Enhanced chlorhexidine skin penetration with eucalyptus oil

Background Chlorhexidine digluconate (CHG) is a widely used skin antiseptic, however it poorly penetrates the skin, limiting its efficacy against microorganisms residing beneath the surface layers of skin. The aim of the current study was to improve the delivery of chlorhexidine digluconate (CHG) when used as a skin antiseptic. Method Chlorhexidine was applied to the surface of donor skin and its penetration and retention under different conditions was evaluated. Skin penetration studies were performed on full-thickness donor human skin using a Franz diffusion cell system. Skin was exposed to 2% (w/v) CHG in various concentrations of eucalyptus oil (EO) and 70% (v/v) isopropyl alcohol (IPA). The concentration of CHG (µg/mg of skin) was determined to a skin depth of 1500 µm by high performance liquid chromatography (HPLC). Results The 2% (w/v) CHG penetration into the lower layers of skin was significantly enhanced in the presence of EO. Ten percent (v/v) EO in combination with 2% (w/v) CHG in 70% (v/v) IPA significantly increased the amount of CHG which penetrated into the skin within 2 min. Conclusion The delivery of CHG into the epidermis and dermis can be enhanced by combination with EO, which in turn may improve biocide.

Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc

Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.

Mediators of monocyte activity in inflammation

C-reactive protein (CRP) is the prototypic acute phase serum protein in humans. CRP is currently one of the best markers of inflammatory disease and disease activity. One of the keys cells involved in inflammation within chronic inflammatory diseases is the monocyte. Monocytes are able to modulate inflammation through cytokine expression, cytosolic peroxide formation, adhesion molecule expression and subsequent adhesion/migration to sites of inflammation. CRP has been previously shown to bind directly to monocytes through Fc receptors. However this observation is not conclusive and requires further investigation. The effects of incubation of CRP with human primary and monocytic cell lines were examined using monocytic cytokine expression, adhesion molecule expression and adhesion to endothelial cells and intracellular peroxide formation, as end points. Monocytic intracellular signalling events were investigated after interaction of CRP with specific CRP receptors on monocytes. These initial signalling events were examined for their role in modulating monocytic adhesion molecule and cytokine expression. Monocyte recruitment and retention in the vasculature is also influenced by oxidative stress. Therefore the effect of 6 weeks of antioxidant intervention in vivo was examined on monocytic adhesion molecule expression, adhesion to endothelial cells ex vivo and on serum CRP concentrations, pre- and post- supplementation with the antioxidants vitamin C and vitaInin E. In summary, CRP is able to bind FcγRIIa. CRP binding FcγR initiates an intracellular signalling cascade that phosphorylates the non-receptor tyrosine kinase, Syk, associated with intracellular tyrosine activating motifs on the cytoplasmic tail of Fcγ receptors. CRP incubations increased phosphatidyl inositol turnover and Syk phosphorylation ultimately lead to Ca2+ mobilisation in monocytes. CRP mediated Syk phosphorylation in monocytes leads to an increase in CD 11b and IL-6 expression. CRP engagement with monocytes also leads to an increase in peroxide production, which can be inhibited in vitro using the antioxidants α-tocopherol and ascorbic acid. CRP mediated CD 11b expression is not redox regulated by CRP mediated changes in cytosolic peroxides. The FcyRIla polymorphism at codon 131 effects the phenotypic driven changes described in monocytes by CRP, where R/R allotypes have a greater increase in CD11b, in response to CRP, which may be involved in promoting the monocytic inflammatory response. CRP leads to an increase in the expression of pro-inflammatory cytokines, which alters the immune phenotype of circulating monocytes. Vitamin C supplementation reduced monocytic adhesion to endothelial cells, but had no effect on serum levels of CRP. Where long-term antioxidant intervention may provide benefit from the risk of developing vascular inflammatory disease, by reducing monocytic adhesion to the vasculature. In conclusion CRP appears to be much more than just a marker of ongoing inflammation or associated inflammatory disease and disease activity. This data suggests that at pathophysiological concentrations, CRP may be able to directly modulate inflammation through interacting with monocytes and thereby alter the inflammatory response associated with vascular inflammatory diseases.

