The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals : consequences for occupational and environmental medicine

The importance of the isoform CYP2E1 of the human cytochrome P-450 superfamily of enzymes for occupational and environmental medicine is derived from its unique substrate spectrum that includes a number of highly important high-production chemicals, such as aliphatic and aromatic hydrocarbons, solvents and industrial monomers (i.a. alkanes, alkenes, aromatic and halogenated hydrocarbons). Many polymorphic genes, such as CYP2E1, show considerable differences in allelic distribution between different human populations. The polymorphic nature of the human CYP2E1 gene is significant for inter-individual differences in toxicity of its substrates. Since the substrate spectrum of CYP2E1 includes many compounds of basic relevance to industrial toxicology, a rationale for metabolic interactions of different CYP2E1 substrates is provided. In-depth research into the inter-individual phenotypic differences of human CYP2E1 enzyme activities was enabled by the recognition that the 6-hydroxylation of the drug chlorzoxazone is mediated by CYP2E1. Studies on CYP2E1 phenotyping have pointed to inter-individual variations in enzyme activities. There are consistent ethnic differences in CYP2E1 enzyme expression, mostly demonstrated between European and Japanese populations, which point to a major impact of genetic factors. The most frequently studied genetic polymorphisms are the restriction fragment length polymorphisms PstI/RsaI (mutant allele: CYP2E1*5B) located in the 5′-flanking region of the gene, as well as the DraI polymorphism (mutant allele: CYP2E1*6) located in intron 6. These polymorphisms are partly related, as they form the common allele designated CYP2E1*5A. Striking inter-ethnic differences between Europeans and Asians appear with respect to the frequencies of the CYP2E1*5A allele (only approximately 5% of Europeans are heterozygous, but 37% of Asians are, whilst 6% of Asians are homozygous). Available studies indicate a wide variation in human CYP2E1 expression, which are very likely based on complex gene-environment interactions. Major inter-ethnic differences are apparent on the genotyping and the phenotyping levels. Selected cases are presented where inter-ethnic variations of CYP2E1 may provide likely explanations for unexplained findings concerning industrial chemicals that are CYP2E1 substrates. Possible consequences of differential inter-individual and inter-ethnic susceptibilities are related to individual expressions of clinical symptoms of chemical toxicity, to results of biological monitoring of exposed workers, and to the interpretation of results of epidemiological or molecular-epidemiological studies.

European aspects of standard setting in occupational hygiene and medicine

Occupational standards concerning the allowable concentrations of chemical compounds in the ambient air of workplaces have been established in several countries at national levels. With the integration of the European Union, a need exists for establishing harmonized Occupational Exposure Limits. For analytical developments, it is apparent that methods for speciation or fractionation of carcinogenic metal compounds will be of increasing practical importance for standard setting. Criteria of applicability under field conditions, cost-effectiveness, and robustness are practical driving forces for new developments. When the European Union issued a list of 62 chemical substances with Occupational Exposure Limits in 2000, 25 substances received a 'skin' notation. The latter indicates that toxicologically significant amounts may be taken up via the skin. Similar notations exist on national levels. For such substances, monitoring concentrations in ambient air will not be sufficient; biological monitoring strategies will gain further importance in the medical surveillance of workers who are exposed to such compounds. Proceedings in establishing legal frameworks for a biological monitoring of chemical exposures within Europe are paralleled by scientific advances in this field. A new aspect is the possibility of a differential adduct monitoring, using blood proteins of different half-life or lifespan. This technique allows differentiation between long-term mean exposure to reactive chemicals and short-term episodes, for example, by accidental overexposure. For further analytical developments, the following issues have been addressed as being particularly important: New dose monitoring strategies, sensitive and reliable methods for detection of DNA adducts, cytogenetic parameters in biological monitoring, methods to monitor exposure to sensitizing chemicals, and parameters for individual susceptibilities to chemical toxicants.

