Dapsone-induced agranulocytosis. The role of xenobiotic-metabolizing enzymes demonstrated by a case report [Dapson-induzierte Agranulozytose]

A 34-year-old female patient with a three year history of generalized granuloma annulare was treated systemically with dapsone (DADPS). Six weeks after the onset of treatment, the patient developed an extensive tonsillitis of the base of the tongue with fever and malaise. Routine laboratory work showed a leukocytopenia with agranulocytosis. Further investigation revealed a marked decrease of the enzyme activity of N-acetyltransferase 2, which plays an important role in dapsone metabolism. Treatment included the cessation of dapsone, antibiotic coverage, and G-CSF leading to the rapid improvement of symptoms and normalization of leukocyte counts. Dapsone-induced angina agranulocytotica is a rare event and is interpreted as an idiosyncratic reaction. Depending on genetic polymorphisms of various enzymes, dapsone can be metabolized to immunologically or toxicologically relevant intermediates. Because of the risk of severe hematologic reactions, dapsone should only be employed for solid indications and with appropriate monitoring. [Article in German]

Markers of genetic susceptibility in human environmental hygiene and toxicology : the role of selected CYP, NAT and GST genes

Inherited genetic traits co-determine the susceptibility of an individual to a toxic chemical. Special emphasis has been put on individual responses to environmental and industrial carcinogens, but other chronic diseases are of increasing interest. Polymorphisms of relevant xenobiotic metabolising enzymes may be used as toxicological susceptibility markers. A growing number of genes encoding enzymes involved in biotransformation of toxicants and in cellular defence against toxicant-induced damage to the cells has been identified and cloned, leading to increased knowledge of allelic variants of genes and genetic defects that may result in a differential susceptibility toward environmental toxicants. "Low penetrating" polymorphisms in metabolism genes tend to be much more common in the population than allelic variants of "high penetrating" cancer genes, and are therefore of considerable importance from a public health point of view. Positive associations between cancer and CYP1A1 alleles, in particular the *2C I462V allele, were found for tissues following the aerodigestive tract. Again, in most cases, the effect of the variant CYP1A1 allele becomes apparent or clearer in connection with the GSTM1 null allele. The CYP1B1 codon 432 polymorphism (CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squameous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has also pointed to interactive effects. Of particular interest for the industrial and environmental field is the isozyme CYP2E1. Several genotypes of this isozyme have been characterised which seem to be associated with different levels of expression of enzyme activity. The acetylator status for NAT2 can be determined by genotyping or by phenotyping. In the pathogenesis of human bladder cancer due to occupational exposure to "classical" aromatic amines (benzidine, 4-aminodiphenyl, 1-naphthylamine) acetylation by NAT2 is regarded as a detoxication step. Interestingly, the underlying European findings of a higher susceptibility of slow acetylators towards aromatic amines are in contrast to findings in Chinese workers occupationally exposed to aromatic amines which points to different mechanisms of susceptibility between European and Chinese populations. Regarding human bladder cancer, the hypothesis has been put forward that genetic polymorphism of GSTM1 might be linked with the occurrence of this tumour type. This supports the hypothesis that exposure to PAH might causally be involved in urothelial cancers. The human polymorphic GST catalysing conjugation of halomethanes, dihalomethanes, ethylene oxide and a number of other industrial compounds could be characterised as a class theta enzyme (GSTT1) by means of molecular biology. "Conjugator" and "non-conjugator" phenotypes are coincident with the presence and absence of the GSTT1 gene. There are wide variations in the frequencies of GSTT1 deletion (GSTT1 *0/0) among different ethnicities. Human phenotyping is facilitated by the GST activity towards methyl bromide or ethylene oxide in erythrocytes which is representative of the metabolic GSTT1 competence of the entire organism. Inter-individual variations in xenobiotic metabolism capacities may be due to polymorphisms of the genes coding for the enzymes themselves or of the genes coding for the receptors or transcription factors which regulate the expression of the enzymes. Also, polymorphisms in several regions of genes may cause altered ligand affinity, transactivation activity or expression levels of the receptor subsequently influencing the expression of the downstream target genes. Studies of individual susceptibility to toxicants and gene-environment interaction are now emerging as an important component of molecular epidemiology.

