Activation of the G protein-coupled sulfakinin receptor inhibits blood meal intake in the mosquito Aedes aegypti.

Little is known about the blood-feeding physiology of arbovirus vector Aedes aegypti although this type of mosquito is known to transmit infectious diseases dengue, Zika, yellow fever, and chikungunya. Blood feeding in the female A. aegypti mosquito is essential for egg maturation and for transmission of disease agents between human subjects. Here, we identify the A. aegypti sulfakinin receptor gene SKR from the A. aegypti genome and show that SKR is expressed at different developmental stages and in varied anatomical localizations in the adult mosquito (at three days after eclosion), with particularly high expression in the CNS. Knockingdown sulfakinin and sulfakinin receptor gene expression in the female A. aegypti results in increased blood meal intake, but microinjection in the thorax of the sulfakinin peptide 1 and 2 both inhibits dose dependently blood meal intake (and delays the time course of blood intake), which is reversible with receptor antagonist. Sulfakinin receptor expressed ectopically in mammalian cells CHO-K1 responds to sulfakinin stimulation with persistent calcium spikes, blockable with receptor antagonist. These data together suggest that activation of the Gq protein-coupled (i.e., calcium-mobilizing) sulfakinin receptor inhibits blood meal intake in female A. aegypti mosquitoes and could serve as a strategic node for the future control of A. aegypti mosquito reproduction/population and disease transmission.

Nondietary psychological app program leads to sustained weight loss due to trained physiological satiety perception.

Obese people are mostly unable to maintain successful weight loss after the end of a dietary change. One reason is that conventional weight reduction concepts neglect physiological hunger and satiety perception, leading to a relapse to previous eating habits on the long run. We examined the long-term efficacy of a psychological smartphone weight loss program, which avoids any dietary instructions and aims at relearning of satiety perception. Parameters of body weight alterations and psychological features, for example, satiety perception, food cravings, and emotional eating, were explored in a nonrandomized experimental study comprising 75 obese participants. Measurements occurred at baseline, two times during program application, as well as at 6- and 12-month follow-up. Participants displayed significant weight loss during the entire study period (p = .029) and showed an improved body composition at the 6-month follow-up (p = .018). These effects were associated with increased satiety perception, as well as reduced food cravings, and emotional eating habits. Notably, all improvements in measured parameters significantly sustained between the end of the program and the 12-month follow-up (p < .005 for all). Psychological relearning of satiety perception may outclass dietary approaches in terms of long-term efficiency.

Nutrient clustering, NOVA classification, and nutrient profiling: How do they overlap, and what do they predict about food palatability?

We compared the performance of three food categorisation metrics in predicting palatability (taste pleasantness) using a dataset of 52 foods, each rated virtually (online) by 72-224 participants familiar with the foods in question, as described in Appetite 193 (2024) 107124. The metrics were nutrient clustering, NOVA, and nutrient profiling. The first two of these metrics were developed to identify, respectively: 'hyper-palatable' foods (HPFs); and ultra-processed foods (UPFs), which are claimed to be 'made to be hyper-palatable'. The third metric categorises foods as high fat, sugar, salt (HFSS) foods versus non-HFSS foods. There were overlaps, but also significant differences, in categorisation of the foods by the three metrics: of the 52 foods, 35 (67%) were categorised as HPF, and/or UPF, and/or HFSS, and 17 (33%) were categorised as none of these. There was no significant difference in measured palatability between HPFs and non-HPFs, nor between UPFs and non-UPFs (p ≥ 0.412). HFSS foods were significantly more palatable than non-HFSS foods (p = 0.049). None of the metrics significantly predicted food reward (desire to eat). These results do not support the use of hypothetical combinations of food ingredients as proxies for palatability, as done explicitly by the nutrient clustering and NOVA metrics. To discover what aspects of food composition predict palatability requires measuring the palatability of a wide range of foods that differ in composition, as we do here.

Social predation by a nudibranch mollusc.

