Student belief about the value of challenge.

BACKGROUND: The undergraduate curriculum tends to focus on how individuals can cope with stress especially when transitioning from the classroom to the clinical workplace environment. Often this carries the message that stress is bad, yet little attention has been paid to the influence of one's belief regarding the value of stress for learning. Because stress is often perceived as bad, we chose to use the term 'challenge' in exploring the associations amongst belief of the value of challenge, the challenge experienced, the perceived learning, affect and staff support. METHODS: At the end of each clinical module within a medical curriculum, medical students rated the perceived learning, degree of challenge, affect, support and the value of challenge for learning. The value and associations amongst these variables were analysed. RESULTS: The challenge for students varied according to the type of module. Students generally considered that challenge promoted rather than hindered learning. The level of challenge experienced may influence the perception of the value of challenge for learning. However, when challenge was regarded as beneficial, this was strongly, positively associated with perceived learning, positive affect and support. DISCUSSION: Students who believe challenge is positive also perceive that such challenges promote learning. Likewise students who regard challenge as negative are less likely to learn from such challenges. The positive relationship between the belief of the value of challenge with affect and support may have positive implications for well-being. It is contended that curriculum planners should acknowledge the potential positive influence of stressors in clinical education and that challenge can be seen as valuable when there is student support and measures associated with maintaining a positive affect.

The sensitivity of fast muscle contractile function to the major components of the sarcomere Ca(2+)-cycling system.

A reaction-diffusion model of a muscle sarcomere was developed to evaluate the sensitivity of force characteristics to diffusion and Ca(2+)-cycling components. The model compared well to experimental force measurements. Diffusion led to Ca(2+) gradients that enhanced maximal force and accelerated relaxation compared to when diffusion was infinitely fast. However, a modest increase in sarcomere length or radius led to a decrease in maximal force. Lowering the Ca(2+) release rate caused a lower maximal force, but increasing the rate led to only modest gains in maximal force while incurring much greater ATP costs associated with reuptake. Greater parvalbumin binding rates decreased maximal force but enhanced relaxation, and this effect was magnified when Ca(2+) uptake rates were lowered as may occur during fatigue. These results show a physiological set of parameters that lead to a functional sarcomere of known dimensions and contractile function, and the effects of parameter variation on muscle function.

Identification of an oculomotor biomarker of preclinical Huntington disease.

The authors examined oculomotor function to identify a biomarker of disease progression in genetically confirmed preclinical and early clinical Huntington disease (HD). Initiation deficits of voluntary-guided, but not reflexive, saccades were characteristic of preclinical HD. Saccadic slowing and delayed reflexive saccades were demonstrated in clinical but not preclinical HD. Saccadic measures provide biomarkers of disease progression in both preclinical and early clinical stages of HD.

Apolipoprotein epsilon3 allele is associated with persistent hepatitis C virus infection.

BACKGROUND: Host genetic factors may significantly influence the ability to clear hepatitis C virus (HCV) following infection. HCV is associated with very low density lipoproteins (VLDL) and low density lipoproteins (LDL) in the host's circulation. Apolipoprotein E (APOE) is found in VLDL and binds to potential receptors involved in HCV entry into cells, the LDL receptor, and the scavenger receptor protein SR-B1. The APOE gene is polymorphic with three alleles coding for three isoforms: Apo-epsilon2, Apo-epsilon3, and Apo-epsilon4. The aim of this study was to assess if these functional polymorphisms determine disease outcome in HCV infected individuals. METHODS: The APOE genotype was determined in 420 Northern European patients with evidence of exposure to HCV. Genotype and allele distribution were compared with those of 288 healthy controls and progression of liver disease and viral clearance were analysed according to APOE allele status. RESULTS: The APOE*E2 and APOE*E4 alleles were both associated with a reduced likelihood of chronic infection (odds ratio (OR) 0.39 (95% confidence interval (CI) 0.211-0.728), p = 0.003; and OR 0.6 (95% CI 0.38-0.96), p = 0.032) and there was a notable absence of the E2E2 genotype in the HCV antibody positive group compared with the control population (p = 0.0067). Overall the genotypes carrying the E2 allele (E2,E3 and E2,E4) were associated with the equivalent of a 3-5-fold reduction in the risk of chronic HCV infection (genotype relative risk 0.36 and 0.20, respectively). CONCLUSION: This study indicates that functional APOE gene polymorphisms may be a determinant of outcome in HCV infection. We hypothesise that the E2 allele may protect against viral persistence via defective binding of HCV lipoviral particles to the cellular receptors involved in entry of these infectious particles.

Resistance and susceptibility to weight gain: individual variability in response to a high-fat diet.

An obesigenic environment is a potent force for promoting weight gain. However, not all people exposed to such an environment become obese; some remain lean. This means that some people are susceptible to weight gain (in a weight-promoting environment) and others are resistant. Identifying the characteristics of appetite control and food motivation in these two groups could throw light on the causes of weight gain and how this can be either treated or prevented. We have investigated the issue experimentally by identifying people who habitually consume a high-fat diet (greater than 43% fat energy). These individuals have been termed high-fat phenotypes. We have compared individuals, of the same age (mean=37 years old) and gender (male), who have gained weight (BMI=34) or who have remained lean (BMI=22). The susceptible individuals are characterised by a cluster of characteristics including a weak satiety response to fatty meals, a maintained preference for high-fat over low-energy foods in the post-ingestive satiety period, a strong hedonic attraction to palatable foods and to eating, and high scores on the TFEQ factors of Disinhibition and Hunger. The analysis of large databases suggests that this profile of factors contributes to an average daily positive energy balance from food of approximately 0.5 MJ. This profile of characteristics helps to define the symptomatology of a thrifty phenotype.

Coercion in mental healthcare: the principle of least coercive care.

