Perceived relevance mediates the relationship between professional identity and attitudes towards interprofessional education in first-year university students.

The strength of health science students' identification with their chosen profession is associated with their attitudes towards interprofessional education (IPE). However, little is known about the factors that might mediate this relationship. In this article, we examine the relationships between professional identification, communication and teamwork skills, perceived relevance of IPE, and positive and negative attitudes towards IPE. A sample of 444 first-year university students from 25 health science professions enrolled in a first-year interprofessional program participated in this research by completing a questionnaire. Data were analysed using path analysis. Positive IPE attitudes were more strongly endorsed than negative IPE attitudes. Perceived relevance of IPE to future careers was the strongest predictor of both positive and negative attitudes to IPE, and fully mediated the effect of professional identity. Self-reported communication and teamwork skills were a significant negative predictor of negative attitudes to IPE only, and the effect was not mediated by perceived relevance. These findings indicate that IPE may be particularly challenging for students who do not have confidence in their abilities to communicate and work effectively in teams. Building these skills through alternative communication technologies may decrease negative attitudes. In order to maintain or increase positive attitudes towards IPE in introductory programs that span professions, the curriculum needs to be designed to demonstrate relevance to the future careers of participating students.

Quantitative magnetic resonance imaging in a naturally occurring canine model of spinal cord injury.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To analyze magnetic resonance imaging (MRI) evaluator agreement in dogs with spinal cord injury (SCI) caused by intervertebral disk herniation (IVDH) using semiautomated and manual lesion segmentation and to analyze the associations between MRI and functional outcome. SETTING: United States of America. METHODS: T2-weighted MRIs from dogs with SCI resulting from thoracolumbar IVDH were identified from a database. Evaluators categorized MRIs on the basis of the presence or absence of a T2-hyperintense spinal cord lesion in axial and sagittal images. A semiautomated segmentation algorithm was developed and used to estimate the lesion volume. Agreement between evaluators and between semiautomated and manual segmentation was analyzed. The relationships of qualitative and quantitative MRIs with behavioral functional outcome were analyzed. RESULTS: Axial images more commonly depicted lesions compared with sagittal images. Lesions in axial images had more consistent associations with functional outcome compared with sagittal images. There was imperfect qualitative agreement, and lesion volume estimation was imprecise. However, there was improved precision using semiautomated segmentation compared with manual segmentation. CONCLUSION: Lesion volume estimation in dogs with naturally occurring SCI caused by IVDH is challenging, and axial images have important advantages compared with sagittal images. The semiautomated segmentation algorithm described herein shows promise but may require further refinement.

Discontinuation of clozapine: a 15-year naturalistic retrospective study of 320 patients.

OBJECTIVE: Clozapine is underutilized in the management of treatment-resistant schizophrenia. To understand contributing factors, we analyzed the frequency and causes of clozapine discontinuations that occurred over a 15-year period in a clinical setting. METHOD: Data were extracted from computerized records and from mandatory termination reports for discontinuation events 1993-2007. The reasons for termination were analyzed. RESULTS: Over half of the patients (n = 183/320; 57%) had at least one discontinuation (median time 609 days). The two most common causes for discontinuation were non-adherence (35%) and side-effects (28%). Hematological side-effects accounted for 45% of all side-effect associated discontinuations; most such patients remained eligible for clozapine treatment, and a significant fraction remained on clozapine after rechallenge. Central nervous system side-effects accounted for 35% of side-effect induced discontinuations. General factors significantly associated with discontinuation were African American race, older age at initiation of clozapine and less improvement in psychiatric symptoms. CONCLUSION: In addition to anticipating and addressing causes of non-adherence, psychiatrists should consider clozapine rechallenge in eligible patients and implement measures to mitigate clozapine-associated sedation, seizures, and other side-effects. Future studies should particularly address why African American and older patients may be more likely to discontinue clozapine.

Reliability and validity of the parent efficacy for child healthy weight behaviour (PECHWB) scale.