Evidence of a conserved role for Chlamydia HtrA in the replication phase of the chlamydial developmental cycle

Identification of the HtrA inhibitor JO146 previously enabled us to demonstrate an essential function for HtrA during the mid-replicative phase of the Chlamydia trachomatis developmental cycle. Here we extend our investigations to other members of the Chlamydia genus. C. trachomatis isolates with distinct replicative phase growth kinetics showed significant loss of viable infectious progeny after HtrA was inhibited during the replicative phase. Mid-replicative phase addition of JO146 was also significantly detrimental to Chlamydia pecorum, Chlamydia suis and Chlamydia cavie. These data combined indicate that HtrA has a conserved critical role during the replicative phase of the chlamydial developmental cycle.

Potential role of EPB41L3 (Protein 4.1B/Dal-1) as a target for treatment of advanced prostate cancer

Background: Loss of erythrocyte membrane protein band 4.1-like 3 (EPB41L3; aliases: protein 4.1B, differentially expressed in adenocarcinoma of the lung-1 (Dal-1)) expression has been implicated in tumor progression. Objective: To evaluate literature describing the role of EPB41L3 in tumorigenesis and metastasis, and to consider whether targeting this gene would be useful in the treatment of prostate cancer. Methods: A literature review of studies describing EPB41L3 and its aliases was conducted. Online databases (NCBI, SwissProt) were also interrogated to collect further data. Results/conclusion: A growing body of evidence supports a role for loss of EPB41L3 in tumor progression, including in prostate cancer. Therapeutic strategies that could be harnessed to upregulate EPB41L3 gene expression in prostate cancer cells are currently being developed.

Development of an electronic role-play assessment initiative in bioscience for nursing students

Devising authentic assessments for subjects with large enrolments is a challenge. This study describes an electronic role-play assessment for approximately 600 first-year nursing students to learn and apply pathophysiology (bioscience) concepts to nursing practice. Students used Microsoft Office PowerPoint® to prepare electronic role-plays both between a nurse and patient, and between two nurses, thus simulating workplace scenarios. Student feedback demonstrated that respondents found this assessment useful for learning pathophysiology, and for applying pathophysiology to a nursing clinical setting. This electronic presentation circumvented issues associated with a traditional oral presentation such as embarrassment and logistics of scheduling groups, and rated well with students of non-English speaking background. The electronic role-play assessment initiative encouraged students to apply their bioscience knowledge to a clinical setting, and allowed students to conceptualise the importance of bioscience within both the nursing degree and the profession.

Progesterone regulation of implantation-related genes: new insights into the role of oestrogen

Genomic profiling was performed on explants of late proliferative phase human endometrium after 24-h treatment with progesterone (P) or oestradiol and progesterone (17 beta-E-2+P) and on explants of menstrual phase endometrium treated with 17 beta-E-2+P. Gene expression was validated with real-time PCR in the samples used for the arrays, in endometrium collected from early and mid-secretory phase endometrium, and in additional experiments performed on new samples collected in the menstrual and late proliferative phase. The results show that late proliferative phase human endometrium is more responsive to progestins than menstrual phase endometrium, that the expression of several genes associated with embryo implantation (i.e. thrombomodulin, monoamine oxidase A, SPARC-like 1) can be induced by P in vitro, and that genes that are fully dependent on the continuous presence of 17 beta-E-2 during P exposure can be distinguished from those that are P-dependent to a lesser extent. Therefore, 17 beta-E-2 selectively primes implantation-related genes for the effects of P.

The role of counselling in healing from sexual assault in childhood from the phenomenological perspective of men and women

Serious Childhood Sexual Assault (CSA) has the potential for a wide range of extreme difficulties, not only in childhood but for many years to come. However, the lasting negative impacts are not inevitable and with the right help, those who have experienced CSA can go on to enjoy whole and fulfilling lives. The question posed in this research is “What comprises “the right help”? The present study qualitatively investigated the narratives of men and women with regard to what was deemed important components of counselling which facilitated their healing from childhood sexual assault. Participants consisted of 21 women and 11 men who had sought both individual and group counselling to work through issues stemming from traumatic sexual assault in childhood. Findings presented here describe three superordinate themes which were essential in the healing process, incorporating abuse-specific, client-specific and practitioner-specific components. A final superordinate theme of negative experiences in counselling is also presented, describing unhelpful or negative counselling experiences. Similarities between men and women as to the important components of counselling was remarkable, however important gender differences were also observed.

