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Summary Objective Research suggests that individuals seeking weight loss treatment do so for a variety of reasons. Limited work has explored relations of reasons for weight loss to patient characteristics or to weight loss outcomes. The current study examined these relations. Methods The sample consisted of 588 patients in a 15‐week fee‐for‐service weight loss programme. Prior to the intervention, patients completed questionnaires including items on reasons for weight loss, demographic characteristics, and a variety of weight‐based characteristics. Patients' weight change outcomes were expressed as percent weight loss and also categorized into one of three previously described weight loss trajectories. Results The results of chi‐squared and t‐test analyses suggested that endorsement of health concerns, mobility concerns, or another person's recommendation was associated with higher body mass index (BMI) and older age. These reasons were more likely to be endorsed by White patients than Black patients and by male patients than female patients. Endorsement of doctor recommendation was more likely to be seen among Black patients than White patients. There was no significant relation of any weight loss reason with weight loss outcome. Conclusions While certain reasons for weight loss were more often cited by certain patient groups, no specific reason predicted a better or worse outcome.

Inhibition of the enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) represents a potential mechanism for improving pain conditions. ASP3662 is a potent and selective inhibitor of 11β‐HSD1. Two phase I clinical studies were conducted to assess the safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of single and multiple ascending doses of ASP3662 in healthy young and elderly non‐Japanese and young Japanese subjects. Nonlinear, more than dose‐proportional PKs were observed for ASP3662 after single‐dose administration, particularly at lower doses (≤ 6 mg); the PKs at steady state were dose proportional, although the time to ASP3662 steady state was dose dependent at lower doses (≤ 2 mg). Similar PKs were observed among young Japanese, young non‐Japanese, and elderly non‐Japanese subjects. Specific inhibition of 11β‐HSD1 occurred after both single and multiple doses of ASP3662. A marked dissociation between PKs and PDs was observed after single but not multiple doses of ASP3662. ASP3662 was generally safe and well tolerated.

This paper presents a symbolic description of the design process of the switch transistors for the cross- coupled charge pump applications. Discrete-time analog circuits are usually designed by the numerical algorithms in the professional simulator software which can be an extremely time-consuming process in contrast to described analytical procedure. The significant part of the pumping losses is caused by the reverse current through the switch transistors due to continuous-time voltage change on the main capacitors. Design process is based on the analytical expression of the time response characteristics of the pump stage as an analog system with using BSIM model equations. The main benefit of the article is the analytical transistors sizing formula, so that the maximum voltage gain is achieved. The diode transistor is dimensioned for the pump requirements, as the maximal pump output ripple voltage, current, etc. The characteristics of the proposed circuit has been verified by simulation in ELDO Spice. Results are valid for N-stage charge pump and also applicable for other model equations as PSP, EKV.

There is substantial evidence that glutamate can modulate the effects of 5-hydroxytryptamine2A (5-HT2A) receptor activation through stimulation of metabotropic glutamate2/3 (mGlu2/3) receptors in the prefrontal cortex. Here we show that constitutive deletion of the mGlu2 gene profoundly attenuates an effect of 5-HT2A receptor activation using the mouse head twitch response (HTR). MGlu2 and mGlu3 receptor knockout (KO) as well as age-matched ICR (CD-1) wild type (WT) mice were administered (±)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and observed for head twitch activity. DOI failed to produce significant head twitches in mGlu2 receptor KO mice at a dose 10-fold higher than the peak effective dose in WT or mGlu3 receptor KO mice. In addition, the mGlu2/3 receptor agonist LY379268, and the mGlu2 receptor positive allosteric modulator (PAM) CBiPES, potently blocked the HTR to DOI in WT and mGlu3 receptor KO mice. Conversely, the mGlu2/3 receptor antagonist LY341495 (10 mg/kg) increased the HTR produced by DOI (3 mg/kg) in mGlu3 receptor KO mice. Finally, the mGlu2 receptor potentiator CBiPES was able to attenuate the increase in the HTR produced by LY341495 in mGlu3 receptor KO mice. Taken together, all of these results are consistent with the hypothesis that that DOI-induced head twitches are modulated by mGlu2 receptor activation. These results also are in keeping with a critical autoreceptor function for mGlu2 receptors in the prefrontal cortex with differential effects of acute vs. chronic perturbation (e.g., constitutive mGlu2 receptor KO mice). The robust attenuation of DOI-induced head twitches in the mGlu2 receptor KO mice appears to reflect the critical role of glutamate in ongoing regulation of 5-HT2A receptors in the prefrontal cortex. Future experiments with inducible knockouts for the mGlu2 receptor and/or selective mGlu3 receptor agonists/PAMs/antagonists could provide an important tools in understanding glutamatergic modulation of prefrontal cortical 5-HT2A receptor function.

