Hindbrain Double-Negative Feedback Mediates Palatability-Guided Food and Water Consumption.

Hunger and thirst have distinct goals but control similar ingestive behaviors, and little is known about neural processes that are shared between these behavioral states. We identify glutamatergic neurons in the peri-locus coeruleus (periLCVGLUT2 neurons) as a polysynaptic convergence node from separate energy-sensitive and hydration-sensitive cell populations. We develop methods for stable hindbrain calcium imaging in free-moving mice, which show that periLCVGLUT2 neurons are tuned to ingestive behaviors and respond similarly to food or water consumption. PeriLCVGLUT2 neurons are scalably inhibited by palatability and homeostatic need during consumption. Inhibition of periLCVGLUT2 neurons is rewarding and increases consumption by enhancing palatability and prolonging ingestion duration. These properties comprise a double-negative feedback relationship that sustains food or water consumption without affecting food- or water-seeking. PeriLCVGLUT2 neurons are a hub between hunger and thirst that specifically controls motivation for food and water ingestion, which is a factor that contributes to hedonic overeating and obesity.

Tiger beetles produce anti-bat ultrasound and are probable Batesian moth mimics.

Echolocating bats and their eared insect prey are in an acoustic evolutionary war. Moths produce anti-bat sounds that startle bat predators, signal noxiousness, mimic unpalatable models and jam bat sonar. Tiger beetles (Cicindelidae) also purportedly produce ultrasound in response to bat attacks. Here we tested 19 tiger beetle species from seven genera and showed that they produce anti-bat signals to playback of authentic bat echolocation. The dominant frequency of beetle sounds substantially overlaps the sonar calls of sympatric bats. As tiger beetles are known to produce defensive chemicals such as benzaldehyde and hydrogen cyanide, we hypothesized that tiger beetle sounds are acoustically advertising their unpalatability. We presented captive big brown bats (Eptesicus fuscus) with seven different tiger beetle species and found that 90 out of 94 beetles were completely consumed, indicating that these tiger beetle species are not aposematically signalling. Instead, we show that the primary temporal and spectral characteristics of beetle warning sounds overlap with sympatric unpalatable tiger moth (Arctinae) sounds and that tiger beetles are probably Batesian mimics of noxious moth models. We predict that many insect taxa produce anti-bat sounds and that the acoustic mimicry rings of the night sky are hyperdiverse.

Incorporation of patient-reported outcomes in early-phase clinical trials for childhood and adolescent cancer.

INTRODUCTION: The assessment of quality of life (QoL) should be one of the main objectives in paediatric clinical trials. Even though researchers, regulators and advocates support the use of patient-reported outcomes (PROs), this has not been fully implemented. The aim of this study is to assess the measurement of QoL and the usage of PROs, palatability assessments and medication diaries in early-phase clinical trials for childhood and adolescent cancer. METHODS: Early-phase clinical trials for children and adolescents with cancer opened between 2005 and 2022 at the Royal Marsden Hospital (London, UK) and Vall d'Hebron University Hospital (Barcelona, Spain) were interrogated for trial characteristics and the use of QoL questionnaires, PROs, palatability assessments and medication diaries. RESULTS: Overall, 72 clinical trials were analysed: 12 (16.7%) evaluated QoL and eight (11.1%) evaluated PROs. Palatability was tested in 21/40 (52.5%) trials of oral drugs and 23/72 (31.9%) incorporated medication diaries. No studies mentioned patient involvement in the trial protocol. Use of PROs increased from one of 36 (2.8%) to seven of 36 (19.4%) between the first period (2005-2016) and the second period (2017-2022) (p = .02). Implementation of medication diaries increased from seven of 36 (19.4%) to 16/36 (44.4%) in each period, respectively (p = .02). CONCLUSION: Only a minor proportion of the international/multicentric early-phase trials evaluated included QoL/PROs and medication diaries or palatability questionnaires to help assess these, although this trend seems to be increasing over recent years. Greater implementation of QoL/PROs has the potential to improve the patient's wellbeing and facilitate symptom control, to enhance patient/parent involvement in future trial designs and to provide information for drug prioritisation.

Warming suppresses grassland recovery in biomass but not in community composition after grazing exclusion in a Mongolian grassland.