BACKGROUND: Interventions for childhood overweight and obesity that target parents as the agents of change by increasing parent self-efficacy for facilitating their child's healthy weight behaviours require a reliable and valid tool to measure parent self-efficacy before and after interventions. Nelson and Davis developed the Parent Efficacy for Child Healthy Weight Behaviour (PECHWB) scale with good preliminary evidence of reliability and validity. The aim of this research was to provide further psychometric evidence from an independent Australian sample. METHODS: Data were provided by a convenience sample of 261 primary caregivers of children aged 4-17 years via an online survey. PECHWB scores were correlated with scores on other self-report measures of parenting efficacy and 2- to 4-week test-retest reliability of the PECHWB was assessed. RESULTS: The results of the study confirmed the four-factor structure of the PECHWB (Fat and Sugar, Sedentary Behaviours, Physical Activity, and Fruit and Vegetables) and provided strong evidence of internal consistency and test-retest reliability, as well as good evidence of convergent validity. CONCLUSION: Future research should investigate the properties of the PECHWB in a sample of parents of overweight or obese children, including measures of child weight and actual child healthy weight behaviours to provide evidence of the concurrent and predictive validity of PECHWB scores.

Interplay of concurrent positive and negative interpersonal events in the prediction of daily negative affect and fatigue for rheumatoid arthritis patients.

OBJECTIVE: The purpose of this study was to examine the interaction of daily concurrent positive interpersonal events (PIE) and negative interpersonal events (NIE) on the daily experience of negative affect and fatigue in a sample of men and women with rheumatoid arthritis. Two hypotheses were made. The blunting hypothesis predicted that NIE would nullify the beneficial influence of PIE on outcome measures, and the buffering hypothesis predicted that PIE would offset the adverse influence of NIE. DESIGN: Participants completed up to 30 consecutive daily diaries. Multilevel modeling was used to examine the day-to-day dependencies among study variables. MAIN OUTCOME MEASURES: The primary outcomes were daily negative affect and fatigue. RESULTS: In support of the blunting hypothesis, on days when NIE were diminished, PIE were associated with a greater reduction in fatigue. In contrast, consistent with the buffering hypothesis, on days when PIE were elevated, NIE were associated with a lesser increase in negative affect. CONCLUSION: The examination of concurrent PIE and NIE provides a unique perspective on the role of interpersonal events in affective and physiological outcomes, beyond that which can be gained from the examination of either type of event in isolation.

Thioredoxin-interacting protein (txnip) is a glucocorticoid-regulated primary response gene involved in mediating glucocorticoid-induced apoptosis.

Glucocorticoid hormones induce apoptosis in lymphoid cells. This process is transcriptionally regulated and requires de novo RNA/protein synthesis. However, the full spectrum of glucocorticoid-regulated genes mediating this cell death process is unknown. Through gene expression profiling we discovered that the expression of thioredoxin-intereacting protein (txnip) mRNA is significantly induced by the glucocorticoid hormone dexamethasone not only in the murine T-cell lymphoma line WEHI7.2, but also in normal mouse thymocytes. This result was confirmed by Northern blot analysis in multiple models of dexamethasone-induced apoptosis. The induction of txnip mRNA by dexamethasone appears to be mediated through the glucocorticoid receptor as it is blocked in the presence of RU486, a glucocorticoid receptor antagonist. Deletion and mutation analysis of the txnip promoter identified a functional glucocorticoid response element in the txnip promoter. Reporter assays demonstrated that this glucocorticoid response element was necessary and sufficient for induction of txnip by dexamethasone. Expression of a GFP-TXNIP fusion protein was sufficient to induce apoptosis in WEHI7.2 cells, and repression of endogenous txnip by RNA interference inhibited dexamethasone-induced apoptosis in WEHI7.2 cells. Together, these findings indicate that txnip is a novel glucocorticoid-induced primary target gene involved in mediating glucocorticoid-induced apoptosis.

Vulnerability to stress among women in chronic pain from fibromyalgia and osteoarthritis.

