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Recently there has been an increased interest to develop specialised dosage forms that are better suited to specific patient populations, such as paediatrics and geriatrics. In these patient populations the acceptability of the oral dosage form can be paramount to the products success. However, many Active Pharmaceutical Ingredients (APIs) are known to cause an aversive taste response. One way to increase the acceptability and to enhance the palatability of the formulation is to design coated taste-masked particulate-based dosage forms. The masking of poorly tasting drugs with physical barriers such as polymer coatings can be utilised to prevent the release of drug within the oral cavity, thus preventing a taste response. However, currently, there are few assessment tools and models available to test the efficiency of these particulate-based taste-masked formulations. The rat brief access taste aversion model has been shown to be useful in assessment of taste for liquid dosage forms. However, the applicability of the rat model for particulate-based taste masked formulations is yet to be assessed. It is not understood whether dissolution, solubility and thus exposure of the drug to taste receptors would be the same in rat and human. Therefore, rat saliva must be compared to human saliva to determine the likelihood that drug release would be similar within the oral cavity for both species. In this study rat saliva was characterised for parameters known to be important for drug dissolution, such as pH, buffer capacity, surface tension, and viscosity. Subsequently dissolution of model bitter tasting compounds, sildenafil citrate and efavirenz, in rat saliva was compared to dissolution in human saliva. For all parameters characterised and for the dissolution of both drugs in rat saliva, a substantial difference was observed when compared to human saliva. This discrepancy in saliva parameters and dissolution of model drugs suggests that preclinical taste evaluation of particulate-based taste-masked formulations suggests rat is not a good model for predicting taste of solid dosage forms or undissolved drug where dissolution is required. Alternative preclinical in vivo models in other species, or improved biorelevant in vitro models should be considered instead., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Spironolactone, an antagonist of aldosterone, initially used as a potassium-sparing diuretic, was subsequently shown to be a very effective adjunctive agent in the treatment of patients with heart failure with reduced ejection fraction, by halting the disease progression, with significant beneficial effects on both morbidity and mortality. Other uses comprise resistant hypertension, edema in patients with cirrhosis, and other on- and off-label uses. Recent data indicate that spironolactone also may offer some symptomatic relief in patients with heart failure and preserved ejection fraction. However, a variable percentage of patients, particularly among the aged group, may have difficulty in swallowing or may be unable to swallow tablets and thus are deprived of the benefits of such therapy. In 2017, the FDA approved a liquid suspension formulation of spironolactone, CaroSpir ® , which will enable more heart failure and other patients in need of aldosterone inhibition to avail themselves of the protective and beneficial effects of spironolactone. The new drug formulation comes as a banana-flavored oral suspension that contains 25 mg/5 mL of spironolactone, supplied in 4-ounce (118 mL) and 16-ounce (473 mL) bottles. The details of this drug formulation development and the benefits of spironolactone use in patients with heart failure with a focus on patient selection are herein reviewed., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Manolis et al.)

Murine strain differences occur for both intakes of and preferences for sugars and fats. Previous studies demonstrated that the muscarinic cholinergic receptor antagonist, scopolamine (SCOP) more potently reduced sucrose and saccharin intakes in inbred C57BL/6 and BALB/c than SWR mice, sucrose-conditioned flavor preferences (CFP) expression in BALB/c, but not C57BL/6 or SWR mice, and sucrose-CFP acquisition in BALB/c relative to SWR and C57BL/6 mice. Although fat intake and fat-CFP are observed in all three strains, strain-specific effects were previously observed following dopamine D1, opiate and NMDA receptor antagonism of sweet and fat intake and CFP. The present study investigated whether muscarinic receptor antagonism differentially affected fat (Intralipid) intake and preferences in these strains by examining whether SCOP altered fat (Intralipid) intake and fat-CFP expression and acquisition in BALB/c, C57BL/6 and SWR mice. SCOP (0.1-10 mg/kg) significantly reduced Intralipid (5%) intake in all three strains across 2 h. In fat-CFP expression experiments, food-restricted mice consumed one flavored (conditioned stimulus (CS)+, 5 sessions) Intralipid (5%) solution and a differently-flavored (CS-, 5 sessions) Intralipid (0.5%) solution. Two-bottle CS choice tests with the two flavors mixed in 0.5% Intralipid occurred following vehicle and two SCOP doses (1, 5 mg/kg). SCOP elicited small, but significant reductions in fat-CFP expression in BALB/c and C57BL/6, but not SWR mice. In fat-CFP acquisition experiments, separate groups of BALB/c, C57BL/6 and SWR mice were treated prior to the ten acquisition training sessions with vehicle or two SCOP (2.5, 5 mg/kg) doses followed by six two-bottle choice tests without injections. SCOP eliminated fat-CFP