bluuebunny/crossref_metadata_2025 huggingface dataset:
Vacuolar Transport of the Medicinal Alkaloids from Catharanthus roseus Is Mediated by a Proton-Driven Antiport
Authors: Carqueijeiro Inês , Noronha Henrique , Duarte Patrícia , Gerós Hernâni , Sottomayor Mariana
Published: May 2013

Catharanthus roseus is one of the most studied medicinal plants due to the interest in their dimeric terpenoid indole alkaloids (TIAs) vinblastine and vincristine, which are used in cancer chemotherapy. These TIAs are produced in very low levels in the leaves of the plant from the monomeric precursors vindoline and catharanthine and, although TIA biosynthesis is reasonably well understood, much less is known about TIA membrane transport mechanisms. However, such knowledge is extremely important to understand TIA metabolic fluxes and to develop strategies aimed at increasing TIA production. In this study, the vacuolar transport mechanism of the main TIAs accumulated in C. roseus leaves, vindoline, catharanthine, and α-3′,4′-anhydrovinblastine, was characterized using a tonoplast vesicle system. Vindoline uptake was ATP dependent, and this transport activity was strongly inhibited by NH4  + and carbonyl cyanide m-chlorophenyl hydrazine and was insensitive to the ATP-binding cassette (ABC) transporter inhibitor vanadate. Spectrofluorimetry assays with a pH-sensitive fluorescent probe showed that vindoline and other TIAs indeed were able to dissipate an H+ gradient preestablished across the tonoplast by either vacuolar H+-ATPase or vacuolar H+-pyrophosphatase. The initial rates of H+ gradient dissipation followed Michaelis-Menten kinetics, suggesting the involvement of mediated transport, and this activity was species and alkaloid specific. Altogether, our results strongly support that TIAs are actively taken up by C. roseus mesophyll vacuoles through a specific H+ antiport system and not by an ion-trap mechanism or ABC transporters.
Motivations for energy efficiency refurbishment in owner‐occupied housing
Authors: Organ Samantha , Proverbs David , Squires Graham
Published: May 2013

Purpose

The existing housing stock needs substantial adaptation to meet national and international carbon reduction targets. The largest proportion of housing is owner‐occupied, and will require improvement works which go beyond those measures provided through the Green Deal and similar programmes. Therefore, the motivation of owner‐occupiers to perform more substantial energy efficiency refurbishments is essential to facilitate greater action. This paper aims to address these issues.

Design/methodology/approach

A synthesis of the extant literature from a range of disciplines reveals the role of motivation and the factors influencing motivation and pro‐environmental action in the context of the home. Based on this synthesis of the literature, a new motivation model for energy efficiency refurbishment in the owner‐occupied housing stock is then described.

Findings

The study has found that multiple factors affect motivation to refurbish in the owner‐occupied housing stock. Key motivations for energy efficient refurbishment can be categorized into the broad themes of economic, social, and environmental motivations. These motivations will be affected by a wide number of interrelated internal and external factors and mediated by the emotions of the individual. The model presented demonstrates the relationship between the multiple factors that affect energy efficiency refurbishment in relation to specific contexts.

Originality/value

The study represents a potential addition to motivational theory and concepts for use within the field of energy efficient refurbishment of the owner‐occupied housing stock. Implications for future government policy and towards raising the motivation of owner‐occupiers are identified: it can be used to shape national and local policy and information campaigns to motivate energy efficiency refurbishment in the owner‐occupied housing stock. To be successful, this should take differing internal factors and contexts into consideration and the dynamic nature of owner‐occupier motivation. The model can also be used by industry professionals to better understand the owner‐occupier customer motivations for energy efficiency refurbishment and therein provide a better service.
Export market exploitation and exploration and performance
Authors: Lisboa Ana , Skarmeas Dionysis , Lages Carmen
Published: May 2013

Purpose

– Drawing on the resource advantage and organisational learning literatures, this paper aims to investigate the linear, moderated, complementary and non-linear effects of export market exploitation and exploration on export performance.

Design/methodology/approach

– A quantitative study was performed using an online survey. The final sample consisted of 267 Portuguese export manufacturing firms. Data were analysed using structural equation modelling.

Findings

– Export market exploitation and exploration is positively and negatively related to export performance in a linear way, respectively. Export market exploration improves export performance under high levels of export market turbulence. Balancing export market exploitation with export market exploration enhances export performance. High levels of export market exploitation provide an additional boost to performance.

Practical implications

– This study contributes to a better understanding of how market exploitation and exploration relate to performance in the export context. To enhance export performance, managers should deploy high levels of export market exploitation, pursue export market exploration in dynamic export markets, and maintain a balance between export market exploitation and exploration.

Originality/value

– This paper contributes to the export marketing field by shedding light on the complex nature of the relationships among export market exploitation, exploration and performance. Overall, the results provide novel evidence concerning the internal and external contingencies that affect the success of export market exploitation and exploration.
Acceptance of enterprise blog for service industry
Authors: Hsing Wu Chien , Kao Shu‐Chen , Lin Hsin‐Hui
Published: May 2013

Purpose

The rapid growth of blogs over the Internet has gradually attracted the attention of enterprises that want to engage in business and develop their online communication channels for customer relationships. The study aims to develop and examine the determinants of enterprise blog (E‐Blog) adoption for the service industry. Organization size is used as a moderating factor to disclose its influence on the effects of the variables.

