Nanoarchitectonics of Bactericidal Coatings Based on CaCO3-Nanosilver Hybrids.

Antimicrobial coatings provide protection against microbes colonization on surfaces. This can prevent the stabilization and proliferation of microorganisms. The ever-increasing levels of microbial resistance to antimicrobials are urging the development of alternative types of compounds that are potent across broad spectra of microorganisms and target different pathways. This will help to slow down the development of resistance and ideally halt it. The development of composite antimicrobial coatings (CACs) that can host and protect various antimicrobial agents and release them on demand is an approach to address this urgent need. In this work, new CACs based on microsized hybrids of calcium carbonate (CaCO3) and silver nanoparticles (AgNPs) were designed using a drop-casting technique. Polyvinylpyrrolidone and mucin were used as additives. The CaCO3/AgNPs hybrids contributed to endowing colloidal stability to the AgNPs and controlling their release, thereby ensuring the antibacterial activity of the coatings. Moreover, the additives PVP and mucin served as a matrix to (i) control the distribution of the hybrids, (ii) ensure mechanical integrity, and (iii) prevent the undesired release of AgNPs. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) techniques were used to characterize the 15 µm thick CAC. The antibacterial activity was determined against Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa, three bacteria responsible for many healthcare infections. Antibacterial performance of the hybrids was demonstrated at concentrations between 15 and 30 µg/cm2. Unloaded CaCO3 also presented bactericidal properties against MRSA. In vitro cytotoxicity tests demonstrated that the hybrids at bactericidal concentrations did not affect human dermal fibroblasts and human mesenchymal stem cell viability. In conclusion, this work presents a simple approach for the design and testing of advanced multicomponent and functional antimicrobial coatings that can protect active agents and release them on demand.

Dose of reduced z-axis length of computed tomography angiography (CTA) of the chest for pulmonary embolism using 64-detector rows and adaptive iterative reconstruction techniques.

The objective of this study is to compare the dose of CT angiography (CTA) for the diagnosis of pulmonary embolism (PE) performed using a reduced z-axis to conventional CTA for PE, both using adaptive iterative reconstruction technique on a 64-detector row device. The institutional review board approved a waiver of informed consent. A study was performed to consecutive patients having CTA for PE in the emergency department (ED). The patients underwent a reduced z-axis CTA from the top of the aortic arch to the bottom of the heart using the appropriate CT parameters and standard IV contrast injections. All patients had scans performed with 40 % ASIR and had a breast shield placed to limit breast dose. Per ED ordering criteria, the reduced z-axis protocol was appropriate for patients under 50 years old with no significant comorbidity. The control group consisted of patients from the same time period under 50 years of age who received a full z-axis scan. Technical parameters were the same for both groups other than scan length. Dose-length product (DLP) and volume CT dose index (CTDIvol) were the parameters used to evaluate differences in radiation dose to patients. The average effective dose of the full z-axis group was significantly higher (10.9 mSv (SD 4.7, range = 2.8-22)) compared to the reduced z-axis group (5.5 mSv (SD 3.0, range = 1.6-13, p < 0.001). The average effective dose for the reduced z-axis group was 49 % less than that of the full z-axis group. Reducing the z-axis of a CTA for PE significantly reduces effective radiation dose.

Science, practice and mythology: a definition and examination of the implications of scientism in medicine.

Scientism is a philosophy which purports to define what the world 'really is'. It adopts what the philosopher Thomas Nagel called 'an epistemological criterion of reality', defining what is real as that which can be discovered by certain quite specific methods of investigation. As a consequence all features of experience not revealed by those methods are deemed 'subjective' in a way that suggests they are either not real, or lie beyond the scope of meaningful rational inquiry. This devalues capacities that (we argue) are in fact essential components of good reasoning and virtuous practice. Ultimately, the implications of scientism for statements of value undermine value-judgements essential for science itself to have a sound basis. Scientism has implications, therefore, for ontology, epistemology and also for which claims we can assert as objective truths about the world. Adopting scientism as a world view will have consequences for reasoning and decision-making in clinical and other contexts. We analyse the implications of this approach and conclude that we need to reject scientism if we are to avoid stifling virtuous practice and to develop richer conceptions of human reasoning.