acquisition in all three strains. Thus, muscarinic receptor signaling mediates learning, and to a lesser degree maintenance of fat-CFP while maximally inhibiting fat intake in the three strains., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: JUUL is a closed-system e-cigarette that uses disposable pods with high concentrations of nicotine. JUUL use among youth arose exponentially since 2015, thus, it is essential to understand youths' reasons for liking/disliking JUUL to inform the regulation of the product., Methods: A cross-sectional survey was conducted in 4 high schools in Connecticut in 2018 (N = 3170). The survey assessed JUUL use in the past month and reasons for liking/disliking JUUL, which included pharmacological effects (e.g., subjective nicotine and/or flavor effects), product characteristics (e.g., flavors, nicotine, shape), peer influence (e.g., friends' use), comparisons to other e-cigarettes (e.g., lower harm), and concealability (e.g., hide from authority)., Results: 30.2% (N = 956) were past-month users who used a JUUL on an average of 13.6 days (SD = 11.7; 25% reported daily use). The top reasons for liking JUUL were: "it gives me a buzz" (52%), "I like the flavors" (43%), and "my friends use it" (36%). The top reasons for disliking JUUL were: "the pods are expensive" (57%), "nicotine is too high" (20%), and "it gives me a headache" (18%). Regression models indicated that liking JUUL because of the buzz, ability to help concentrate, nicotine level, and ease of hiding it from teachers were associated with more days of use in the past month, while peer influence was negatively associated. Furthermore, disliking the high cost of pods was associated with more frequent use., Conclusions: Comprehensive policies that regulate device characteristics that appeal to youth (e.g., nicotine level, flavors) are needed to prevent JUUL use among youth., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: The popularity of electronic cigarettes (e-cigarettes) has increased worldwide among youth, even in countries like Mexico that ban them. This study aimed to assess the correlates of e-cigarette use frequency among Mexican students who currently use ecigarettes, as well as to describe their reasons for use., Methods: Data were analyzed from a school-based survey of 57 public middle schools from the three largest cities in Mexico. Primary analyses were confined to those who used e-cigarettes in the prior 30 days. Censored binomial models for truncated distributions were estimated, regressing lifetime and past month frequency of use on participant sociodemographics, other substance use (smoking, alcohol, drugs), technophilia (appeal of new technologies), characteristics of e-cigarettes used, and family's and friends' use of nicotine products., Results: Being male (APR = 1.93 95% CI 1.53-2.44), using drugs, (APR = 1.51 95% CI 1.03-2.20), higher technophilia (APR = 1.66 CI 1.21-2.29) and having a family member who uses e-cigarettes and cigarettes were associated with more frequent use in the last month. Students who preferred fruit and combined flavors had used e-cigarettes more often in their lifetime compared to students who preferred mint/menthol flavors., Conclusions: Some risk factors for more frequent e-cigarette use among Mexican youth are similar to those foudn in other countries (having relatives who use ecigarettes, using drugs, and use of fruit flavors). Additionally, the novel measure of technophilia was positively associated with frequency of e-cigarette use. The appeal of flavors, in particular, suggests the importance of reducing youth access to flavored products to impede product initiation and progression., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Use of electronic cigarettes (e-cigarettes) has increased exponentially since their appearance on the U.S. market around 2007. To provide preclinical models of vaping that incorporate olfactory cues and chemosensory effects (including flavors) that play a role in human vaping behavior, the feasibility of using a modified e-cigarette device for delivery of aerosolized nicotine was examined in a nicotine discrimination procedure in mice., Methods: Adult female and male C57BL/6 mice were trained to discriminate 0.75 mg/kg subcutaneous (s.c.) nicotine from saline. After determination of a s.c. nicotine dose-effect curve, aerosolized freebase nicotine and nicotine-containing tobacco products (i.e., non-flavored and Arctic Blast e-liquids) were evaluated., Results: Nicotine (s.c.) dose-dependently substituted in mice of both sexes, although females showed less sensitivity and greater variability. By contrast, aerosolized nicotine, regardless of formulation, produced concentration-dependent increases up to maximum of 46-62% nicotine-associated responding. Brain nicotine concentrations for each sex were similar for s.c. 0.75 mg/kg nicotine and 30 mg/ml freebase nicotine., Conclusions: Mice of both sexes readily acquired s.c. nicotine discrimination, but females showed less sensitivity. Further, all three formulations of aerosolized nicotine produced increases in nicotine-like responding in mice of each sex. However, the maximum magnitude of these increases did not engender a similar degree of substitution as s.c. 0.75 mg/kg nicotine, despite similar brain concentrations of nicotine at 30 mg/ml aerosolized nicotine. Additional research is needed for determination of the reason(s); however, results here demonstrate initial feasibility for examination of the discriminative stimulus effects of vaped drugs such as nicotine., (Copyright © 2019 Elsevier B.V. All rights reserved.)

