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BACKGROUND: Macronutrient 'preloads' can stimulate glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), slow gastric emptying, and reduce postprandial glycemic excursions. After sweet preloads, these effects may be signaled by sodium-glucose cotransporter-1 (SGLT1), sweet taste receptors, or both. OBJECTIVE: We determined the effects of 4 sweet preloads on GIP and GLP-1 release, gastric emptying, and postprandial glycemia. DESIGN: Ten healthy subjects were studied on 4 separate occasions each. A preload drink containing 40 g glucose, 40 g tagatose/isomalt mixture (TIM), 40 g 3-O-methylglucose (3OMG; a nonmetabolized substrate of SGLT1), or 60 mg sucralose was consumed 15 min before a (13)C-octanoic acid-labeled mashed potato meal. Blood glucose, plasma total GLP-1 and GIP, serum insulin, and gastric emptying were determined. RESULTS: Both glucose and 3OMG stimulated GLP-1 and GIP release in advance of the meal (each P < 0.05), whereas TIM and sucralose did not. The overall postprandial GLP-1 response was greater after glucose, 3OMG, and TIM than after sucralose (P < 0.05), albeit later after TIM than the other preloads. The blood glucose and insulin responses in the first 30 min after the meal were greatest after glucose (each P < 0.05). Gastric emptying was slower after both 3OMG and TIM than after sucralose (each P < 0.05). CONCLUSIONS: In healthy humans, SGLT1 substrates stimulate GLP-1 and GIP and slow gastric emptying, regardless of whether they are metabolized, whereas the artificial sweetener sucralose does not. Poorly absorbed sweet tastants (TIM), which probably expose a greater length of gut to nutrients, result in delayed GLP-1 secretion but not in delayed GIP release. These observations have the potential to optimize the use of preloads for glycemic control. This trial was registered at www.actr.org.au as ACTRN12611000775910. Copyright © 2012 American Society for Nutrition [ABSTRACT FROM AUTHOR]

The ability of a male autistic savant (TR) to play two unfamiliar piano pieces after listening to a tape-recording was tested, closely following the procedures of Sloboda, Hermelin, and O'Connor (1985). Other components of TR's musical ability--pitch recognition, improvisation, and ability to provide harmonic accompaniment--were also examined. TR's musical precocity was examined in relation to his general level of intellectual functioning as indexed by a battery of standardized psychological tests of intelligence, memory, reading, visual organization, and creativity. His parents and two male siblings also completed tests of intelligence. Results from psychometric testing indicated that TR has idiosyncratic levels of cognitive functioning with difficulties in verbal reasoning but high levels of concentration and memory. His speed of information processing, as indicated by Inspection Time, and was better than average. TR demonstrated perfect pitch recognition and other family members also demonstrated excellent relative pitch. TR's ability to recall and perform structured music within both the diatonic and whole-tone systems was exceptional but dependent upon his familiarity with musical structure and was therefore organized and rule-driven. Furthermore, TR demonstrated competence in improvisation and composition, albeit restricted by his adherence to structural representations of familiar musical rules. [ABSTRACT FROM AUTHOR]

Objective: To determine whether or not limited caregiver health literacy is associated with adherence to a daily multi-vitamin with iron regimen in infants.Methods: 110 caregiver/infant dyads were enrolled in a prospective study to assess the relationship between caregiver health literacy and adherence to a daily multi-vitamin with iron regimen for infants. Households were contacted biweekly over a 3-month period. Adherence was based upon caregiver report. High adherence, our primary outcome, was defined as the administration of the multi-vitamin with iron on 5-7 days over the past week.Results: As measured by the Short Test of Functional Health Literacy in Adults (S-TOFHLA), 18% of caregivers had limited health literacy skills. Caregivers with limited health literacy skills were more likely to have higher adherence than caregivers with adequate health literacy, after adjusting for a number of possible confounding variables (AOR=2.13; 95% 1.20-3.78).Conclusion: Caregivers with limited health literacy were twice as likely to report high adherence to a daily multi-vitamin with iron regimen in infants as caregivers with adequate health literacy in adjusted analysis.Practice Implications: Health literacy may exert a differential influence on adherence depending upon the complexity of the desired health behavior. [ABSTRACT FROM AUTHOR]

Context: Pregnancy increases nutrient demand, but how nutrient uptake and its determinants adapt to facilitate this is unclear., Objective: This review aimed to identify and characterize evidence and evidence gaps regarding changes in gastrointestinal nutrient absorption and its determinants during pregnancy in monogastric mammals., Data Sources: A scoping review of peer-reviewed sources was conducted across PubMed, Scopus, Web of Science, Embase, and ProQuest (theses and dissertations) databases., Data Extraction: Data extracted included species, pregnancy stages and outcomes. Where sufficient data for a given outcome was available, relative values were summarized graphically or in tables, to allow comparison across pregnancy stages and/or small intestine regions. Searches identified 26 855 sources, of which only 159 were eligible. Mechanistic studies were largely restricted to rodents, and most compared non- and late-pregnant groups, with fewer studies including early- or mid-pregnant groups., Data Analysis: During pregnancy, there is some evidence for greater capacity for glucose uptake but unchanged amino acid uptake, and good evidence for increased uptake of calcium, iron, and zinc, and slower gastrointestinal passage of nutrients. The available evidence indicates that acute glucose uptake, gastric emptying, and the activities of sucrase, maltase, and lactase do not change during pregnancy. Gaps in the knowledge include the effects of pregnancy on uptake of specific amino acids, lipids, and most minerals and vitamins., Conclusion: The results indicate that the gastrointestinal tract adapts during pregnancy to facilitate increased nutrient absorption. Additional data is required in order to assess the underlying mechanisms for and impacts on the absorption of many nutrients, as well as to determine the timing of these adaptations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Lay Abstract: Most research about autism spectrum disorder (ASD) in females has looked at autistic features in people who have already received diagnoses. Because our understanding of ASD has been shaped by the difficulties of males, females may experience different difficulties and may not meet the criteria for diagnosis because of a skewed concept of ASD. We extracted detailed information from the assessment reports of 222 children who were either diagnosed with ASD (156 children) or not diagnosed despite many ASD traits (78 children). Females were less likely to have restricted interests, especially females who did not receive an ASD diagnosis. Females who did not receive an ASD diagnosis tended to show more ability in social and emotional reciprocity than what would qualify them for a diagnosis. We also found sex-/gender-specific profiles of body use and speech mannerisms. Many behaviours were more closely linked with an ASD diagnosis for males and others for females, suggesting that behaviours may be interpreted differently depending on the child's sex/gender. We discuss implications for assessing females for ASD in the context of this evidence.