In two investigations, we studied vulnerability to the negative effects of stress among women in chronic pain from 2 types of musculoskeletal illnesses, fibromyalgia syndrome (FMS) and osteoarthritis (OA). In Study 1, there were 101 female participants 50 to 78 years old: 50 had FMS, 29 had OA knee pain and were scheduled for knee surgery, and 22 had OA but were not planning surgery. Cross-sectional analyses showed that the three groups were comparable on demographic variables, personality attributes, negative affect, active coping, and perceived social support. As expected, FMS and OA surgery women reported similar levels of bodily pain, and both groups scored higher than OA nonsurgery women. However, women with FMS reported poorer emotional and physical health, lower positive affect, a poorer quality social milieu, and more frequent use of avoidant coping with pain than did both groups of women with OA. Moreover, the perception and use of social support were closely tied to perceived social stress only among the FMS group. In Study 2, we experimentally manipulated negative mood and stress in 41 women 37 to 74 years old: 20 women had FMS, and 21 women had OA. Participantsfrom each group were randomly assigned to either a negative mood induction or a neutral mood (control) condition, and then all participants discussed a stressful interpersonal eventfor 30 min. Stress-related increases in pain were exacerbated by negative mood induction among women with FMS but not women with OA, and pain during stress was associated with decreases in positive affect in women with FMS but not women with OA. These findings suggest that among women with chronic pain, those with FMS may be particularly vulnerable to the negative effects of social stress. They have fewer positive affective resources, use less effective pain-coping strategies, and have more constrained social networks than their counterparts with OA, particularly those who experience similar levels ofpain. They also seem to experience more prolonged stress-related increases in pain under certain circumstances, all of which may contribute to a lowering of positive affect and increased stress reactivity over time.

DNA polymerases as engines for biotechnology.

This review examines the DNA polymerases, a class of enzymes that has been an essential tool for molecular biology research. Several families of DNA polymerases have been defined based on amino acid sequence comparisons, and new enzymes are continually being discovered, driving the expansion of the current classifications. Structural similarities among the enzymes are examined, as well as the functions of the various subunits and enzyme domains. The natural variety of polymerase activities has been harnessed for applications such as amplification, labeling, and detection of DNA sequences. In addition, enhancements to DNA polymerases by genetic engineering will be described, such as enzymes specifically designed for DNA sequencing by improving the incorporation of dideoxynucleotide terminators. Reverse transcription, the ability to use RNA as a template for DNA synthesis, is described for the application of making cDNA. We believe that new and unanticipated applications will emerge as new polymerases and mutated polymerases are created and characterized.

Rational design and synthesis of novel 2,5-disubstituted cis- and trans-piperidine derivatives exhibiting differential activity for the dopamine transporter.

Herein, we report the rational design and synthesis of novel 2,5-disubstituted piperidine derivatives in the cis and trans isomeric forms. Out of these two isomers, the cis-isomer, 7a, was found to exhibit the most potent activity and selectivity for the dopamine transporter. These novel derivatives represent conformationally constrained version of piperidine analogue of GBR compounds.

Total synthesis of SR 121463 A, a highly potent and selective vasopressin v(2) receptor antagonist.

SR 121463 A, 1, is a promising nonpeptide prototype for potent and selective antagonism of the vasopressin V(2) receptor subtype and, thus, a candidate for control of the clinically debilitating condition of hyponatremia and its associated syndromes. In the present work, we present a novel and stereoselective synthesis that stems from the preparation of three key intermediates: the substituted benzenesulfonyl chloride 2, the N-protected oxindole 3, and protected dibromide 4. The synthesis of 1 has been achieved in good overall yield, each step proceeding in greater than 80% yield. In addition, intermediate 2 and the syn isomer of 1 were prepared with complete control of stereochemistry. The latter reduction appears to proceed by lithium cation mediated chelation control. Molecular mechanics calculations with the MM3* and MMFF force fields underscore geometric and energetic aspects of the reaction.