2,4-Decadienal (E,E-) occurs naturally in foods and is also used as a flavoring ingredient. In vivo micronucleus studies were used to evaluate the potential for 2,4-decadienal to cause genotoxic effects. Male Han Wistar rats were dosed either by intraperitoneal injection or by gavage in two independent studies. The animals (12/group) received 25, 50, or 100 mg/kg bw of 2,4-decadienal via intraperitoneal injection, or 350, 700, or 1400 mg/kg bw via gavage. Dose-dependent decreases in the percentages of peripheral blood reticulocytes were observed in both studies, indicating that the target tissue was exposed to toxic levels of 2,4-decadienal. No induction of micronuclei in the bone marrow polychromatic erythrocytes or the peripheral blood reticulocytes was observed in either study. These results, coupled with previous mutagenicity studies, support the overall conclusion that 2,4-decadienal does not present a concern for genotoxicity., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: A rapidly evolving tobacco marketplace highlights the timeliness of the FDA's authority to regulate tobacco, specifically the role that flavorings in nicotine-containing electronic cigarette (ECIG) liquids have on public health. This study aimed to evaluate the extent to which ECIG liquid flavor and nicotine concentration influenced subjective measures of abuse liability among young adult cigarette (cig) smokers., Methods: Young adult (18-21 y.o.) smokers (M = 10.1 cig/day, no regular ECIG use history) completed 7 Latin-square ordered conditions each preceded by 12 h. nicotine/tobacco abstinence. Conditions were own brand cig (OB) and eGo-style ECIG paired with three liquid flavors (cream, tropical fruit, tobacco/menthol) varying in nicotine concentration (0 or 36 mg/ml). Products were administered in two 10-puff bouts in each condition. Heart rate/blood pressure (HR/BP) and tobacco/nicotine abstinence symptoms, nicotine/general drug effects, and acceptability measures were assessed repeatedly throughout sessions. Mixed linear models were followed-up with Tukey's HSD t-tests., Results: HR/BP indicated nicotine exposure during nicotine-containing conditions. OB and tobacco/menthol 36 mg/ml conditions produced significant decreases in ratings of cig smoking urges. Nicotine/drug effects were elevated significantly for OB and 36 mg/ml ECIG conditions with one exception noted for the tobacco/menthol 0 mg/ml condition. OB had the highest acceptability ratings, and ECIG condition results varied by acceptability item., Conclusions: Among young adult smokers, ECIG conditions containing nicotine were positively associated with several subjective measures of abuse liability but not all. Flavors did not consistently mask/enhance effects observed. Results reinforce continued examination of ECIG-delivered nicotine and liquid flavors in relationship to abuse liability., (Copyright © 2019. Published by Elsevier B.V.)

Flavored tobacco products appeal to youth, and jurisdictions have implemented policy interventions to reduce youth tobacco initiation. This study reviews the process, challenges, and compliance monitoring of a flavored tobacco sales restriction. New York City (NYC) passed a policy restricting the sale of flavored non-cigarette tobacco products in 2009. To describe the policy's passage, legal defense, implementation, and enforcement, we conducted stakeholder interviews, reviewed legislative and legal records, and analyzed administrative data on retailer inspections and violations. Extensive public and policy maker education efforts preceded this policy. Barriers included opposition to the policy's passage and a tobacco manufacturer's lawsuit that sought to halt the law's implementation and to establish that NYC lacked the authority to restrict the sale of flavored products. The city implemented the flavored tobacco policy as intended and it withstood legal challenges. NYC integrated enforcement into the city's retailer compliance monitoring infrastructure, and the violation rate is low. Our investigation of NYC's experience with flavored tobacco policy implementation and enforcement can provide policy makers and health professionals with insights relevant to policy implementation, expand understanding of the potential impact of these kinds of policies, and inform compliance monitoring efforts.