Design/methodology/approach

The research model of the empirical study integrates three composites: social exchange theory, innovation diffusion theory, and organization dynamics. For the results, data are analyzed by using factor analysis to derive the actual composites and structural equation model to test the hypotheses.

Findings

The main results show the following findings. First, social exchange via E‐Blog fosters enterprise reputation. Second, enterprises are doubtful whether they can build online relationships via E‐Blog with their customers and E‐Blog visitors. Third, virtual trust and the unknown virtual social structure are barriers for enterprises in using E‐Blog. Fourth, E‐Blog adopters are likely to be purpose‐sensitive as the numbers of blog type increase.

Practical implications

The research findings reveal that E‐Blog vendors and agents should emphasize reputation development to attract the attention of their customers (enterprises). In addition, small‐ to medium‐sized enterprises prefer the relative advantages and simplicity of E‐Blogging. In contrast, large enterprises are more concerned with competition pressure and market dynamics involved in the adoption attitude. These findings would be useful for E‐Blog service providers to analyze the requirements of their customers. In addition, E‐Blog vendors and agents should persuade enterprises adopting E‐Blog to ease competition pressure, particularly for large firms who have not adopted the technology. Finally, E‐Blog platforms and vendors should emphasize that E‐Blog can help increase reputation by attracting the attention of enterprises to adopt E‐Blogging.

Originality/value

In the virtual socialization process, the blog has been developing its own characteristics that are linked to social behaviour. This link explains social change and stability in cyberspace from the social psychology and sociology points of view. The research findings differ from those of previous research because early studies focused on individual Internet user blog participation without placing emphasis on the adoption intention of enterprises. The findings of this study will be helpful for both E‐Blog service providers and enterprises.
Factors influencing sociability in educational MMORPGs – a fuzzy AHP approach
Authors: Lee Chun‐Chia , Hwa Hsu Shang , Chang Jen‐Wei
Published: May 2013

Purpose

Sociability is considered to be important to the success of educational MMORPGs. The purpose of this study was to access the relative weights of these sociability factors which the authors garnered from the literature on educational MMORPGs.

Design/methodology/approach

The authors used fuzzy‐AHP approach to access the relative weights of these sociability factors they garnered from the literature on educational MMORPGs. To do this, a questionnaire using a pair‐wise comparison data input format was administered to 242 school teachers to gather assessments for the factors.

Findings

The authors found five most important factors affecting sociability – cooperation, team‐based reward, discussion of strategy, reputation, and social navigation.

Originality/value

Although prior studies have identified various factors that facilitate sociability in educational MMORPGs, the relative importance of these factors has not been determined. The results can not only be used to help educational MMORPG developers focus on the most important sociability factors and propose specific guidelines for designing educational MMORPGs, but can also identify the best design strategy for promoting sociability of educational MMORPGs.
Queering beauty: fatshionistas in the fatosphere
Authors: Gurrieri Lauren , Cherrier Hélène
Published: May 2013

Purpose

The purpose of this paper is to analyse the representations and experiences of beauty amongst fat women to understand how females located outside of the normative ideal consume, express, challenge and resist “straight” beauty.

Design/methodology/approach

A netnographic approach is taken to analyse 922 blog posts written by five female “fatshionistas” who play a significant role in the Australian fat activism movement.

Findings

The research findings illustrate that fatshionistas (re)negotiate cultural notions of beauty through three performative acts – coming out as fat, mobilising fat citizenship and flaunting fat.

Research limitations/implications

The study demonstrates how beauty is negotiated as a mode of praxis, a performance in the interaction of day‐to‐day life, whereby the possibilities for multiple and provisional beauties are highlighted.

Practical implications

Given the active participation of those outside of the idealised form in “mainstream” beauty consumption, practitioners should make visible multiple bodily representations that are not reduced to an unhelpful construction of what is considered to be “real”.

Originality/value

By emphasising the lived experience of beauty as something subjective, communal and resistant, this research poses a challenge to mainstream marketing that constructs beauty as normative, singular and conformist. The paper further calls for a “queering” of the gender research agenda within marketing to better interrogate the linkages between an individual's fluid and contested identity work, consumption and marginalised or excluded status within the marketplace.
Fault tree analysis considering sequence dependence and repairable input events
Authors: Yuge Tetsushi , Ozeki Shinya , Yanagi Shigeru
Published: May 2013

Purpose

This paper aims to present two methods for calculating the steady state probability of a repairable fault tree with priority AND gates and repeated basic events when the minimal cut sets are given.

Design/methodology/approach

The authors consider a situation that the occurrence of an operational demand and its disappearance occur alternately. We assume that both the occurrence and the restoration of the basic event are statistically independent and exponentially distributed. Here, restoration means the disappearance of the occurring event as a result of a restoration action. First, we obtain the steady state probability of an output event of a single‐priority AND gate by Markov analysis. Then, we propose two methods of obtaining the top event probability based on an Inclusion‐Exclusion method and by considering the sum of disjoint probabilities.