The identification and characterization of hydrazinyl urea-based antibacterial agents through combinatorial chemistry.

An effort to identify novel inhibitors of peptidoglycan synthesis with antibacterial activity resulted in the discovery of a series of biaryl urea-based antibacterial agents through isolation of a by-product from a mixture-based combinatorial library of semi-carbazones and subsequent parallel synthesis efforts. The compounds were shown to possess broad spectrum antibacterial activity against gram-positive drug resistant pathogens, and showed apparent specificity for disruption of the bacterial cell wall biosynthesis pathway.

The role of stressful events in the relationship between positive and negative affects: evidence from field and experimental studies.

Three studies are presented that examine the effects of stress on the relationship between positive and negative affective states. In the first study, recently bereaved and disabled older adults were compared to matched control groups without these recent stressors. Negative affect was inversely correlated with positive affect to a significantly greater extent for the highly stressed groups compared with controls. In a second study, older adults were exposed to a laboratory stressor, and their positive and negative affective reactions recorded. Immediately following a speech stressor task, the inverse correlation between positive and negative affect was significantly greater than in pre- and postassessments of affects. The third study was an attempt to replicate and extend the findings from Study 2 with a mid-aged sample of women. The speech stressor had the same effects as in Study 2. A second stressor, which induced pain through immersion of an arm into cold water, had no effects on the correlation between affective states. Alternative explanations for these effects and the implications for cognitive interventions are discussed.

Hostile attitudes predict elevated vascular resistance during interpersonal stress in men and women.

OBJECTIVE: Existing research indicates that hostility is associated with enhanced blood pressure responses during social stress, but little is known about the hemodynamic patterns underlying these blood pressure increases, particularly in women. The present study examined hemodynamic responses to a low-anger interpersonal stressor, testing the hypotheses that hostile individuals show enhanced vascular responses and that low hostile individuals show enhanced myocardial responses. METHODS: Eighty undergraduate men and women were categorized as high or low in hostility on the basis of median splits of Cook-Medley Hostility Scale scores. Participants discussed a controversial topic with a confederate who disagreed with them, and hemodynamic responses were assessed with impedance cardiography. RESULTS: High hostile individuals exhibited greater increases in diastolic blood pressure and total peripheral resistance and smaller increases in cardiac output during an interpersonal stressor than did low hostile individuals. Systolic blood pressure and heart rate increases were greater among high hostile relative to low hostile females and comparable among low and high hostile males. Affective responses and task perceptions were generally similar for high and low hostile participants, but the relationship between task perception and hemodynamic responses varied on the basis of hostility level. CONCLUSIONS: These findings suggest that hostility in both men and women is associated with heightened vascular and dampened cardiac responsivity to interpersonal stress that is not deliberately anger provoking. Moreover, they indicate that the associations between task perception and hemodynamic responses vary between high and low hostile individuals.

Oral contraceptive use and hemodynamic, lipid, and fibrinogen responses to smoking and stress in women.

The effects of acute smoking and oral contraceptive (OC) use on cardiovascular, lipid, and fibrinogen stress responses were examined in 52 female smokers and nonsmokers, half of whom were using OCs. Women smoked or sham-smoked a cigarette and then performed 2 stressful tasks. Stress elicited increases in total and low-density lipoprotein cholesterol, and in triglycerides among women who smoked, and in fibrinogen among all women. Smokers who used OCs had greater blood pressure increases to smoking and to stress than did smokers who did not use OCs. OC use was also associated with enhanced total peripheral resistance stress responses among women who smoked and cardiac output stress responses among women who sham-smoked. Results suggest that OC use moderates cardiovascular reactivity in smokers but not nonsmokers, enhancing vascular responsivity to smoking combined with stress and myocardial responsivity to stress alone.