Vanillin propylene glycol acetal (VPGA) has been used as a flavoring agent. Here, we performed a 13-week subchronic toxicity study of VPGA in F344 rats with oral administration by gavage at doses of 0, 100, 300, and 1000 mg/kg body weight (BW)/day. In the 1000 mg/kg BW group, loss of vigorous activity and listlessness immediately after administration were observed for both sexes throughout the experimental period. Reduction of body weight gain was noted in both sexes at 1000 mg/kg BW. Serum biochemistry demonstrated significant increases in total protein, albumin, total cholesterol, calcium, inorganic phosphorus, and γ-glutamyl transpeptidase in both sexes at 1000 mg/kg BW and increases in the albumin/globulin ratio and urea nitrogen in the male 1000 mg/kg BW group. A significant increase in relative liver weight was detected in both sexes at 1000 mg/kg BW. Histopathologically, centrilobular hepatocellular hypertrophy in the liver was observed in both sexes at 1000 mg/kg BW. In addition, the incidence of fatty changes in hepatocytes in the male 1000 mg/kg BW group was decreased compared with that in the control. Based on these results, the no-observed-adverse-effect level for VPGA was evaluated to be 300 mg/kg BW/day for both sexes in the current study., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Flavored waterpipe (WP) tobacco is the main type of tobacco used by young WP smokers, and a major factor attracting youth to smoke. However, evidence regarding the effect of limiting flavor on WP smokers' experience continues to be lacking. This study aims at evaluating the effect of flavor restriction on WP smokers' toxicant exposure, smoking topography, subjective experiences and harm perception., Methods: Thirty-two WP smokers completed two, 45-minute ad libitum smoking sessions (preferred flavor vs non-flavored tobacco) in a crossover design pilot study. Plasma nicotine concentration and exhaled carbon monoxide (eCO) were measured before and after each smoking session. Puff topography was recorded throughout the smoking session. Participants completed survey questionnaires assessing subjective smoking experiences and harm perception., Results: Significant differences were observed in plasma nicotine concentration between the two WP tobacco conditions, with a higher increase in plasma nicotine concentration following the flavored tobacco session. There were no significant differences between the two WP tobacco conditions for eCO and smoking topography measures. Compared with the non-flavored WP tobacco, we documented enhanced subjective smoking measures of satisfaction, calmness, taste, puff liking and enjoyment following the preferred flavored WP tobacco session. Cigarette harm perception was significantly higher among participants after smoking their preferred flavor compared with non-flavored WP tobacco., Conclusions: Limiting tobacco flavor has a substantial effect on WP smokers' nicotine exposure, subjective experience and harm perception. Therefore, eliminating or restricting WP flavors could be an essential element of comprehensive tobacco control policies to reduce the appeal of WP tobacco products for youth., Implications: This study highlights the important role of flavor in shaping WP smokers' experiences and exposures and the potential impact that regulating flavored WP tobacco may have on curbing WP use among youth in the US. Such regulations may reduce the appeal and the interest in WP smoking initiation and continued use., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Free radicals and carbonyls produced by electronic cigarettes (e-cigs) have the potential to inflict oxidative stress. Recently, Juul e-cigs have risen drastically in popularity; however, there is no data on nicotine and oxidant yields from this new e-cig design., Methods: Aerosol generated from four different Juul flavors was analyzed for carbonyls, nicotine, and free radicals. The e-liquids were analyzed for propylene glycol (PG) and glycerol (GLY) concentrations. To determine the effects of e-liquid on oxidant production, Juul pods were refilled with nicotine-free 30:70 or 60:40 PG:GLY with or without citral., Results: No significant differences were found in nicotine (164 ± 41 µg/puff), free radical (5.85 ± 1.20 pmol/puff), formaldehyde (0.20 ± 0.10 µg/puff), and acetone (0.20 ± 0.05 µg/puff) levels between flavors. The PG:GLY ratio in e-liquids was ~30:70 across all flavors with GLY being slightly higher in tobacco and mint flavors. In general, when Juul e-liquids were replaced with nicotine-free 60:40 PG:GLY, oxidant production increased up to 190% and, with addition of citral, increased even further., Conclusions: Juul devices produce free radicals and carbonyls, albeit, at levels substantially lower than those observed in other e-cig products, an effect only partially because of a low PG:GLY ratio. Nicotine delivery by these devices was as high as or higher than the levels previously reported from cigarettes., Implications: These findings suggest that oxidative stress and/or damage resulting from Juul use may be lower than that from cigarettes or other e-cig devices; however, the high nicotine levels are suggestive of a greater addiction potential., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Maple syrup urine disease (MSUD) is a rare metabolic disorder with a worldwide prevalence of 1 in every 185,000 live births. However, certain populations display a significant overexpression of the disorder where incidence is reported to be 1 in every 52,541 new-borns. The first-line therapy for MSUD involves a strict dietary leucine restriction and oral supplementation of isoleucine and valine. The dose administered to patients requires strict tailoring according to age, weight and blood levels. In current clinical practice, however, practitioners still have to prepare extemporaneous formulations due to the lack of suitable oral treatments for MSUD. Herein, we