Findings

The closed form expression of steady state probability of a priority AND gate is derived. The proposed methods for obtaining the top event probability are compared numerically with conventional Markov analysis and Monte Carlo simulation to verify the effectiveness. The result shows the effectiveness of the authors’ methods.

Originality/value

The methodology presented shows a new solution for calculating the top event probability of repairable dynamic fault trees.
Novel polymeric support materials for jetting based additive manufacturing processes
Authors: Fahad M. , Dickens P. , Gilbert M.
Published: May 2013

Purpose

Jetting‐based additive manufacturing processes are gaining attention due to their high speed of operation, accuracy and resolution. Support material plays an important role in the additive manufacturing of parts by using processes that utilise jetting (inkjet) technology. This research aims to present novel support material compositions consisting of methylcellulose (MC) and propylene glycol or butylene glycol. These compositions form gels which are easy to remove and provide the advantage of reusability.

Design/methodology/approach

MC was mixed in propylene glycol or butylene glycol in different concentrations and examined for gel formation on heating and subsequent cooling. The viscosity and surface tension of these compositions were measured at temperatures suitable for jetting. Gel strength was characterised using texture analysis.

Findings

The viscosity and surface tension values at elevated temperatures (i.e. 800°C) show the suitability of these compositions for jetting‐based additive manufacturing processes. Due to their softness, these gels can be removed easily and their low melting points (i.e. near 500°C) allow their reusability as support materials.

Practical implications

This paper provides a novel approach of using polymer gels as support materials for additive manufacturing processes. These gels are easy to prepare and enhance the sustainability due to their reusability.

Originality/value

Although, MC in water have shown to form gels and these aqueous gels have been used in many applications such as medicine and food industries, the compositions presented in this paper are unique. Such combinations of MC and non‐aqueous solvents (i.e. propylene glycol and butylene glycol) have not been discussed before and provide an early step towards a new application area (i.e. additive manufacturing) for these gels.
Police officer acceptance of new innovation: the case of crisis intervention teams
Authors: Schaefer Morabito Melissa , Watson Amy , Draine Jeffrey
Published: May 2013

Purpose

The purpose of this paper is to examine the predictors of officer attitudes toward Crisis Intervention Teams, a new innovation designed to improve police response to people with mental illnesses.

Design/methodology/approach

The current study uses data from a larger study of the Chicago Police Department (CPD) Crisis Intervention Team (CIT) program. CIT and Non‐CIT officers were surveyed in four districts. To examine the predictors of officer perceptions of crisis intervention teams, OLS regression is used.

Findings

Neither CIT nor non‐CIT officers seem to show the kinds of negative views of CIT that have undercut other social welfare based police innovations. Among CIT trained officers, those who had the opportunity to practice their new skills by responding to mental health related calls for service had more positive attitudes toward the program than those who did not.

Originality/value

This paper adds to both the Crisis Intervention Team and innovation literatures by examining an important aspect of the CIT implementation process. A model is developed that explores the correlates of officer support for the innovation and the conditions necessary for its successful implementation.
Ontological approach to enhance results of business process mining and analysis
Authors: Jareevongpiboon Wirat , Janecek Paul
Published: May 2013

Purpose

The purpose of this paper is to propose a solution to the problem of a lack of machine processable semantics in business process management.

Design/methodology/approach

The paper introduces a methodology that combines domain and company‐specific ontologies and databases to obtain multiple levels of abstraction for process mining and analysis. The authors valuated this approach with a real case study from the apparel domain, using a prototype system and techniques developed in the Process Mining Framework (ProM). The results of this approach are compared with similar research.

Findings

Semantically enriching process execution data can successfully raise analysis from the syntactic to the semantic level, and enable multiple perspectives of analysis on business processes. Combining this approach with complementary research in semantic business process management (SBPM) can provide results comparable to multidimensional analysis in data warehouse and on line analytical processing (OLAP) technologies.

Originality/value

The approach and prototype described in this paper improve the richness of semantics available for open‐source process mining and analysis tools like ProM, and the richness and detail of the resulting analysis.
Perceived vision‐based leadership effects on staff satisfaction and commitment at a Thai energy provider
Authors: Kantabutra Sooksan , Rungruang Parisa
Published: May 2013

Purpose

This paper aims to examine relationships between vision realization factors (vision communication, motivation and empowerment of employees), employee satisfaction, and affective organizational commitment in a state‐owned energy provider in Thailand.

Design/methodology/approach

Subjects are drawn randomly from employees working at the Thai state‐owned energy provider who completed a questionnaire made up of valid and reliable instruments that measure each of the variables studied. Hypotheses are tested through a series of regression analyses.

Findings

Findings indicate that vision communication, motivation and empowerment of employees, and follower affective organizational commitment are three direct predictors of enhanced employee satisfaction. Empowerment of employees and employee satisfaction are two direct predictors of employee affective organizational commitment. These findings indicate a reciprocal relationship between employee satisfaction and affective organizational commitment, with a stronger effect from employee satisfaction on affective organizational commitment than the reverse.