Understanding public response to a congestion charge : a random-effects ordered logit approach

Public acceptance is consistently listed as having an enormous impact on the implementation and success of a congestion charge scheme. This paper investigates public acceptance of such a scheme in Australia. Surveys were conducted in Brisbane and Melbourne, the two fastest growing Australian cities. Using an ordered logit modeling approach, the survey data including stated preferences were analyzed to pinpoint the important factors influencing people’s attitudes to a congestion charge and, in turn, to their transport mode choices. To accommodate the nature of, and to account for the resulting heterogeneity of the panel data, random effects were considered in the models. As expected, this study found that the amount of the congestion charge and the financial benefits of implementing it have a significant influence on respondents’ support for the charge and on the likelihood of their taking a bus to city areas. However, respondents’ current primary transport mode for travelling to the city areas has a more pronounced impact. Meanwhile, respondents’ perceptions of the congestion charge’s role in protecting the environment by reducing vehicle emissions, and of the extent to which the charge would mean that they travelled less frequently to the city for shopping or entertainment, also have a significant impact on their level of support for its implementation. We also found and explained notable differences across two cities. Finally, findings from this study have been fully discussed in relation to the literature.

Responsible reconstruction : The architect's role

This paper investigates the role of the architect in post-disaster reconstruction and questions their ability to facilitate per- manent building solutions. There is an ever-increasing population of refugees and internally displaced persons due to disasters and conflicts who have a basic need for shelter. To date, housing solutions for such people has tended to focus on short-term, temporary shelter solutions that have been largely unsuccessful. This increasing demand for shelter has led to an emerging group of architects skilled in post-disaster reconstruction. These architects acknowledge that shelter is critical to survival, but believe architects should focus on rebuilding in a manner that is quick, durable but permanent. They believe that an architect skilled in post-disaster reconstruction can produce solutions that meet the requirement of the emergency phase, through to semi-permanent and even permanent homes, without wasting time and money on interim shelters. Case Study Research was used to examine and evaluate the assistance provided by Emergency Architects Australia (EAA) to the Kei Gold community in the Solomon Islands after the 2007 earthquake and tsunami. The results indicate that an architect’s response to a disaster must go beyond providing temporary shelter; they must create permanent building solutions that respond to the site and the culture while servicing the needs of the communi- ty. The vernacular reconstruction methods implemented by EAA in Kei Gold Village have been successful in develop- ing permanent housing solutions. Further research and development is required to gain a broader understanding of the role of the architect in disasters of varying scales and typologies.

Young Australian adults' beliefs about alcohol's role in sexual aggression and victimisation

Beliefs and misconceptions about sex, gender, and rape have been explored extensively to explain people’s attributions concerning alcohol-involved sexual violence. However, less is known about the specific beliefs that people hold about how alcohol facilitates sexual aggression and victimisation. The present study aimed to identify these alcohol-related beliefs among young Australian adults. Six men and nine women (N = 15; 18-24 years) in focus groups (n = 13) and interviews (n = 2) were asked to discuss the role of alcohol in a hypothetical alcohol-involved rape. Using a consensual qualitative research methodology, the effects of alcohol that were seen to introduce, progress, and intensify risks for rape were: increased confidence; character transformation: impaired cognition; behavioural disinhibition; altered sexual negotiation; enhanced self-centredness; impaired awareness of wrongdoing; increased/decreased sexual assertiveness; and compromised self-protection. Some of the beliefs identified in this study are not currently captured in alcohol expectancy measures which assess people’s beliefs about alcohol’s effects on cognition, emotion, and behaviour. This study’s findings offer a conceptual basis for the development of a new alcohol expectancy measure that can be used in future rape-perception research.

Explicating the role of sexual coercion and vulnerability: Alcohol expectancies in rape attributions

Despite evidence suggesting that alcohol expectancies may influence people’s rape perceptions, no study to date has measured context-specific expectancies comprehensively. This study represents an initial investigation of the role of sexual coercion and vulnerability alcohol expectancies in young Australian adults’ rape blame attributions. Using a vignette method, it was hypothesised that participants’ stronger expectancy endorsement would predict lesser perpetrator blame and greater victim blame. Participants (N = 210; 34.9% males; 18-25 years) read a hypothetical rape scenario and rated dimensions of blameworthiness attributed to the intoxicated sexual perpetrator and victim. Participants completed the Sexual Coercion and Sexual Vulnerability sub-scales of the Drinking Expectancy Sexual Vulnerabilities Questionnaire for the targets self, men, and women in addition to measures of traditional gender role attitudes and rape myth acceptance. Hierarchical multiple regressions revealed that, as expected, stronger sexual coercion expectancy predicted lower perpetrator blame and greater victim blame. Self-oriented expectancy predicted evaluations of the perpetrator whereas other-oriented expectancy predicted victim evaluations. These effects were robust after controlling for gender role attitudes and rape myth acceptance. Alcohol expectancies appear to be part of a network of beliefs and attitudes which perpetuate biased rape attributions and may be useful to challenge in altering rape perceptions.

