Locating Mental Health in Black and White Men: A Q-methodological Study

'Race' as identified by skin colour has been traditionally associated with the notion of the Other. In western culture the black man as Other has acted as a type of repository into which white men have projected anxieties about, for example, their sexuality. In psychologized, post-colonial culture such projections have taken on a different form and in this study we utilize Q-analysis to explore how this manifests itself into a representation of the white man as a type of ideal, contained, thinking subject set in opposition to a representation of the black man as someone who is constituted from without, by his relationship to the external world. We conclude by considering the evaluative and practical implications of this duality for our understanding of the mental health of black and white men.     

Study to evaluate the effectiveness of stress management workshops on response to general and occupational measures of stress

This study was designed to evaluate the effectiveness of stress management training workshops within Zeneca Pharmaceuticals. The study was of cross-sectional design, comparing groups of workshop attendees and non-attendees. In addition, self-rated well-being scores of attendees were compared with results obtained pre-workshop and 2-3 months after the workshop. Employees participating in the study were drawn from the Manufacturing, Research and Development, Sales and Marketing sites of Zeneca Pharmaceuticals located in Cheshire, United Kingdom. Three hundred and ninety persons who had participated in stress management workshops since 1988 were matched for age, gender and department with an equal number of employees who had not attended stress management workshops. Outcome measures included self-rated well-being (as measured by the 30-question General Health Questionnaire), knowledge of company guidance on the management of stress in staff, and an assessment of coping strategies. Subjects who had not attended a stress management workshop were much more likely to have a poor understanding of the principles of management of stress in staff [odds ratio (OR) = 8.3; 95% confidence interval (CI) = 3.3-21.3] and more likely to have poor coping skills (OR = 2.8; CI = 1.3-6.1). However, mean scores for the two measures were similar in attendees and non-attendees. Self-rating of current well-being was strongly associated with the life-events score, but not related to workshop attendance. The study indicates that stress management training workshops reduce the prevalence of employees with a poor understanding of the principles of the management of stress in staff and with poor coping strategies. An improvement in the self-rated well-being observed shortly after the workshop was not sustained.     

Antitumour prodrug development using cytochrome P450 (CYP) mediated activation

An ideal cancer chemotherapeutic prodrug is completely inactive until metabolized by a tumour-specific enzyme, or by an enzyme that is only metabolically competent towards the prodrug under physiological conditions unique to the tumour. Human cancers, including colon, breast, lung, liver, kidney and prostate, are known to express cytochrome P450 (CYP) isoforms including 3A and 1A subfamily members. This raises the possibility that tumour CYP isoforms could be a focus for tumour-specific prodrug activation. Several approaches are reviewed, including identification of prodrugs activated by tumour-specific polymorphic CYPs, use of CYP-gene directed enzyme prodrug therapy and CYPs acting as reductases in hypoxic tumour regions. The last approach is best exemplified by AQ4N, a chemotherapeutic prodrug that is bioreductively activated by CYP3A. This study shows that freshly isolated murine T50/80 mammary carcinoma and RIF-1 fibrosarcoma 4-electron reduces AQ4N to its cytotoxic metabolite, AQ4 (T50/80 Km = 26.7 microM, Vmax = 0.43 microM/mg protein/min; RIF-1 Km = 33.5 microM, Vmax = 0.42 microM/mg protein/min) via AQM, a mono-N-oxide intermediate (T50/80 Km = 37.5 microM; Vmax = 1.4 microM/mg protein/min; RIF-1 Km = 37.5 microM; Vmax = 1.2 microM/mg protein/ min). The prodrug conversion was dependent on NADPH and inhibited by air or carbon monoxide. Cyp3A mRNA and protein were both present in T50/80 carcinoma grown in vivo (RIF-1 not measured). Exposure of isolated tumour cells to anoxia (2 h) immediately after tumour excision increased cyp3A protein 2-3-fold over a 12 h period, after which time the cyp protein levels returned to the level found under aerobic conditions. Conversely, cyp3A mRNA expression showed an initial 3-fold decrease under both oxic and anoxic conditions; this returned to near basal levels after 8-24 h. These results suggest that cyp3A protein is stabilized in the absence of air, despite a decrease in cyp3A mRNA. Such a 'stabilization factor' may decrease cyp3A protein turnover without affecting the translation efficiency of cyp3A mRNA. Confirmation of the CYP activation of AQ4N bioreduction was shown with human lymphoblastoid cell microsomes transfected with CYP3A4, but not those transfected with CYP2B6 or cytochrome P450 reductase. AQ4N is also reduced to AQ4 in NADPH-fortified human renal cell carcinoma (Km = 4 microM, Vmax = 3.5 pmol/mg protein/min) and normal kidney (Km = 4 microM, Vmax = 4.0 pmol/mg protein/min), both previously shown to express CYP3A. Germane to the clinical potential of AQ4N is that although both normal and tumour cells are capable of reducing AQ4N to its cytotoxic species, the process requires low oxygen conditions. Hence, AQ4N metabolism should be restricted to hypoxic tumour cells. The isoform selectivity of AQ4N reduction, in addition to its air sensitivity, indicates that AQ4N haem coordination and subsequent oxygen atom transfer from the active-site-bound AQ4N is the likely mechanism of N-oxide reduction. The apparent increase in CYP3A expression under hypoxia makes this a particularly interesting application of CYPs for tumour-specific prodrug activation.     