Research limitations/implications

How supervisors empower and motivate their subordinates in the Thai state‐owned energy provider still needs a further investigation. The relationship between employee satisfaction and affective organizational commitment needs to be re‐examined by future research, using a different research design and statistical technique.

Practical implications

Leaders at all levels of the state‐owned energy provider should frequently communicate their vision to, motivate and empower their subordinates to enhance subordinate satisfaction and affective commitment.

Originality/value

The body of knowledge about vision‐based leadership in an Asian state‐owned energy provider is scanty. The present study contributes to this area.
Pre‐positioning commodities to repair maritime navigational aids
Authors: Bemley Jessye L. , Davis Lauren B. , Brock Luther G.
Published: May 2013

Purpose

As the intensity of natural disasters increases, there is a need to develop policies and procedures to assist various agencies with moving aid to affected areas. One of the biggest limitations to this process is damage to transportation networks, in particular waterways. To keep waterways safe, aids to navigation (ATONs) are placed in various areas to guide mariners and ships to their final destination. If the ATONs are damaged, then the waterways are left unsafe, making it difficult to move supplies and recover from a disaster. The aim of this paper is to explore the effectiveness of pre‐positioning strategies for port recovery in response to a natural disaster.

Design/methodology/approach

A stochastic facility location model is presented to determine where teams and commodities should be pre‐positioned in order to maximize the number of ATONs repaired, given a constraint on response time. The first stage decisions focus on determining the location of resources. The second stage decisions consist of the distribution of supplies and teams to affected areas.

Findings

Results show the benefit of pre‐positioning and the value of coordination toward the responsiveness of restoring waterways. Furthermore, the relationship between resources, repair time, and response is characterized.

Originality/value

There has been extensive work addressing pre‐positioning as it relates to responding to the needs of populations affected by disasters. However, little has been done to explore pre‐positioning in the context of business recovery from severe weather events.
Education for all and for what? Life‐skills and livelihoods in rural communities
Authors: Poole Nigel , Álvarez Fernando , Penagos Nora , Vázquez Roberto
Published: May 2013

Purpose

The purpose of this paper is to argue for appropriate formal education for rural young people in order to sustain and enhance viable rural communities.

Design/methodology/approach

In reviewing the literature, it bridges the gap between thinking on education and development respectively, and links schooling with the concepts of livelihoods, human and social capital and life‐skills. By way of example, it summarises an empirical study of the content and delivery of tele‐education among indigenous communities in Chiapas, Mexico.

Findings

Developing and emerging economies and regions should prioritise effective and efficient rural education which incorporates practical and technical skills appropriate to the rural context in order to include young people in the agricultural development and agribusiness of rural areas. This means delivery of education that is rural, local and particular to the context, with appropriate technology, pedagogy and curriculum.

Research limitations/implications

The concepts and argument are of wide significance. The case study findings should not be readily generalised but the implications will relevant to many remote and marginalised communities where the rural economy is weak, opportunities are few and education resources are scarce.

Originality/value

The paper links different literatures and, by also drawing on empirical evidence consistent with the literature, makes a case for a significant reorientation of rural education towards appropriate life‐skills in order to create viable rural livelihoods.
Community engagement and social exclusion: the BME experience
Authors: Ijasan K.C. , Ahmed V.
Published: May 2013

Purpose

The endless and recurrent nature of community regeneration is of massive concern to any government due to the financial and human resources requested. Past research has suggested that by involving members of the community in the process of these regeneration activities, past mistakes can be alleviated and so people will feel better appreciated. However, members of the BME groups which make up to 12 per cent of the UK population are not participating optimally. This paper aims to look into the reasons for this lack of participation and make suggestions accordingly.

Design/methodology/approach

This research adopted the triangulation method of research where interviews, literature review and questionnaires sources of data were all used. However, this paper presents only the results of the quantitative method. A total of 250 questionnaires were distributed with 203 completed and returned using snowball method of distribution.

Findings

What emerged from the analysis was that local councils and other regeneration service providers are better channelling more resources at the use of community representatives in areas where there is a dominance of ethnic minority groups.

Social implications

This paper explores community regeneration and identifies the need for partnerships in the process of the delivery of regeneration to a community. It investigates the various levels of community engagement and participation, the cultural diversity of England and discusses the social exclusion situation of BMEs. The paper also discusses the results of a descriptive quantitative analysis of a questionnaire survey which studied BMEs and their experience of community regeneration, both in terms of their housing needs and also the challenges preventing them from effective community engagement.

Originality/value

Practical suggestions are made to assist policy and decision makers in engaging members of the BME community more in regeneration.
Why computer games can be essential for human flourishing
Authors: Fröding Barbro , Peterson Martin
Published: May 2013

Purpose

The purpose of this paper is to argue that playing computer games for lengthy periods of time, even in a manner that will force the player to forgo certain other activities normally seen as more important, can be an integral part of human flourishing.