evaluate the first time use of 3D printing in a hospital setting for the preparation of personalised therapies with the aim of improving safety and acceptability to isoleucine supplementation in paediatric patients suffering from MSUD. This investigation was a single-centre, prospective crossover experimental study. Four paediatric patients with MSUD (aged 3-16 years) were treated at the Clinic University Hospital in Santiago de Compostela, Spain which is a MSUD reference hospital in Europe. The primary objective was to evaluate isoleucine blood levels after six months of treatment with two types of formulations; conventional capsules prepared by manual compounding and personalised chewable formulations prepared by automated 3D printing. A secondary investigation was to evaluate patient acceptability of 3D printed formulations prepared with different flavours and colours. Isoleucine blood levels in patients were well controlled using both types of formulations, however, the 3D printed therapy showed mean levels closer to the target value and with less variability (200-400 µM). The 3D printed formulations were well accepted by patients regarding flavour and colour. The study demonstrates for the first time that 3D printing offers a feasible, rapid and automated approach to prepare oral tailored-dose therapies in a hospital setting. 3D printing has shown to be an effective manufacturing technology in producing chewable isoleucine printlets as a treatment of MSUD with good acceptability., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Although it is well known that food intake is affected by the palatability of food, the actual effect of flavoring on regulation of energy-homeostasis and reward perception by the brain, remains unclear. We investigated the effect of ethyl-butyrate (EB), a common non-caloric food flavoring, on the blood oxygen level dependent (BOLD) response in the hypothalamus (important in regulating energy homeostasis) and ventral tegmental area (VTA; important in reward processes). The 16 study participants (18-25 years, BMI 20-23 kg/m 2 ) drank four study stimuli on separate visits using a crossover design during an fMRI setup in a randomized order. The stimuli were; plain water, water with EB, glucose solution (50gram/300 ml) and glucose solution with EB. BOLD responses to ingestion of the stimuli were determined in the hypothalamus and VTA as a measure of changes in neuronal activity after ingestion. In the hypothalamus and VTA, glucose had a significant effect on the BOLD response but EB flavoring did not. Glucose with and without EB led to similar decrease in hypothalamic BOLD response and glucose with EB resulted in a decrease in VTA BOLD response. Our results suggest that the changes in neuronal activity in the hypothalamus are mainly driven by energy ingestion and EB does not influence the hypothalamic response. Significant changes in VTA neuronal activity are elicited by energy combined with flavor.

Purpose: The aim of the article was to examine flavors of alternative tobacco products most commonly used by young adults (YAs)., Methods: California YA (N = 365; mean age = 20.0 years) were surveyed in 2018 about the first and usual flavors of alternative tobacco products used. Flavor categories were fruit, candy, menthol, mint, coffee, spice, alcohol, wintergreen, and tobacco., Results: Fruit and mint were the most common flavors used (pod-based e-cigarettes: 35.4% and 29.3%; other e-cigarettes: 52.7% and 23.1%; hookah: 45.4% and 18.5%; cigars/cigarillos: 22.4% and 6.9%, respectively). For other e-cigarettes and hookah, candy was also popular (20.5% and 14.8%, respectively). For pod-based and other e-cigarettes, menthol was widely used (13.4% and 17.0%, respectively). Approximately half of the ever-flavor users reported they "usually" used the same flavors across products (menthol users: 52.2%; fruit users: 51.7%; mint users: 44.0%; and candy users: 43.8%)., Conclusions: YA are clearly using flavors, specifically fruit, mint, candy, and menthol, in their tobacco products., (Copyright © 2019 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Monosodium glutamate (MSG) is a widely-consumed taste enhancer which has been implicated in the aetiology of renal and hepatic dysfunction in adults and their offspring. There is increasing evidence on the therapeutic properties of Coconut Water (CW) in kidney and liver disorders. This study investigated the effects of CW on renal and hepatic functions in offspring of MSG-fed dams. Twelve female Wistar rats (120 - 140 g) were grouped into four as follows; Control (10 ml/Kg distilled water), MSG (0.08 mg/Kg), CW (10 ml/Kg) and MSG+CW. Treatments were given orally daily commencing two weeks prior to mating, throughout mating and gestation until parturition. All dams received standard rodent diet and drinking water ad libitum throughout the study. After weaning on Post-Natal Day (PND) 28, serum was obtained from offspring for assay of liver and renal function. Histological analysis of the livers and kidneys were performed on both dams and offspring. There was no significant difference in liver enzymes, urea, creatinine and albumin levels amongst the offspring on PND 28. However, liver and kidney sections from MSG dams and their offspring showed early degenerative changes which were not evident in renal and hepatic tissues from CW and MSG+CW dams and offspring. These observations suggest that coconut water protects against monosodium glutamate-induced renal and hepatic dysfunction in dams and offspring.

The study of e-cigarette aerosol properties can inform public health while longer-term epidemiological investigations are ongoing. The determination of aerosol levels of known toxins, as well as of molecules with unknown inhalation toxicity profiles, affords specific information for estimating the risks of e-cigarettes and for uncovering areas that should be prioritized for further investigation.