Coercive practices are relatively common in mental healthcare, but coercion is ethically problematic because it involves acting against an individual's autonomy. However, coercion is often poorly defined in mental health literature, resulting in problems in considering coercion from an ethical perspective. This paper challenges the traditional paternalistic justification for coercive practices in mental healthcare, and argues that the failure to make a conceptual distinction between what counts as coercive practice and what justifies coercive practice results in instances of unjustified use of coercion. It also results in the failure to recognize other justifications for coercive practice. We propose a broad definition of coercion that recognizes the prevalence of coercion in mental healthcare. In particular, we wish to recognize the potential for persuasion and manipulation of clients' wishes to be coercive. We argue that there should be a prima facie ban on coercion in mental healthcare, and that the use of coercive practices needs to be justified in the specific circumstances of each case. The presupposition that mental illness involves limited autonomy cannot be taken to justify use of coercion. We outline a principle of least coercive intervention that we think has the potential to lessen the prevalence and extent of coercion in mental healthcare.

Erythromelalgia: an endothelial disorder responsive to sodium nitroprusside.

Erythromelalgia is an unusual syndrome of painful vasodilatation. Aetiopathology is probably different in children and adults. Presentation can be severe and associated with hypertension. Dramatic benefit from infused nitroprusside suggests the disorder could represent a dysfunctional endothelium.

Clinical experience with 202 adults receiving extracorporeal membrane oxygenation for cardiac failure: survival at five years.

OBJECTIVES: We sought to determine 5-year survival after extracorporeal membrane oxygenation for cardiac failure and its predictors, to assess survival and its predictors after bridging to transplantation or weaning from extracorporeal membrane oxygenation, and to identify factors influencing the likelihood of these outcomes. METHODS: Two hundred two adults (mean age, 55 +/- 14 years) were supported with extracorporeal membrane oxygenation between 1992 and July 1999 after cardiac failure. Follow-up extended to 7.5 years (mean, 3.8 +/- 2 years). Multivariable hazard function analysis identified predictors of survival, and logistic regression identified the determinants of bridging or weaning. RESULTS: Survival at 3 days, 30 days, and 5 years was 76%, 38%, and 24%, respectively. Patients surviving 30 days had a 63% 5-year survival. Risk factors (P <.1) included older age, reoperation, and thoracic aorta repair. Forty-eight patients were bridged to transplantation, and 71 were weaned with intent for survival. Survival was similar after either outcome (44% vs 40% 5-year survival, respectively). Failure to bridge or wean included (P <.03) renal and hepatic failure on extracorporeal membrane oxygenator support, occurrence of a neurologic event, and absence of infection. The dominant modes of death were cardiac failure and multisystem organ failure. CONCLUSIONS: Extracorporeal membrane oxygenation is versatile and salvages some patients who would otherwise die. Improvement in intermediate-term outcome will require a multidisciplinary approach to protect organ function and limit organ injury before and during this support.

Time resolution of binding and membrane insertion of a mitochondrial signal peptide: correlation with structural changes and evidence for cooperativity.

Utilizing a recently developed novel fluorescence technique [Wall et al. (1995) Mol. Membr. Biol. 12, 183-192], it is shown that the interactions of p25, the leader peptide of subunit IV of cytochrome c oxidase, with phospholipid membranes can be identified in real time. p25 is observed to bind following stopped-flow mixing of the peptide with phospholipid membranes with rate constants up to about 700 s-1 and then insert into the membrane with rate constants on the order of 0.4 s-1. Comparison of these processes with similarly time-resolved experiments performed with a stopped-flow CD spectrometer revealed that p25 does not become alpha-helical upon binding to the membrane. Following membrane insertion, however, p25 was observed to adopt an alpha-helical configuration. The temperature dependency of these processes was then found to yield activation energies for the respective components of the p25-membrane interaction.

Social variation in attitudes to obesity in children.

OBJECTIVE: To evaluate variations in children's attitudes to obesity in relation to age, gender and social class. DESIGN: Evaluation of sex, age and social class differences in judgements of figure drawings varying in body shape. SUBJECTS: 180 children aged from 4-11 from six schools, varying in the social background of their pupils. MEASUREMENTS: Self ratings of body shape, choices of ideal body shape now and in adulthood from a range of line drawings of figures varying in fatness, and behavioural and personality stereotype judgements of illustrations of thin, average and fat children. RESULTS: Few children in this age group were fat and few felt too fat; though a substantial minority felt too thin. Girls selected thinner ideal figures than boys. Children demonstrated strongly negative attitudes to obesity, which were less favourable among those who were older and from the higher social status schools. CONCLUSION: There are significant social variations in attitudes to obesity which might be important in understanding variations in the prevalence of obesity and weight control practices.

The use of fluoresceinphosphatidylethanolamine (FPE) as a real-time probe for peptide-membrane interactions.

The characterization of fluoresceinphosphatidylethanolamine (FPE) as a real-time indicator of the electrostatic nature of a membrane surface is described. The conditions appropriate for the labelling of membranes and the implementation of FPE as a tool to monitor the interactions of various peptides with model membranes are outlined. It is shown that of the membrane-active peptides studied, Naja naja kaouthia cardiotoxin and pyrularia thionin bind to certain model membranes without insertion. Whereas the leader sequence of the nuclear encoded subunit IV of mammalian cytochrome c oxidase (E.C. 1.9.3.1), known as p-25, and melittin appear to bind and then partially insert into the membrane. It seems evident also that melittin does not adopt a fully transmembrane configuration. Melittin is known to promote membrane lysis and by employing a rapid-kinetic technique it is shown that the time-course of such lysis does not appear to correlate with peptide binding, but following binding a significant proportion of melittin must become inserted into the membrane before lysis appears to commence.