Adult Type 3 Adenylyl Cyclase–Deficient Mice Are Obese

Background: A recent study of obesity in Swedish men found that polymorphisms in the type 3 adenylyl cyclase (AC3) are associated with obesity, suggesting the interesting possibility that AC3 may play a role in weight control. Therefore, we examined the weight of AC3 mice over an extended period of time. Methodology/Principal Findings: We discovered that AC3 2/2 mice become obese as they age. Adult male AC3 2/2 mice are about 40 % heavier than wild type male mice while female AC3 2/2 are 70 % heavier. The additional weight of AC3 2/2 mice is due to increased fat mass and larger adipocytes. Before the onset of obesity, young AC3 2/2 mice exhibit reduced physical activity, increased food consumption, and leptin insensitivity. Surprisingly, the obesity of AC3 2/2 mice is not due to a loss of AC3 from white adipose and a decrease in lipolysis. Conclusions/Significance: We conclude that mice lacking AC3 exhibit obesity that is apparently caused by low locomotor activity, hyperphagia, and leptin insensitivity. The presence of AC3 in primary cilia of neurons of the hypothalamus suggests that cAMP signals generated by AC3 in the hypothalamus may play a critical role in regulation of body weight

Assessing the Quality of Clinical Teachers: A Systematic Review of Content and Quality of Questionnaires for Assessing Clinical Teachers

BACKGROUND: Learning in a clinical environment differs from formal educational settings and provides specific challenges for clinicians who are teachers. Instruments that reflect these challenges are needed to identify the strengths and weaknesses of clinical teachers. OBJECTIVE: To systematically review the content, validity, and aims of questionnaires used to assess clinical teachers. DATA SOURCES: MEDLINE, EMBASE, PsycINFO and ERIC from 1976 up to March 2010. REVIEW METHODS: The searches revealed 54 papers on 32 instruments. Data from these papers were documented by independent researchers, using a structured format that included content of the instrument, validation methods, aims of the instrument, and its setting. Results : Aspects covered by the instruments predominantly concerned the use of teaching strategies (included in 30 instruments), supporter role (29), role modeling (27), and feedback (26). Providing opportunities for clinical learning activities was included in 13 instruments. Most studies referred to literature on good clinical teaching, although they failed to provide a clear description of what constitutes a good clinical teacher. Instrument length varied from 1 to 58 items. Except for two instruments, all had to be completed by clerks/residents. Instruments served to provide formative feedback ( instruments) but were also used for resource allocation, promotion, and annual performance review (14 instruments). All but two studies reported on internal consistency and/or reliability; other aspects of validity were examined less frequently. CONCLUSIONS: No instrument covered all relevant aspects of clinical teaching comprehensively. Validation of the instruments was often limited to assessment of internal consistency and reliability. Available instruments for assessing clinical teachers should be used carefully, especially for consequential decisions. There is a need for more valid comprehensive instruments

Impact of inactivity and exercise on the vasculature in humans

The effects of inactivity and exercise training on established and novel cardiovascular risk factors are relatively modest and do not account for the impact of inactivity and exercise on vascular risk. We examine evidence that inactivity and exercise have direct effects on both vasculature function and structure in humans. Physical deconditioning is associated with enhanced vasoconstrictor tone and has profound and rapid effects on arterial remodelling in both large and smaller arteries. Evidence for an effect of deconditioning on vasodilator function is less consistent. Studies of the impact of exercise training suggest that both functional and structural remodelling adaptations occur and that the magnitude and time-course of these changes depends upon training duration and intensity and the vessel beds involved. Inactivity and exercise have direct “vascular deconditioning and conditioning” effects which likely modify cardiovascular risk

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior

Genetic polymorphism PC-1 K121Q and ethnic susceptibility to insulin resistance.

Genetic susceptibility may be responsible for high prevalence of insulin resistance in Asian Indians. This study was carried out in samples of local Asian Indians and Caucasians to determine whether plasma cell membrane glycoprotein (PC)-1 K121Q and insulin receptor substrate-1 (IRS-1) G972A polymorphisms contribute significantly to susceptibility to insulin resistance in Asian Indians. The frequency of carrying at least one copy of the PC-1 121Q variant in Asian Indians was significantly higher than that in Caucasians (P = 0.01), but the frequency was similar for IRS-1 972A (6% and 7%). A significantly higher insulin area under the curve during oral glucose tolerance testing (P < 0.0001) and lower insulin sensitivity during hyperinsulinemic-euglycemic clamps (P = 0.04) were found in Asian Indians with PC-1 121Q variant compared with Asian Indians with wild-type PC-1 and with Caucasians with or without the polymorphism. IRS-1 972A was not associated with any change in insulin sensitivity. We conclude that the PC-1 K121Q polymorphism associates with primary insulin resistance in migrant Asian Indians. A relatively high frequency of this polymorphism thus may be one factor contributing to insulin resistance susceptibility in Asian Indians. This finding indicates the need for expanded studies on the association between PC-1 K121Q and insulin resistance in a representative sample of the Asian Indian population