Social predation is a common strategy used by predators to subdue and consume prey. Animals that use this strategy have many ways of finding each other, organizing behaviors and consuming prey. There is wide variation in the extent to which these behaviors are coordinated and the stability of individual roles. This study characterizes social predation by the nudibranch mollusc, Berghia stephanieae, which is a specialist predator that eats only the sea anemone, Exaiptasia diaphana. A combination of experimental and modeling approaches showed that B. stephanieae does predate upon E. diaphana in groups. The extent of social feeding was not altered by length of food deprivation, suggesting that animals are not shifting strategies based on internal state. It was unclear what cues the individual Berghia used to find each other; choice assays testing whether they followed slime trails, were attracted to injured anemones, or preferred conspecifics feeding did not reveal any cues. Individuals did not exhibit stable roles, such as leader or follower, rather the population exhibited fission-fusion dynamics with temporary roles during predation. Thus, the Berghia provides an example of a specialist predator of dangerous prey that loosely organizes social feeding, which persists across hunger states and uses temporary individual roles; however, the cues that it uses for aggregation are unknown.

Effects of acute consumption of a beverage based on extruded whole-grain pearl millet flour on glycemic and insulinemic control, food intake, and appetite sensation in eutrophic adults: A randomized cross-over clinical trial.

OBJECTIVES: Whole-grain pearl millet is a nutritious cereal source of dietary fiber, vitamins, minerals, and bioactive compounds. It offers health benefits such as glycemic control and satiety. Extrusion cooking for diverse formulations, including beverages, can alter its chemical composition, impacting the nutritional value. This study aimed to evaluate the sensory acceptability of an extruded millet flour beverage and its acute effects on glycemic index (GI), glycemic and insulinemic response, food intake, and subjective appetite sensations in euglycemic and eutrophic adults. METHODS: This is an acute, single-blind, randomized, controlled, cross-over clinical study comprising 14 euglycemic and eutrophic adults. Initially, beverages based on whole extruded millet flour were developed, and sensorially and chemically analyzed. Next, a clinical trial was conducted with participants undergoing four sessions and consuming one of the following options: extruded millet beverage, a maltodextrin control beverage, or a glucose solution administered in two separate sessions. Blood glucose, insulin, and appetite responses were assessed over a 2-h period, in addition to determining the GI of the beverages and analyzing food intake in the 24 h following each session. RESULTS: The extruded millet flour strawberry-flavored beverage had the best sensory acceptance and was classified as having as high GI. Consumption of the extruded millet beverage showed similar glycemic and insulinemic responses, as well as appetite control and food intake of the subjects, when compared with consumption of the maltodextrin control beverage. CONCLUSIONS: Intake of the extruded millet beverage maintained glycemic and insulinemic responses, appetite control, and food intake in euglycemic and eutrophic subjects.

Viscerosensory signalling to the nucleus accumbens via the solitary tract nucleus.

The nucleus of the solitary tract (NTS) receives direct viscerosensory vagal afferent input that drives autonomic reflexes, neuroendocrine function and modulates behaviour. A subpopulation of NTS neurons project to the nucleus accumbens (NAc); however, the function of this NTS-NAc pathway remains unknown. A combination of neuroanatomical tracing, slice electrophysiology and fibre photometry was used in mice and/or rats to determine how NTS-NAc neurons fit within the viscerosensory network. NTS-NAc projection neurons are predominantly located in the medial and caudal portions of the NTS with 54 ± 7% (mice) and 65 ± 3% (rat) being TH-positive, representing the A2 NTS cell group. In horizontal brainstem slices, solitary tract (ST) stimulation evoked excitatory post-synaptic currents (EPSCs) in NTS-NAc projection neurons. The majority (75%) received low-jitter, zero-failure EPSCs characteristic of monosynaptic ST afferent input that identifies them as second order to primary sensory neurons. We then examined whether NTS-NAc neurons respond to cholecystokinin (CCK, 20 µg/kg ip) in vivo in both mice and rats. Surprisingly, there was no difference in the number of activated NTS-NAc cells between CCK and saline-treated mice. In rats, just 6% of NTS-NAc cells were recruited by CCK. As NTS TH neurons are the primary source for NAc noradrenaline, we measured noradrenaline release in the NAc and showed that NAc noradrenaline levels declined in response to cue-induced reward retrieval but not foot shock. Combined, these findings suggest that high-fidelity afferent information from viscerosensory afferents reaches the NAc. These signals are likely unrelated to CCK-sensitive vagal afferents but could interact with other sensory and higher order inputs to modulate learned appetitive behaviours.

