Negative Cooperativity in NAD(P)H Quinone Oxidoreductase 1 (NQO1).

NAD(P)H quinone oxidoreductase-1 (NQO1) is a homodimeric protein that acts as a detoxifying enzyme or as a chaperone protein. Dicourmarol interacts with NQO1 at the NAD(P)H binding site and can both inhibit enzyme activity and modulate the interaction of NQO1 with other proteins. We show that the binding of dicoumarol and related compounds to NQO1 generates negative cooperativity between the monomers. This does not occur in the presence of the reducing cofactor, NAD(P)H, alone. Alteration of Gly150 (but not Gly149 or Gly174) abolished the dicoumarol-induced negative cooperativity. Analysis of the dynamics of NQO1 with the Gaussian network model indicates a high degree of collective motion by monomers and domains within NQO1. Ligand binding is predicted to alter NQO1 dynamics both proximal to the ligand binding site and remotely, close to the second binding site. Thus, drug-induced modulation of protein motion might contribute to the biological effects of putative inhibitors of NQO1.

Raman spectroscopy as a predictive tool for monitoring osteoporosis therapy in a rat model of postmenopausal osteoporosis.

Pharmacological therapy of osteoporosis reduces bone loss and risk of fracture in patients. Modulation of bone mineral density cannot explain all effects. Other aspects of bone quality affecting fragility and ways to monitor them need to be better understood. Keratinous tissue acts as surrogate marker for bone protein deterioration caused by oestrogen deficiency in rats. Ovariectomised rats were treated with alendronate (ALN), parathyroid hormone (PTH) or estrogen (E2). MicroCT assessed macro structural changes. Raman spectroscopy assessed biochemical changes. Micro CT confirmed that all treatments prevented ovariectomy-induced macro structural bone loss in rats. PTH induced macro structural changes unrelated to ovariectomy. Raman analysis revealed ALN and PTH partially protect against molecular level changes to bone collagen (80% protection) and mineral (50% protection) phases. E2 failed to prevent biochemical change. The treatments induced alterations unassociated with the ovariectomy; increased beta sheet with E2, globular alpha helices with PTH and fibrous alpha helices with both ALN and PTH. ALN is closest to maintaining physiological status of the animals, while PTH (comparable protective effect) induces side effects. E2 is unable to prevent molecular level changes associated with ovariectomy. Raman spectroscopy can act as predictive tool for monitoring pharmacological therapy of osteoporosis in rodents. Keratinous tissue is a useful surrogate marker for the protein related impact of these therapies.The results demonstrate utility of surrogates where a clear systemic causation connects the surrogate to the target tissue. It demonstrates the need to assess broader biomolecular impact of interventions to examine side effects.

A Preliminary Evaluation of the Ability of Keratotic Tissue to Act as a Prognostic Indicator of Hip Fracture Risk.

Studies have shown that Raman spectroscopic analysis of fingernail clippings can help differentiate between post-menopausal women who have and who have not suffered a fracture. However, all studies to date have been retrospective in nature, comparing the proteins in nails sourced from women, post-fracture. The objective of this study was to investigate the potential of a prospective test for hip fracture based on spectroscopic analysis of nail tissue. Archived toenail samples from post-menopausal women aged 50 to 63 years in the Nurses' Health Study were obtained and analysed by Raman spectroscopy. Nails were matched case-controls sourced from 161 women; 82 who underwent a hip fracture up to 20 years after nail collection and 81 age-matched controls. A number of clinical risk factors (CRFs) from the Fracture Risk Assessment (FRAX) tool had been assessed at toenail collection. Using 80% of the spectra, models were developed for increasing time periods between nail collection and fracture. Scores were calculated from these models for the other 20% of the sample and the ability of the score to predict hip fracture was tested in model with and without the CRFs by comparing the odds ratios (ORs) per 1 SD increase in standardised predictive values. The Raman score successfully distinguished between hip fracture cases and controls. With only the score as a predictor, a statistically significant OR of 2.2 (95% confidence interval [CI]: 1.5-3.1) was found for hip fracture for up to 20 years after collection. The OR increased to 3.8 (2.6-5.4) when the CRFs were added to the model. For fractures limited to 13 years after collection, the OR was 6.3 (3.0-13.1) for the score alone. The test based on Raman spectroscopy has potential for identifying individuals who may suffer hip fractures several years in advance. Higher powered studies are required to evaluate the predictive capability of this test.

Raman spectroscopy predicts the link between claw keratin and bone collagen structure in a rodent model of oestrogen deficiency.