Small intestinal satiation pathways involve nutrient-induced stimulation of chemoreceptors leading to release of satiety hormones from intestinal enteroendocrine cells (ECCs). Whether adaptations in these pathways contribute to increased maternal food intake during pregnancy is unknown. To determine the expression of intestinal nutrient-sensors and satiety hormone transcripts and proteins across pregnancy in mice. Female C57BL/6J mice (10-12 weeks old) were randomized to mating and then tissue collection at early- (6.5 d), mid- (12.5 d) or late-pregnancy (17.5 d), or to an unmated age matched control group. Relative transcript expression of intestinal fatty acid, peptide and amino acid and carbohydrate chemoreceptors, as well as gut hormones was determined across pregnancy. The density of G-protein coupled receptor 93 (GPR93), free fatty acid receptor (FFAR) 4, cholecystokinin (CCK) and glucagon-like peptide1 (GLP-1) immunopositive cells was then compared between non-pregnant and late-pregnant mice. Duodenal GPR93 expression was lower in late pregnant than non-pregnant mice (P < 0.05). Ileal FFAR1 expression was higher at mid- than at early- or late-pregnancy. Ileal FFAR2 expression was higher at mid-pregnancy than in early pregnancy. Although FFAR4 expression was consistently lower in late-pregnant than non-pregnant mice (P < 0.001), the density of FFAR4 immunopositive cells was higher in the jejunum of late-pregnant than non-pregnant mice. A subset of protein and fatty acid chemoreceptor transcripts undergo region-specific change during murine pregnancy, which could augment hormone release and contribute to increased food intake. Further investigations are needed to determine the functional relevance of these changes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Lay Abstract: Recognizing and understanding the perspectives of others-also called theory of mind-is important for effective communication. Studies have found that some autistic individuals have greater difficulty with theory of mind compared to non-autistic individuals. One purported theory of mind measure is the Reading the Mind in the Eyes Test (RMET). This test presents participants with photographs of pairs of eyes and asks them to identify the emotion displayed by each pair of eyes from four choices. Some researchers have argued that the multiple-choice format of the RMET may not be an accurate measure of theory of mind, as participants could simply be guessing or using a process of elimination to select the correct answer. Participants may also be disadvantaged if they are not familiar with the specific emotion words used in the multiple-choice answers. We examined whether a free-report (open-ended) format RMET would be a more valid measure of theory of mind than the multiple-choice RMET. Autistic and non-autistic adults performed better on the multiple-choice RMET than the free-report RMET. However, both versions successfully differentiated autistic and non-autistic adults, irrespective of their level of verbal ability. Performance on both versions was also correlated with another well-validated adult measure of theory of mind. Thus, the RMET's multiple-choice format does not, of itself, appear to underpin its ability to differentiate autistic and non-autistic adults.