We conducted a 4-year temperature manipulation experiment in a Mongolian grassland to examine the effect of daytime and nighttime warming on grassland recovery after grazing exclusion. After constructing a livestock exclusion fence in the grassland, we established daytime and daytime-and-nighttime warming treatments within the fenced area by a combination of open-top chambers (OTC) and electric heaters. We measured the numbers of plants and aboveground biomass by species after recording percentage vegetation cover every summer for three warming treatments inside the fence-non-warming, daytime warming, and daytime-and-nighttime warming-and for the grassland outside of the fence. OTCs increased daytime temperature by about 2.0 °C, and heaters increased nighttime temperature by 0.9 °C during the growing period. Grazing exclusion had little effect on grassland biomass but reduced the abundance of poorly palatable species and modified plant community composition. Daytime warming decreased soil moisture and lowered aboveground biomass within the fenced grassland but had little effect on plant community composition. Nighttime warming lowered soil moisture further but its effects on grassland biomass and community composition were undetectable. We concluded that recovery of plant biomass in grasslands degraded by grazing would be lowered by future climate warming through soil drying. Because warming had little effect on the recovery of community composition, adverse effects of warming on grassland recovery might be offset by improving plant productivity through mitigation of soil drying by watering. Soil drying due to nighttime warming might have detectable effects on vegetation when warming persists for a long time.

Conditioned overconsumption is dependent on reinforcer type in lean, but not obese, mice.

Associative learning can drive many different types of behaviors, including food consumption. Previous studies have shown that cues paired with food delivery while mice are hungry will lead to increased consumption in the presence of those cues at later times. We previously showed that overconsumption can be driven in male mice by contextual cues, using chow pellets. Here we extended our findings by examining other parameters that may influence the outcome of context-conditioned overconsumption training. We found that the task worked equally well in males and females, and that palatable substances such as high-fat diet and Ensure chocolate milkshake supported learning and induced overconsumption. Surprisingly, mice did not overconsume when sucrose was used as the reinforcer during training, suggesting that nutritional content is a critical factor. Interestingly, we also observed that diet-induced obese mice did not learn the task. Overall, we find that context-conditioned overconsumption can be studied in lean male and female mice, and with multiple reinforcer types.

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.

Ethnoveterinary uses of forage plants for domesticated ruminants in Malakand agency, Pakistan.

Plant ethnoveterinary uses are evident in various studies around the world, but the ethnoveterinary practices of forage species are not widely reported. Traditional knowledge is rapidly disappearing because of urbanization and commercial activities. The purpose of this study was to document plant species used by the local communities in Malakand Agency, Pakistan for foraging and ethnoveterinary purposes. Twenty different localities in the study area were surveyed for documentation of forage species and related traditional ethnoveterinary knowledge used for livestock. Semistructured questionnaires and field walks were used to conduct 67 interviews with local farmers and herdsmen. A total of 91 forage species from 26 families were documented, as well as their ethnoveterinary applications. Poaceae and Fabaceae were dominant families with 45% and 15% of species respectively. Among the forage species documented, 62 were highly palatable, 26 were moderately palatable and 12 were less palatable. The region's major veterinary diseases are flu, ringworms, inflammations, low milk production, constipation, bloat, mastitis, pneumonia and wounds. The 62 forage species were reported for the first time for various veterinary uses. This study revealed that local communities commonly use a diverse range of forage species in conjunction with indigenous knowledge of ethnoveterinary uses. These forage species have the potential to overcome the recent fodder shortage. Such studies will be beneficial to the commercial production of such forage species.

Determining the effects of Candida utilis-fermented pea starch vs. unfermented pea starch, alone or in whole diets, on palatability and glycemic response in dogs and cats.