Prescribing for nausea in palliative care : A cross-sectional national survey of Australian palliative medicine doctors

Background: Nausea can be a debilitating symptom for patients with a life-limiting illness. While addressing reversible components, nonpharmacological strategies and antiemetics are the main therapeutic option. The choice of medication, dose, and route of administration remain highly variable. Objective: The aim of this study was to codify the current clinical approaches and quantify any variation found nationally. Methods: A cross-sectional study utilizing a survey of palliative medicine clinicians examined prescribing preferences for nausea using a clinical vignette. Respondent characteristics, the use of nonpharmacological interventions, first- and second-line antiemetic choices, commencing and maximal dose, and time to review were collected. Results: Responding clinicians were predominantly working in palliative medicine across a range of settings with a 49% response rate (105/213). The main nonpharmacological recommendation was “small, frequent snacks.” Metoclopramide was the predominant first-line agent (69%), followed by haloperidol (26%), while second-line haloperidol was the predominant agent (47%), with wide variation in other nominated agents. Respondents favoring metoclopramide as first-line tended to use haloperidol second-line (65%), but not vice versa. Maximal doses for an individual antiemetic varied up to tenfold. Conclusion: For nausea, a commonly encountered symptom in palliative care, clinicians' favored metoclopramide and haloperidol; however, after these choices, there was large variation in antiemetic selection. While most clinicians recommended modifying meal size and frequency, use of other nonpharmacological therapies was limited.

Informatics to support patient choice between diverse medical systems

Culturally, philosophically and religiously diverse medical systems including Western medicine, Traditional Chinese Medicine, Ayurvedic Medicine and Homeopathic Medicine, once situated in places and times relatively unconnected from each other, currently co-exist to a point where patients must choose which system to consult. These decisions require comparative analyses, yet the divergence in key underpinning assumptions is so great that comparisons cannot easily be made. However, diverse medical systems can be meaningfully juxtaposed for the purpose of making practical decisions if relevant information is presented appropriately. Information regarding privacy provisions inherent in the typical practice of each medical system is an important element in this juxtaposition. In this paper the information needs of patients making decisions regarding the selection of a medical system are examined.

The association between the measurement of adherence to anti-diabetes medicine and the HbA1c

BACKGROUND: Adherence to medicines is important in subjects with diabetes, as nonadherence is associated with an increased risk of morbidity and mortality. However, it is not clear whether there is an association between adherence to medicines and glycaemic control, as not all studies have shown this. One of the reasons for this discrepancy may be that, although there is a standard measure of glycaemic control i.e. HbA1c, there is no standard measure of adherence to medicines. Adherence to medicines can be measured either qualitatively by Morisky or non-Morisky methods or quantitatively using the medicines possession ratio (MPR). AIMS OF THE REVIEW: The aims of this literature review are (1) to determine whether there is an association between adherence to anti-diabetes medicines and glycaemic control, and (2) whether any such association is dependent on how adherence is measured. Methods A literature search of Medline, CINAHL and the Internet (Google) was undertaken with search terms; 'diabetes' with 'adherence' (or compliance, concordance, persistence, continuation) with 'HbA1c' (or glycaemic control). RESULTS: Twenty-three studies were included; 10 qualitative and 12 quantitative studies, and one study using both methods. For the qualitative methods measurements of adherence to anti-diabetes medicines (non-Morisky and Morisky), eight out of ten studies show an association with HbA1c. Nine of ten studies using the quantitative MPR, and two studies using MPR for insulin only, have also shown an association between adherence to anti-diabetes medicines and HbA1c. However, the one study that used both Morisky and MPR did not show an association. Three of the four studies that did not show a relationship, did not use a range of HbA1c values in their regression analysis. The other study that did not show a relationship was specifically in a low income population. CONCLUSIONS: Most studies show an association between adherence to anti-diabetes medicines and HbA1c levels, and this seems to be independent of method used to measure adherence. However, to show an association it is necessary to have a range of HbA1c values. Also, the association is not always apparent in low income populations.

Mapping mountains : a morphological study of traditional highland settlements in Chittagong Hill tracts of Bangladesh

This thesis is a morphological study of the settlement patterns of the diverse hill groups in Chittagong Hill Tracts – a mountainous borderland of Bangladesh in South Asia. It examines the settlement morphology of a hill town, using a combination of both quantitative and qualitative methods, and explains the recurrent neighbourhood types of the highland groups in relation to their urbanisation. The research findings related to the settlements of diverse cultural groups in a cross-border region of the Asian uplands are also relevant to similar contexts and enquiries. Furthermore, the developed methodological framework that facilitated the data collection process in CHT's culturally diverse regions is also applicable to the investigation of geographic areas with similar socio-cultural complexities. Finally, this research specifically contributes to the literature of cross-cultural studies of highland towns and vernacular settlements in the Asian context.