Design/methodology/approach

The authors' claim is based on a modern reading of Aristotle'sNichomacean Ethics. It should be emphasized that the authors do not argue that computer gaming and other similar online activities are central to all people under all circumstances; but only seek to show that the claim holds true for some people under some circumstances and the authors try to spell out the relevant circumstances in detail.

Findings

The authors provide a list of situations in which playing computer games for lengthy periods of time, in a manner that will force the player to forgo certain other activities normally seen as more important, is an integral part of human flourishing.

Originality/value

The paper puts some novel pressure on the widely‐held belief that playing computer games for lengthy periods of time, in a manner that will force the player to forgo certain other activities normally seen as more important. The paper claims that playing some computer games and partaking in some forms of online activities could be highly conducive to what it actually means in practice to take care of oneself and, to paraphrase Aristotle, to be eager for fine actions.
Mustard seed (Sinapis Alba Linn) attenuates imiquimod‐induced psoriasiform inflammation of BALB/c mice
Authors: Yang Runping , Zhou Qiang , Wen Chunmiao , Hu Jian , Li Hengjin , Zhao Ming , Zhao Hua
Published: May 2013

Psoriasis is a chronic inflammatory autoimmune disease with undefined etiology. All present treatments are symptomatic. The unsatisfactory outcome in the treatment of psoriasis is partially due to the poor compliance to the present therapies with more or less side‐effects. As is known, drug homologous food is a popular intervention of some chronic diseases in Chinese traditional medicine. Mustard seed, consumed largely as a spice and a medicine in China, has recently been found to possess the bioactivities of anti‐oxidation, anti‐inflammation and anticancer. Therefore, it was supposed that mustard seed may have effects on psoriasis, and it was preliminarily validated using a BALB/c mouse model of psoriasiform inflammation induced by the topical application of imiquimod cream (Aldara) for 6 days consecutively. It was found that the forage containing 5% mustard seed obviously attenuated imiquimod‐induced psoriasiform inflammation, but did not clear it completely, accompanied by reduced infiltrations of T cells, plasmacytoid dendritic cells (pDC) and macrophages in lesional skin; reduced percentages of pDC and macrophages in the composition of immunocytes of spleens; reduced content of lesion nuclear factor‐κB p65, plasma malondialdehyde, lesion inducible nitric oxide synthase, interferon‐α, interleukin (IL)‐17 and IL‐22 at mRNA and protein levels; increased activities of superoxide dismutase, catalase and glutathione peroxidase; and increased percentage of CD4+ T cells and increased ratio of CD4+/CD8+ T cells in the composition of immunocytes of spleen. These results presented herein provide a basis for mustard seed to be used as a promising intervention for psoriasis in the future.
Aberrant expression of BCL11B in mycosis fungoides and its potential role in interferon‐induced apoptosis
Authors: Gu Xiaoguang , Wang Yang , Zhang Gaolei , Li Weiwei , Tu Ping
Published: May 2013

BCL11B is a Kruppel‐like C2H2‐type zinc finger transcription factor, which has been associated with several human malignancies. Recent evidence showed that overexpressed BCL11B conferred chemoresistance to malignant T cells and that inhibiting BCL11B led to increased apoptosis, suggesting its potential pathogenic relevance in cutaneous T‐cell lymphomas (CTCL), which were characterized by the resistance to chemotherapy‐induced apoptosis. To investigate the expression pattern of BCL11B in different stages of mycosis fungoides (MF), quantitative reverse transcription polymerase chain reaction and immunohistochemistry were performed to compare the mRNA and protein expression among different stages of MF and benign inflammatory dermatoses (BID), respectively. BCL11B demonstrated significant upregulation in all stages of MF, compared with BID, in both mRNA expression level and protein level. In addition, BCL11B expression increased with advancing lesion tumor stage and overall disease stage. Further, to evaluate the dynamic expression of BCL11B under CTCL‐directed treatment, BCL11B expression and cell apoptosis were evaluated after interferon (IFN)‐α‐2b and methotrexate treatment on CTCL cell line Hut78 cells. IFN‐α‐2b, but not methotrexate, induced BCL11B inhibition and cell apoptosis, suggesting that BCL11B may play important roles in the anti‐CTCL effect of IFN‐α‐2b. In conclusion, our study demonstrated the overexpression of BCL11B in MF lesions and its potential relevance to disease progression. In addition, we provided evidence for BCL11B inhibitory approaches as a potential treatment to target chemoresistant tumor cells in advanced MF.
Adverse reactions and alleged allergy to local anesthetics: Analysis of 331 patients
Authors: Batinac Tanja , Sotošek Tokmadžić Vlatka , Peharda Vesna , Brajac Ines
Published: May 2013