Philosophical health: Unveiling the patient's personal philosophy with a person-centred method of dialogue.

Grounded in ideas about sense-making and whole-person care with a long intellectual heritage, the movement for Philosophical Health-with its specific conceptions of philosophical care and counselling-is a relatively recent addition to the ongoing debate about understanding better the perspectives of patients to improve health practice. This article locates the development of this movement within the context of broader discussions of person-centred care (PCC), arguing that the approach advocated by defenders of philosophical health can provide a straightforward method for implementing PCC in actual cases. This claim is explained and defended with reference to the SMILE_PH method created by Luis de Miranda (Sense-Making Interviews Looking at Elements of Philosophical Health), an approach recently trialled convincingly with people living with traumatic spinal cord injury.

How similar is the antibacterial activity of silver nanoparticles coated with different capping agents?

Silver nanoparticles (AgNPs) represent one of the most commercialised metal nanomaterials, with an extensive number of applications that span from antimicrobial products to electronics. Bare AgNPs are very susceptible to aggregation, and capping agents are required for their protection and stabilisation. The capping agents can endow new characteristics which can either improve or deteriorate AgNPs (bio)activity. In the present work, five different capping agents were studied as stabilizing agents for AgNPs: trisodium citrate (citrate), polyvinylpyrrolidone (PVP), dextran (Dex), diethylaminoethyl-dextran (DexDEAE) and carboxymethyl-dextran (DexCM). The properties of the AgNPs were studied using a set of methods, including transmission electron microscopy, X-ray diffraction, thermogravimetric analysis and ultraviolet-visible and infrared spectroscopy. Coated and bare AgNPs were also tested against Escherichia coli, methicillin-resistance Staphylococcus aureus and Pseudomonas aeruginosa to analyse their capacity to suppress bacterial growth and eradicate biofilms of clinically relevant bacteria. The results showed that all the capping agents endow long-term stability for the AgNPs in water; however, when the AgNPs are in bacterial culture media, their stability is highly dependent on the capping agent properties due to the presence of electrolytes and charged macromolecules such as proteins. The results also showed that the capping agents have a substantial impact on the antibacterial activity of the AgNPs. The AgNPs coated with the Dex and DexCM were the most effective against the three strains, due to their better stability which resulted in the release of more silver ions, better interactions with the bacteria and diffusion into the biofilms. It is hypothesized that the antibacterial activity of capped AgNPs is governed by a balance between the AgNPs stability and their ability to release silver ions. Strong adsorption of capping agents like PVP on the AgNPs endows higher colloidal stability in culture media; however, it can decrease the rate of Ag+ release from the AgNPs and reduce the antibacterial performance. Overall, this work presents a comparative study between different capping agents on the properties and antibacterial activity of AgNPs, highlighting the importance of the capping agent in their stability and bioactivity.

Vaterite vectors for the protection, storage and release of silver nanoparticles.

Silver nanoparticles (AgNPs) have found widespread commercial applications due to their unique physical and chemical properties. However, their relatively poor stability remains a main problem. An ideal way to improve the stability of AgNPs is not only to endow colloidal stability to individual nanoparticles but also to protect them from environmental factors that induce their agglomeration, like variation of ionic strength and pH, presence of macromolecules, etc. Mesoporous calcium carbonate vaterite crystals (CaCO3 vaterite) have recently attracted significant attention as inexpensive and biocompatible carriers for the encapsulation and controlled release of both drugs and nanoparticles. This work aimed to develop an approach to load AgNPs into CaCO3 vaterite without affecting their properties. We focused on improving the colloidal stability of AgNPs by using different capping agents, and understanding the mechanism behind AgNPs loading and release from CaCO3 crystals. Various methods were applied to study the AgNPs and CaCO3 crystals loaded with AgNPs (CaCO3/AgNPs hybrids), such as scanning and transmission electron microscopy, X-ray diffraction, infrared and mass spectrometry. The results demonstrated that polyvinylpyrrolidone and positively charged diethylaminoethyl-dextran can effectively keep the colloidal stability of AgNPs during co-precipitation with CaCO3 crystals. CaCO3/AgNPs hybrids composed of up to 4 % weight content of nanoparticles were produced, with the loading mechanism being well-described by the Langmuir adsorption model. In vitro release studies demonstrated a burst release of stable AgNPs at pH 5.0 and a sustained release at pH 7.5 and 9.0. The antibacterial studies showed that these hybrids are effective against Escherichia coli, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, three important bacteria responsible for nosocomial infections. The developed approach opens a new way to stabilise, protect, store and release AgNPs in a controlled manner for their use as antimicrobial agents.