Current research suggests yeast fermentation has the potential to improve palatability of pea-based diets for both cats and dogs. However, to be useful, fermentation should not compromise other healthy attributes of peas such as a low glycemic response. Fermentation of uncooked pea starch with Candida utilis (ATCC 9950) appeared to increase crude protein, crude fiber content, inorganic compounds (phosphorus and iron) and phenols. Whole diets were designed with fermented and unfermented pea starch to assess palatability, food intake, and glycemic responses in unacclimated, mixed sex Beagle dogs and mixed breed cats (n = 8 and n = 7, respectively). For palatability testing, a control diet was formulated with 30% corn starch as well as test diets with 30% inclusion of fermented or unfermented pea starch (all lab-made), then compared to a commercial diet containing pea starch (Legacy/Horizon). Fermentation had little effect on rapidly digestible starch either in uncooked starch form or when incorporated into whole diets, but did decrease resistant starch by 15% and increase slowly digestible starch by 20%. Palatability tests using either two choices or four choices at a time revealed a significant preference for the fermented pea starch diet (p < 0.01) in both species. For the glycemic responses, a total of four different pea products were included: unfermented pea starch, fermented pea starch, and 30% inclusion of unfermented and fermented pea starch in whole formulated diets. There were no significant changes in glycemic responses with the fermented pea diet compared to the unfermented diet, demonstrating that healthful low glycemic properties of pea starch were retained after C. utilis fermentation. Overall, C. utilis-fermentation technique was successfully adapted to pea starch where it resulted in increased palatability and food intake in dogs and cats, with potential to positively contribute to overall health benefits for both species.

Acceptability of an Orange-Flavoured Zinc Sulphate Dispersible Tablet in the Management of Acute Diarrhoea in Under-five Children in Lagos, Nigeria.

BACKGROUND: Acute diarrhoea is a significant cause of morbidity and mortality in children under five, especially in subSaharan Africa. The WHO recommends using oral rehydration solution (ORS) and zinc therapy for its management, but the metallic taste of zinc often hinders adherence. METHOD: This prospective open-label intervention study took place at three health facilities in Lagos, Southwest Nigeria, involving children aged 3 to 59 months with acute diarrhoea. Sociodemographic and diarrhoea-related data were obtained. Palatability was assessed using a 5-point hedonic scale, and adherence was determined by the proportion of prescribed zinc sulfate tablets consumed. Caregivers received a 10-day supply of the study drug and ORS sachets for each child, along with participant diaries for tracking drug intake, palatability scores, and adverse events. Follow-up was conducted on Days 3 and 7, and diaries were collected between Days 10 and 14. RESULTS: Out of the 294 participants, most caregivers were mothers (86.0%), had at least a secondary education (88.1%), and were employed (70.7%). The majority of children were male (54.2%), and under 18 months old (52.2%). The average palatability score was 2.65 (±0.78), with no significant differences based on age or gender. Mean adherence was 93.03%, with 89.3% achieving ≥80% adherence, and adherence did not significantly differ by age or gender. The only reported adverse event, vomiting, decreased from 18.8% on Day 1 to 0.5% on Day 10. CONCLUSION: The study indicates that the orange-flavored dispersible zinc sulfate tablet is well-accepted by children aged 3 to 59 months with acute diarrhoea in Lagos, Nigeria.

CONTEXTE: La diarrhée aiguë est une cause significative de morbidité et de mortalité chez les enfants de moins de cinq ans, en particulier en Afrique subsaharienne. L'OMS recommande l'utilisation de la solution de réhydratation orale (SRO) et de la thérapie au zinc pour sa prise en charge, mais le goût métallique du zinc entrave souvent l'observance. MÉTHODE: L'étude d'intervention prospective à ciel ouvert a eu lieu dans trois établissements de santé à Lagos, dans le sud-ouest du Nigeria, impliquant des enfants de 3 à 59 mois souffrant de diarrhée aiguë. Des données sociodémographiques et liées à la diarrhée ont été obtenues. La palatabilité a été évaluée à l'aide d'une échelle hédonique à 5 points, et l'observance a été déterminée par la proportion de comprimés de sulfate de zinc prescrits consommés. Les aidants ont reçu une provision de 10 jours du médicament de l'étude et des sachets de SRO pour chaque enfant, ainsi que des journaux de suivi pour noter la prise du médicament, les scores de palatabilité et les événements indésirables. Un suivi a été effectué aux jours 3 et 7, et les journaux ont été collectés entre les jours 10 et 14. RÉSULTATS: Sur les 294 participants, la plupart des aidants étaient des mères (86,0%), avaient au moins une éducation secondaire (88,1%), et étaient employées (70,7%). La majorité des enfants étaient de sexe masculin (54,2%) et avaient moins de 18 mois (52,2%). La note moyenne de palatabilité était de 2,65 (±0,78), sans différences significatives en fonction de l'âge ou du sexe. L'observance moyenne était de 93,03%, avec 89,3% atteignant une observance ≥ 80%, et l'observance ne différait pas de manière significative en fonction de l'âge ou du sexe. Le seul événement indésirable signalé, les vomissements, est passé de 18,8% le jour 1 à 0,5% le jour 10. CONCLUSION: L'étude indique que le comprimé de sulfate de zinc dispersible à l'arôme d'orange est bien accepté par les enfants de 3 à 59 mois souffrant de diarrhée aiguë à Lagos, au Nigeria. MOTS-CLÉS: Diarrhée, moins de cinq ans, Enfants, Arôme d'orange, Comprimés de zinc, Palatabilité, Acceptabilité, Échelle hédonique, Lagos, Nigeria.