The aim of this study was to determine the prevalence of true local anesthetic (LA) allergy among patients referred for suspected hypersensitivity and to describe the main characteristics of adverse drug reactions (ADR) induced byLAin our population. We retrospectively analyzed the medical files of patients referred to the Department of Dermatovenereology, University Hospital Center Rijeka,Rijeka,Croatia, for the investigation ofLAhypersensitivity in the period betweenJanuary 2000 andDecember 2012. A total of 331 patients underwent skin testing and, in cases of negative results, subcutaneous exposition toLA. In patients with suspected delayed reaction, patch test was performed. Altogether, 331 patients reported 419 independentADRoccurring during 346 procedures. Most commonly, patients reported having only oneADR, but 41 (12.4%) of them had two reactions, 14 (4.2%) had three, five (1.5%) had four and in one patient (0.3%) fiveADRtoLAwere observed. The majority of reactions occurred during dental procedures when most commonly lidocaine and articaine were used. Local reactions were reported in 44 patients, whereas 490 general symptoms occurred during 375 independentADRin 287 patients. The most common symptoms were cardiovascular system reactions in 89 patients (18.2%). Allergic reaction was detected in three patients (0.91%). One patient showed immediate‐type reaction to bupivacaine and two patients had a delayed‐type reaction to lidocaine. Adverse reactions toLAare common and are mostly due to their pharmacological properties and drug combinations or psychogenic origin. Allergic accidents toLAare rare.
Twist1 in tumor cells and α‐smooth muscle actin in stromal cells are possible biomarkers for metastatic giant basal cell carcinoma
Authors: Motegi Sei‐ichiro , Yamada Kazuya , Ishikawa Osamu
Published: May 2013

We previously reported a case of giant basal cell carcinoma (BCC) in a 75‐year‐old Japanese man, who subsequently developed a pulmonary metastasis. With regard to the pathogenesis of metastasis of BCC, recently, it has been reported that high levels of expression of Twist1 and N‐cadherin in primary and metastatic tumor cells, suggesting that Twist1 expression and an epithelial–mesenchymal transition (EMT) of tumor cells are important for the promotion of tumor invasion and subsequent metastasis. In this report, we identified the expressions of Twist1 in tumor cells and α‐smooth muscle actin (α‐SMA) in stromal cells in the primary and metastatic sites of giant BCC. These results suggest that Twist1‐induced EMT of tumor cells might have been associated with distant organ metastasis in our case, and the presence of α‐SMA‐positive myofibroblasts surrounding a BCC nest can be one of hallmarks of the aggressiveness of BCC.
Possible influences of plasticity and genetic/maternal effects on species coexistence: nativeGammarus fasciatusfacing exotic amphipods
Authors: Derry Alison M. , Kestrup Åsa M. , Hendry Andrew P.
Published: May 2013

Native species might be able to persist in the face of a detrimental exotic invader by occupying refuge habitats where the exotic is not successful. These refuges might then provide demographic subsidies that enhance persistence of the native species in areas of coexistence with the exotic species. Phenotypic plasticity of the native species could play a critical role in this process by allowing individuals dispersing from refuge to invaded habitats to adaptively modify their phenotypes, thereby enhancing the subsidy. By contrast, locally adapted genetic or maternal differences between native populations could result in fitness disadvantages for dispersers at invaded habitats, thereby reducing the subsidy.

We studied phenotypic variation in a native amphipod (Gammarus fasciatus) across ion gradients inLacSt.Louis,Québec,Canada. Ion gradients determine refuge vs. invaded habitats because native amphipods are found in both ion‐poor and ion‐rich habitats, whereas exotic (Echinogammarus ischnus) amphipods are found only in the latter.

We tested for plastic vs. genetic/maternal contributions to spatial variation (ion‐rich vs. ion‐poor habitats) in native amphipod fitness components: postmoult calcification, body size, larval survival, time to first reproduction and fecundity. We did so by comparing the following: (i) F0(collected from the wild) individuals between the two habitats – some of which were reared for a time under varying conditions in the laboratory; and (ii) F1(reared in the laboratory for their entire lives) individuals from the two habitats under a variety of water conditions.

We found strong plastic effects on postmoult calcification – it was more rapid in ion‐rich water. We found genetic/maternal differences in time to reproduction (almost twice as long in ion‐poor amphipods), fecundity and larval survival (higher in ion‐poor amphipods) in early summer. These plastic effects and genetic/maternal differences are likely to be adaptive.

Plasticity and genetic/maternal effects both could influence the efficacy of ion‐poor populations in providing demographic subsidies that aid native persistence at ion‐rich habitats where exotic amphipods are present. These effects could thus have important consequences for native species persistence in the presence of non‐native species.
Molecular insights from dysregulation of the thiazide‐sensitive WNK/SPAK/NCC pathway in the kidney: Gordon syndrome and thiazide‐induced hyponatraemia
Authors: Glover Mark , O'Shaughnessy Kevin M
Published: May 2013

Human blood pressure is dependent on balancing dietary salt intake with its excretion by the kidney. Mendelian syndromes of altered blood pressure demonstrate the importance of the distal nephron in this process and of the thiazide‐sensitive pathway in particular.