Molecular identification of three co-occurring and easily misidentified octopus species using PCR–RFLP techniques

Octopus vulgaris, Octopus cyanea and Callistoctopus ornatus may co-occur in near-shore shallow reef habitats across the Southwestern Indian Ocean. All three species are harvested, both by small vessels and individual spearfishers and are of considerable socio-economic importance. Phenotypic-based discrimination of the three species is unreliable and at present species-specific catch data are not collected, preventing evaluation of species specific fisheries effects. In light of increasing exploitation rates the development of an unambiguous means of species discrimination is required for sustainable management and conservation of species and intraspecific stocks. In this study, a simple, cost effective, molecular technique to differentiate the three species is described.     

The influence of vestibular stimulation on metabolism and body composition

Obesity, diabetes and metabolic disease represent an ongoing and rapidly worsening public health issue in both the developed, and much of the developing world. Although there are many factors that influence fat storage, it has been clearly demonstrated that the homeostatic cornerstone of metabolism lies within the hypothalamus. Moreover, neuronal damage to vital areas of the hypothalamus can drive reregulation or dysregulation of endocrine function, energy expenditure and appetite, thereby promoting a shift in overall metabolic function towards a state of obesity. Therefore, identification of treatments that influence the hypothalamus to improve obesity and associated metabolic diseases has long been a medical goal. Interestingly, evidence from animal studies suggests that activating the vestibular system, specifically the macular gravity receptor, influences the hypothalamus in a way that decreases body fat storage and causes a metabolic shift towards a leaner state. Given that the macular element of the vestibular system has been shown to activate with transdermal electrical stimulation applied to the mastoids, this may be a potential therapeutic approach for obesity, diabetes or related metabolic diseases, whereby repetitive stimulation of the vestibular system influences hypothalamic control of metabolic homeostasis, thereby encouraging decreased fat storage. Here, we present an up-to-date review of the current literature surrounding the vestibular influence of the hypothalamus and associated homeostatic sites in the context of current and novel therapeutic approaches for improved clinical management of obesity and diabetes.     

Paraoxonase polymorphisms PON1 192 and 55 and longevity in Italian centenarians and Irish nonagenarians. A pooled analysis

BACKGROUND: PON1, an arylesterase, associated with high density lipoprotein (HDL), protects low density lipoprotein (LDL) against oxidative modification. Common polymorphisms PON1 55 (L/M) and 192 (Q/R) in the PON1 gene associate with atherosclerosis and heart disease. Because long-lived people seem protected from premature vascular death, we conducted a pooled statistical analysis to assess any association between these polymorphisms and longevity in a large combined group of Italian centenarians and octo/nonagenarians from Northern Ireland (NI). MATERIALS AND METHODS: Separated DNA was available from 1479 subjects from Italy and Northern Ireland (NI). In Italy 308 centenarians (males 67, females 241, mean age 100.8, SD2.1 years) and 579 young controls (males 347, females 232, mean age 40.7, SD 12.7 years) were included in the study. In NI, 296 octo/nonagenarians (males 92, females 204, mean age 89.8, SD 5.7 years) and 296 young sex-matched subjects (mean age 13.0, SD 1.4 years) had available DNA. PON1 55 (L/M) and 192 (Q/R) polymorphisms were studied using a PCR-RFLP approach. RESULTS: There was a significant difference in PON1 192 genotypes in Italian centenarians compared to younger controls (X(2)= 6.8, df = 2 p= 0.03) and a similar but non significant trend between octo/nonagenarian and young subjects in NI (X(2) = 4.0, df=2, p=0.14). Using logistic regression analysis on the combined Italian and Irish datasets, there was a small survival advantage for centenarian and octo/nonagenarian subjects who were heterozygous for PON1 192 R allele, (OR 1.3, CI 1-1.6; p=0.04 with a stepwise increase for RR homozygous subjects (OR 1.7, CI 1.1-2.6; p = 0.02) compared to QQ subjects. Comparing R and Q alleles there was a survival advantage for octo/nonagenarian/centenarian subjects who carried the R allele (OR 1.3, CI 1.1-1.5; p = 0.007) but there was no sex-specific effect p =0.77) LL, LM and MM genotypes of PON 55 polymorphisms showed similar frequencies in Italy (39.9, 47.0, 13.1%) and Ireland (39.5, 48.6, 11.9%) with no age or sex-related differences. The PON1 192R/Q and PON55L/M loci were in strong linkage disequilibrium with a Lewontin's D' coefficient -0.928 (elderly) and -0.965 (young). There was a significant difference in haplotype frequency of these linked loci in older compared to younger subjects (Likelihood Ratio X(2) = 9.60, df = 3, p= 0.02). CONCLUSION: These data suggest a modest association between the 192R allele and longevity in two very elderly populations in two European countries. Being homozygous for 192 RR further enhances survival advantage but this effect was not found to be sex specific. This finding is of interest because the 192R allele has previously been associated with increased risk of coronary heart disease. On the other hand, the 192R allele shows higher enzymatic activity, using paraoxon as substrate, and we postulate that its role in the metabolism of potentially toxic chemicals or other metabolic pathways may be important in survival to very old age.     