Background: Electronic cigarettes (EC) may aid some smokers in reducing combustible tobacco use. Smokers with psychiatric co-morbidities tend to have higher nicotine dependence and worse outcomes, so may particularly benefit from alternative cessation aids. EC characteristics, like nicotine level and flavor, may influence EC's appeal to smokers. Nicotine level may impact EC's efficacy in reducing combustible cigarette use., Methods: Non-treatment-seeking cigarette smokers with medical/psychiatric co-morbidities rated 'liking' of ECs varying in nicotine level (12 mg, 24 mg) and flavor (menthol, 'slim'-tobacco, 'burley'-tobacco), during an open-label Choice Procedure. Smokers (N = 43) chose ECs for a 4-week take-home-trial, and used EC and/or combustible cigarettes as they wished. Analyses examined ratings and choice by nicotine level and flavor, and the relationship between consistent take-home choice of 12 mg versus 24 mg baseline demographic/smoking characteristics, and outcomes (cigarettes/day, nicotine intake, motivation to quit smoking) during take-home-trial and one-month follow-up., Results: Smokers who chose menthol-flavor, tobacco-flavor and/or 24 mg nicotine e-liquids for the first take-home week rated these conditions as more 'liked' than alternative options, at baseline. Groups who chose 12 mg versus 24 mg throughout the take-home trial did not significantly differ on baseline characteristics, or smoking-related outcomes within the take-home trial, however, motivation to quit smoking increased more from baseline to one-month follow-up in choosers of higher nicotine (24 mg) ECs., Conclusions: Associations between subjective ratings and subsequent choice support feasibility of open-label choice-procedures in EC trials. Access to 12 mg or 24 mg nicotine ECs was associated with reduced smoking, and 24 mg ECs with increased motivation to quit smoking in smokers with medical/psychiatric co-morbidities., (Copyright © 2018. Published by Elsevier Ltd.)

Electronic cigarette uses propylene glycol and glycerol to deliver nicotine and flavors to the lungs. Given the hundreds of different brands, the thousands of flavors available and the variations in nicotine concentrations, it is likely that electronic cigarette settings and e-liquid composition affect the size distribution of particles emitted and ultimately pulmonary deposition. We used the inExpose e-cigarette extension to study two separate modes of operation of electronic cigarettes, namely power-controlled and the temperature-controlled. We also assessed several e-liquids based on propylene glycol and glycerol concentrations, nicotine content, and selected monomolecular flavoring agents (menthol, vanillin, and maltol). Particle size distribution was measured using a Condensation Particle Counter and a Scanning Mobility Particle Sizer spectrometer. Lung deposition was predicted using the International Commission on Radiological Protection model. For all resistance coils, increase in power delivery generated larger particles while maintaining a higher coil temperature generated smaller particles. Increase in glycerol concentration led to the generation of larger particles. With regard to flavors, we showed that despite minor effect of menthol and maltol, vanillin dramatically increased particle size. Presence of nicotine also increased particle size. Finally, particles emitted by the electronic cigarette were predicted to mainly deposit in the alveoli and conditions generating larger particle sizes led to a reduction in predicted lung deposition. This study shows that coil temperature, propylene glycol and glycerol concentrations, presence of nicotine, and flavors affect the size of particles emitted by an electronic cigarette, directly affecting predicted lung deposition of these particles., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background: Although salt taste preference is malleable in adults, no research to date has focused on children, whose dietary sodium intake exceeds recommended intake and whose salt taste preferences are elevated., Objective: This proof-of-principle trial determined whether 8-wk exposure to low-sodium cereal (LSC) increased children's acceptance of its taste and changed their salty and sweet taste preferences., Methods: Children (n = 39; ages 6-14 y; 67% female) were randomly assigned to ingest LSC or regular-sodium cereal (RSC) 4 times/wk for 8 wk. The cereals, similar in sugar (3 g/cup compared with 2 g/cup) and energy content (100 kcal/cup) yet different in sodium content (200 mg sodium/cup compared with 64 mg sodium/cup), were chosen based on taste evaluation by a panel of children. Mothers completed daily logs on children's cereal intake. At baseline and after the exposure period, taste tests determined which cereal children preferred and measured children's most preferred amount of salt (primary outcomes), and most preferred amount of sucrose and salt taste detection thresholds (secondary outcomes). Repeated measures ANOVAs were conducted on primary and secondary outcomes, and generalized estimating equations were conducted on amount of cereal ingested at home over time., Results: Both treatment groups accepted and ate the assigned cereal throughout the 8-wk exposure. There were no group × time interactions in salt detection thresholds (P = 0.32) or amount of salt (P = 0.30) and sucrose (P = 0.77) most preferred, which were positively correlated (P = 0.001). At baseline and after the exposure, the majority in both groups preferred the taste of the RSC relative to LSC (P > 0.40)., Conclusions: Children showed no change in salt preference but readily ate the LSC for 8 consecutive weeks. Findings highlight the potential for reducing children's dietary salt intake by incorporating low-sodium foods in the home environment without more preferred higher-salt versions of these foods. This trial was registered at clinicaltrials.gov as NCT02909764., (Copyright © American Society for Nutrition 2019.)

