Obesity is often attributed to an addiction to high-calorie foods. However, the effect of “food addiction” explanations on weight-related stigma remains unclear. In two online studies, participants (n = 439, n = 523, respectively, recruited from separate samples) read a vignette about a target female who was described as ‘very overweight’. Participants were randomly allocated to one of three conditions which differed in the information provided in the vignette: (1) in the “medical condition”, the target had been diagnosed with food addiction by her doctor; (2) in the “self-diagnosed condition”, the target believed herself to be a food addict; (3) in the control condition, there was no reference to food addiction. Participants then completed questionnaires measuring target-specific stigma (i.e., stigma towards the female described in the vignette), general stigma towards obesity (both studies), addiction-like eating behavior and causal beliefs about addiction (Study 2 only). In Study 1, participants in the medical and self-diagnosed food addiction conditions demonstrated greater target-specific stigma relative to the control condition. In Study 2, participants in the medical condition had greater target-specific stigma than the control condition but only those with low levels of addiction-like eating behavior. There was no effect of condition on general weight-based stigma in either study. These findings suggest that the food addiction label may increase stigmatizing attitudes towards a person with obesity, particularly within individuals with low levels of addiction-like eating behavior.

Rolapitant [(Varubi), 5S,8S)-8-[[(1R)-1-[3,5 bis(trifluoromethyl phenyl]ethoxy]methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one] is a high-affinity NK1 receptor antagonist that was approved in September 2015 as a treatment for nausea and vomiting caused by chemotherapy. In vivo rolapitant moderately inhibits CYP2D6 for at least 7 days after one 180 mg dose. Due to the long inhibition time, we investigated rolapitant as a possible mechanism-based inactivator of CYP2D6. Rolapitant docked in the active site of CYP2D6 and displayed type I binding to CYP2D6 with a K s value of 1.2 6 0.4 mM. However, in NADPH-, time-, and concentration-dependent assays of CYP2D6 activity, no evidence for mechanism-based inactivation and no metabolites of rolapitant were observed. Stopped-flow binding studies yielded a k on /k off (K d) value of 6.2 mM. The IC 50 value for rolapitant inhibition of CYP2D6 activity was 24 mM, suggesting that inhibition is not due to tight binding of rolapitant to CYP2D6. By Lineweaver-Burk analysis, rolapitant behaved as a mixed, reversible inhibitor. The K i values of 20 and 34 mM were determined by Dixon analysis, with bufuralol and dextromethorphan as reporter substrates, respectively, and drug-drug interaction modeling did not predict the reported in vivo inhibition. The interaction of rolapitant with CYP2D6 was also examined in 1 microsecond molecular dynamics simulations. Rolapitant adopted multiple low-energy binding conformations near the active site, but at distances not consistent with metabolism. Given these findings, we do not see evidence that rolapitant is a mechanismbased inactivator. Moreover, the reversible inhibition of CYP2D6 by rolapitant may not fully account for the moderate inhibition described in vivo.

The 4N carpets are a class of infinitely ramified self-similar fractals with a large group of symmetries. For a 4N -carpet F , let {Fn} n≥0 be the natural decreasing sequence of compact pre-fractal approximations with ∩nFn = F . On each Fn, let E(u, v) = F N ∇u • ∇vdx be the classical Dirichlet form and un be the unique harmonic function on Fn satisfying a mixed boundary value problem corresponding to assigning a constant potential between two specific subsets of the boundary. Using a method introduced by Barlow and Bass [2], we prove a resistance estimate of the following form: there is ρ = ρ(N ) > 1 such that E(un, un)ρ n is bounded above and below by constants independent of n. Such estimates have implications for the existence and scaling properties of Dirichlet forms on F .

The 4 ⁢ N {4N} -carpets are a class of infinitely ramified self-similar fractals with a large group of symmetries. For a 4 ⁢ N {4N} -carpet F, let { F n } n ≥ 0 {\{F_{n}\}_{n\geq 0}} be the natural decreasing sequence of compact pre-fractal approximations with ⋂ n F n = F {\bigcap_{n}F_{n}=F} . On each F n {F_{n}} , let ℰ ⁢ ( u , v ) = ∫ F N ∇ ⁡ u ⋅ ∇ ⁡ v ⁢ d ⁢ x {\mathcal{E}(u,v)=\int_{F_{N}}\nabla u\cdot\nabla v\,dx} be the classical Dirichlet form and u n {u_{n}} be the unique harmonic function on F n {F_{n}} satisfying a mixed boundary value problem corresponding to assigning a constant potential between two specific subsets of the boundary. Using a method introduced by [M. T. Barlow and R. F. Bass, On the resistance of the Sierpiński carpet, Proc. Roy. Soc. Lond. Ser. A 431 (1990), no. 1882, 345–360], we prove a resistance estimate of the following form: there is ρ = ρ ⁢ ( N ) > 1 {\rho=\rho(N)>1} such that ℰ ⁢ ( u n , u n ) ⁢ ρ n {\mathcal{E}(u_{n},u_{n})\rho^{n}} is bounded above and below by constants independent of n. Such estimates have implications for the existence and scaling properties of Brownian motion on F.