Importance of monoamine oxidase A in the bioactivation of neurotoxic analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a potent dopaminergic neurotoxin that causes biochemical, pharmacological, and pathological deficits in experimental animals similar to those seen in human parkinsonian patients. All of the deficits can be prevented by treating mice with selective inhibitors of monoamine oxidase B (MAO-B), including deprenyl, prior to MPTP administration. We now report that the dopaminergic neurotoxicity of two potent MPTP analogs, namely the 2'-methyl and 2'-ethyl derivatives (2'-MeMPTP and 2'-EtMPTP), cannot be prevented by deprenyl pretreatment. However, the neurotoxicity of these two analogs can be prevented by pretreatment with a combination of deprenyl and the selective MAO-A inhibitor clorgyline at doses that are sufficient to almost completely inhibit both MAO-B and MAO-A activities. Moreover, the neurotoxicity of 2'-EtMPTP (but not of 2'-MeMPTP and MPTP) can be significantly attenuated by clorgyline alone. There was a parallel between the capacity of the MAO inhibitors to decrease the brain content of the pyridinium species after administration of the tetrahydropyridines and the capacity of the MAO inhibitors to protect against the neurotoxic action of the tetrahydropyridines. The data support the conclusion that both 2'-MeMPTP and 2'-EtMPTP are bioactivated to pyridinium species to a significant extent by MAO-A. Further, it appears that the formation of the pyridinium species plays an important role in the neurotoxic process.     

Spatially independent activity patterns in functional MRI data during the Stroop color-naming task

A method is given for determining the time course and spatial extent of consistently and transiently task-related activations from other physiological and artifactual components that contribute to functional MRI (fMRI) recordings. Independent component analysis (ICA) was used to analyze two fMRI data sets from a subject performing 6-min trials composed of alternating 40-sec Stroop color-naming and control task blocks. Each component consisted of a fixed three-dimensional spatial distribution of brain voxel values (a “map”) and an associated time course of activation. For each trial, the algorithm detected, without a priori knowledge of their spatial or temporal structure, one consistently task-related component activated during each Stroop task block, plus several transiently task-related components activated at the onset of one or two of the Stroop task blocks only. Activation patterns occurring during only part of the fMRI trial are not observed with other techniques, because their time courses cannot easily be known in advance. Other ICA components were related to physiological pulsations, head movements, or machine noise. By using higher-order statistics to specify stricter criteria for spatial independence between component maps, ICA produced improved estimates of the temporal and spatial extent of task-related activation in our data compared with principal component analysis (PCA). ICA appears to be a promising tool for exploratory analysis of fMRI data, particularly when the time courses of activation are not known in advance.     

An integrative review exploring the physical and psychological harm inherent in using restraint in mental health inpatient settings

In Western society, policy and legislation seeks to minimize restrictive interventions, including physical restraint; yet research suggests the use of such practices continues to raise concerns. Whilst international agreement has sought to define physical restraint, diversity in the way in which countries use restraint remains disparate. Research to date has reported on statistics regarding restraint, how and why it is used, and staff and service user perspectives about its use. However, there is limited evidence directly exploring the physical and psychological harm restraint may cause to people being cared for within mental health inpatient settings. This study reports on an integrative review of the literature exploring available evidence regarding the physical and psychological impact of restraint. The review included both experimental and nonexperimental research papers, using Cooper's (1998) five‐stage approach to synthesize the findings. Eight themes emerged: Trauma/retraumatization; Distress; Fear; Feeling ignored; Control; Power; Calm; and Dehumanizing conditions. In conclusion, whilst further research is required regarding the physical and psychological implications of physical restraint in mental health settings, mental health nurses are in a prime position to use their skills and knowledge to address the issues identified to eradicate the use of restraint and better meet the needs of those experiencing mental illness.