Although the ability of autistic adults to recognize others' emotions has been extensively studied, less attention has been given to how they respond to these emotions. We examined two aspects of autistic and non-autistic adults' responsiveness to the emotional expressions of non-autistic actors: their perspectives on the appropriate way of responding to others' emotions and their awareness of others' perceptions of the likely appropriateness of such responses. Autistic (N = 63) and non-autistic (N = 67) adult samples viewed videos of 74 dyadic social interactions displaying different examples of 12 emotions expressed by one actor in response to the behavior of the other. After each video, participants (a) nominated the emotion expressed by the first actor, (b) offered their perspective on what would constitute an appropriate empathic response by the second actor, and (c) indicated their confidence in that response. Although the autistic group provided fewer appropriate empathic responses-operationalized via a panel's interpretations of normative responses-than the non-autistic group, within-group variability was marked, and the effect was weak and largely confined to basic emotions. Autistic individuals were, however, considerably less confident in their responses. Examination of the relationships between confidence in and the appropriateness of empathic responses provided no indication in either group of reliable discrimination of appropriate from inappropriate empathic responses or finely tuned metacognitive awareness of variations in appropriateness. In sum, autistic adults' perspectives on the appropriate empathic reactions to non-autistic adults' emotions were not unilaterally or markedly different to those of non-autistic adults., (© 2023 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Social interactions can drive distinct gene expression profiles which may vary by social context. Here we use female sailfin molly fish ( Poecilia latipinna ) to identify genomic profiles associated with preference behavior in distinct social contexts: male interactions (mate choice) versus female interactions (shoaling partner preference). We measured the behavior of 15 females interacting in a non-contact environment with either two males or two females for 30 min followed by whole-brain transcriptomic profiling by RNA sequencing. We profiled females that exhibited high levels of social affiliation and great variation in preference behavior to identify an order of magnitude more differentially expressed genes associated with behavioral variation than by differences in social context. Using a linear model (limma), we took advantage of the individual variation in preference behavior to identify unique gene sets that exhibited distinct correlational patterns of expression with preference behavior in each social context. By combining limma and weighted gene co-expression network analyses (WGCNA) approaches we identified a refined set of 401 genes robustly associated with mate preference that is independent of shoaling partner preference or general social affiliation. While our refined gene set confirmed neural plasticity pathways involvement in moderating female preference behavior, we also identified a significant proportion of discovered that our preference-associated genes were enriched for 'immune system' gene ontology categories. We hypothesize that the association between mate preference and transcriptomic immune function is driven by the less well-known role of these genes in neural plasticity which is likely involved in higher-order learning and processing during mate choice decisions., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Multiple studies have independently investigated the associations of the consumption of individual beverage types and specific plasma biomarkers with the risk of type 2 diabetes (T2D). However, as individuals do not consume single beverage types exclusively and plasma biomarkers do not act in isolation, it remains unclear how patterns of beverage consumption and plasma biomarker networks associate both with each other and T2D risk., Objectives: We aimed to elucidate potential dietary determinants of T2D risk by defining a model that describes habitual beverage consumption profiles in relation to identified networks of circulating plasma biomarkers., Methods: This study included 1,461 case and 1,568 control participants from case-control studies of T2D nested within the Nurses' Health Study. Participants completed validated semiquantitative food frequency questionnaires that assessed habitual beverage consumption, and they provided blood samples from which 27 plasma biomarkers of cardiometabolic risk were identified. Common exploratory factor analysis (EFA) identified factors that separately described beverage consumption profiles and biomarker networks. Multivariable-adjusted regression elucidated the relationships between beverage and biomarker factors and T2D risk., Results: EFA revealed five factors describing unique beverage consumption profiles and seven factors describing biomarker networks. The factor describing alcoholic beverage consumption was associated with a reduced risk of T2D (odds ratio [OR]: 0.50 [0.40, 0.64], P<0.001) mediated, in part, by the factor describing increased concentrations of adiponectin biomarkers (19.9% [12.0, 31.1] P = 0.004). The factor describing low-calorie sweetened beverage (LCSBs) consumption was associated with an increased risk of T2D (OR: 1.33 [1.03, 1.72], P = 0.021), and the factor describing lower concentrations of insulin-like growth factor binding proteins 1 and 2, and soluble leptin receptor, and increased leptin concentrations (P = 0.005)., Conclusions: Moderate alcohol consumption was associated with reduced T2D risk, mediated in part by increased circulating adiponectin. LCSB consumption was associated with both increased T2D risk and perturbed insulin-like growth factor and leptin signaling., (Copyright © 2023. Published by Elsevier Inc.)

New Findings: What is the central question of this study? Body mass and food intake change during the female ovarian cycle: does glucose transport by the small intestine also vary? What is the main finding and its importance? We have optimised Ussing chamber methodology to measure region-specific active glucose transport in the small intestine of adult C57BL/6 mice. Our study provides the first evidence that jejunal active glucose transport changes during the oestrous cycle in mice, and is higher at pro-oestrus than oestrus. These results demonstrate adaptation in active glucose uptake, concurrent with previously reported changes in food intake., Abstract: Food intake changes across the ovarian cycle in rodents and humans, with a nadir during the pre-ovulatory phase and a peak during the luteal phase. However, it is unknown whether the rate of intestinal glucose absorption also changes. We therefore mounted small intestinal sections from C57BL/6 female mice (8-9 weeks old) in Ussing chambers and measured active ex vivo glucose transport via the change in short-circuit current (∆I sc ) induced by glucose. Tissue viability was confirmed by a positive ∆I sc response to 100 µM carbachol following each experiment. Active glucose transport, assessed after addition of 5, 10, 25 or 45 mM d-glucose to the mucosal chamber, was highest at 45 mM glucose in the distal jejunum compared to duodenum and ileum (P < 0.01). Incubation with the sodium-glucose cotransporter 1 (SGLT1) inhibitor phlorizin reduced active glucose transport in a dose-dependent manner in all regions (P < 0.01). Active glucose uptake induced by addition of 45 mM glucose to the mucosal chamber in the absence or presence of phlorizin was assessed in jejunum at each oestrous cycle stage (n = 9-10 mice per stage). Overall, active glucose uptake was lower at oestrus compared to pro-oestrus (P = 0.025). This study establishes an ex vivo method to measure region-specific glucose transport in the mouse small intestine. Our results provide the first direct evidence that SGLT1-mediated glucose transport in the jejunum changes across the ovarian cycle. The mechanisms underlying these adaptations in nutrient absorption remain to be elucidated., (© 2023 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Lay Abstract: Difficulties in reading others' minds make it difficult to anticipate their future behaviour. It has often been argued that such difficulties contribute to autistic individuals becoming enmeshed in criminal activity. However, supportive scientific evidence is virtually non-existent. We compared the ability of groups of autistic and non-autistic adults of similar intellectual ability to detect dodgy or suspicious behaviour across a wide range of scenarios. Although the autistic group performed more poorly than the non-autistic group on an established measure of mindreading, there were no group differences in the ability to detect dodginess. Nor did we find any evidence that detecting dodgy behaviour was associated with the degree of autistic traits reported by individual participants. However, when we combined the two groups, difficulty reading the minds of others was indeed associated with poorer detection of dodginess, thus highlighting a characteristic of individuals that may well increase the likelihood of becoming involved in crime or exploited for autistic and non-autistic individuals alike.