Appetite sensation improvement by synbiotic supplementation in patients with metabolic syndrome: A randomized controlled clinical trial.

The potential link between dysbiosis, features of metabolic syndrome (MetS), inflammation, and sensation impairment has been recently recognized. However, in this context, there are few indications available regarding the effects of co-supplementation with Bacillus indicus, Bacillus coagulans, and fructooligosaccharide (FOS) prebiotics on patients with MetS. Therefore, this study aimed to investigate the effects of synbiotic supplementation on glycemic indices, inflammatory biomarkers, and appetite among adults with MetS. This study is a randomized, double-blind, placebo-controlled clinical trial conducted in the Endocrine and Metabolism Research Center outpatient clinic in Isfahan, Iran. Fifty-eight MetS patients were randomly assigned to receive either synbiotics (n = 29) or placebo (n = 29) supplementation twice per day for 8 weeks. Finally, 55 patients were recruited for analyses (28 in the intervention group and 27 in the placebo group). Random permuted blocks and a computer-generated random number table were used for treatment allocation. No adverse effects were reported during the study. There were no significant differences in glycemic indices and inflammatory markers within- and between groups (all p > .05). However, a significant increase in the sensation of fullness was documented in the synbiotic group. In conclusion, the eight-week treatment did not improve glycemic control and inflammatory markers. Nevertheless, it demonstrated potential efficacy in enhancing participants' appetite sensations, warranting further evaluation in longer intervention periods during future clinical trials.

Atg8/LC3 controls systemic nutrient surplus signaling in flies and humans.

Organisms experience constant nutritional flux. Mechanisms at the interface of opposing nutritional states-scarcity and surplus-enable organismal energy homeostasis. Contingent on nutritional stores, adipocytes secrete adipokines, such as the fat hormone leptin, to signal nutrient status to the central brain. Increased leptin secretion underlies metabolic dysregulation during common obesity, but the molecular mechanisms regulating leptin secretion from human adipocytes are poorly understood. Here, we report that Atg8/LC3 family proteins, best known for their role in autophagy during nutrient scarcity, play an evolutionarily conserved role during nutrient surplus by promoting adipokine secretion. We show that in a well-fed state, Atg8/LC3 promotes the secretion of the Drosophila functional leptin ortholog unpaired 2 (Upd2) and leptin from human adipocytes. Proteomic analyses reveal that LC3 directs leptin to a secretory pathway in human cells. We identified LC3-dependent extracellular vesicle (EV) loading and secretion (LDELS) as a required step for leptin release, highlighting a unique secretory route adopted by leptin in human adipocytes. In Drosophila, mutations to Upd2's Atg8 interaction motif (AIM) result in constitutive adipokine retention. Atg8-mediated Upd2 retention alters lipid storage and hunger response and rewires the bulk organismal transcriptome in a manner conducive to starvation survival. Thus, Atg8/LC3's bidirectional role in nutrient sensing-conveying nutrient surplus and responding to nutrient deprivation-enables organisms to manage nutrient flux effectively. We posit that decoding how bidirectional molecular switches-such as Atg8/LC3-operate at the nexus of nutritional scarcity and surplus will inform therapeutic strategies to tackle chronic metabolic disorders.

Volitionally Regulated Breathing with Prolonged Expiration Influences Food Craving and Impulsivity.