Osteoporosis is a common disease characterised by reduced bone mass and an increased risk of fragility fractures. Low bone mineral density is known to significantly increase the risk of osteoporotic fractures, however, the majority of non-traumatic fractures occur in individuals with a bone mineral density too high to be classified as osteoporotic. Therefore, there is an urgent need to investigate aspects of bone health, other than bone mass, that can predict the risk of fracture. Here, we successfully predicted association between bone collagen and nail keratin in relation to bone loss due to oestrogen deficiency using Raman spectroscopy. Raman signal signature successfully discriminated between ovariectomised rats and their sham controls with a high degree of accuracy for the bone (sensitivity 89%, specificity 91%) and claw tissue (sensitivity 89%, specificity 82%). When tested in an independent set of claw samples the classifier gave 92% sensitivity and 85% specificity. Comparison of the spectral changes occurring in the bone tissue with the changes occurring in the keratin showed a number of common features that could be attributed to common changes in the structure of bone collagen and claw keratin. This study established that systemic oestrogen deficiency mediates parallel structural changes in both the claw (primarily keratin) and bone proteins (primarily collagen). This strengthens the hypothesis that nail keratin can act as a surrogate marker of bone protein status where systemic processes induce changes.

Secondary school pupils' food choices around schools in a London borough: Fast food and walls of crisps.

The objective was to observe and document food behaviours of secondary school pupils from schools in a London borough. The research design combined a number of methods which included geographic information system (GIS) mapping of food outlets around three schools, systemised observations of food purchasing in those outlets before, during and after school, and focus groups conducted with pupils of those schools to gather their views in respect to those food choices. Results are summarised under the five 'A's of Access, Availability, Affordability and Acceptability & Attitudes: Access in that there were concentrations of food outlets around the schools. The majority of pupil food purchases were from newsagents, small local shops and supermarkets of chocolate, crisps (potato chips), fizzy drinks and energy drinks. Availability of fast food and unhealthy options were a feature of the streets surrounding the schools, with 200 m the optimal distance pupils were prepared to walk from and back to school at lunchtime. Affordability was ensured by the use of a consumer mentality and pupils sought out value for money offers; group purchasing of 'two for one' type offers encouraged this trend. Pupils reported healthy items on sale in school as expensive, and also that food was often sold in smaller portion sizes than that available from external food outlets. Acceptability and Attitudes, in that school food was not seen as 'cool', queuing for school food was not acceptable but queuing for food from takeaways was not viewed negatively; for younger pupils energy drinks were 'cool'. In conclusion, pupils recognised that school food was healthier but provided several reasons for not eating in school related to the five 'A's above.

The two common polymorphic forms of human NRH-quinone oxidoreductase 2 (NQO2) have different biochemical properties.

There are two common forms of NRH-quinone oxidoreductase 2 (NQO2) in the human population resulting from SNP rs1143684. One has phenylalanine at position 47 (NQO2-F47) and the other leucine (NQO2-L47). Using recombinant proteins, we show that these variants have similar steady state kinetic parameters, although NQO2-L47 has a slightly lower specificity constant. NQO2-L47 is less stable towards proteolytic digestion and thermal denaturation than NQO2-F47. Both forms are inhibited by resveratrol, but NQO2-F47 shows negative cooperativity with this inhibitor. Thus these data demonstrate, for the first time, clear biochemical differences between the variants which help explain previous biomedical and epidemiological findings.

Portuguese households' diet quality (adherence to Mediterranean food pattern and compliance with WHO population dietary goals): trends, regional disparities and socioeconomic determinants.

OBJECTIVE: To evaluate households' diet-quality trends and regional disparities, as well as to identify the influence of its socioeconomic determinants. METHODS/SUBJECTS: Two dietary indexes were applied: a revised Healthy Diet Indicator version (HDIr) and the Mediterranean Adequacy Index (MAI). The socioeconomic differences between households with low-diet quality (if their scoring in HDIr or MAI was below the national median) and the remaining ones were analysed by means of logistic regression. Representative samples of households among each region were analysed. RESULTS: Adherence to a Mediterranean diet was poor in all Portuguese regions; the proportion of households adhering to it has diminished in the North, Centre, Lisbon and Tejo valley. The proportion of households with high HDIr decreased in the North, Centre, Lisbon and Tejo valley and Algarve. In multivariate analysis, households whose head had secondary or higher education, living in semi-urban or urban areas, from the Azores region, within the higher income or outside home food expenditures groups were more likely to be in low-quality diet. CONCLUSIONS: The decreasing adherence to a Mediterranean food pattern and the diminishing compliance with World Health Organization dietary goals show that Portuguese households have reduced their diet quality. The observed influence of urbanization and region on diet quality highlights the importance of considering regional nutrition strategies.

Public health and the role of the nurse: the need for greater clarity.