Reports of cybercrime being committed by people on the autism spectrum often imply that autism may be more prevalent among cybercriminals than the general population, although this remains unproven. In an online survey of 302 participants, we found that autistic individuals (n = 25) were more likely to report engagement in cybercrime than non-autistic individuals, but this relationship was not mediated by advanced digital skills or deficits in theory of mind. Furthermore, independent of autism diagnosis, autistic traits were not significantly associated with self-reported cyber-criminality. We propose that there may be additional factors moderating the relationship between autism, autistic traits, and cybercrime, such as specific autistic characteristics, understanding of cybercrime, and willingness to disclose criminal activity., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study provided preliminary validation of the Autism Detection in Early Childhood-Virtual (ADEC-V) for telehealth assessment of possible autism. Participants were 121 children (24.79% female) aged 18-47 months who completed telehealth evaluations at a large pediatric hospital in the Midwestern United States between October 2020 and February 2021. The ADEC-V showed good sensitivity (0.82) and specificity (0.78) and was significantly correlated with other ASD symptom measures (i.e., CARS-2, ADI-R). Internal consistency was acceptable (α = 0.77). These results need replication in a larger and broader sample including more children without ASD. This preliminary validation study identifies the ADEC-V as a promising measure for telehealth ASD assessments in young children., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Despite the importance of clinical judgement in autism spectrum disorder (ASD) assessment, little is currently known about challenges faced by diagnosticians when the client is female, any sex/gender biases during the assessment process, and how these issues affect diagnostic outcomes. Forty-seven ASD diagnosticians completed a questionnaire containing two hypothetical case studies (a 'male' and 'female' ASD presentation), with sex/gender randomly assigned within each. Diagnosticians reported greater ASD symptom severity when female sex/gender pseudonyms were allocated to the case studies, but their confidence in ASD diagnosis was similar regardless of condition. Diagnosticians identified a large number of challenges associated with assessing females for ASD. Many of these related to sex/gender differences in ASD presentation and limitations of diagnostic instruments., (© 2021. Crown.)

Emotion recognition difficulties are considered to contribute to social-communicative problems for autistic individuals. Prior research has been dominated by a focus on forced-choice recognition response accuracy for static face presentations of basic emotions, often involving small samples. Using free-report and multiple-choice response formats, we compared emotion recognition in IQ-matched autistic (N = 63) and nonautistic (N = 67) adult samples using 12 face emotion stimuli presented in three different stimulus formats (static, dynamic, social) that varied the degree of accompanying contextual information. Percent agreement with normative recognition responses (usually labeled "recognition accuracy") was slightly lower for autistic adults. Both groups displayed marked inter-individual variability and, although there was considerable overlap between groups, a very small subset of autistic individuals recorded lower percent agreement than any of the nonautistic sample. Overall, autistic individuals were significantly slower to respond and less confident. Although stimulus type, response format, and emotion affected percent agreement, latency and confidence, their interactions with group were nonsignificant and the associated effect sizes extremely small. The findings challenge notions that autistic adults have core deficits in emotion recognition and are more likely than nonautistic adults to be overwhelmed by increasingly dynamic or complex emotion stimuli and to experience difficulties recognizing specific emotions. Suggested research priorities include clarifying whether longer recognition latencies reflect fundamental processing limitations or adjustable strategic influences, probing age-related changes in emotion recognition across adulthood, and identifying the links between difficulties highlighted by traditional emotion recognition paradigms and real-world social functioning. LAY SUMMARY: It is generally considered that autistic individuals are less accurate than nonautistic individuals at recognizing other people's facial emotions. Using a wide array of emotions presented in various contexts, this study suggests that autistic individuals are, on average, only slightly less accurate but at the same time somewhat slower when classifying others' emotions. However, there was considerable overlap between the two groups, and great variability between individuals. The differences between groups prevailed regardless of how stimuli were presented, the response required or the particular emotion., (© 2022 International Society for Autism Research and Wiley Periodicals LLC.)