Introduction: Smokers with severe mental illness (SMI) are more likely to start smoking and less likely to quit. Menthol may facilitate smoking progression, dependence, and maintenance by reducing harshness and irritation from smoking and providing a unique sensory experience during use. High rates of menthol use have been reported in smokers with SMI, but information on young adults with SMI has not been reported., Methods: This study provides a secondary analysis to assess the impact of menthol use in a pilot trial of brief tobacco interventions. Participants were assessed at baseline and again at a 3-month follow-up with structured interviews and breath carbon monoxide to confirm self-reported 7-day abstinence at follow-up., Results: Participants included 81 young adult smokers with SMI, mean age of 24.2 years (SD = 3.6; range 18-30). Overall, 58% of the group reported that they recently used a menthol-flavored product. Menthol use was correlated with race (African American [18/21, 85.7%] vs. White [24/53, 45.3%] or other race [5/7, 71.4%]; χ2 = 10.7, p = .005) and more lifetime psychiatric hospitalizations (t = 2.39, p = .02), but not with cigarettes per day, nicotine dependence, quit attempts over the follow-up period, nor with achieving biologically confirmed abstinence at the follow-up assessment., Conclusions: The high prevalence of menthol-flavored cigarette use in this study group is consistent with previous reports of high rates of menthol use among young adults, Blacks, and middle-aged SMI smokers. This study supports existing evidence that policies to restrict menthol flavoring in combustible tobacco products could reduce smoking in young adults with SMI., Implications: High rates of menthol use have been reported in middle-aged smokers with SMI, but information on young adults with SMI has not been reported. In this study, more than half (58%) of 81 young adult smokers with SMI used a menthol-flavored product. Menthol use was associated with race and with history of psychiatric hospitalizations. The research supports existing evidence that policies to restrict menthol flavoring in combustible tobacco products could reduce smoking in young adults with SMI., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study was conducted to evaluate the taste and grittiness of two formulations of Riomet ® ER (metformin hydrochloride for extended release [ER] oral suspension 100 mg/mL) differing only in their flavoring agents (strawberry and grape) in comparison with two commercially available immediate-release (IR) formulations of metformin, Riomet ® Cherry (metformin hydrochloride oral solution 500 mg/5 mL) and metformin IR tablets (metformin hydrochloride IR tablets 500 mg), in healthy human subjects aged 10-70 years., Methods: Five comparison sets (i.e., Riomet ® Cherry vs. Riomet ® ER Strawberry; Riomet ® Cherry vs. Riomet ® ER Grape; metformin IR vs. Riomet ® ER Strawberry; metformin IR vs. Riomet ® ER Grape; and Riomet ® Cherry vs. metformin IR) were evaluated. Riomet ® ER was reconstituted as instructed on the label. Metformin IR tablets were crushed one at a time into a fine powder using a pharmaceutical pill crusher and mixed with 5 mL of water. A 2.5-mL dose of each product was administered to each subject. Subjects were instructed not to swallow any of the products. Each product in the comparison set was rated by the subjects for taste and grittiness according to a 7-point hedonic facial scale and a 5-point level of agreement scale. A comparison questionnaire was also completed by the subjects after evaluating each set. In all, 56 subjects were enrolled and 55 subjects completed the study. The taste preference was statistically evaluated., Results and Conclusions: All Riomet ® formulations were significantly preferred overall to metformin IR crushed tablets. Both the strawberry and the grape flavors of Riomet ® ER tended to be preferred to Riomet ® Cherry.

Intraduodenal activity of taste receptors reduces food intake. Taste receptors are expressed throughout the entire gastrointestinal tract. Currently, there are no data available on the effects of distal taste receptor activation. In this study, we investigate the effect of intraduodenal and/or intraileal activation of taste receptors on food intake and satiety. In a single-blind randomized crossover trial, fourteen participants were intubated with a naso-duodenal-ileal catheter and received four infusion regimens: duodenal placebo and ileal placebo (DPIP), duodenal tastants and ileal placebo (DTIP), duodenal placebo and ileal tastants (DPIT), duodenal tastants and ileal tastants (DTIT). Fifteen minutes after cessation of infusion, subjects received an ad libitum meal to measure food intake. Visual analog scale scores for satiety feelings were collected at regular intervals. No differences in food intake were observed between the various interventions (DPIP: 786.6 ± 79.2 Kcal, DTIP: 803.3 ± 69.0 Kcal, DPIT: 814.7 ± 77.3 Kcal, DTIT: 834.8 ± 59.2 Kcal, p = 0.59). No differences in satiety feelings were observed. Intestinal infusion of tastants using a naso-duodenal-ileal catheter did not influence food intake or satiety feelings. Possibly, the burden of the four-day naso-duodenal-ileal intubation masked a small effect that tastants might have on food intake and satiety.