Gordon syndrome (GS), the phenotypic inverse of the salt‐wasting Gitelman syndrome, is a condition of hyperkalaemic hypertension that is reversed by low‐dose thiazide diuretics or a low‐salt diet. Variants within at least four genes [i.e. with‐no‐lysine(K) kinase 1 (WNK1), WNK4, kelch‐like family member 3 (KLHL3) and cullin 3 (CUL3)] can cause the phenotype of GS. Details are still emerging for some of these genes, but it is likely that they all cause a gain‐of‐function in the thiazide‐sensitive Na+–Cl− cotransporter (NCC) and hence salt retention. Herein, we discuss the key role of STE20/sporulation‐specific protein 1 (SPS1)‐related proline/alanine‐rich kinase (SPAK), which functions as an intermediary between the WNKs and NCC and for which a loss‐of‐function mutation produces a Gitelman‐type phenotype in a mouse model.

In addition to Mendelian blood pressure syndromes, the study of patients who develop thiazide‐induced‐hyponatraemia (TIH) may give further molecular insights into the role of the thiazide‐sensitive pathway for salt reabsorption. In the present paper we discuss the key features of TIH, including its high degree of reproducibility on rechallenge, possible genetic predisposition and mechanisms involving excessive saliuresis and water retention.

Together, studies of Gordon syndrome and TIH may increase our understanding of the molecular regulation of sodium trafficking via the thiazide‐sensitive pathway and have important implications for hypertensive patients, both in the identification of new antihypertensive drug targets and avoidance of hyponatraemic side‐effects.
Disease pattern and chronic illness in rural China: The Hong Kong Red Cross basic health clinic after 2008 Sichuan earthquake
Authors: Hung Kevin KC , Lam Eva CC , Chan Emily YY , Graham Colin A
Published: May 2013

Background

Medical teams might have difficulties preparing for deployment to rural towns due to a lack of prior information. The study objective was to identify the health needs and chronic disease prevalence of rural Chinese following a major earthquake.

Methods

Hong Kong Red Cross organised a basic healthcare team to Yanmen town, Jiangyou 3 weeks after the 2008 Sichuan earthquake. A cross‐sectional records‐based study of all patients treated by the Hong Kong Red Cross basic healthcare team from 1 June to 19 June 2008 was conducted.

Results

Two thousand and thirty‐four individual patient encounters occurred during the 19‐day period. Musculoskeletal, respiratory and gastrointestinal problems were the top three categories and accounted for 30.4%, 17.4% and 12.7%, respectively. The 43.4% of the 762 patients with blood pressure measurements were above the recognised criteria for hypertension.

Conclusions

We identified that the management of chronic diseases was an important issue, especially with the high prevalence of hypertension found in our study. Medical responders need to be aware of the potential pre‐existing disease burden in the community, with the possible exacerbation in post‐disaster situations. Careful planning on the use of treatment guidelines with particular focus on the local health resources available and issues with continuation of care will provide better care for the patients.
Confined aquifers as viral reservoirs
Authors: Smith Renee J. , Jeffries Thomas C. , Roudnew Ben , Seymour Justin R. , Fitch Alison J. , Simons Keryn L. , Speck Peter G. , Newton Kelly , Brown Melissa H. , Mitchell James G.
Published: May 2013

Knowledge about viral diversity and abundance in deep groundwater reserves is limited. We found that the viral community inhabiting a deep confined aquifer in South Australia was more similar to reclaimed water communities than to the viral communities in the overlying unconfined aquifer community. This similarity was driven by high relative occurrence of the single‐stranded DNA viral groups Circoviridae, Geminiviridae and Microviridae, which include many known plant and animal pathogens. These groups were present in a 1500‐year‐old water situated 80 m below the surface, which suggests the potential for long‐term survival and spread of potentially pathogenic viruses in deep, confined groundwater. Obtaining a broader understanding of potentially pathogenic viral communities within aquifers is particularly important given the ability of viruses to spread within groundwater ecosystems.
Respiratory virology and microbiology in intensive care units: a prospective cohort study
Authors: Østby Anne‐Cathrine , Gubbels Sophie , Baake Gerben , Nielsen Lars Peter , Riedel Casper , Arpi Magnus
Published: May 2013

Our aim was to determine the frequency of 12 common respiratory viruses in patients admitted to intensive care units with respiratory symptoms, evaluate the clinical characteristics and to compare the results to routine microbiological diagnostics. Throat swabs from 122 intensive care‐patients >18 years with acute respiratory symptoms were collected upon admission and analysed with multiplex real‐time polymerase chain reaction, for 12 community respiratory viruses. Blood and respiratory tract specimens were analysed for bacteria and fungi upon clinicians' request. Clinical and paraclinical data were collected. Viruses were detected in 19 (16%) of the 122 study patients. Five virus‐positive patients (26%) had possible clinically relevant bacteria or fungi co‐detected. Patients with exacerbation in COPD were associated with a viral infection (p = 0.02). Other comorbidities, clinical and paraclinical parameters, and death were independent of a viral infection or co‐detection of bacteria/fungi. In conclusion, respiratory viruses were frequently detected in the patients. The investigated clinical and paraclinical parameters were not different in viral infections compared to other agents, thus respiratory viruses likely have similar impact on the clinical course as other agents. In 25% of the virus‐positive patients, polymicrobial aetiology was identified. Comprehensive and sensitive diagnostic methods should be emphasized to enhance respiratory diagnostics.
Review article: antitumoural immunity in colorectal cancer – current and potential future implications in clinical practice
Authors: Koudougou C. , Bonneville M. , Matysiak‐Budnik T. , Touchefeu Y.
Published: May 2013

Background

Most of the current research in gastrointestinal oncology is focused on biology of cancer itself, but there is growing interest in the patient's immune system response and its relation with cancer cells.

