Kappa opioid receptor activation increases thermogenic energy expenditure which drives increased feeding.

Opioid receptors, including the kappa opioid receptor (KOR), exert control over thermoregulation and feeding behavior. Notably, activation of KOR stimulates food intake, leading to postulation that KOR signaling plays a central role in managing energy intake. KOR has also been proposed as a target for treating obesity. Herein, we report studies examining how roles for KOR signaling in regulating thermogenesis, feeding, and energy balance may be interrelated using pharmacological interventions, genetic tools, quantitative thermal imaging, and metabolic profiling. Our findings demonstrate that activation of KOR in the central nervous system causes increased energy expenditure via brown adipose tissue activation. Importantly, pharmacologic, or genetic inhibition of brown adipose tissue thermogenesis prevented the elevated food intake triggered by KOR activation. Furthermore, our data reveal that KOR-mediated thermogenesis elevation is reversibly disrupted by chronic high-fat diet, implicating KOR signaling as a potential mediator in high-fat diet-induced weight gain.

Academic neurosurgery in the UK: present and future directions.

Academic neurosurgery encompasses basic science and clinical research efforts to better understand and treat diseases of relevance to neurosurgical practice, with the overall aim of improving treatment and outcome for patients. In this article, we provide an overview of the current and future directions of British academic neurosurgery. Training pathways are considered together with personal accounts of experiences of structured integrated clinical academic training and unstructured academic training. Life as an academic consultant is also described. Funding is explored, for the specialty as a whole and at the individual level. UK academic neurosurgical organisations are highlighted. Finally, the UK's international standing is considered.

Evaluation of testing strategies to identify infected animals at a single round of testing within dairy herds known to be infected with Mycobacterium avium ssp. paratuberculosis.

As part of a broader control strategy within herds known to be infected with Mycobacterium avium ssp. paratuberculosis (MAP), individual animal testing is generally conducted to identify infected animals for action, usually culling. Opportunities are now available to quantitatively compare different testing strategies (combinations of tests) in known infected herds. This study evaluates the effectiveness, cost, and cost-effectiveness of different testing strategies to identify infected animals at a single round of testing within dairy herds known to be MAP infected. A model was developed, taking account of both within-herd infection dynamics and test performance, to simulate the use of different tests at a single round of testing in a known infected herd. Model inputs included the number of animals at different stages of infection, the sensitivity and specificity of each test, and the costs of testing and culling. Testing strategies included either milk or serum ELISA alone or with fecal culture in series. Model outputs included effectiveness (detection fraction, the proportion of truly infected animals in the herd that are successfully detected by the testing strategy), cost, and cost-effectiveness (testing cost per true positive detected, total cost per true positive detected). Several assumptions were made: MAP was introduced with a single animal and no management interventions were implemented to limit within-herd transmission of MAP before this test. In medium herds, between 7 and 26% of infected animals are detected at a single round of testing, the former using the milk ELISA and fecal culture in series 5 yr after MAP introduction and the latter using fecal culture alone 15 yr after MAP introduction. The combined costs of testing and culling at a single round of testing increases with time since introduction of MAP infection, with culling costs being much greater than testing costs. The cost-effectiveness of testing varied by testing strategy. It was also greater at 5 yr, compared with 10 or 15 yr, since MAP introduction, highlighting the importance of early detection. Future work is needed to evaluate these testing strategies in subsequent rounds of testing as well as accounting for different herd dynamics and different levels of herd biocontainment.

A comparative assessment of culture and serology in the diagnosis of brucellosis in dairy cattle.