INTRODUCTION: Previously, an intervention involving volitional slow breathing reduced trait food craving with protective effects on cardiac vagal activity (CVA). Breathing with a low inspiration-to-expiration (i/e) ratio also increases CVA. High CVA was separately associated with low unregulated eating and lesser impulsivity. Hence, the present study assessed breathing with a low i/e for effects on state food craving, hunger and satiety, state impulsivity, and heart rate variability (HRV) in healthy obese persons. METHODS: Forty obese persons were randomized to two groups. The intervention group (mean age ± SD, 41.15 ± 12.63, M:F, 10:10) practiced metronome-regulated breathing with low i/e at 12 breaths per minute (expiration 72% of total breath duration) and attained expiration 55.8% of total breath duration, while the active control group (mean age ± SD, 44.45 ± 11.06, M:F, 13:07) sat motionless and directed their gaze and awareness to the stationary metronome without modifying their breath consciously. The HRV was recorded before, during, and after breathing intervention (or control) (standard limb lead I, acquisition at 2,000 Hz, with an LF filter = 0.5 Hz and HF filter = 50 Hz). Time-domain and frequency-domain HRV parameters were obtained with Kubios software. State food craving, and hunger and satiety were recorded before and after the intervention/control. RESULTS: The intervention group decreased total state food craving scores and the sub-domains (i.e., desire to eat, positive reinforcement, lack of control and hunger), increased current satisfaction with food, decreased total state impulsivity (repeated measures ANOVA, p < 0.05 in all cases), increased HF-HRV and RMSSD (linear mixed model analyses with age and gender as fixed factors; p < 0.05 in all cases) during the intervention compared to the preceding baseline. The intervention group also showed an increase in positive mood and a decrease in aroused and negative mood states. CONCLUSION: Changes in state food craving and impulsivity could be related to an increase in HRV or to changes in subjective relaxation and positive mood or to both.

Manipulation of feeding patterns in high fat diet fed rats improves microbiota composition dynamics, inflammation and gut-brain signaling.

Chronic consumption of high fat (HF) diets has been shown to increase meal size and meal frequency in rodents, resulting in overeating. Reducing meal frequency and establishing periods of fasting, independently of caloric intake, may improve obesity-associated metabolic disorders. Additionally, diet-driven changes in microbiota composition have been shown to play a critical role in the development and maintenance of metabolic disorders. In this study, we used a pair-feeding paradigm to reduce meal frequency and snacking episodes while maintaining overall intake and body weight in HF fed rats. We hypothesized that manipulation of feeding patterns would improve microbiota composition and metabolic outcomes. Male Wistar rats were placed in three groups consuming either a HF, low fat diet (LF, matched for sugar), or pair-fed HF diet for 7 weeks (n = 11-12/group). Pair-fed animals received the same amount of food consumed by the HF fed group once daily before dark onset (HF-PF). Rats underwent oral glucose tolerance and gut peptide cholecystokinin sensitivity tests. Bacterial DNA was extracted from the feces collected during both dark and light cycles and sequenced via Illumina MiSeq sequencing of the 16S V4 region. Our pair-feeding paradigm reduced meal numbers, especially small meals in the inactive phase, without changing total caloric intake. This shift in feeding patterns reduced relative abundances of obesity-associated bacteria and maintained circadian fluctuations in microbial abundances. These changes were associated with improved gastrointestinal (GI) function, reduced inflammation, and improved glucose tolerance and gut to brain signaling. We concluded from these data that targeting snacking may help improve metabolic outcomes, independently of energy content of the diet and hyperphagia.

A Randomized, Crossover Trial Assessing Appetite, Energy Metabolism, Blood Biomarkers, and Ad Libitum Food Intake Responses to a Mid-Morning Pecan Snack vs. an Equicaloric High-Carbohydrate Snack in Healthy Volunteers with Overweight/Obesity.