Growing evidence suggests that autistic females are more likely to be diagnostically overlooked than males, perhaps due to differences in ASD presentations (van Wijngaarden-Cremers in JAMA 44:627-635, 2014). To investigate specific behaviours in which differences lie, we analysed profiles of 777 children using the Childhood Autism Rating Scale (Scholper in JAMA 29:489-493, 2010) or Gilliam Autism Rating Scale (Gilliam, 2014). Males demonstrated greater difficulty in six CARS2-ST items and seven behaviours on the GARS-3, mostly reflecting restricted and repetitive behaviours. Across all instruments, the only area in which females showed greater difficulty was fear or nervousness (CARS2-ST). No meaningful differences emerged from the CARS2-HF analysis. Where males showed greater difficulty, females were more likely to present with developmentally typical behaviour., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Emotion recognition difficulties are considered to contribute to social-communicative problems for autistic individuals and awareness of such difficulties may be critical for the identification and pursuit of strategies that will mitigate their adverse effects. We examined metacognitive awareness of face emotion recognition responses in autistic (N = 63) and non-autistic (N = 67) adults across (a) static, dynamic and social face emotion stimuli, (b) free- and forced-report response formats, and (c) four different sets of the six "basic" and six "complex" emotions. Within-individual relationships between recognition accuracy and post-recognition confidence provided no indication that autistic individuals were poorer at discriminating correct from incorrect recognition responses than non-autistic individuals, although both groups exhibited marked inter-individual variability. Although the autistic group was less accurate and slower to recognize emotions, confidence-accuracy calibration analyses provided no evidence of reduced sensitivity on their part to fluctuations in their emotion recognition performance. Across variations in stimulus type, response format and emotion, increases in accuracy were associated with progressively higher confidence, with similar calibration curves for both groups. Calibration curves for both groups were, however, characterized by overconfidence at the higher confidence levels (i.e., overall accuracy less than the average confidence level), with the non-autistic group contributing more decisions with 90%-100% confidence. Comparisons of slow and fast responders provided no evidence of a "hard-easy" effect-the tendency to exhibit overconfidence during hard tasks and underconfidence during easy tasks-suggesting that autistic individuals' slower recognition responding may reflect a strategic difference rather than a processing speed limitation. LAY SUMMARY: It is generally considered that autistic individuals may have difficulty recognizing other people's facial emotions. However, little is known about their awareness of any emotion recognition difficulties they may experience. This study indicates that, although there is considerable individual variability, autistic adults were as sensitive to variations in the accuracy of their recognition of others' emotions as their non-autistic peers., (© 2022 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Social status is a critical factor determining health outcomes in human and nonhuman social species. In social hierarchies with reproductive skew, individuals compete to monopolize resources and increase mating opportunities. This can come at a significant energetic cost leading to trade-offs between different physiological systems. In particular, changes in energetic investment in the immune system can have significant short and long-term effects on fitness and health. We have previously found that dominant alpha male mice living in social hierarchies have increased metabolic demands related to territorial defense. In this study, we tested the hypothesis that high-ranking male mice favor adaptive immunity, while subordinate mice show higher investment in innate immunity. We housed 12 groups of 10 outbred CD-1 male mice in a social housing system. All formed linear social hierarchies and subordinate mice had higher concentrations of plasma corticosterone (CORT) than alpha males. This difference was heightened in highly despotic hierarchies. Using flow cytometry, we found that dominant status was associated with a significant shift in immunophenotypes towards favoring adaptive versus innate immunity. Using Tag-Seq to profile hepatic and splenic transcriptomes of alpha and subordinate males, we identified genes that regulate metabolic and immune defense pathways that are associated with status and/or CORT concentration. In the liver, dominant animals showed a relatively higher expression of specific genes involved in major urinary production and catabolic processes, whereas subordinate animals showed relatively higher expression of genes promoting biosynthetic processes, wound healing, and proinflammatory responses. In spleen, subordinate mice showed relatively higher expression of genes facilitating oxidative phosphorylation and DNA repair and CORT was negatively associated with genes involved in lymphocyte proliferation and activation. Together, our findings suggest that dominant and subordinate animals adaptively shift immune profiles and peripheral gene expression to match their contextual needs., (Copyright © 2022. Published by Elsevier Inc.)

Although people diagnosed with autism spectrum disorder (ASD) are not more likely to commit crimes, they are overrepresented in the criminal justice system as reported by Howlin (Autism and Asperger syndrome: Preparing for adulthood, Routledge, 2004). This may, in part, be due to unfavourable interactions with the criminal judiciary. Evidence suggests the autistic population are perceived unfavourably in adjudicative proceedings resulting in harsher penalties. The present study explores whether ASD offenders (ASD-O) receive longer sentences compared to national sentencing data. Sentencing data from the Australian Bureau of Statistics (ABS) were used to compare ASD-O with similar offences. ASD-O attracted longer sentences across all offence classifications. Inferential analyses indicated sexual assault sentences were significantly higher in the ASD-O sample. No significant differences were found for murder, manslaughter, and assault., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To determine the serum bile acid (BA) response to 75-g oral glucose in individuals without diabetes, and whether this is attenuated in patients with 'early' type 2 diabetes (T2D) and related to the glycaemic response at 2 hours in either group., Methods: Forty newly diagnosed, treatment-naïve Han Chinese T2D subjects and 40 age-, gender-, and body mass index-matched controls without T2D ingested a 75-g glucose drink after an overnight fast. Plasma glucose and serum concentrations of total and individual BAs, fibroblast growth factor-19 (FGF-19), total glucagon-like peptide-1 (GLP-1), and insulin, were measured before and 2 hours after oral glucose., Results: Fasting total BA levels were higher in T2D than control subjects (P < .05). At 2 hours, the BA profile exhibited a shift from baseline in both groups, with increases in conjugated BAs and/or decreases in unconjugated BAs. There were increases in total BA and FGF-19 levels in control (both P < .05), but not T2D, subjects. Plasma glucose concentrations at 2 hours related inversely to serum total BA levels in control subjects (r = -0.42, P = .006). Total GLP-1 and the insulin/glucose ratio were increased at 2 hours in both groups, and the magnitude of the increase was greater in control subjects., Conclusions: The serum BA response to a 75-g oral glucose load is attenuated in patients with 'early' T2D, as is the secretion of FGF-19 and GLP-1, while in individuals without T2D it correlates with 2-hour plasma glucose levels. These observations support a role for BAs in the regulation of postprandial glucose metabolism., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Autistic adults often experience difficulties in taking the perspective of others, potentially undermining their social interactions. We evaluated a quick, forced-choice version of the Adult Theory of Mind (A-ToM) test, which was designed to assess such difficulties and comprehensively evaluated by Brewer et al. (2017). The forced-choice version (the A-ToM-Q) demonstrated discriminant, concurrent, convergent and divergent validity using samples of autistic (N = 96) and non-autistic adults (N = 75). It can be administered in a few minutes and machine-scored, involves minimal training and facilitates large-scale, live, or web-based testing. It permits measurement of response latency and self-awareness, with response characteristics on both measures enhancing understanding of the nature and extent of perspective taking difficulties in autistic individuals., (© 2021. The Author(s).)