Staying in nursing:what factors determine whether nurses intend to remain employed?

Aim. To test a model of eight thematic determinants of whether nurses intend to remain in nursing roles. Background. Despite the dramatic increase in the supply of nurses in England over the past decade, a combination of the economic downturn, funding constraints and more generally an ageing nursing population means that healthcare organizations are likely to encounter long-term problems in the recruitment and retention of nursing staff. Design. Survey. Method. Data were collected from a large staff survey conducted in the National Health Service in England between September-December 2009. A multi-level model was tested using MPlus statistical software on a sub-sample of 16,707 nurses drawn from 167 healthcare organizations. Results. Findings were generally supportive of the proposed model. Nurses who reported being psychologically engaged with their jobs reported a lower intention to leave their current job. The perceived availability of developmental opportunities, being able to achieve a good work-life balance and whether nurses' encountered work pressures were also influencing factors on their turnover intentions. However, relationships formed with colleagues and patients displayed comparatively small relationships with turnover intentions. Conclusion. The focus at the local level needs to be on promoting employee engagement by equipping staff with the resources (physical and monetary) and control to enable them to perform their tasks to standards they aspire to and creating a work environment where staff are fully involved in the wider running of their organizations, communicating to staff that patient care is important and the top priority of the organization. © 2012 Blackwell Publishing Ltd.

Reinforced thermoplastics for engineering applications

The effect of mechano-chemically bound polypropylene modifiers on the mechanical performance and thermal-oxidative stability of polypropylene composites has been studied. The mechanical performance of unmodified polypropylene containing silane coupled glass and Rockwool (mineral) fibre was poor by comparison with a similar commercially produced glass reinforced composite; this was attributed to poor fibre-matrix adhesion. Mechano-chemical binding with unsaturated additives was obtained in the presence of a free radical initiator (di-cumyl peroxide). This process was inhibited by stabilisers present in commercial grades of polypropylene composites by chemical bond formation between the chemically bound modifier and the silane coupling agent on the fibre surface, resulting in a dramatic improvement in the mechanical properties, dimensional stability and retention of mechanical performance after immersion in fluids typically found in under-bonnet environments.A feature unique to some of these modifiers was their ability not only to enhance the mechanical properties of polypropylene composites to levels substantially in excess of currently available commercial materials, but their ability to act as effective thermal-oxidative polypropylene stabilisers. The mode of action was shown to be a chain-breaking mechanism and as a result of the high binding levels achieved during melt processing, these modifiers were able to efficiently stabilise polypropylene in the most severe volatilising and solvent-extracting environments, thus giving much better protection to the polymer than currently available commercially stabilised grades of polypropylene.

An emerging consensus on aquaporin translocation as a regulatory mechanism

Water passes through cell membranes relatively slowly by diffusion. In order to maintain water homeostasis, the rapid and specific regulation of cellular water flow is mediated by the aquaporin (AQP) family of membrane protein water channels. The wide range of tissues that are known to express AQPs is reflected by their involvement in many physiological processes and diseases; thirteen human AQPs have been identified to date and the majority are highly specific for water while others show selectivity for water, glycerol and other small solutes. Receptor mediated translocation, via hormone activation, is an established method of AQP regulation, especially for AQP2. There is now an emerging consensus that the rapid and reversible translocation of other AQPs from intracellular vesicles to the plasma membrane, triggered by a range of stimuli, confers altered membrane permeability thereby acting as a regulatory mechanism. This review examines the molecular components that may enable such AQP regulation; these include cytoskeletal proteins, kinases, calcium and retention or localization signals. Current knowledge on the dynamic regulation of sub-cellular AQP translocation in response to a specific trigger is explored in the context of the regulation of cellular water flow. © 2013 Informa UK, Ltd.