BACKGROUND: The differential effects of pecans versus other popular snack foods on appetite and blood markers of metabolism and satiety have not been well studied. This study investigated the effects of a single mid-morning snack of pecans or tortilla chips on subjective appetite, food intake, blood measures of hormones and metabolites, and resting energy expenditure. METHODS: Twenty participants with overweight and obesity were enrolled in a within-participants, randomized crossover trial. Participants had indwelling catheters placed for blood sampling and were fed a standardized breakfast, followed two hours later by a 250 kcal snack of either pecans or tortilla chips, and then by a self-selected lunch. Visual analog scale (VAS) appetite measures, blood markers, and energy expenditure were taken at intervals after food consumption. RESULTS: VAS ratings, energy, food intake and macronutrient composition did not differ between treatment conditions, but glucose and insulin were significantly more elevated after tortilla chips. Free fatty acids (FFA), triglycerides (TG), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) were higher after consuming pecans compared to tortilla chips. CONCLUSIONS: Pecan consumption improves postprandial glucose and insulin profiles which would be beneficial to individuals at risk of developing type 2 diabetes. Further studies are needed to investigate whether increased relative secretion of PYY and GLP-1 after eating pecans versus tortilla chips may affect subjective appetite and energy intake if consumed chronically.

Gastrointestinal delivery of bitter hop extract reduces appetite and food cravings in healthy adult women undergoing acute fasting.

Background: Dietary restrictions or reductions such as fasting for weight loss are often difficult to adhere to due to increased appetite and food cravings. Recently, gastrointestinal delivery of bitter hops has been shown to be effective at reducing appetite in men. Our aim was to determine the effect of a bitter hop extract on appetite and cravings in women, using a 24 h, water-only fast. Methods: This was a randomized, double-blind, cross-over treatment study. Thirty adult women were recruited and required to fast for 24 h from 1800 h to 1800 h on three occasions and given an ad libitum meal to break each fast. Treatments of either a placebo or one of two doses (high dose; HD: 250 mg or low dose; LD: 125 mg) of a bitter hop-based appetite suppressant (Amarasate®) were given twice per day at 16 and 20 h into the fast. Results: The HD and LD treatment groups exhibited a significant (p < 0.05) reduction in appetite and cravings for food when compared to the placebo control. Two participants reported loose stools and one reported heartburn while on the HD treatment, and one participant reported loose stools while on the LD treatment. Conclusion: These data suggest that appetite suppressant co-therapy may be useful in reducing hunger during fasting in women and shows that gastrointestinal delivery of bitter compounds may also be an effective method of reducing cravings for food.This trial received ethical approval from the Northen B New Zealand Human Disability and Ethics committee (Northern B Health and Disability Ethics Committee (2022 EXP 10995) and was prospectively registered with the Australian New Zealand Clinical Trial Registry (ACTRN12622000107729).

Influence of baking time and formulation of part-baked wheat sourdough bread on the physical characteristics, sensory quality, glycaemic index and appetite sensations.

Raw materials and process parameters in bread production can modulate the glycemic index, which on itself has been linked with provision of better hunger satisfaction and maintaining better satiation. The objective of this research was to investigate if using unrefined wheat flour or the addition of intact cereals in formulation or alternating the baking time would have an effect on physical characteristics, sensory quality, glycaemic index and appetite sensations in wheat sourdough bread. In the study, three types of commercial part-baked frozen sourdough bread, baked to the final baking for two different times (long and short baking time) were used. A randomized controlled crossover trial was performed with 10 healthy adults who consumed sufficient quantity of bread to ingest 50 g available carbohydrates. Participants self-reported appetite sensations (desire to eat, hunger, fullness, satisfaction, appetite) on a 10 cm visual analog scale (VAS) scale in a course of 180 min. In addition, bread products were subjected to overall acceptability and different sensory attributes were examined on JAR "just about right" scale. Different bread formulations (refined flour, unrefined wheat flour, cereal flour or intact cereals) and different length of baking time significantly influenced (p < 0.005) physical, textural and sensory features of products. The alternation of aforementioned parameters decreased the glycemic index, but not significantly (p > 0.005). No correlation was found between lower GI, satiety and satiation. Liking score and incremental area under the curve (iAUC) of satiety and satiation were calculated as highest in sourdough bread with added cereals.