Context: Both gastric emptying and the secretion of glucagon-like peptide-1 (GLP-1) are major determinants of postprandial glycemia in health and type 2 diabetes (T2D). GLP-1 secretion after a meal is dependent on the entry of nutrients into the small intestine, which, in turn, slows gastric emptying., Objective: To define the relationship between gastric emptying and the GLP-1 response to both oral and small intestinal nutrients in subjects with and without T2D., Methods: We evaluated: (i) the relationship between gastric emptying (breath test) and postprandial GLP-1 levels after a mashed potato meal in 73 individuals with T2D; (ii) inter-individual variations in GLP-1 response to (a) intraduodenal glucose (4 kcal/min) during euglycemia and hyperglycemia in 11 healthy and 12 T2D, subjects, (b) intraduodenal fat (2 kcal/min) in 15 T2D subjects, and (c) intraduodenal protein (3 kcal/min) in 10 healthy subjects; and (iii) the relationship between gastric emptying (breath test) of 75 g oral glucose and the GLP-1 response to intraduodenal glucose (4 kcal/min) in 21 subjects (9 healthy, 12 T2D)., Results: The GLP-1 response to the mashed potato meal was unrelated to the gastric half-emptying time (T50). The GLP-1 responses to intraduodenal glucose, fat, and protein varied substantially between individuals, but intra-individual variation to glucose was modest. The T50 of oral glucose was related directly to the GLP-1 response to intraduodenal glucose (r = 0.65, P = 0.002)., Conclusion: In a given individual, gastric emptying is not a determinant of the postprandial GLP-1 response. However, the intrinsic gastric emptying rate is determined in part by the responsiveness of GLP-1 to intestinal nutrients., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We hypothesized that autistic adults may be erroneously judged as deceptive or lacking credibility due to demonstrating unexpected and atypical behaviors. Thirty autistic and 29 neurotypical individuals participated in video-recorded interviews, and we measured their demonstration of gaze aversion, repetitive body movements, literal interpretation of figurative language, poor reciprocity, and flat affect. Participants (N = 1410) viewed one of these videos and rated their perception of the individual's truthfulness or credibility. The hypothesis was partially supported, with autistic individuals perceived as more deceptive and less credible than neurotypical individuals when telling the truth. However, this relationship was not influenced by the presence of any of the target behaviors, but instead, by the individual's overall presentation., (© 2021. The Author(s).)

Objective: The aim of this review is to characterize the current state of literature and knowledge regarding adaptations of gastrointestinal nutrient absorption, and the determinants of this absorption during pregnancy in monogastric mammals., Introduction: Energy demands increase significantly during pregnancy due to the metabolic demands associated with placental and fetal growth, and the deposition of fat stores that support postnatal lactation. Previous studies have examined anatomical changes within the small intestine, but have focused on specific pregnancy stages or specific regions of the small intestine. Importantly, little is known about changes in nutrient absorption during pregnancy, and the underlying mechanisms that lead to these changes. An understanding of these adaptations will inform research to improve pregnancy outcomes for both mothers and newborns in the future., Inclusion Criteria: This review will include primary literature that describes gastrointestinal nutrient absorption and/or its determinants during pregnancy in monogastric mammals, including humans and rodents. Only data for normal pregnancies will be included, and models of pathology and illness will be excluded. Studies must include comparisons between pregnant animals at known stages of pregnancy, and non-pregnant controls, or compare animals at different stages of pregnancy., Methods: The following databases will be searched for literature on this topic: PubMed, Scopus, Web of Science, Embase, MEDLINE, and ProQuest Dissertations and Theses. Evidence screening and selection will be carried out independently by two reviewers, and conflicts will be resolved through discussion with additional members of the review team. Data will be extracted and presented in tables and/or figures, together with a narrative summary., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 JBI.)

Aims: This study investigated the nutrient-mediated modulation of total ghrelin (TG) and acyl ghrelin (AG) secretion from the mouse gastric mucosa, and the role of long-chain fatty acid chemosensors, FFAR4 and CD36, in lipid-mediated modulation of TG and AG release., Methods: Ex-vivo experiments were conducted using mouse gastric mucosa to examine the effects of nutrients (D-glucose, L-phenylalanine, peptone (mixture of oligopeptides & single amino acids), D-mannitol, α-linolenic acid and fat emulsion (intralipid)) on TG and AG secretion. Additionally, inhibition of FFAR4 and CD36 on α-linolenic acid and intralipid-mediated regulation of TG and AG secretion was assessed., Results: TG and AG secretion were unaffected by glucose and D-mannitol. Peptone stimulated the release of TG and AG. In contrast, L-phenylalanine reduced AG secretion only. Intralipid reduced TG secretion and stimulated AG secretion, and α-linolenic acid reduced AG release, without affecting TG mobilisation. Modulation of ghrelin secretion by lipids occurred in an FFAR4 and CD36-independent manner., Conclusion: Ghrelin secretion is modulated in a nutrient-specific manner by proteins and lipids, with TG and AG displaying independent responses to the same stimuli. In addition, FFAR4 and CD36 do not participate in modulation of TG and AG secretion by α-linolenic acid and intralipid., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A sufficient and balanced maternal diet is critical to meet the nutritional demands of the developing fetus and to facilitate deposition of fat reserves for lactation. Multiple adaptations occur to meet these energy requirements, including reductions in energy expenditure and increases in maternal food intake. The central nervous system plays a vital role in the regulation of food intake and energy homeostasis and responds to multiple metabolic and nutrient cues, including those arising from the gastrointestinal tract. This review describes the nutrient requirements of pregnancy and the impact of over- and undernutrition on the risk of pregnancy complications and adult disease in progeny. The central and peripheral regulation of food intake is then discussed, with particular emphasis on the adaptations that occur during pregnancy and the mechanisms that drive these changes, including the possible role of the pregnancy-associated hormones progesterone, estrogen, prolactin, and growth hormone. We identify the need for deeper mechanistic understanding of maternal adaptations, in particular, changes in gut-brain axis satiety signaling. Improved understanding of food intake regulation during pregnancy will provide a basis to inform strategies that prevent maternal under- or overnutrition, improve fetal health, and reduce the long-term health and economic burden for mothers and offspring., (© 2021 The Obesity Society.)