Writing for success:mentoring as a pedagogical tool – a cross- institutional study

The prominent position given to academic writing across contemporary academia is reflected in the substantive literature and debate devoted to the subject over the past 30 years. However, the massification of higher education, manifested by a shift from elite to mass education, has brought the issue into the public arena, with much debate focusing on the need for ‘modern-day' students to be taught how to write academically (Bjork et al., 2003; Ganobcsik-Williams, 2006). Indeed, Russell (2003) argued that academic writing has become a global ‘problem' in Higher Education because it sits between two contradictory pressures (p.V). On one end of the university ‘experience' increasing numbers of students, many from non-traditional backgrounds, enter higher education bringing with them a range of communication abilities. At the other end, many graduates leave university to work in specialised industries where employers expect them to have high level writing skills (Ashton, 2007; Russell, 2003; Torrence et al., 1999). By drawing attention to the issues around peer mentoring within an academic writing setting in three different higher education Institutions, this paper makes an important contribution to current debates. Based upon a critical analysis of the emergent findings of an empirical study into the role of peer writing mentors in promoting student transition to higher education, the paper adopts an academic literacies approach to discuss the role of writing mentoring in promoting transition and retention by developing students' academic writing. Attention is drawn to the manner in which student expectations of writing mentoring actually align with mentoring practices - particularly in terms of the writing process and critical thinking. Other issues such as the approachability of writing mentors, the practicalities of accessing writing mentoring and the wider learning environment are also discussed.

Angel grants employees their wish – for time off in return for high performance:new breed of incentives based on what staff really want from their employer

Purpose – Describes a new breed of HR strategies that encourage employee involvement and commitment as part of high-performance working (HPW). Design/methodology/approach – Focuses on managing employee attitudes and skills through careful attention to leadership, reward and job-design policies. Highlights the differences between people's formal employment contracts and their less formal “psychological contracts”, and emphasizes the importance of the latter. Provides a case study of UK recruitment consultancy Angel Services Group Ltd, which allows staff who meet their daily targets to go home an hour early. Findings – Urges companies to have processes in place to understand the needs of individual employees. This can be done through leadership policies that require all supervisors and managers not only to manage their staff but also to know them as people. Practical implications – Emphasizes that organizations need to see HPW initiatives as part of the normal way of managing people, and not as “flavour of the month”. Originality/value – Outlines a wide range of initiatives that could help organizations to gain their employees' commitment.

How HR can inspire the teamwork that allows innovation to flourish

Innovation is vital if organisations are to deal effectively with social and economic change. Yet few studies have looked at the relationship between teamworking and innovation – or, indeed, other organisational outcomes. Our research aimed to fill this gap by exploring the extent to which team-based working in small- and medium- sized manufacturing organisations predicted product innovation. The results show that levels of innovation are higher in organisations using work-based teams than in those with alternative structural arrangements. We also found that effective HRM practices, such as sophisticated selection, induction, appraisal, training and remuneration management, created an environment that allowed teams to excel. The study drew on a variety of sources, including data on organisational-level innovation gathered through a postal survey. Respondents gave estimates of the number of new or adapted products developed in the past two years. They also detailed the percentage of production workers involved in making the new products; sales turnover accounted for by these products; and how far production processes had been changed to accommodate the innovations. We measured HRM effectiveness and the extent of teamworking via interviews with the relevant HR or production manager. We then rated each organisation on a scale of one to five, according to how effective its HRM practices were. We also examined the percentage of staff at management and shopfloor levels engaged in teamworking. The research design was longitudinal, in that the data on product innovation was collected six months to a year after the main questionnaire on teamworking was conducted. Other studies addressing these questions have tended to be cross-sectional, measuring both variables at the same time. Longitudinal studies generally make a stronger case for causality. Perhaps of most theoretical significance is the finding that teamworking combined with effective HR systems explains more of the variance for product innovation than teamworking alone. This is in line with J Richard Hackman (1990), who argued that organisational context affected team performance in various ways – for example, through offering a framework for the administration of reward and the exchange of knowledge and through promoting learning-oriented beliefs. Our work supports these ideas. This study also has practical implications. Increasing the number of teams may be an important step in determining the extent to which they can innovate on a sustained basis. Organisations should therefore consider what HRM practices are most likely to foster team innovation. They might, for example, explore how helpful it would be to develop team-based appraisal and better designed teamworking training. Developing support structures that enable teams to achieve outstanding performance may present a challenge, but our results suggest that such an approach will be worth the effort. Key points: • The greater the percentage of staff working in teams, the higher the level of innovation. • This applies to both management and production teams. • Where sophisticated and effective HRM practices are in place, the relationship between team-based working and product innovation becomes more pronounced. • Both cross-sectional and longitudinal analyses show strong relationships between team-based working and product innovation.