Independent effects of volume and energy density manipulation on energy intake and appetite in healthy adults: A randomized, controlled, crossover study.

Consuming enough energy to meet high energy demands can be challenging for military personnel wherein logistical constraints limit food availability. Increasing dietary energy density (ED) and/or volume density (VD) of rations may be countermeasures, but whether positive linear associations between ED and energy intake (EI) hold at moderate-to-high ED and VD is unclear. This study examined the effects of covertly increasing the ED and VD of moderate ED (≥1.6 kcal/g) foods on appetite and energy intake. Twenty healthy men completed four 2-day treatments in random order by consuming a standardized diet containing three experimental food items (EXP) engineered using leavening, physical compression and fat manipulation to be isovolumetric but lower (L) or higher (H) in ED and VD creating four treatments: LED/LVD, LED/HVD, HED/LVD, HED/HVD. Consumption of EXP was compulsory during two meals and a snack, but remaining intake was self-selected (SSF). Results failed to show any ED-by-VD interactions. During LVD, EI was lower for EXP (-417 kcal [95%CI: 432, -402], p < 0.01) and TOTAL (SSF + EXP) (-276 kcal [95%CI: 470, -83], p = 0.01) compared to HVD, while SSF EI did not differ (140 kcal [-51, 332], p = 0.15). During LED, EI for EXP (-291 kcal [95%CI: 306, -276], p < 0.01) was lower than HED, while SSF EI was higher than HED (203 kcal 95%CI: [12, 394], p = 0.04) and TOTAL EI did not differ (-88 kcal [-282, 105], p = 0.36). Thus, when a small isovolumetric portion of the diet was manipulated, increasing the VD of moderate ED foods failed to elicit compensatory reductions in ad libitum EI while increasing the ED of moderate ED foods did. Findings may support VD manipulation of moderate ED foods as a strategy to promote increased short-term EI in environments wherein logistical burden may limit food volume.

Examining the Direct and Indirect Effects of Postprandial Amino Acid Responses on Markers of Satiety following the Acute Consumption of Lean Beef-Rich Meals in Healthy Women with Overweight.

The consumption of protein-rich foods stimulates satiety more than other macronutrient-rich foods; however, the underlying mechanisms-of-action are not well-characterized. The objective of this study was to identify the direct and indirect effects of postprandial amino acid (AA) responses on satiety. Seventeen women (mean ± SEM, age: 33 ± 1 year; BMI: 27.8 ± 0.1 kg/m2) consumed a eucaloric, plant-based diet containing two servings of lean beef/day (i.e., 7.5 oz (207 g)) for 7 days. During day 6, the participants completed a 12 h controlled-feeding, clinical testing day including repeated satiety questionnaires and blood sampling to assess pre- and postprandial plasma AAs, PYY, and GLP-1. Regression and mediation analyses were completed to assess AA predictors and hormonal mediators. Total plasma AAs explained 41.1% of the variance in perceived daily fullness (p < 0.001), 61.0% in PYY (p < 0.001), and 66.1% in GLP-1 (p < 0.001) concentrations, respectively. Several individual AAs significantly predicted fluctuations in daily fullness, PYY, and GLP-1. In completing mediation analyses, the effect of plasma leucine on daily fullness was fully mediated by circulating PYY concentrations (indirect effect = B: 0.09 [Boot 95% CI: 0.032, 0.17]) as no leucine-fullness direct effect was observed. No other mediators were identified. Although a number of circulating AAs predict satiety, leucine was found to do so through changes in PYY concentrations in middle-aged women.

Identification of sulfakinin receptor regulating feeding behavior and hemolymph trehalose homeostasis in the silkworm, Bombyx mori.