Iatrogenic pneumomediastinum and subcutaneous emphysema as a complication of colonoscopy with cold forceps biopsy.

A 58-year-old woman underwent outpatient colonoscopy with multiple cold forceps biopsy for evaluation of a presumptive diagnosis of ulcerative colitis. Six hours following the procedure, she developed subcutaneous crepitus and presented to the emergency department, where chest X-ray revealed pneumomediastinum and subcutaneous emphysema. Our case discusses this unusual complication of colonoscopy and its diagnosis and management.

Response-Forty-Seven Years Later: Further Studies in Disappointment?

This paper provides a commentary on "Vascular amputees: A study in disappointment" (Little et al. 1974) and its significance in the development of the disability rights movement, as well as the movements for values-based medicine and person-centred health and social care.

Stigma, epistemic injustice, and "looked after children": The need for a new language.

This article examines the processes that contribute to the stigmatization of a group of people typically identified as "children in care" or "looked after children." In particular, we will look at the ways that we (adults, professionals, and carers) interact with these children, based on their status as both children and members of a socially marginalized and disadvantaged group, and how these modes of interaction can inhibit dialogue-a dialogue that is needed if we are to base our conceptions regarding the needs of these children on a more accurate understanding of their experiences and perspective. The problem is particularly challenging because the very terminology we use in the care community to identify this group is a product of the damaging preconceptions that have affected our interactions with its members and, we argue, it serves to reinforce those preconceptions. Using Fricker's work on epistemic injustice, in conjunction with evidence regarding how accusations of abuse and neglect of these children have been addressed in numerous cases, we illustrate the problems we have in hearing the voices of members of this group and the harmful effects this has on their own ability to understand and articulate their experiences. These problems represent "barriers to disclosure" that need to be surmounted if we are to establish a more inclusive dialogue. Currently, dialogue between these children and those of us charged to "look after" them is too often characterized by a lack of trust: not only in terms of the children feeling that their word is not taken seriously, that their claims are not likely to be believed, but also in their feeling that they cannot trust those to whom they might disclose abuse or neglect. The goals of the paper are modest in that we aim simply to open up the debate on how to meet this epistemic challenge, noting that there are specific problems that extend beyond those already identified for hearing the voices of other victims of epistemic injustice. Explicitly recognizing the nature and extent of the problem still leaves us a long way from its solution, but it is a crucial start.

Philosophy and the clinic: Stigma, respect and shame.

Since its foundation in 2010, the annual philosophy thematic edition of this journal has been a forum for authors from a wide range of disciplines and backgrounds, enabling contributors to raise questions of an urgent and fundamental nature regarding the most pressing problems facing the delivery and organization of healthcare. Authors have successfully exposed and challenged underlying assumptions that framed professional and policy discourse in diverse areas, generating productive and insightful dialogue regarding the relationship between evidence, value, clinical research and practice. These lively debates continue in this thematic edition, which includes a special section on stigma, shame and respect in healthcare. Authors address the problems with identifying and overcoming stigma in the clinic, interactional, structural and phenomenological accounts of stigma and the 'stigma-shame nexus'. Papers examine the lived experience of discreditation, discrimination and degradation in a range of contexts, from the labour room to mental healthcare and the treatment of 'deviancy' and 'looked-after children'. Authors raise challenging questions about the development of our uses of language in the context of care, and the relationship between stigma, disrespect and important analyses of power asymmetry and epistemic injustice. The relationship between respect, autonomy and personhood is explored with reference to contributions from an important conference series, which includes analyses of shame in the context of medically unexplained illness, humour, humiliation and obstetric violence.