Evaluation of options for energy recovery from municipal solid waste in India using the hierarchical analytical network process

In this paper a Hierarchical Analytical Network Process (HANP) model is demonstrated for evaluating alternative technologies for generating electricity from MSW in India. The technological alternatives and evaluation criteria for the HANP study are characterised by reviewing the literature and consulting experts in the field of waste management. Technologies reviewed in the context of India include landfill, anaerobic digestion, incineration, pelletisation and gasification. To investigate the sensitivity of the result, we examine variations in expert opinions and carry out an Analytical Hierarchy Process (AHP) analysis for comparison. We find that anaerobic digestion is the preferred technology for generating electricity from MSW in India. Gasification is indicated as the preferred technology in an AHP model due to the exclusion of criteria dependencies and in an HANP analysis when placing a high priority on net output and retention time. We conclude that HANP successfully provides a structured framework for recommending which technologies to pursue in India, and the adoption of such tools is critical at a time when key investments in infrastructure are being made. Therefore the presented methodology is thought to have a wider potential for investors, policy makers, researchers and plant developers in India and elsewhere. © 2013 Elsevier Ltd. All rights reserved.

Disturbing visual working memory:electrophysiological evidence for a role of the prefrontal cortex in recovery from interference

Single cell recordings in monkeys support the notion that the lateral prefrontal cortex (PFC) controls reactivation of visual working memory representations when rehearsal is disrupted. In contrast, recent fMRI findings yielded a double dissociation for PFC and the medial temporal lobe (MTL) in a letter working memory task. PFC was engaged in interference protection during reactivation while MTL was prominently involved in the retrieval of the letter representations. We present event-related potential data (ERP) that support PFC involvement in the top-down control of reactivation during a visual working memory task with endogenously triggered recovery after visual interference. A differentiating view is proposed for the role of PFC in working memory with respect to endogenous/exogenous control and to stimulus type. General implications for binding and retention mechanisms are discussed.

GABAB receptor-mediated activation of astrocytes by gamma-hydroxybutyric acid

The gamma-aminobutyric acid (GABA) metabolite gamma-hydroxybutyric acid (GHB) shows a variety of behavioural effects when administered to animals and humans, including reward/addiction properties and absence seizures. At the cellular level, these actions of GHB are mediated by activation of neuronal GABAB receptors (GABABRs) where it acts as a weak agonist. Because astrocytes respond to endogenous and exogenously applied GABA by activation of both GABAA and GABABRs, here we investigated the action of GHB on astrocytes on the ventral tegmental area (VTA) and the ventrobasal (VB) thalamic nucleus, two brain areas involved in the reward and proepileptic action of GHB, respectively, and compared it with that of the potent GABABR agonist baclofen. We found that GHB and baclofen elicited dose-dependent (ED50: 1.6 mM and 1.3 µM, respectively) transient increases in intracellular Ca2+ in VTA and VB astrocytes of young mice and rats, which were accounted for by activation of their GABABRs and mediated by Ca2+ release from intracellular store release. In contrast, prolonged GHB and baclofen exposure caused a reduction in spontaneous astrocyte activity and glutamate release from VTA astrocytes. These findings have key (patho)physiological implications for our understanding of the addictive and proepileptic actions of GHB.