PIP: This study examined the association between the use of oral contraceptives (OCs) and the hemodynamic stress responses of nonsmokers, abstinent and recent smokers, and the effects of acute smoking and OC use on stress-related changes in atherogenic lipid and fibrinogen levels. The study comprised 52 female smokers and nonsmokers, with half using OCs. Women were asked to perform two stressful activities after smoking or sham-smoking. An increase in total and low-density lipoprotein cholesterol and triglycerides was observed among women who smoked, and in fibrinogen among all women. Systolic Blood Pressure was higher among women who smoked and used OCs, while higher diastolic blood pressure was found among women who smoked regardless of OC use. The use of OCs resulted in an increase in the total peripheral resistance stress responses among female smokers and increased cardiac output among women who sham-smoked. Results suggest that cardiovascular reactivity is moderated by OC use in smokers but not in nonsmokers, while vascular responsivity is enhanced when combined with stress.

Association of negative and positive social ties with fibrinogen levels in young women.

The associations between positive and negative aspects of social relationships and fibrinogen, a risk factor for coronary heart disease (CHD), were examined in young, healthy women recruited from the community (n = 46) and from a college campus (n = 42). For community women, the perception that individuals in their social networks frequently undermined them was related to higher fibrinogen, independent of perceived frequency of support. For college women, fibrinogen was elevated among women with frequent undermining only when they also reported infrequent support. After controlling for other risk factors, the associations between social ties and fibrinogen remained significant in both samples. These results indicate that positive and negative social ties are associated with fibrinogen levels and suggest that social relationships may affect CHD risk in part through their influence on fibrinogen.

Body fat distribution and hemodynamic stress responses in premenopausal obese women: a preliminary study.

To examine the relationship between body fat distribution and hemodynamic stress responses, cardiovascular responses to a speech task and a forehead cold pressor task were evaluated with 24 premenopausal women classified a priori as either centrally or peripherally obese. Results showed that women with central adiposity exhibited greater stress-related increases in diastolic blood pressure and total peripheral resistance, whereas women with peripheral adiposity exhibited greater stress-related increases in cardiac output. Depression, self-consciousness, hostility, and mood scores did not explain significant variance in the stress response differences between regional adiposity groups. The findings suggest that central adiposity may increase the risk of cardiovascular disease in women at least in part by enhancing vascular responses to stress.

Is life more difficult on Mars or Venus? A meta-analytic review of sex differences in major and minor life events.

We conducted a meta-analysis of studies examining sex differences in reported levels of stress, considering the impact of: (a) the age and representativeness of sample participants, (b) whether life events were weighted or unweighted by participants for impact or severity, (c) the major versus minor nature of the stress, and (d) the life domain of the stressor. Overall, the meta-analysis of 119 studies including 83,559 participants found that females were exposed to more stress than were males (d=.123, r=.061). However, there was considerable heterogeneity among studies, with greater effect sizes associated with: (a) life events weighted by participants for impact, (b) adolescents compared to both younger and older samples, (c) major life stressors compared to minor stressors, and (d) interpersonal relationship stressors compared to work stressors. In none of the subgroup analyses did males experience considerably more stress than females. Evaluation of a subsample of 39 studies that examined gender differences in psychological symptoms revealed that females reported more symptoms of depression, anxiety, and psychosomatic problems (d=.282, r=.139) and that the sex difference in reports of psychological symptoms accounted for approximately 4% of the variance in the sex differences in reports of stress. Possible explanations for the observed patterning of effects are discussed, as are recommendations for further research.

MR teleradiology network serving remote imaging centers.

The operational experience of a commercial teleradiology practice utilizing a wide-area ISDN network linking six imaging centers located in two states will be reviewed. Open magnet designs were chosen to complement existing high-field units available in each community. Image data was first acquired than transmitted without compression at 128 Kbytes/s to a central reading site located in McLean, Virginia for interpretation by a team of radiologists. Average transmission time was 6-8 minutes. System design allows optimal utilization of radiologists expertise in imaging interpretation while reserving the on-site patient management responsibilities such as gadolinium contrast injections and sedation to a nonradiologists physician and/or nurse practitioner. Over 15,000 teleradiology readings have been rendered via this network by January 1998.