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In mammals, brown adipose tissue (BAT) is activated rapidly in response to cold in order to maintain body temperature. Although BAT has been studied greatly in small animals, it is difficult to measure the activity of BAT in humans. Therefore, little is known about the heat-generating capacity and physiological significance of BAT in humans, including the degree to which components of the diet can activate BAT. This is due to the limitations in the currently most used method to assess the activation of BAT-radiolabeled glucose (fluorodeoxyglucose or 18 FDG) measured by positron emission tomography-computerized tomography (PET-CT). This method is usually performed in fasted subjects, as feeding induces glucose uptake by the muscles, which can mask the glucose uptake into the BAT. This paper describes a detailed protocol for quantifying total-body human energy expenditure and substrate utilization from BAT thermogenesis by combining indirect calorimetry, infrared thermography, and blood glucose monitoring in carbohydrate-loaded adult males. To characterize the physiological significance of BAT, measures of the impact of BAT activity on human health are critical. We demonstrate a protocol to achieve this by combining carbohydrate loading and indirect calorimetry with measurements of supraclavicular changes in temperature. This novel approach will help to understand the physiology and pharmacology of BAT thermogenesis in humans.

The 5-hydroxytryptamine 3 (5-HT 3 ) receptor belongs to the pentameric ligand-gated cation channel superfamily. Humans have five different 5-HT 3 receptor subunits: A to E. The 5-HT 3 receptors are located on the cell membrane, but a previous study suggested that mitochondria could also contain A subunits. In this article, we explored the distribution of 5-HT 3 receptor subunits in intracellular and cell-free mitochondria. Organelle prediction software supported the localization of the A and E subunits on the inner membrane of the mitochondria. We transiently transfected HEK293T cells that do not natively express the 5-HT 3 receptor with an epitope and fluorescent protein-tagged 5HT3A and 5HT3E subunits. Fluorescence microscopy and cell fractionation indicated that both subunits, A and E, localized to the mitochondria, while transmission electron microscopy revealed the location of the subunits on the mitochondrial inner membrane, where they could form heteromeric complexes. Cell-free mitochondria isolated from cell culture media colocalized with the fluorescent signal for A subunits. The presence of A and E subunits influenced changes in the membrane potential and mitochondrial oxygen consumption rates upon exposure to serotonin; this was inhibited by pre-treatment with ondansetron. Therefore, it is likely that the 5-HT 3 receptors present on mitochondria directly impact mitochondrial function and that this may have therapeutic implications.

Using a combination of respiratory gas exchange, infrared thermography, and blood glucose (BGL) analysis, we have investigated the impact of Capsicum annuum (C. annuum) fruit powder (475 mg) or caffeine (100 mg) on metabolic activity in a placebo controlled (lactose, 100 mg) double-blinded three-way cross-over-design experiment. Metabolic measurements were made on day 1 and day 7 of supplementation in eight adult male participants (22.2 ± 2 years of age, BMI 23 ± 2 kg/m 2 , x̅ ± SD). Participants arrived fasted overnight and were fed a high carbohydrate meal (90 g glucose), raising BGL from fasting baseline (4.4 ± 0.3 mmol/L) to peak BGL (8.5 ± 0.3 mmol/L) 45 min after the meal. Participants consumed the supplement 45 min after the meal, and both caffeine and C. annuum fruit powder restored BGL (F (8,178) = 2.2, p = 0.02) to near fasting levels within 15 min of supplementation compared to placebo (120 min). In parallel both supplements increased energy expenditure (F (2, 21) = 175.6, p < 0.001) over the 120-min test period (caffeine = 50.74 ± 2 kcal/kg/min, C. annuum fruit = 50.95 ± 1 kcal/kg/min, placebo = 29.34 ± 1 kcal/kg/min). Both caffeine and C. annuum fruit powder increased supraclavicular fossa temperature (F (2,42) = 32, p < 0.001) on both day 1 and day 7 of testing over the 120-min test period. No statistical difference in core temperature or reference point temperature, mean arterial pressure or heart rate was observed due to supplementation nor was any statistical difference seen between day 1 and day 7 of intervention. This is important for implementing dietary ingredients as potential metabolism increasing supplements. Together the results imply that through dietary supplements such as caffeine and C. annuum , mechanisms for increasing metabolism can be potentially targeted to improve metabolic homeostasis in people., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Van Schaik, Kettle, Green, Wundersitz, Gordon, Irving and Rathner.)