5-Hydroxytryptamine2A (5-HT2A) receptors are enriched in layers I and Va of the rat prefrontal cortex and neocortex and their activation increases the frequency of glutamatergic excitatory post-synaptic potentials/currents (EPSP/Cs) onto layer V pyramidal cells. A number of other G-protein coupled receptors (GPCRs) are also enriched in cortical layers I and Va and either induce (α1-adrenergic and orexin2) or suppress (metabotropic glutamate2 [mGlu2], adenosine A1, μ-opioid) both 5-HT-induced EPSCs and head twitches or head shakes induced by the phenethylamine hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI). Another neurotransmitter receptor also localized to apparent thalamocortical afferents to layers I and Va of the rat prefrontal cortex and neocortex is the β2-adrenergic receptor. Therefore, we conducted preliminary electrophysiological experiments with rat brain slices examining the effects of epinephrine on electrically-evoked EPSPs following bath application of DOI (3 μM). Epinephrine (0.3–10 μM) suppressed the late EPSPs produced by electrical stimulation and DOI. The selective β2-adrenergic receptor antagonist ICI-118,551 (300 nM) resulted in a rightward shift of the epinephrine concentration-response relationship. We also tested the selective β2-adrenergic receptor agonist clenbuterol and the antagonist ICI-118,551 on DOI-induced head twitches. Clenbuterol (0.3–3 mg/kg, i.p.) suppressed DOI (1.25 mg/kg, i.p.)-induced head twitches. This clenbuterol effect appeared to be at least partially reversed by the selective β2-adrenergic receptor antagonist ICI-118,553 (0.01–1 mg/kg, i.p.), with significant reversal at doses of 0.1 and 1 mg/kg. Thus, β2-adrenergic receptor activation reverses the effects of phenethylamine hallucinogens in the rat prefrontal cortex. While Gi/Go-coupled GPCRs have previously been shown to suppress both the electrophysiological and behavioral effects of 5-HT2A receptor activation in the mPFC, the present work appears to extend this suppressant action to a Gs-coupled GPCR. Furthermore, the modulation of 5-HT2A receptor activation-induced glutamate release onto mPFC layer V pyramidal neurons apical dendrites by a range GPCRs in rat brain slices appears to results in behaviorally salient effects of relevance when screening for novel CNS therapeutic drugs.

1-substituted-3-(2-phenylquinazolin-4-yl) thioureas (7) were produced by an intramolecular cycloaddition reaction of 1-substitued-3-[(2-cyanophenylimino) phenylmethyl] thioureas (3). These compounds in turn were prepared by the reaction of N-(2-cyanophenyl)benzimidoyl isothiocyanate (2) with primary amines. The structures of products 7 were confirmed by FTIR, 1H-NMR, 13C-NMR, mass spectroscopy and X-ray crystallography.

During wakefulness and in absence of performing tasks or sensory processing, the default-mode network (DMN), an intrinsic central nervous system (CNS) network, is in an active state. Non-human primate and human CNS imaging studies have identified the DMN in these two species. Clinical imaging studies have shown that the pattern of activity within the DMN is often modulated in various disease states (e.g., Alzheimer's, schizophrenia or chronic pain). However, whether the DMN exists in awake rodents has not been characterized. The current data provides evidence that awake rodents also possess 'DMN-like' functional connectivity, but only subsequent to habituation to what is initially a novel magnetic resonance imaging (MRI) environment as well as physical restraint. Specifically, the habituation process spanned across four separate scanning sessions (Day 2, 4, 6 and 8). At Day 8, significant (p

A study was made of the erosion wear of the blades of pitched blade impellers in a suspension of silicious sand (CV= 5 %, d=0.325 mm, degree of hardness "7.5") in water under a turbulent flow regime of agitated charge when complete homogeneity of the suspension was achieved. Two aims of the study were defined: the dependence of the rate of the erosion process of the impeller blades on impeller frequency of revolution and on the size of the mixing equipment. Experiments were carried out on pilot plant mixing equipment of two sizes (geometrically similar) made of stainless steel (diameters of cylindrical vessels T1 = 200 mm and T2 = 300 mm, diameters of impellers D1 = 100 mm and D2= 66. 7 mm, impeller off bottom clearances h1 = 100 mm and h2= 66. 7 mm, respectively) equipped with four radial baffles (width b1 = 30 mm, b2 =20 mm, respectively) and an impeller with four inclined plane blades (pitch angle α =30°, 45°, relative blade with W/D = 0.2) made of rolled brass (Brinnel hardness 40-50 BM) always pumping the liquid downwards towards the float vessel bottom. The wear of the impeller was described by an analytical approximation in exponential form with two parameters (the wear rate constant k and the geometrical parameters of the worn blade C) calculated by the least squares method from the experimentally found profile of the worn leading edge of the impeller blades. While the wear rate constant exhibits a monotonous dependence on the pitch angle only, the geometric parameter is dependent both on the pitch angle and in linear form on the impeller tip speed. Thus in the procedure for scaling up the rate of erosion wear of the pitched blade impellers in a suspension of higher solid particle hardness, the decision process parameters are the impeller blade pitch angle and the impeller tip speed.