Aim

To review the impact of the antitumoural immune response on epidemiology, prognosis and treatment of colorectal cancer.

Methods

Search of the literature published in English using the PubMed database.

Results

The role of the immune system in the antitumoural immunosurveillance is clearly supported by the increased incidence of colorectal cancer and adenomatous polyps in immunosuppressed patients. Moreover, the degree of infiltration of the tumours by the immune cells has been shown to be a strong prognostic factor of both disease recurrence and survival. The immune system plays an important role in the chemotherapy‐induced cell death. New therapeutic strategies targeting the antitumoural immunity are being currently investigated with promising results.

Conclusion

Better knowledge of antitumoural immune system can have a major impact on patients' management in daily clinical practice. Colorectal cancer screening is an important issue in immunosuppressed patients, and recommendations should be refined for selected high‐risk patients. The use of an immune score to guide the therapeutic strategies in the adjuvant setting should be supported. Further and larger clinical trials are necessary to accelerate the development of innovative immune therapies.
Binding kinetics differentiates functional antagonism of orexin‐2 receptor ligands
Authors: Mould R , Brown J , Marshall F H , Langmead C J
Published: May 2013

Orexin receptor antagonism represents a novel approach for the treatment of insomnia that directly targets sleep/wake regulation. Several such compounds have entered into clinical development, including the dual orexin receptor antagonists, suvorexant and almorexant. In this study, we have used equilibrium and kinetic binding studies with the orexin‐2 (OX2) selective antagonist radioligand, [3H]‐EMPA, to profile several orexin receptor antagonists. Furthermore, selected compounds were studied in cell‐based assays of inositol phosphate accumulation and ERK‐1/2 phosphorylation in CHO cells stably expressing the OX2 receptor that employ different agonist incubation times (30 and 5 min, respectively). EMPA, suvorexant, almorexant and TCS‐OX‐29 all bind to the OX2 receptor with moderate to high affinity (pKI values ≥ 7.5), whereas the primarily OX1 selective antagonists SB‐334867 and SB‐408124 displayed low affinity (pKI values ca. 6). Competition kinetic analysis showed that the compounds displayed a range of dissociation rates from very fast (TCS‐OX2‐29, koff = 0.22 min−1) to very slow (almorexant, koff = 0.005 min−1). Notably, there was a clear correlation between association rate and affinity. In the cell‐based assays, fast‐offset antagonists EMPA and TCS‐OX2‐29 displayed surmountable antagonism of orexin‐A agonist activity. However, both suvorexant and particularly almorexant cause concentration‐dependent depression in the maximal orexin‐A response, a profile that is more evident with a shorter agonist incubation time. Analysis according to a hemi‐equilibrium model suggests that antagonist dissociation is slower in a cellular system than in membrane binding; under these conditions, almorexant effectively acts as a pseudo‐irreversible antagonist.

Linked Articles

This article is part of a themed section on Orexin Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐2
The relationship between serum 25‐hydroxy vitamin D, parathormone and bone mineral density in Indian population
Authors: Garg M. K. , Tandon N. , Marwaha R. K. , Menon A. S. , Mahalle N.
Published: May 2013

Objectives

Vitamin D deficiency (VDD) is a global problem. Not all patients with VDD have clinical manifestations or secondary hyperparathyroidism. We studied the interaction between serum 25‐hydroxy vitamin D (25OHD), parathormone (PTH) and bone mineral density (BMD) in Indian adolescents and adults.

Design

Population survey.

Patients

A total of 1829 adolescents and 1346 adults aged 50 years and above were analysed in this study.

Measurements

Serum biochemistry, 25OHD, PTH and BMD were estimated. Subjects were grouped according to quartiles of serum PTH. VDD was defined as severe (25OHD ≤ 5 ng/ml), moderate (25OHD ≤ 10 ng/ml) and mild (25OHD ≤ 20 ng/ml) and secondary hyperparathyroidism (SHPT) when serum PTH levels >65 pg/ml.

Results

Only 30–40% of subjects with moderate and severe VDD, respectively, had SHPT. BMD decreased from Quartile 1 to Quartile 4 of PTH at all sites among adolescents and adults, with only a marginal decline in serum 25OHD levels between these quartiles. Further, within each PTH quartile, there was no difference in BMD according to categories of VDD. Analysing BMD in the different PTH quartiles, the PTH cut‐offs beyond which BMD showed a significant decline, was 35 pg/ml in adolescents and 53 pg/ml in adults.

Conclusions

Less than half of the subjects with VDD have SHPT. BMD levels start to decline at PTH values currently considered to be normal. These data suggest the need to redefine SHPT in different age groups keeping in mind the relationship between PTH and BMD. This may also influence the decision to supplement subjects with VDD.