The role of other people and emotion for blood donation : an altruistic social service

Blood donation is a critical part of health services with a viable blood supply underpinning an effective health program in any country. Typically blood is provided by voluntary donations from citizens and is therefore reliant on the goodwill and altruistic commitment of donors. In Australia, like many other developed nations, there are many challenges in maintaining a sufficient and sustainable blood supply. The Australian Red Cross Blood Service Donor and Community research group aim is to understand the barriers, motivations and perceptions of donors. Blood donation is a ‘people-processing’ service (Lovelock 1983, Russell-Bennett et al 2013) with the marketing exchange relating to bodily fluid rather than money and is an altruistic social service that has no direct benefit for the customer donor rather the benefit is for other people and society (Kotler and Zaltman 1971). Emotion has been shown to be a motivator and a barrier in a variety of Blood Service studies, this is a key insight that is further explored in the current study. Other key social factors that impact blood donor behavior are classified as social because they involve perceptions of other people’s beliefs and responses (such as moral or subjective norms), peer pressure, other people’s expectations and other people as a form of support. Given that emotions are social phenomena (Parkinson 1996), this study focuses on the role of other people in the blood donation process and how other people relates to the emotional experience of blood donors. We argue in this paper that overcoming emotional barriers to blood donation by leveraging the role of other people will influence low donation rates in Australia. To date, there has been little evidence in service research that identifies. In this paper we explore how other people influence the emotional experience of donors and how, donor emotions create the need for other people as a coping resource.

Integrating ‘role play’ in assessment to strengthen professional conduct and accountability of students : a pilot study

BACKGROUND In a process engineering setting, graduates are frequently allocated reviews of existing operations or required to scope new production processes by their supervisors with a view to improving or expanding on operations and overall productivity. These tasks may be carried out in teams and in consultation with the process engineer’s immediate line manager or a more experienced engineer, such as the Production or Maintenance Manager; ultimately reporting to senior management, which is frequently a non-engineer. Although professional skills development is part of engineering curricula, ‘professional conduct’ and ‘accountability’ required for dealing with peers and superiors in industry is not very well addressed at university. Consequently, upon graduation, many students are, in terms of knowledge and experience in this area, underprepared to work effectively in industry settings. PURPOSE The purpose of this study was to develop and implement a role-play scenario within a core 2nd year process engineering unit, so that students could gain knowledge, skills and experience in different aspects (and nuances) of professional conduct and accountability. DESIGN/METHOD In the role-play scenario, students worked in ‘engineering production teams’ to design a process for an iconic Queensland fruitcake and to present their solution and recommendations (culminating in a poster presentation) to an assessment panel consisting of staff, role-playing as, ‘production and plant managers’. Students were assessed on several areas, including professionalism using a criteria referenced assessment guide by a 3-member cross-disciplinary staff panel consisting of a Business Faculty lecturer, an engineer from industry and the lecturer of the Process Engineering unit. Professional conduct and accountability was gauged through direct questioning by the panel. Feedback was also sought from students on various aspects through a survey questionnaire after the role play activity at the end of semester. RESULTS Overall, the role play was very well performed with students achieving an average score of 79.3/100 (distinction grade). Professional conduct as assessed by panel was on average better than scores given for professional accountability (4.0 compared with 3.6 out of 5). Feedback from students indicated that the learning activities had contributed to their overall understanding of the content and the role of process engineers. Industry involvement was rated very highly as contributing to their learning at 4.8 (on Likert scale from 1 – 5) and the poster presentation was rated at 3.6. CONCLUSIONS This pilot study was successful in implementing a new assessment task for modelling professional conduct and accountability within a 2nd year core unit. This task incorporated a role-play activity and there was evidence to suggest that this and associated learning tasks were successful in broadening students’ understanding and skills in this area required for engineering practice. Following feedback given by students and staff, improvements will be made to the nature of the problem, how it is defined, its assessment, and the approach taken in the role-play scenario when the unit is offered in 2014.

Taking up the discourse : theory or praxis

This article responds to the invitation extended by Carney to engage in a dialogue on the topic of graduate legal research units. In his paper, Carney stated the approach of the Sydney course as being to teach theory rather than skills, to "pursue academic goals over skill competencies... ". The Faculty of Law at Queensland University of Technology introduced a postgraduate legal research unit in 1993 with different perspectives and purposes to the Sydney course, and given this experience, the opportunity for a discussion on aspects of such units including the theoretical versus practical approach to teaching cannot be ignored.