Feeding behavior, the most fundamental physiological activity, is controlled by two opposing groups of factors, orexigenic and anorexigenic factors. The sulfakinin family, an insect analogue of the mammalian satiety factor cholecystokinin (CCK), has been shown to suppress food intake in various insects. Nevertheless, the mechanisms through which sulfakinin regulates feeding behavior remain a biological question. This study aimed to elucidate the signaling pathway mediated by the anorexigenic peptide sulfakinin in Bombyx mori. We identified the Bombyx mori neuropeptide G protein-coupled receptor A9 (BNGR-A9) as the receptor for sulfakinin through functional assays. Stimulation with sulfakinin triggered a swift increase in intracellular IP3, Ca2+, and a notable enhancement of ERK1/2 phosphorylation, in a manner sensitive to a Gαq-specific inhibitor. Treatment with synthetic sulfakinin resulted in decreased food consumption and average body weight. Additionally, administering synthetic sulfakinin to silkworms significantly elevated hemolymph trehalose levels, an effect markedly reduced by pre-treatment with BNGR-A9 dsRNA. Consequently, our findings establish the sulfakinin/BNGR-A9 signaling pathway as a critical regulator of feeding behavior and hemolymph trehalose homeostasis in Bombyx mori, highlighting its roles in the negative control of food intake and the positive regulation of energy balance.

The nature of training in flavor preference learning determines the underlying associative structure.

Pairing a palatable flavor (US) with an initially neutral flavor cue (CS) results in an acquired conditioned preference for the latter. Two main associations have been proposed to explain the acquisition of flavor preferences: Flavor-Flavor and Flavor-Nutrient learning. Although the hedonic reaction triggered by US consumption has also been suggested as a possible additional component underlying acquired flavor preference, this issue has received little attention. Here we explored whether the amount of training to the CS-US compound can favor the formation of a Flavor-Hedonic reaction association using rats as subjects and sucrose as the US. We expected that the more exposure to the CS-US compound, the stronger the S-R type association. Since S-R associations are not sensitive to devaluation procedures, we used a Sensory-Specific Satiety procedure to devalue the US after conditioning and then measured preferences for the CS. On Experiment 1 with a short restrictive training (classic procedure), preference for the CS was decreased after devaluation of the US compared to the control condition. On Experiment 2, with short unrestrictive training, preference for the CS was again weakened. Experiment 3 with a long unrestrictive training, rats expressed preference for the CS regardless of the devaluation procedure. These results suggest that, as with an instrumental paradigm, extensive training in flavor preference learning undermines the US devaluation effect.

Does glucose-dependent insulinotropic polypeptide receptor blockade as well as agonism have a role to play in management of obesity and diabetes?

Recent approval of the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, tirzepatide, for the management of type 2 diabetes mellitus (T2DM) has reinvigorated interest in exploitation of GIP receptor (GIPR) pathways as a means of metabolic disease management. However, debate has long surrounded the use of the GIPR as a therapeutic target and whether agonism or antagonism is of most benefit in management of obesity/diabetes. This controversy appears to be partly resolved by the success of tirzepatide. However, emerging studies indicate that prolonged GIPR agonism may desensitise the GIPR to essentially induce receptor antagonism, with this phenomenon suggested to be more pronounced in the human than rodent setting. Thus, deliberation continues to rage in relation to benefits of GIPR agonism vs antagonism. That said, as with GIPR agonism, it is clear that the metabolic advantages of sustained GIPR antagonism in obesity and obesity-driven forms of diabetes can be enhanced by concurrent GLP-1 receptor (GLP-1R) activation. This narrative review discusses various approaches of pharmacological GIPR antagonism including small molecule, peptide, monoclonal antibody and peptide-antibody conjugates, indicating stage of development and significance to the field. Taken together, there is little doubt that interesting times lie ahead for GIPR agonism and antagonism, either alone or when combined with GLP-1R agonists, as a therapeutic intervention for the management of obesity and associated metabolic disease.

Gastrointestinal Myoelectrical Activity (GIMA) Biomarker for Noninvasive Diagnosis of Endometriosis.