It is a matter of perspective: Attentional focus rather than dietary restraint drives brain responses to food stimuli.

Brain responses to food are thought to reflect food's rewarding value and to fluctuate with dietary restraint. We propose that brain responses to food are dynamic and depend on attentional focus. Food pictures (high-caloric/low-caloric, palatable/unpalatable) were presented during fMRI-scanning, while attentional focus (hedonic/health/neutral) was induced in 52 female participants varying in dietary restraint. The level of brain activity was hardly different between palatable versus unpalatable foods or high-caloric versus low-caloric foods. Activity in several brain regions was higher in hedonic than in health or neutral attentional focus (p < .05, FWE-corrected). Palatability and calorie content could be decoded from multi-voxel activity patterns (p < .05, FDR-corrected). Dietary restraint did not significantly influence brain responses to food. So, level of brain activity in response to food stimuli depends on attentional focus, and may reflect salience, not reward value. Palatability and calorie content are reflected in patterns of brain activity.

Umami taste perception and preferences of the domestic cat (Felis catus), an obligate carnivore.

The domestic cat (Felis catus) is an obligate carnivore, and as such has a meat-based diet. Several studies on the taste perception of cats have been reported, indicating that their sense of taste has evolved based on their carnivorous diet. Here, we propose that umami (mediated by Tas1r1-Tas1r3) is the main appetitive taste modality for the domestic cat by characterizing the umami taste of a range of nucleotides, amino acids, and their mixtures for cats obtained using complementary methods. We show for the first time that cats express Tas1r1 in taste papillae. The cat umami receptor responds to a range of nucleotides as agonists, with the purine nucleotides having the highest activity. Their umami receptor does not respond to any amino acids alone; however, 11 l-amino acids with a range of chemical characteristics act as enhancers in combination with a nucleotide. l-Glutamic acid and l-Aspartic acid are not active as either agonists or enhancers of the cat umami receptor due to changes in key binding residues at positions 170 and 302. Overall, cats have an appetitive behavioral response for nucleotides, l-amino acids, and their mixtures. We postulate that the renowned palatability of tuna for cats may be due, at least in part, to its specific combination of high levels of inosine monophosphate and free l-Histidine that produces a strong synergistic umami taste enhancement. These results demonstrate the critical role that the umami receptor plays in enabling cats to detect key taste compounds present in meat.

Patient preference for deferasirox film-coated versus dispersible tablet formulation: a sequential-design phase 2 study in patients with thalassemia.

Iron chelation therapy (ICT) is the mainstay of treatment in patients with thalassemia requiring blood transfusions. This phase 2 JUPITER study evaluated patient preference between film-coated tablet (FCT) and dispersible tablet (DT) in transfusion-dependent thalassemia (TDT) or non-TDT (NTDT) patients treated with both formulations in a sequential manner. The primary endpoint was patient-reported preference for FCT over DT, while secondary outcomes included patient reported outcomes (PROs) evaluated by overall preference, and by age, thalassemia transfusion status, and previous ICT status. Out of 183 patients screened, 140 and 136 patients completed the treatment periods 1 and 2 of the core study, respectively. At week 48, the majority of patients preferred FCT over DT (90.3 vs. 7.5%; difference of percentage: 0.83 [95% confidence interval (CI), 0.75-0.89; P < 0.0001]). FCT scored better on secondary PROs and showed less severe gastrointestinal symptoms than DT, except in the change of modified Satisfaction with Iron Chelation Therapy (mSICT) preference scores, which were similar for both the formulations. Patients with TDT had stable ferritin levels, while it showed a downward trend up to week 48 in patients with NTDT on deferasirox treatment. Overall, 89.9% of patients reported ≥ 1 adverse event (AE), of which 20.3% experienced ≥ 1 serious AE. The most common treatment-emergent AEs were proteinuria, pyrexia, urine protein/creatinine ratio increase, diarrhea, upper respiratory tract infections, transaminase increase, and pharyngitis. Overall, this study reinforced the observations from the previous study by showing a distinct patient preference for FCT over DT formulation and further supported the potential benefits of life-long compliance with ICT.