What's so entrepreneurial about intrapreneurs?

This paper discusses the determinants of becoming an intrapreneur. Individuals maximise their utility while deciding among three occupations: independent entrepreneurship, paid employment and intrapreneurship. I show that intrapreneurs resemble employees rather than entrepreneurs. Specifically, comparing the decision-making of intrapreneurs to that of entrepreneurs, the former are significantly more risk averse, expect lower but less uncertain reward and are broadly endowed with a poorer set of entrepreneurial abilities; despite having higher levels of human capital they fail to recognise business opportunities and have lower confidence in their entrepreneurial skills. A distinction within the category of intrapreneurship, based on the level of engagement and therefore the level of personal risks they bear, adds to our understanding of intrapreneurship. Engaged intrapreneurs, i. e., intrapreneurs that expect to acquire an ownership stake in the business, unlike the rest of intrapreneurs, share the attributes usually assumed to characterise entrepreneurs. © 2011 Springer Science+Business Media, LLC.

Teaching our children when to eat:how parental feeding practices inform the development of emotional eating-a longitudinal experimental design

Background: Emotional eating in children has been related to the consumption of energy-dense foods and obesity, but the development of emotional eating in young children is poorly understood. Objectives: We evaluated whether emotional eating can be induced in 5-7-y-old children in the laboratory and assessed whether parental use of overly controlling feeding practices at 3-5 y of age predicts a greater subsequent tendency for children to eat under conditions of mild stress at ages 5-7 y. Design: Forty-one parent-child dyads were recruited to participate in this longitudinal study, which involved parents and children being observed consuming a standard lunch, completing questionnaire measures of parental feeding practices, participating in a research procedure to induce child emotion (or a control procedure), and observing children's consumption of snack foods. Results: Children at ages 5-7 y who were exposed to a mild emotional stressor consumed significantly more calories from snack foods in the absence of hunger than did children in a control group. Parents who reported the use of more food as a reward and restriction of food for health reasons with their children at ages 3-5 y were more likely to have children who ate more under conditions of negative emotion at ages 5-7 y. Conclusions: Parents who overly control children's food intake may unintentionally teach children to rely on palatable foods to cope with negative emotions. Additional research is needed to evaluate the implications of these findings for children's food intake and weight outside of the laboratory setting. This trial was registered at clinicaltrials.gov as NCT01122290.

Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1 monocytes

Atherosclerosis is a chronic inflammatory disease occurring within the artery wall. A crucial step in atherogenesis is the infiltration and retention of monocytes into the subendothelial space of large arteries induced by chemokines and growth factors. Angiopoietin-1 (Ang-1) regulates angiogenesis and reduces vascular permeability and has also 15 been reported to promote monocyte migration in vitro. We investigated the role of Ang-1 in atherosclerosis-prone apolipoprotein-E (Apo-E) knockout mouse. Apo-E knockout (Apo-E-/-) mice fed a western or normal chow diet received a single iv injection of adenovirus encoding Ang-1 or control vector. Adenovirus-mediated systemic expression of Ang-1 induced a significant increase in early atherosclerotic lesion size and monocyte/macrophage accumulation compared with control animals receiving empty vector. Ang-1 significantly increased plasma MCP-1 and VEGF levels as measured by ELISA. FACS analysis showed that Ang-1 selectively increased inflammatory Gr1þmonocytes in the circulation, while the cell-surface 25 expression of CD11b, which mediates monocyte emigration, was significantly reduced. Ang-1 specifically increases circulating Gr1þinflammatory monocytes and increases monocyte/macrophage retention in atherosclerotic plaques, thereby contributing to development of atherosclerosis.