines there is high agreement in category II, low reliability, low sensitivity and high specificity in prediction of acidemia. With FIGO and NICE guidelines there is higher reliability, a trend towards higher sensitivity, and lower specificity in prediction of acidemia. This article is protected by copyright. All rights reserved

Generating real-world evidence on the quality use, benefits and safety of medicines in australia: History, challenges and a roadmap for the future

Australia spends more than $20 billion annually on medicines, delivering significant health benefits for the population. However, inappropriate prescribing and medicine use also result in harm to individuals and populations, and waste of precious health resources. Medication data linked with other routine collections enable evidence generation in pharmacoepidemiology; the science of quantifying the use, effectiveness and safety of medicines in real-world clinical practice. This review details the history of medicines policy and data access in Australia, the strengths of existing data sources, and the infrastructure and governance enabling and impeding evidence generation in the field. Currently, substantial gaps persist with respect to cohesive, contemporary linked data sources supporting quality use of medicines, effectiveness and safety research; exemplified by Aus-tralia’s limited capacity to contribute to the global effort in real-world studies of vaccine and dis-ease-modifying treatments for COVID-19. We propose a roadmap to bolster the discipline, and population health more broadly, underpinned by a distinct capability governing and streamlining access to linked data assets for accredited researchers. Robust real-world evidence generation requires current data roadblocks to be remedied as a matter of urgency to deliver efficient and equitable health care and improve the health and well-being of all Australians

Adenosine-guided pulmonary vein isolation versus conventional pulmonary vein isolation in patients undergoing atrial fibrillation ablation: An updated meta-analysis

BACKGROUND: Recurrent atrial fibrillation episodes following pulmonary vein isolation (PVI) are frequently due to reconnection of PVs. Adenosine can unmask dormant conduction, leading to additional ablation to improve AF-free survival. We performed a meta-analysis of the literature to assess the role of adenosine testing in patients undergoing atrial fibrillation (AF) ablation. METHODS: PubMed, EMBASE, and Cochrane databases were searched through until December 2015 for studies reporting on the role of adenosine guided-PVI versus conventional PVI in AF ablation. RESULTS: Eleven studies including 4099 patients undergoing AF ablation were identified to assess the impact of adenosine testing. Mean age of the population was 61 ± 3 years: 25% female, 70% with paroxysmal AF. Follow up period of 12.5 ± 5.1 months. A significant benefit was observed in the studies published before 2013 (OR = 1.75; 95%CI 1.32–2.33, p < 0.001, I2 = 11%), retrospective (OR = 2.05; 95%CI 1.47–2.86, p < 0.001, I2 = 0%) and single-centre studies (OR = 1.58; 95%CI 1.19–2.10, p = 0.002, I2 = 30%). However, analysis of studies published since 2013 (OR = 1.41; 95% CI 0.87–2.29, p = 0.17, I2 = 75%) does not support any benefit from an adenosine-guided strategy. Similar findings were observed by pooling prospective case-control (OR = 1.39; 95%CI 0.93–2.07, p = 0.11, I2 = 75%), and prospective randomized controlled studies (OR = 1.62; 95%CI 0.81–3.24, p = 0.17, I2 = 86%). Part of the observed high heterogeneity can be explained by parameters such as dormant PVs percentage, use of new technology, improvement of center/operator experience, patients' characteristics including gender, age, and AF type. CONCLUSIONS: Pooling of contemporary data from high quality prospective case–control & prospective randomized controlled studies fails to show the benefit of adenosine-guided strategy to improve AF ablation outcomes

Reducing the clique and chromatic number via edge contractions and vertex deletions.

We consider the following problem: can a certain graph parameter of some given graph G be reduced by at least d, for some integer d, via at most k graph operations from some specified set S, for some given integer k? As graph parameters we take the chromatic number and the clique number. We let the set S consist of either an edge contraction or a vertex deletion. As all these problems are NP-complete for general graphs even if d is fixed, we restrict the input graph G to some special graph class. We continue a line of research that considers these problems for subclasses of perfect graphs, but our main results are full classifications, from a computational complexity point of view, for graph classes characterized by forbidding a single induced connected subgraph H