This article reviews theoretical and empirical arguments for and against various theories that explain the classic Ponzo illusion and its variants from two different viewpoints concerning the role of perceived depth in size distortions. The first viewpoint argues that all Ponzo-like illusions are driven by perceived depth. The second viewpoint argues that the classic Ponzo illusion is unrelated to depth perception. This review will give special focus to the first viewpoint and consists of three sections. In the first section, the role of the number of pictorial depth cues and previous experience in the strength of all Ponzo-like illusions are discussed. In the second section, we contrast the first viewpoint against the theories that explain the classic Ponzo illusion with mechanisms that are unrelated to depth perception. In the last section, we propose a Bayesian-motivated reconceptualization of Richard Gregory's misapplied size constancy theory that explains Ponzo-variant illusions in terms of prior information and prediction errors. The new account explains why some studies have provided inconsistent evidence for misapplied size constancy theory., (© 2021. The Psychonomic Society, Inc.)

Context: Movement of the human body is essential for the interaction of an individual within their environment and contributes to both physical and emotional quality of life. Movement system disorders (MSDs) are kinesiopathologic conditions that result from either altered movement patterns, trauma, or pathology. A screening tool may facilitate earlier diagnosis and treatment of acute MSDs. This tool could prevent progression to chronic conditions, leading to better patient outcomes and quality of life., Objectives: Our study evaluated whether a screening tool would be able to accurately screen individuals for MSDs, explore comorbidities that may predict the prevalence of MSDs, and identify why people do not discuss these problems with their primary care provider (PCP)., Methods: A multisite, observational study in a primary care setting. Data were analyzed to determine the psychometric properties of the screening question. Logistic regression was performed to explore the relationship of comorbidities with MSDs. Thematic analysis was performed to explore why patients do not discuss these issues with their PCP., Results: The point prevalence of MSDs was determined to be 78%. The sensitivity of the screening question was determined to be good (70%). Arthritis, obesity, sleep disorders, and gastroesophageal reflux disease (GERD) were significant predictors for an MSD. Thematic analysis regarding why patients do not discuss the MSD with their physician revealed: (1) the perceived lack of importance of the problem; (2) the lack of access to healthcare, and (3) the acuity of the problem., Conclusions: Screening for an MSD and associated comorbidities could prevent the transition of acute conditions to chronic conditions. If PCPs can identify predictors and factors associated with an MSD, they may be able to screen for MSDs more effectively. Earlier identification of MSDs may facilitate earlier treatment and prevent costs associated with resulting chronic disorders and persistent pain and disability., (© 2021 Christine Kettle et al., published by De Gruyter, Berlin/Boston.)

5-hydroxytryptamine type 3 (5-HT 3 ) receptors are ligand gated ion channels, which clearly distinguish their mode of action from the other G-protein coupled 5-HT or serotonin receptors. 5-HT 3 receptors are well established targets for emesis and gastrointestinal mobility and are used as adjunct targets in treating schizophrenia. However, the distribution of these receptors is wider than the nervous system and there is potential that these additional sites can be targeted to modulate inflammatory and/or metabolic conditions. Recent progress in structural biology and pharmacology of 5-HT 3 receptors have provided profound insights into mechanisms of their action. These advances, combined with insights into clinical relevance of mutations in genes encoding 5-HT 3 subunits and increasing understanding of their implications in patient's predisposition to diseases and response to the treatment, open new avenues for personalized precision medicine. In this review, we recap on the current status of 5-HT 3 receptor-based therapies using a biochemical and physiological perspective. We assess the potential for targeting 5-HT 3 receptors in conditions involving metabolic or inflammatory disorders based on recent findings, underscoring the challenges and limitations of this approach.