There is evidence that public health is currently taking centre stage in the challenge to improve the population's health. This represents a change from the 1980s and 1990s where health promotion was the dominant concept among community nurses. Public health means different things to different people and while nurses have a role to play, there is a need to be more precise about their specific contribution. The creation of public health nursing posts across the UK is contribution to this confusion, as there is little emerging consensus as to what professionals in these posts should do. At present, there does not appear to be a dominant strategy or model of working. A preliminary analysis of job advertisements for public health nursing posts indicates a requirement for a 'supercharged' health visitor to work in a specific area to provide a link between the professional and lay communities. The emphasis is on community development with little on population health. Government policy on public health clearly highlights the important role of nurses in contributing to the public health agenda. The current role and function of public health nursing posts may not allow them to be classed as specialist public health nurses/nursing and to provide educational opportunities for nurses to develop the knowledge and skills which will enable them to work alongside medical and other healthcare colleagues in the pursuit of specialist public health practitioner status.

Patient education and health promotion: clinical health promotion--the conceptual link.

A model linking health promotion, health education and patient education is presented. Claims to health education being distinguishable from patient education on the basis of setting and working with well, as opposed to sick, individuals are disputed. Many health education encounters create the role of proto-patient for the individual receiving care. A further distinction is made between patient education and clinical health promotion on the basis of the focus of care as seen by the professional. The linking elements in the model are those of the patient role and relationships adopted, another distinction is seen in the area of the focus of the encounter. Traditional patient education focuses on the disease process whereas clinical health promotion emphasises the place of illness in the person's life and looks to influence non-medical factors that impinge on the disease.

The public health nursing role: an overview of future trends.

In this article, the authors consider the current state of public health nursing and the function it fulfils. Describing the development of the public health movement and the policies which inform current strategies, they suggest that a more appropriate role is needed for public health nursing to address the needs of the wider community rather than simply acting as a focus for the provision of general practice services.

Nursing and health education: victim blaming.

Health education may contribute to creating victims. In this article, the concept of victim blaming, and how the victim role is created, is explored using transactional analysis. Specifically, the Drama Triangle is used as a tool for analysis rather than a model for practice.

A sociological approach to health promotion for nurses in an institutional setting.

This paper sets out to examine health promotion practice in hospital settings from a sociological viewpoint. It starts by tracing the development of health promotion among hospital and community nurses. The influences that professional and institutional structures and agendas have in health promotion are explored and a model of operation is proposed. The main emphasis is that health promotion is not an activity relying solely on skills acquisition by the nurse, but one that requires recognition of where power and control are located. A model of working is proposed which takes account of the institutional and professional agendas and the need to balance these with the needs and rights of the patient.

Nursing and health promotion practice: the creation of victims and winners in a political context.

Current political changes to the British National Health Service and the development of nursing as a profession contribute to the individualization of health. Such trends view the client as a victim of his or her behaviour and encourages a form of health promotion which focuses on the individual and ignores or decontextualizes social problems. Nursing needs to examine issues of power and control in health promotion encounters and not simply view health promotion as benign encounters. Health promotion practice needs to focus not on the development of skills as the central component but on the relationship between the nurse and the client. A simple shift in nursing from using communication skills to persuade, to using counselling skills does not evade the charge of victim blaming. Health promotion needs to place health and its influences within a context.

Health promotion: time for an audit.

This article examines how health promotion models are used in practice. The conceptual base of health promotion models is reviewed with particular relevance to the interaction between professional and client, and in relation to The Health of the Nation targets. The author argues that health promotion models are being used by professionals purely to achieve targets and, as a consequence, important information on clients' socio-economic circumstances is being ignored. A framework for a 'health promotion audit' is offered.

The importance of third-party reimbursement for NPS.

Lack of third-party reimbursement is one of the major impediments to the use of nurse practitioner services. Although NPs have been successful in obtaining third-party reimbursement under some health care plans, barriers still exist, such as opposition by medical societies, procedural problems and restrictive interpretations of state licensure laws. Consumer education about available health care and legislative involvement of NPs are two ways to attain third-party reimbursement for NPs. However, NPs first must have a clear understanding of third-party reimbursement, including how it is mandated and which providers and services are covered, before they can educate the consumer and become involved with legislation.

The relationship between individual dietary constituents and antipyrine metabolism in Indo-Pakistani immigrants to Britain.

1 Antipyrine clearance has been measured from serial saliva samples in 36 healthy adult Indo-Pakistani immigrants to Britain, to assess the effect of dietary differences within this population. 2 Clearance (mean +/- s.e. mean) was significantly slower in 16 lactovegetarians (0.54 +/- 0.06 ml min -1 kg -1) than in the subjects who ate meat regularly (0.91 +/-0.07 ml min -1 kg -1). 3 The absence of meat from the diet was associated with a significantly smaller daily intake of dietary protein, which was abnormally low by Western standards. 4 It is likely that the contrast in daily protein intake between the dietary subgroups was largely responsible for the differences observed in antipyrine clearance.