Background/Objectives: Endometriosis represents substantial direct and indirect healthcare costs impacted by an absence of uniformly accurate, non-invasive diagnostic tools. We endeavored to demonstrate gastrointestinal myoelectrical activity (GIMA) biomarkers, unique to endometriosis, will allow non-invasive, uniformly accurate diagnosis or exclusion of endometriosis. Methods: Prospective open-label comparative study of 154 patients, age ≥ 18, with or without diagnosed endometriosis. Population included 62 non-endometriosis controls (Cohort 1), 43 subjects with surgically/histologically confirmed endometriosis (Cohort 2), and 49 subjects with abdominal pain and negative imaging (Cohort 3). Non-invasive electroviscerography (EVG) recorded GIMA biomarkers from three abdominal electrodes before and 30 min post water load protocol. Cohort 2 had postoperative EVG and Cohort 3 had preoperative EVG. Calculated specificity, sensitivity, negative predictive value (NPV), positive predictive value (PPV), and predictive probability or C-statistic used univariate, multivariate, linear, and logistical regression analyses of the area under the curve (AUC) at all frequency and time points, including age and pain covariants. Results: The non-endometriosis cohort differed significantly from the endometriosis cohorts (p < 0.001) for median (IQR) and AUC percent frequency distribution of power at baseline, 10 min, 20 min, and 30 min post water load at all frequency ranges: 15-20 cpm, 30-40 cpm, and 40-50 cpm. The endometriosis cohorts were statistically similar (p > 0.05). GIMA biomarker threshold scoring demonstrated 95%/91% sensitivity and PPV, 96%/95% specificity and NPV, and a C-statistic of >99%/98%, respectively, for age subsets. GIMA biomarkers in Cohort 3 predicted 47/49 subjects positive and 2/49 negative for endometriosis, confirmed surgically. Hormonal therapy, surgical stage, nor pain score affected diagnostic accuracy. Conclusions: EVG with GIMA biomarker detection distinguished participants with and without endometriosis based upon endometriosis-specific GIMA biomarkers threshold scoring.

How did the use of the social marketing approach in Egyptian communities succeed in improving breastfeeding practices and infants' growth?

INTRODUCTION: Improving breastfeeding practices does not always link to interventions relying only on improving nutrition awareness and education but needs cultural and behavioral insights . AIM: This study aimed to evaluate the changes in core breastfeeding indicators as a result of the use of social marketing (SM) approach for improving breastfeeding practices of Egyptian women and the physical growth of infants aged 6 to 12 months. The core breastfeeding indicators were: Early initiation of breastfeeding within one hour of birth, Predominant and exclusive breastfeeding to 6 months (EBF), Bottle feeding with formula, continued breastfeeding to 1 and 2 years, and responsiveness to cues of hunger and satiety. METHODS: A quasi-experimental longitudinal study with a posttest-only control design was done over 3 years in three phases; the first was in-depth interviews and formative research followed by health education and counseling interventions and ended by measuring the outcome. Motivating mothers' voluntary behaviors toward breastfeeding promotion "feeding your baby like a baby" was done using SM principles: product, price, place, and promotion. The interventions targeted 646 pregnant women in their last trimester and delivered mothers and 1454 women in their childbearing period. The statistical analysis was done by using SPSS program, version 26. RESULTS: Most mothers showed significantly increased awareness about the benefits of breastfeeding and became interested in breastfeeding their children outside the house using the breastfeeding cover (Gawn) (p < 0.05). Breastfeeding initiation, exclusive breastfeeding under 6 months, frequency of breastfeeding per day, and percentage of children who continued breastfeeding till 2 years, were significantly increased (from 30%, 23%, 56%, and 32% to 62%, 47.3%, 69%, and 43.5% respectively). The girls who recorded underweight results over boys during the first year of life were significantly improved (p < 0.01) after the intervention (from 52.1% to 18.8% respectively). At the same time, girls found to be obese before the intervention (15.6%) became no longer obese. CONCLUSIONS: Improvement for the majority of the key breastfeeding indicators and physical growth of infants indicates that raising a healthy generation should start by promoting breastfeeding practices that are respectable to societal norms.