To investigate the usefulness of culture for the confirmation of brucellosis in cattle, a comparison of culture and serology was undertaken on 248 animals in four dairy herds where the disease was active. Paired supramammary (SM), retropharyngeal (RP), and internal iliac (IL) lymph nodes were cultured, and five serological tests were deployed: the microserum agglutination test (MSAT), complement fixation test (CFT), the indirect (iELISA) and competitive ELISA, and the fluorescence polarisation assay (FPA). Brucella abortus was isolated from 86.8% of animals on combined culture of all three lymph nodes. Individually, the highest isolation rate was from the RP (90.5% of culture positives). Of culture positive animals, 13.7% and 6.2% were positive from the RP and SM alone, respectively. Approximately half of the positive cultures yielded <10 colonies/culture plate. Although 80.9% of animals were positive in at least one serological test, only 45.2% were positive in all five. For culture-positive animals, the MSAT was the most sensitive test (71.8%). Of the culture-negative animals 67.7% were positive in at least one test, while 12.9% were positive in all five. Titres were higher in animals culture-positive from the SM, and there was a direct correlation between higher titres and higher colony counts in SM cultures. Only 8.9% of animals were both culture-negative and seropositive (in at least one test), while 16.5% were culture-positive and seronegative in all five tests. The results highlight and validate the sensitivity of bacteriological culture in confirming a diagnosis of bovine brucellosis. While the MSAT and FPA were the most sensitive serological tests, a significant percentage of infected animals were undetectable using these standard serological assays.

In-house human immunodeficiency virus-1 genotype resistance testing to determine highly active antiretroviral therapy resistance mutations in Hong Kong.

OBJECTIVE: To determine the frequency of highly active antiretroviral therapy resistance mutations in the viral pol gene of human immunodeficiency virus-1 (HIV-1) genotypes that circulate in Hong Kong, by means of an in-house HIV-1 genotyping system. DESIGN: Retrospective study. SETTING: Two HIV clinics in Hong Kong. PATIENTS: A modified in-house genotyping resistance test was used to sequence the partial pol gene in 1165 plasma samples from 965 patients. The performance of our test was cross-compared with the US Food and Drug Administration-approved ViroSeq HIV-1 genotyping system. The results of genotyping were submitted to the Stanford HIV-1 drug resistance database for analysis. RESULTS: The cost-effective in-house genotypic resistance test (US$40) demonstrated comparable performance to the US Food and Drug Administration-approved ViroSeq system. The detection limit of this in-house genotypic resistance test could reach 400 copies/mL for both HIV-1 subtype B and CRF01_AE, which were the predominant genotypes in Hong Kong. Drug resistance mutations were detected only in post-treatment samples from treatment-failure patients. However, there was no significant difference in the frequency of drug resistance mutations between subtype B and CRF01_AE. CONCLUSION: Our cost-effective in-house genotypic resistance test detected no significant difference in drug resistance-related mutations frequencies between HIV-1 subtype B and CRF01_AE in Hong Kong. A drug resistance-related mutations database for different HIV-1 genotypes should be established in Hong Kong to augment guidance for HIV treatment.

Cost-effectiveness of an early assessment service for young people with early psychosis in Hong Kong.

OBJECTIVE: The Early Assessment Service for Young People with Early Psychosis (EASY) was developed in Hong Kong in 2001 to provide a comprehensive and integrated approach for early detection and intervention for young people suffering from first episode psychosis. The present study examined the cost-effectiveness of the service over a period of 24 months compared to standard care. METHOD: This is a historical control study. Sixty-five patients who presented to the EASY service in 2001 with first episode psychosis were individually matched (on age, sex and diagnosis) with 65 patients who received standard psychiatric care in a precursor service (pre-EASY) between 1999 and 2000. A retrospective cost-effectiveness analysis was conducted over a period of 24 months. The overall average cost of service utilization per patient and the effects on hospitalization rate were compared using bootstrapping analysis. Cost per point improvement in Positive and Negative Syndrome Scale (PANSS) was also computed with sensitivity analysis. Only direct costs were analysed in the current study. RESULTS: There was no significant difference in service utilization between the EASY and pre-EASY standard care groups. The cost-effectiveness acceptability curve, which was used to explore uncertainty in estimates of cost and effects, suggested that there was a probability of at least 94% that the EASY model was more cost-effective than the pre-EASY service in reducing psychiatric inpatient admissions. EASY patients also showed superior results in average cost per unit improvement in PANSS. CONCLUSIONS: EASY is likely to be more cost-effective in improving outcomes, particularly in reducing hospitalization and improving clinical symptoms among young people with first episode psychosis. This study provides a perspective from the east Asian region, and supports further development of similar services, particularly in the local setting. However, further studies with a longer follow up period and larger sample size are required to verify these findings.