Campylobacter jejuni activates NF-kappaB independently of TLR2, TLR4, Nod1 and Nod2 receptors.

Campylobacter jejuni activates the host transcription factor NF-kappaB that regulates the expression of a number of genes involved in the inflammatory response to bacterial infection. Signaling pathways leading to NF-kappaB by pathogens and/or their products include transmembrane Toll-like receptors (TLRs) and intracellular receptors nucleotide-binding oligomerization domain proteins (Nods). This study was carried out to investigate the role of TLRs (TLR2 and TLR4) and Nods (Nod1 and Nod2) receptors in mediating NF-kappaB activation by C. jejuni. By means of transfecting receptors/molecules under study and measuring reporter gene activity, NF-kappaB activation and subsequent cytokine production by live, heat-killed C. jejuni, or boiled cell extract (BCE) were observed in a range of tissue culture cell lines. This activation is reduced upon transfection of cells with the dominant negative versions (DNV) of TLR-adaptor molecule MyD88. NF-kappaB activation was observed to be augmented in cell lines transfected with TLR2, Nod1, and Nod2 but not with TLR4. Additionally, NF-kappaB activation by C. jejuni was observed to be independent of Nod1 and Nod2 in cells transfected with DNV of these receptors. NF-kappaB activation pathway by C. jejuni may represent a novel mechanism utilising unknown receptors up-regulated by yet to be characterized active component(s). To our knowledge, such observations have not been previously reported for C. jejuni or any other food-borne pathogen.

Reduced Z-axis coverage multidetector CT angiography for suspected acute pulmonary embolism could decrease dose and maintain diagnostic accuracy.

Multidetector computed tomographic angiography (MDCTA) is the method of choice for evaluation of suspected acute pulmonary embolism (PE) in most patients because it is accurate and widely available. The use of computed tomography, including MDCTA for PE, has risen dramatically over the last several years with an attendant rise in radiation exposure. Many methods currently employed to reduce radiation dose may affect image quality and potentially affect diagnostic accuracy. Reducing Z-axis coverage would decrease radiation dose without any effect on image quality. This study was performed to assess the effect on the accuracy of MDCTA for suspected acute PE if the Z-axis coverage was reduced to the anatomic range from the top of the aortic arch through the heart. Two hundred ninety-five examinations were performed on a 64-detector-row MDCT and interpreted as positive for PE from July 2005 to February 2008. When the anatomic range of these data sets were retrospectively reduced and reinterpreted for PE, no case was interpreted as negative for PE. The Z-axis coverage was reduced by 37%. In the interest of keeping radiation doses as low as reasonably achievable, further research in this area is warranted.

Multilocus sequence typing of Cronobacter sakazakii and Cronobacter malonaticus reveals stable clonal structures with clinical significance which do not correlate with biotypes.