Maternal chemical defenses predict offspring defenses in a dendrobatid poison frog.

Within and among populations, alkaloid defenses of the strawberry poison frog (Oophaga pumilio) vary spatially, temporally, and with life history stage. Natural variation in defense has been implicated as a critical factor in determining the level of protection afforded against predators and pathogens. Oophaga pumilio tadpoles sequester alkaloids from nutritive eggs and are, thus, entirely dependent on their mothers for their defense. However, it remains unclear how tadpole alkaloid composition relates to that of its mother and how variation in maternally provisioned defenses might result in varying levels of protection against predators. Here, we demonstrate that natural variation in the alkaloid composition of a mother frog is reflected as variation in her tadpole's alkaloid composition. Tadpoles, like mother frogs, varied in their alkaloid composition but always contained the identical alkaloids found in their mother. Alkaloid quantity in tadpoles was highly correlated with alkaloid quantity in their mothers. Additionally, alkaloid quantity was the best predictor of tadpole palatability, wherein tadpoles with higher alkaloid quantities were less palatable. Mother frogs with greater quantities of alkaloids are, thus, providing better protection for their offspring by provisioning chemical defenses during one of the most vulnerable periods of life.

Chronic sugar exposure increases daily intake of sugars but decreases avidity for sweeteners in mice.

Little is known about how chronic sugar consumption impacts avidity for and daily intake of sugars. This issue is topical because modern humans exhibit high daily intakes of sugar. Here, we exposed sugar-naïve C57BL/6 mice (across two 28-day exposure periods, EP1 and EP2) to a control (chow and water) or experimental (chow, water and a 11 or 34% sugar solution) diet. The sugar solutions contained sucrose, glucose syrups, or high-fructose syrups. We used brief-access tests to measure appetitive responses to sucralose and sucrose solutions at three time points: baseline (before EP1), after EP1, and after EP2. We used lick rates to infer palatability, and number of trials initiated/test to infer motivation. Exposure to the control diet had no impact on lick rates or number of trials initiated for sucralose and sucrose. In contrast, exposure to the experimental diets reduced licking for the sweeteners to varying degrees. Lick rates were reduced by exposure to sugar solutions containing the 11% glucose syrups, 34% sucrose, 34% glucose syrups and 34% high-fructose syrups. The number of trials initiated was reduced by exposure to all of the sugar solutions. Despite the exposure-induced reductions in avidity for the sweetener solutions, daily intakes of virtually all of the sugar solutions increased across the exposure periods. We conclude that (i) chronic consumption of sugar solutions reduced avidity for the sweetened solutions, (ii) the extent of this effect depended on the concentration and type of sugar, and (iii) avidity for sweet-tasting solutions could not explain the persistently high daily intake of sugar solutions in mice.

Palatability of Aripiprazole Gummies Prepared from Commercially Available Products: Pharmaceutical Formulation for Improving Patient Adherence.