Geochemistry-based coral palaeoclimate studies and the potential of ‘non-traditional’ (non-massive Porites) corals : recent developments and future progression

Understanding the natural variability of the Earth's climate system and accurately identifying potential anthropogenic influences requires long term, geographically distributed records of key climate indicators, such as temperature and precipitation that extend prior to the last 400. years of the Holocene. Reef corals provide an excellent source of high resolution climate records, and importantly represent the tropical marine environment where palaeoclimate data are urgently required. Recent decades have seen significant improvement in our understanding of coral biomineralisation, the associated uptake of geochemical proxies and methods of identifying and understanding the effects of both early and late, post depositional diagenetic alteration. These processes all have significant implications for interpreting geochemical proxies relevant to palaeoclimatic reconstructions. This paper reviews the current 'state of the art' in terms of coral based palaeoclimate reconstructions and highlights a key remaining problem. The majority of coral based palaeoclimate research has been derived from massive colonies of Porites. However, massive Porites are not globally abundant and may not provide material of a particular age of interest in those regions where they are present. Therefore, there is great potential for alternate coral genera to act as complimentary climate archives. While it remains critical to consider five key factors - vital effects, differential growth morphologies, geochemical heterogeneity in the skeletal ultrastructure, transfer equation selection and diagenetic screening of skeletal material - in order to allow the highest level of accuracy in coral palaeoclimate reconstructions, it is also important to develop alternate taxa for palaeoclimate studies in regions where Porites colonies are absent or rare. Currently as many as nine genera other than Porites have proven at least limited utility in palaeothermometry, most of which are found in the Atlantic/Caribbean region where massive Porites do not exist. Even branching taxa such as Acropora have significant potential to preserve environmental archives. Increasing this capability will greatly expand the number of potential geochemical archives available for longer term temporal records of palaeoclimate.

Isolation of microvascular endothelial cells from cadaveric corneal limbus

Limbal microvascular endothelial cells (L-MVEC) contribute to formation of the corneal-limbal stem cell niche and to neovascularization of diseased and injuries corneas. Nevertheless, despite these important roles in corneal health and disease, few attempts have been made to isolate L-MVEC with the view to studying their biology in vitro. We therefore explored the feasibility of generating primary cultures of L-MVEC from cadaveric human tissue. We commenced our study by evaluating growth conditions (MesenCult-XF system) that have been previously found to be associated with expression of the endothelial cell surface marker thrombomodulin/CD141, in crude cultures established from collagenase-digests of limbal stroma. The potential presence of L-MVEC in these cultures was examined by flow cytometry using a more specific marker for vascular endothelial cells, CD31/PECAM-1. These studies demonstrated that the presence of CD141 in crude cultures established using the MesenCult-XF system is unrelated to L-MVEC. Thus we subsequently explored the use of magnetic assisted cell sorting (MACS) for CD31 as a tool for generating cultures of L-MVEC, in conjunction with more traditional endothelial cell growth conditions. These conditions consisted of gelatin-coated tissue culture plastic and MCDB-131 medium supplemented with fetal bovine serum (10% v/v), D-glucose (10 mg/mL), epidermal growth factor (10 ng/mL), heparin (50 μg/mL), hydrocortisone (1 μg/mL) and basic fibroblast growth factor (10 ng/mL). Our studies revealed that use of endothelial growth conditions are insufficient to generate significant numbers of L-MVEC in primary cultures established from cadaveric corneal stroma. Nevertheless, through use of positive-MACS selection for CD31 we were able to routinely observe L-MVEC in cultures derived from collagenase-digests of limbal stroma. The presence of L-MVEC in these cultures was confirmed by immunostaining for von Willebrand factor (vWF) and by ingestion of acetylated low-density lipoprotein. Moreover, the vWF+ cells formed aligned cell-to-cell ‘trains’ when grown on Geltrex™. The purity of L-MVEC cultures was found to be unrelated to tissue donor age (32 to 80 years) or duration in eye bank corneal preservation medium prior to use (3 to 10 days in Optisol) (using multiple regression test). Optimal purity of L-MVEC cultures was achieved through use of two rounds of positive-MACS selection for CD31 (mean ± s.e.m, 65.0 ± 20.8%; p<0.05). We propose that human L-MVEC cultures generated through these techniques, in conjunction with other cell types, will provide a useful tool for exploring the mechanisms of blood vessel cell growth in vitro.