BACKGROUND: The Cronobacter genus (Enterobacter sakazakii) has come to prominence due to its association with infant infections, and the ingestion of contaminated reconstituted infant formula. C. sakazakii and C. malonaticus are closely related, and are defined according their biotype. Due to the ubiquitous nature of the organism, and the high severity of infection for the immunocompromised, a multilocus sequence typing (MLST) scheme has been developed for the fast and reliable identification and discrimination of C. sakazakii and C. malonaticus strains. It was applied to 60 strains of C. sakazakii and 16 strains of C. malonaticus, including the index strains used to define the biotypes. The strains were from clinical and non-clinical sources between 1951 and 2008 in USA, Canada, Europe, New Zealand and the Far East. RESULTS: This scheme uses 7 loci; atpD, fusA, glnS, gltB, gyrB, infB, and pps. There were 12 sequence types (ST) identified in C. sakazakii, and 3 in C. malonaticus. A third (22/60) of C. sakazakii strains were in ST4, which had almost equal numbers of clinical and infant formula isolates from 1951 to 2008. ST8 may represent a particularly virulent grouping of C. sakazakii as 7/8 strains were clinical in origin which had been isolated between 1977 - 2006, from four countries. C. malonaticus divided into three STs. The previous Cronobacter biotyping scheme did not clearly correspond with STs nor with species. CONCLUSION: In conclusion, MLST is a more robust means of identifying and discriminating between C. sakazakii and C. malonaticus than biotyping. The MLST database for these organisms is available online at http://pubmlst.org/cronobacter/.

Induction of a chemoattractant transcriptional response by a Campylobacter jejuni boiled cell extract in colonocytes.

BACKGROUND: Campylobacter jejuni, the commonest cause of bacterial diarrhoea worldwide, can also induce colonic inflammation. To understand how a previously identified heat stable component contributes to pro-inflammatory responses we used microarray and real-time quantitative PCR to investigate the transcriptional response to a boiled cell extract of Campylobacter jejuni NCTC 11168. RESULTS: RNA was extracted from the human colonocyte line HCA-7 (clone 29) after incubation for 6 hours with Campylobacter jejuni boiled cell extract and was used to probe the Affymetrix Human Genome U133A array. Genes differentially affected by Campylobacter jejuni boiled cell extract were identified using the Significance Score algorithm of the Bioconductor software suite and further analyzed using the Ingenuity Pathway Analysis program. The chemokines CCL20, CXCL3, CXCL2, Interleukin 8, CXCL1 and CXCL6 comprised 6 of the 10 most highly up-regulated genes, all with Significance Scores > or = 10. Members of the Tumor Necrosis Factor alpha/Nuclear Factor-kappaB super-family were also significantly up-regulated and involved in the most significantly regulated signalling pathways (Death receptor, Interleukin 6, Interleukin 10, Toll like receptor, Peroxisome Proliferator Activated Receptor-gamma and apoptosis). Ingenuity Pathway Analysis also identified the most affected functional gene networks such as cell movement, gene expression and cell death. In contrast, down-regulated genes were predominantly concerned with structural and metabolic functions. CONCLUSION: A boiled cell extract of Campylobacter jejuni has components that can directly switch the phenotype of colonic epithelial cells from one of resting metabolism to a pro-inflammatory one, particularly characterized by increased expression of genes for leukocyte chemoattractant molecules.

Neonatal enteral feeding tubes as loci for colonisation by members of the Enterobacteriaceae.

BACKGROUND: The objective of this study was to determine whether neonatal nasogastric enteral feeding tubes are colonised by the opportunistic pathogen Cronobacter spp. (Enterobacter sakazakii) and other Enterobacteriaceae, and whether their presence was influenced by the feeding regime. METHODS: One hundred and twenty-nine tubes were collected from two neonatal intensive care units (NICU). A questionnaire on feeding regime was completed with each sample. Enterobacteriaceae present in the tubes were identified using conventional and molecular methods, and their antibiograms determined. RESULTS: The neonates were fed breast milk (16%), fortified breast milk (28%), ready to feed formula (20%), reconstituted powdered infant formula (PIF, 6%), or a mixture of these (21%). Eight percent of tubes were received from neonates who were 'nil by mouth'. Organisms were isolated from 76% of enteral feeding tubes as a biofilm (up to 107 cfu/tube from neonates fed fortified breast milk and reconstituted PIF) and in the residual lumen liquid (up to 107 Enterobacteriaceae cfu/ml, average volume 250 mul). The most common isolates were Enterobacter cancerogenus (41%), Serratia marcescens (36%), E. hormaechei (33%), Escherichia coli (29%), Klebsiella pneumoniae (25%), Raoultella terrigena (10%), and S. liquefaciens (12%). Other organisms isolated included C. sakazakii (2%),Yersinia enterocolitica (1%),Citrobacter freundii (1%), E. vulneris (1%), Pseudomonas fluorescens (1%), and P. luteola (1%). The enteral feeding tubes were in place between < 6 h (22%) to > 48 h (13%). All the S. marcescens isolates from the enteral feeding tubes were resistant to amoxicillin and co-amoxiclav. Of additional importance was that a quarter of E. hormaechei isolates were resistant to the 3rd generation cephalosporins ceftazidime and cefotaxime. During the period of the study, K. pneumoniae and S. marcescens caused infections in the two NICUs. CONCLUSION: This study shows that neonatal enteral feeding tubes, irrespective of feeding regime, act as loci for the bacterial attachment and multiplication of numerous opportunistic pathogens within the Enterobacteriaceae family. Subsequently, these organisms will enter the stomach as a bolus with each feed. Therefore, enteral feeding tubes are an important risk factor to consider with respect to neonatal infections.