Despite life's diversity, studies of variation often remind us of our shared evolutionary past. Abundant genome sequencing and analyses of gene regulatory networks illustrate that genes and entire pathways are conserved, reused, and elaborated in the evolution of diversity. Predating these discoveries, 19th-century embryologists observed that though morphology at birth varies tremendously, certain stages of vertebrate embryogenesis appear remarkably similar across vertebrates. In the mid to late 20th century, anatomical variability of early and late-stage embryos and conservation of mid-stages embryos (the "phylotypic" stage) was named the hourglass model of diversification. This model has found mixed support in recent analyses comparing gene expression across species possibly owing to differences in species, embryonic stages, and gene sets compared. We compare 186 microarray and RNA-seq data sets covering embryogenesis in six vertebrate species. We use an unbiased clustering approach to group stages of embryogenesis by transcriptomic similarity and ask whether gene expression similarity of clustered embryonic stages deviates from a null expectation. We characterize expression conservation patterns of each gene at each evolutionary node after correcting for phylogenetic nonindependence. We find significant enrichment of genes exhibiting early conservation, hourglass, late conservation patterns in both microarray and RNA-seq data sets. Enrichment of genes showing patterned conservation through embryogenesis indicates diversification of embryogenesis may be temporally constrained. However, the circumstances under which each pattern emerges remain unknown and require both broad evolutionary sampling and systematic examination of embryogenesis across species., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Background and Aims: The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates an array of cytoprotective genes, yet studies in transgenic mice have led to conflicting reports on its role in liver regeneration. We aimed to test the hypothesis that pharmacological activation of Nrf2 would enhance liver regeneration., Approach and Results: Wild-type and Nrf2 null mice were administered bardoxolone methyl (CDDO-Me), a potent activator of Nrf2 that has entered clinical development, and then subjected to two-thirds partial hepatectomy. Using translational noninvasive imaging techniques, CDDO-Me was shown to enhance the rate of restoration of liver volume (MRI) and improve liver function (multispectral optoacoustic imaging of indocyanine green clearance) in wild-type, but not Nrf2 null, mice following partial hepatectomy. Using immunofluorescence imaging and whole transcriptome analysis, these effects were found to be associated with an increase in hepatocyte hypertrophy and proliferation, the suppression of immune and inflammatory signals, and metabolic adaptation in the remnant liver tissue. Similar processes were modulated following exposure of primary human hepatocytes to CDDO-Me, highlighting the potential relevance of our findings to patients., Conclusions: Our results indicate that pharmacological activation of Nrf2 is a promising strategy for enhancing functional liver regeneration. Such an approach could therefore aid the recovery of patients undergoing liver surgery and support the treatment of acute and chronic liver disease., (© 2021 The Authors. HEPATOLOGY published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Objective: Hypothalamic melanocortin 4 receptors (MC4R) are a key regulator of energy homeostasis. Brain-penetrant MC4R agonists have failed, as concentrations required to suppress food intake also increase blood pressure. However, peripherally located MC4R may also mediate metabolic benefits of MC4R activation. Mc4r transcript is enriched in mouse enteroendocrine L cells and peripheral administration of the endogenous MC4R agonist, α-melanocyte stimulating hormone (α-MSH), triggers the release of the anorectic hormones Glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) in mice. This study aimed to determine whether pathways linking MC4R and L-cell secretion exist in humans., Design: GLP-1 and PYY levels were assessed in body mass index-matched individuals with or without loss-of-function MC4R mutations following an oral glucose tolerance test. Immunohistochemistry was performed on human intestinal sections to characterize the mucosal MC4R system. Static incubations with MC4R agonists were carried out on human intestinal epithelia, GLP-1 and PYY contents of secretion supernatants were assayed., Results: Fasting PYY levels and oral glucose-induced GLP-1 secretion were reduced in humans carrying a total loss-of-function MC4R mutation. MC4R was localized to L cells and regulates GLP-1 and PYY secretion from ex vivo human intestine. α-MSH immunoreactivity in the human intestinal epithelia was predominantly localized to L cells. Glucose-sensitive mucosal pro-opiomelanocortin cells provide a local source of α-MSH that is essential for glucose-induced GLP-1 secretion in small intestine., Conclusion: Our findings describe a previously unidentified signaling nexus in the human gastrointestinal tract involving α-MSH release and MC4R activation on L cells in an autocrine and paracrine fashion. Outcomes from this study have direct implications for targeting mucosal MC4R to treat human metabolic disorders., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Glucagon is secreted by pancreatic α cells in response to hypoglycemia and increases hepatic glucose output through hepatic glucagon receptors (GCGRs). There is evidence supporting the notion of extrapancreatic glucagon but its source and physiological functions remain elusive. Intestinal tissue samples were obtained from patients undergoing surgical resection of cancer. Mass spectrometry analysis was used to detect glucagon from mucosal lysate. Static incubations of mucosal tissue were performed to assess glucagon secretory response. Glucagon concentration was quantitated using a highly specific sandwich enzyme-linked immunosorbent assay. A cholesterol uptake assay and an isolated murine colonic motility assay were used to assess the physiological functions of intestinal GCGRs. Fully processed glucagon was detected by mass spectrometry in human intestinal mucosal lysate. High glucose evoked significant glucagon secretion from human ileal tissue independent of sodium glucose cotransporter and KATP channels, contrasting glucose-induced glucagon-like peptide 1 (GLP-1) secretion. The GLP-1 receptor agonist Exendin-4 attenuated glucose-induced glucagon secretion from the human ileum. GCGR blockade significantly increased cholesterol uptake in human ileal crypt culture and markedly slowed ex vivo colonic motility. Our findings describe the human gut as a potential source of extrapancreatic glucagon and demonstrate a novel enteric glucagon/GCGR circuit with important physiological functions beyond glycemic regulation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.