Good adherence to medication is critical for successfully treating psychiatric disorders. Tailor-made pharmaceutical formulations can provide a suitable dosage form to meet the specific needs of individual patients who exhibit poor adherence to industrially manufactured products. Herein, we prepared aripiprazole (ARP) gummies (ARP-Gs) using a commercially available ARP formulation. We aimed to clarify the palatability of ARP-Gs by performing a gustatory sensation test in healthy volunteers. We performed two types of organoleptic masking of ARP-Gs, cocoa- and fruit-flavoured gummies (6.0 mg of ARP/3.5 g of gummy), and conducted two different gustatory sensation tests for each ARP-G. Ten young, healthy volunteers (mean ± standard deviation, 23.7 ± 1.2 years) were enrolled in each trial. The overall palatability of ARP-Gs was evaluated using the 100-mm visual analogue scale (VAS). Receiver operating characteristic (ROC) curve analysis was performed between VAS scores of total ARP-G palatability and acceptability assessed using a 5-point rating scale. Among cocoa-flavoured ARP-Gs, those combining aspartame, cocoa powder, and banana flavour (ABC-ARP-G) exhibited the highest VAS scores for total palatability. Similarly, the VAS scores of grapefruit-flavoured ARP-Gs (GF-ARP-G) showed the highest values considering all fruit-flavoured ARP-Gs. The VAS scores for ABC-ARP-G and GF-ARP-G greatly exceeded the cut-off values of acceptability calculated using the ROC curve. We developed two types of ARP-Gs with organoleptic masking as tailor-made pharmaceutical formulations. ABC-ARP-Gs and GF-ARP-Gs could be acceptable in patients. ARP-Gs could be an alternative to currently available pharmaceutical formulations to enhance their adherence and meet the specific needs of individual patients.

Palatability Evaluation of Sulfamethoxazole/Trimethoprim with Sweetener Using the Two-Bottle Choice Test.

Drug taste, which affects palatability, influences drug adherence. Sensory masking may be used to confound bitter tastes in drugs with other tastes and flavors; however, evaluation of sensory masking is difficult because of the existence of multiple tastes. In this study, a new two-bottle choice test was performed in rats to evaluate bitterness masking and determine the drug-to-sweetener ratio that significantly improves palatability. Sulfamethoxazole and trimethoprim were used as model bitter drugs, and sucralose was used as sweetener. The addition of sucralose and trimethoprim at a 0.13 : 1 ratio resulted in the greatest improvement in preference. This method is a useful new technique for evaluating the palatability of drug formulations.

Meta-analysis of tadpole taste tests: consumption of anuran prey across development and predator strategies.

The risk of predation and the costs and benefits of diverse anti-predator strategies can shift across the life stages of an organism. Yet, empirical examples of ontogenetic switches in defense mechanisms are scarce. Anurans represent an alleged exception; previous meta-analytic work suggests that unpalatability of developing anurans is "rare", whereas adult anurans in many lineages are well defended by toxic and/or unpalatable skin secretions. Here, we revisit the question of the unpalatability of anuran young in a meta-analysis of the relative proportion of prey consumed within 922 predation tests, including 135 anuran species. We tested the hypotheses that a predator's propensity to consume anuran young depends on (1) prey family, (2) predator manipulation strategy, and (3) prey ontogenetic stage. We used a binomial mixed model approach with considerations for multiple effect sizes within studies to evaluate the log odds ratio of the proportion of prey consumed by individual predators. Prey consumption was highly variable, but toads (Bufonidae) were consumed in lower proportions. Chewing invertebrates consumed more anuran prey than biting vertebrates. Late stage tadpoles were more vulnerable to predation than other stages of anuran ontogeny. However, more studies are needed to unravel the roles of development and evolutionary history in the chemical ecology of anuran young. This synthesis provides clear meta-analytic evidence that relative unpalatability is an important component in the anti-predator defenses of young in some anuran families, calling into question the degree to which chemically defended anuran families undergo ontogenetic switches in anti-predator strategies.

Central angiotensinergic mechanisms in female spontaneously hypertensive rats treated with estradiol.