Cardiovascular risk screening before starting stimulant medications and prescribing practices of canadian physicians: impact of the Health Canada advisory.

OBJECTIVE: In May 2006, Health Canada released a statement advising against the use of stimulant medications for patients with cardiac disease after isolated reports of sudden death. The objectives of this study were to determine whether the Health Canada advisory has had an impact on cardiovascular screening of all children with attention-deficit/hyperactivity disorder before stimulants and the medical treatment of children with attention-deficit/hyperactivity disorder and real or potential cardiac problems. METHODS: Two questionnaires were developed and mailed to a sample of noncardiologist physicians and pediatric cardiologists in Canada. The difference in the proportion of noncardiologist-responders who performed a "full screen" before and after the announcement of the Health Canada advisory was analyzed. Willingness to prescribe stimulant medications to children was assessed by using a series of clinical scenarios. RESULTS: A total of 2326 questionnaires were distributed, 717 (31%) of which were returned. The proportion who performed a full screen increased for both noncardiologists and cardiologists after the advisory. There was also a dramatic increase in the use of the "modified screen" by the noncardiologist group and the pediatrician subgroup. There was a considerable decrease in the proportion of noncardiologists who were willing to prescribe stimulant medications to children with potential or actual cardiac issues after the advisory. CONCLUSIONS: The Health Canada advisory has had an impact on clinical practice. It has resulted in an increase in the use of cardiovascular assessment tools before starting stimulants and a decrease in noncardiologists' willingness to prescribe stimulants to those with real or potential cardiac disease. These changes have occurred despite the lack of studies to address the cardiac risks of these medications. Because it will be difficult to assess the true cardiac risks of stimulants, consensus recommendations are needed to determine whether screening is required, what constitutes an appropriate screen, and which children can be treated cautiously with stimulant medications.

Quantitative estimation of left atrial linear dimension on a transthoracic echocardiogram using an electrocardiographic formulaic assessment.

A proportionate and incremental association between left atrial (LA) dilatation on a transthoracic echocardiogram (TTE) and increasing severity in abnormal atrial depolarization can be described by the regression formula: LA dimension in parasternal long-axis view (in millimeters) = 2.47 + 0.29 [P-wave duration (in milliseconds)]. However, prospective testing of this formula for LA quantification with comparison to other TTE indexes is lacking. We prospectively obtained 12-lead electrocardiograms for 72 consecutive patients before individual, nonemergent TTE assessment. P waves were assessed independently to the nearest 10 ms for application of the formula with a Bland-Altman plot. P-wave durations were obtained specifically from lead II and also from any lead that yielded the widest measurement. There was a strong formulaic correlation with LA measurement by TTE (p <0.00000001; r = 0.662), irrespective of electrocardiographic lead used. However, as the measurement difference increased between that in any lead and lead II, correlation strength increased. Correlation was not significantly affected by commonly measured electrocardiographic and TTE indexes, such as, PR interval, QRS complex, and left ventricular end-diastolic as well as systolic dimensions, after adjustment for these variables. Moreover, when the P-wave axis remained within the normal range, the correlation strength increased. The Bland-Altman plot also showed good agreement of LA dimension assessment between formulaic estimation and TTE measurement. In conclusion, there is good agreement and correlation between formulaic estimation and that of TTE for measurement of LA linear dimension. The LA regression formula is an indirect asset that could perhaps supplement LA quantification on TTE in certain circumstances.

Real men do not read labels: the effects of masculinity and involvement on college students' food decisions.

Consumer literature shows that a decision's degree of personal importance and relevance--one's level of involvement in the decision--indicates which type of intervention strategy will be effective in influencing consumers' choices. The authors surveyed 358 college students at a state university in the western United States to test the applicability of involvement on issues of obesity and eating habits. They found food decisions to be of greater personal importance and relevance to female students than to their male counterparts. The results suggest that efforts to address levels of obesity and being overweight among male college students must recognize that men's food choices are very much rooted in the ideology of what it means to be female and male in contemporary American society. The authors advance 5 peripheral-route intervention strategies to augment existing cognitive-oriented, information-based intervention programs.