Ghrelin is a gastric hormone with multiple physiological functions, including the stimulation of food intake and adiposity. It is well established that circulating ghrelin levels are closely associated with feeding patterns, rising strongly before a meal and lowering upon food intake. However, the mechanisms underlying the modulation of ghrelin secretion are not fully understood. The purpose of this review is to discuss current knowledge on the circadian oscillation of circulating ghrelin levels, the neural mechanisms stimulating fasting ghrelin levels and peripheral mechanisms modulating postprandial ghrelin levels. Furthermore, the therapeutic potential of targeting the ghrelin pathway is discussed in the context of the treatment of various metabolic disorders, including obesity, type 2 diabetes, diabetic gastroparesis and Prader-Willi syndrome. Moreover, eating disorders including anorexia nervosa, bulimia nervosa and binge-eating disorder are also discussed., (© 2020 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

All species, including humans, are exposed to endocrine-disrupting chemicals (EDCs). Previous experiments have shown behavioral deficits caused by EDCs that have implications for social competence and sexual selection. The neuromolecular mechanisms for these behavioral changes induced by EDCs have not been thoroughly explored. Here, we tested the hypothesis that EDCs administered to rats during a critical period of embryonic brain development would lead to the disruption of normal social preference behavior, and that this involves a network of underlying gene pathways in brain regions that regulate these behaviors. Rats were exposed prenatally to human-relevant concentrations of EDCs (polychlorinated biphenyls [PCBs], vinclozolin [VIN]), or vehicle. In adulthood, a sociosexual preference test was administered. We profiled gene expression of in preoptic area, medial amygdala, and ventromedial nucleus. Prenatal PCBs impaired sociosexual preference in both sexes, and VIN disrupted this behavior in males. Each brain region had unique sets of genes altered in a sex- and EDC-specific manner. The effects of EDCs on individual traits were typically small, but robust; EDC exposure changed the relationships between gene expression and behavior, a pattern we refer to as dis-integration and reconstitution. These findings underscore the effects that developmental exposure to EDCs can have on adult social behavior, highlight sex-specific and individual variation in responses, and provide a foundation for further work on the disruption of genes and behavior after prenatal exposure to EDCs., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Aim: Gastric emptying is a major determinant of the glycaemic response to carbohydrate and is frequently abnormal in type 2 diabetes (T2DM). There is little information about how chronic glycaemic control affects gastric emptying in T2DM. We evaluated gastric emptying of a 75 g glucose drink in community-based patients with T2DM of short duration with good or poor glycaemic control, and compared this to young and older controls., Methods: T2DM patients managed by diet and/or metformin, either well-controlled or poorly-controlled, together with young and age-matched older controls without diabetes, consumed a 75 g oral glucose drink containing 150 mg 13 C-acetate for evaluation of gastric emptying (breath test) and blood glucose over 180 min., Results: The gastric half-emptying time (T50) was longer in the older than the young non-diabetic subjects (P = 0.041), but shorter in well-controlled T2DM patients than age-matched older controls (P = 0.043). The T50 in poorly-controlled T2DM patients was shorter than in older controls (P = 0.006), but similar to young non-diabetic subjects., Conclusions: Gastric emptying of a glucose drink is delayed with ageing, but more rapid in patients with T2DM of relatively short duration, regardless of their glycaemic status. These observations support interventions that slow gastric emptying to improve postprandial glycaemia in these patients with T2DM., Competing Interests: Declaration of Competing Interest KLJ has received research funding from Sanofi and drug supplies from Merck Sharp & Dohme. MH has participated in the advisory boards and/or symposia for Novo Nordisk, Sanofi, Novartis, Eli Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, and AstraZeneca and has received honoraria for this activity. CKR has received research funding from AstraZeneca, Merck Sharp & Dohme, Eli Lilly, Novartis, and Sanofi. RLY has received research funding from AstraZeneca and Pfizer and drug supplies from Boehringer Ingelheim and Takeda Pharmaceuticals. TW has received travel support from Novartis and Sanofi and research funding from Novartis and AstraZeneca. None of the other authors has any personal or financial conflict of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)