A psychoanalytic exploration of collective trauma among Indigenous Australians and a suggestion for intervention.

OBJECTIVE: Psychoanalysis is used to explore the effects of the annihilation of culture and how this leads to a loss of identification with a collective subjectivity and triggers catastrophic symptoms including loss of collective hope, the rise of addictive and self-destructive behaviours, and the intergenerational transmission of trauma among Indigenous Australian communities. CONCLUSIONS: I propose restorative educational interventions for young Indigenous children that seek to engage them with ancestral memory, cultural narratives, and a sense of purpose so that healing from historically transmitted trauma may be initiated and a grounded sense of subjectivity restored.

Interactions between persons-Knowledge, decision making, and the co-production of practice.

There is now broad agreement that ideas like person-centred care, patient expertise and shared decision-making are no longer peripheral to health discourse, fine ideals or merely desirable additions to sound, scientific clinical practice. Rather, their incorporation into our thinking and planning of health and social care is essential if we are to respond adequately to the problems that confront us: they need to be seen not as "ethical add-ons" but core components of any genuinely integrated, realistic and conceptually sound account of healthcare practice. This, the tenth philosophy thematic edition of the journal, presents papers conducting urgent research into the social context of scientific knowledge and the significance of viewing clinical knowledge not as something that "sits within the minds" of researchers and practitioners, but as a relational concept, the product of social interactions. It includes papers on the nature of reasoning and evidence, the on-going problems of how to 'integrate' different forms of scientific knowledge with broader, humanistic understandings of reasoning and judgement, patient and community perspectives. Discussions of the epistemological contribution of patient perspectives to the nature of care, and the crucial and still under-developed role of phenomenology in medical epistemology, are followed by a broad range of papers focussing on shared decision-making, analysing its proper meaning, its role in policy, methods for realising it and its limitations in real-world contexts.

Patients and agents - or why we need a different narrative: a philosophical analysis.

BACKGROUND: The success of medicine in the treatment of patients brings with it new challenges. More people live on to suffer from functional, chronic or multifactorial diseases, and this has led to calls for more complex analyses of the causal determinants of health and illness. METHODS: Philosophical analysis of background assumptions of the current paradigmatic model. RESULTS: While these factors do not require a radical paradigm shift, they do give us cause to develop a new narrative, to add to existing narratives that frame our thinking about medical care. In this paper we argue that the increased focus on lifestyle and shared decision making requires a new narrative of agency, to supplement the narrative of "the patient". This narrative is conceptually linked to the developing philosophy of person-centred care. CONCLUSIONS: If patients are seen also as "agents" this will result in a substantial shift in practical decisions: The development and adoption of this narrative will help practitioners work with patients to their mutual benefit, harnessing the patients' motivation, shifting the focus from treatment to prevention and preventing unnecessary and harmful treatments that can come out of our preoccupation with the patient narrative. It will also help to shift research efforts, conceptual and empirical, from "treating" and "battling" diseases and their purported "mechanisms" to understanding complex contributing factors and their interplay.