Tools, building blocks, and rewards : traditional media organizations learn to engage with productive audiences

This paper explores how traditional media organizations (such as magazines, music, film, books, and newspapers) develop routines for coping with an increasingly productive audience. While previous studies have reported on how such organizations have been affected by digital technologies, this study makes a contribution to this literature by being one of the first to show how organizational routines for engaging with an increasingly productive audience actually emerge and diffuse between industries. The paper explores to what extent routines employed by two traditional media organizations have been brought in from other organizational settings, specifically from so-called ‘software platform operators’. Data on routines for engaging with productive audiences have been collected from two information-rich cases in the music and the magazine industries, and from eight high-profile software platform operators. The paper concludes that the routines employed by the two traditional media organizations and by the software platform operators are based on the same set of principles: Provide the audience with (a) tools that allow them to easily generate cultural content; (b) building blocks which facilitate their creative activities; and (c) recognition and rewards based on both rationality and emotion.

A high performance liquid chromatography and electrospray ionization mass spectrometry method for the analysis of the natural medicine, Forsythia suspensa

Samples of Forsythia suspensa from raw (Laoqiao) and ripe (Qingqiao) fruit were analyzed with the use of HPLC-DAD and the EIS-MS techniques. Seventeen peaks were detected, and of these, twelve were identified. Most were related to the glucopyranoside molecular fragment. Samples collected from three geographical areas (Shanxi, Henan and Shandong Provinces), were discriminated with the use of hierarchical clustering analysis (HCA), discriminant analysis (DA), and principal component analysis (PCA) models, but only PCA was able to provide further information about the relationships between objects and loadings; eight peaks were related to the provinces of sample origin. The supervised classification models-K-nearest neighbor (KNN), least squares support vector machines (LS-SVM), and counter propagation artificial neural network (CP-ANN) methods, indicated successful classification but KNN produced 100% classification rate. Thus, the fruit were discriminated on the basis of their places of origin.

Job satisfaction of preventive medicine workers in northern Vietnam : a multi-method approach

In the health care industry, Job Satisfaction (JS) is linked with work performance, psychological well-being and employee turnover. Although research into JS among health professionals has a long history worldwide, there has been very little analysis in Vietnam. No study has addressed JS of preventive medicine workers in Vietnam, and there is no reliable and valid instrument in Vietnamese language and context for evaluation of JS in this group. This project was conducted to fill these gaps. The findings contribute evidence regarding factors that influence JS in this sector of the health industry that should be applied to personnel management policies and practices in Vietnam.

Not just what they want, but why they want it: Traditional market research to deep customer insights

Purpose This paper explores advantages and disadvantages of both traditional market research and deep customer insight methods in order to lay the platform for revealing how a relationship between these two domains could be optimised during firm-based innovation. Design/methodology/approach The paper reports on an empirical research study conducted with thirteen Australian based firms engaged in a design-led approach to innovation. Firms were facilitated through a design-led approach where the process of gathering deep customer insights was isolated and investigated further in comparison to traditional market research methods. Findings Results show that deep customer insight methods are able to provide fresh, non-obvious ways of understanding customer needs, problems and behaviours that can become the foundation of new business opportunities. Findings concluded that deep customer insights methods provide the critical layer to understand why customers do and don’t engage with businesses. Revealing why was not accessible in traditional market research methods. Research limitations/implications The theoretical outcome of this study is a complementary methods matrix, providing guidance on appropriate implementation of research methods in accordance with a project’s timeline to optimise the complementation of traditional market research methods with design-led customer engagement methods. Practical implications Deep customer insight methods provide fresh, non-obvious ways of understanding customer needs, problems and behaviours that can become the foundation of new business opportunities. It is hoped that those in a position of data collection are encouraged to experiment and use deep customer insight methods to connect with their customers on a meaningful level and translate these insights into value. Originality/value This paper provides original value to a new understanding how design techniques can be applied to compliment and strengthen existing market research strategies. This is crucial in an era where business competition hinges on a subtle and often intimate understanding of customer needs and behaviours.