Estrogens reduce 0.3 M NaCl intake and palatability in a widely used model of essential hypertension, the spontaneously hypertensive rats (SHRs). Here we investigated whether the inhibitory effects of ß-estradiol (E2, 10 µg/kg b.w. subcutaneously for 8 days) on water deprived partially-rehydrated (WD-PR) ovariectomized (OVX) adult female SHRs (fSHRs, n = 4-10/group) are related to interferences on brain angiotensin II AT1 receptors (AT1r). After WD-PR, E2 reduced 0.3 M NaCl intake (1.3 ± 0.6, vs. vehicle: 3.5 ± 1.2 ml/30 min), the number of hedonic responses to intraoral NaCl infusion (57 ± 11, vs. vehicle: 176 ± 32/min), and the relative angiotensin AT1r (Agtr1a) mRNA expression in the hypothalamus. Losartan (AT1r antagonist, 100 µg) intracerebroventricularly in OVX fSHRs treated with vehicle subcutaneously abolished 0.3 M NaCl intake (0.1 ± 0.1 ml/30 min) and only transiently reduced hedonic responses to intraoral NaCl. Losartan combined with E2 decreased the number of hedonic and increased the number of aversive responses to intraoral NaCl and abolished 0.3 M NaCl intake. E2 also reduced the pressor and dipsogenic responses to intracerebroventricular angiotensin II. The results suggest that AT1r activation increases palatability and induces NaCl intake in WD-PR fSHRs. E2 reduced hypothalamic Agtr1a mRNA expression, which may account for the effects of E2 on NaCl intake and palatability and intracerebroventricular angiotensin II-induced pressor and dipsogenic responses in OVX fSHRs. Future studies considering natural fluctuations in estrogen secretion might help to determine the degree of such interference in brain neuronal activity.

New formulation zinc sulphate acceptability and adherence in children with acute diarrhoea: A prospective, open-label, interventional study in Bangladesh.

AIM: Zinc is an adjunct to oral rehydration salts for management of diarrhoea in children. Due to zinc's unpleasant taste, children often develop nausea and/or vomiting. We aimed to assess acceptability (tolerability) and adherence of improvised formulation of zinc tablet among under-five children with acute diarrhoea. METHODS: This was an open-label intervention trial among 3-59 months old diarrhoeal children attending the outpatient department of Dhaka Hospital, who were enrolled in two age strata, 3 to <18 months and 18-59 months. Zinc tablets 10 or 20 mg per day were prescribed for a total of 10 days for <6 months and ≥6 months age children respectively, with follow-up. Diary-cards were used to record events. RESULTS: In stratum 1, 158 (90.8%) children and in stratum 2, 144 (95.4%) children completed the study as per protocol out of 325 enrolled children. Sociodemographic, clinical and anthropometric measurements were comparable in the two strata except admission diarrhoeal duration (median 3 days vs. 2 days, P = 0.001). Adherence to 10 days treatment was 123 (77.8%) in stratum 1 and 127 (88.2%) in stratum 2. Zinc tablets were tolerated very well/well in 280 (92.7%) children. Vomiting, regurgitation and nausea were observed in 99 (32.8%), 59 (19.5%) and 22 (7.4%) children respectively. Caregivers' willingness to use the same drug in future was 300 (99.3%) among all children. CONCLUSION: Our study findings demonstrate that modified taste and formulation zinc tablets were well tolerated, and caregivers' willingness to use this formulation in future supports its acceptability, adherence and palatability.

Effects of Formulation on the Palatability and Efficacy of In-Feed Praziquantel Medications for Marine Finfish Aquaculture.

Praziquantel (PZQ) provides an effective treatment against monogenean parasitic infestations in finfish. However, its use as an in-feed treatment is challenging due to palatability issues. In this study, five formulations of PZQ beads (1−4 mm) were developed using marine-based polymers, with allicin added as a flavouring agent. All formulations attained PZQ loading rates ≥74% w/w, and the beads were successfully incorporated into fish feed pellets at an active dietary inclusion level of 10 g/kg. When tested for palatability and digestibility in small yellowtail kingfish, the PZQ-loaded beads produced with alginate-chitosan, alginate-Cremophor® RH40, and agar as carriers resulted in high consumption rates of 99−100% with no digesta or evidence of beads in the gastrointestinal tract (GIT) of fish fed with diets containing either formulation. Two formulations produced using chitosan-based carriers resulted in lower consumption rates of 68−75%, with undigested and partly digested beads found in the fish GIT 3 h post feeding. The PZQ-loaded alginate-chitosan and agar beads also showed good palatability in large (≥2 kg) yellowtail kingfish infected with gill parasites and were efficacious in removing the parasites from the fish, achieving >90% reduction in mean abundance relative to control fish (p < 0.001). The two effective formulations were stable upon storage at ambient temperature for up to 18 months, showing residual drug content >90% compared with baseline levels. Overall, the palatability, efficacy and stability data collected from this study suggest that these two PZQ particulate formulations have potential applications as in-feed anti-parasitic medications for the yellowtail kingfish farming industry.