Glutamate excitotoxicity has long been related to Alzheimer's disease (AD) pathophysiology, and it has been shown to affect the major AD-related hallmarks, amyloid-β peptide (Aβ) accumulation and tau phosphorylation (p-tau). We investigated whether oral administration of monosodium glutamate (MSG) has effects in a murine model of AD, the double transgenic mice APP/PS1. We found that AD pathogenic factors appear earlier in APP/PS1 when supplemented with MSG, while wildtype mice were essentially not affected. Aβ and p-tau levels were increased in the hippocampus in young APP/PS1 animals upon MSG administration. This was correlated with increased Cdk5-p25 levels. Furthermore, in these mice, we observed a decrease in the AMPA receptor subunit GluA1 and they had impaired long-term potentiation. The Hebb-Williams Maze revealed that they had memory deficits. We show here for the first time that oral MSG supplementation can accelerate AD-like pathophysiology in a mouse model of AD.

The study was aimed to prepare a co-amorphous system of valsartan (VAL) with vanillin (VAN) for improving its solubility and dissolution followed by its confinement in mesoporous silica particles (MSPs) to stabilise the co-amorphous system and prevent its recrystallization. Amorphous VAL and VAN were obtained through quench-cooling and VAL/VAN binary co-amorphous system (VAL/VAN-CAS) was prepared through solvent evaporation technique. The particle size and morphology of VAL/VAN-CAS-MSPs were studied using scanning electron microscopy (SEM) and solid-state characterisation was performed by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). The in vitro dissolution was investigated by dialysis bag diffusion method. SEM analysis revealed irregular shaped VAL/VAN-CAS-MSPs with a size range of 5-25 μm, while outcomes of DSC and XRPD confirmed the formation of VAL/VAN-CAS. The in vitro dissolution profiles demonstrated a significantly increased dissolution in first 60 minutes from VAL/VAN-CAS (∼68%) and VAL/VAN-CAS-MSPs (∼76%) compared to powder VAL (∼25%).

The objective of study was to develop Aceclofenac fast dispersible compacted pellets with improved taste and fast drug release. Pellets were prepared by extrusion spheronization technique followed by direct compression to make compacted pellets. Formulations were comprised of sucrose, mannitol, ac-di-sol, aspartame, pine apple flavor and magnesium stearate. A mixture of distilled water and isopropyl alcohol (1:1) was used for wet massing. The effect of ac-di-sol on the drug release pattern was examined and dissolution profile comparison was established. All formulations followed First order and Weibull models and f2 values indicated dissimilarity with the marketed immediate release product. Taste of compacted pellets was evaluated by a panel of 12 human volunteers. Formulation P5 was found to be an optimized formulation due to satisfactory quality attributes.

Effects of food-added monosodium glutamate (MSG) on neurobehaviour, serum biochemical parameters, malondialdehyde (MDA) levels, and changes in cerebral cortex, liver and kidney morphology were assessed in mice fed standard diet (SD) or high-fat diet (HFD). Animals were assigned to 8 groups [SD control, HFD control, and six groups fed MSG plus SD or HFD at 0.1, 0.2 and 0.4 g/kg of feed]. Animals were fed for 8 weeks, behavioural tests were conducted, and blood was taken for estimation of biochemical parameters and MDA level. Whole brain was homogenised for neurochemical assays, while the cerebrum, liver and kidneys were processed for histology. In groups fed MSG/SD, there was a decrease in weight gain, increase in food-intake, an increase in locomotion, a decrease in rearing/grooming, and a decrease in anxiety-response. Also observed were derangements in biochemical parameters, increased MDA, and alteration of renal morphology. Compared to HFD, MSG/HFD groups had reduction in weight gain, food-intake, grooming and anxiety-response, an increase in locomotion, and improved memory. Protection against biochemical derangements and HFD-induced organ injuries were also observed. In conclusion, the findings suggest that possible interactions that may occur between dietary constituents and MSG are determinants of the effects of food-added MSG in mice., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Scope: Maltol (3-hydroxy-2-methy-4-pyrone), a potent antioxidative agent, typically is used to enhance flavor and preserve food. This study evaluated its effects on preventing diabetic peripheral neuropathy (DPN) in streptozotocin (STZ)-induced diabetic rats and explored its mechanisms., Methods and Results: We intraperitoneally injected Sprague-Dawley (SD) rats with STZ (65 mg kg-1, ip) and treated the rats with different doses of maltol after 4 weeks of injection. During treatment, we evaluated motor nerve conduction velocity (MNCV) and thermal and mechanical hyperalgesia and assayed the oxidative stress, Na+-K+-ATPase activity, and apoptosis. Repeated treatment with maltol for 12 weeks significantly improved thermal and mechanical hyperalgesia, increased the MNCV, elevated the Na+-K+-ATPase activity, and ameliorated oxidative stress and apoptosis in STZ-induced diabetic rats. We coincubated RSC96 cells, a Schwann cell line, with maltol and hydrogen peroxide (H2O2, 0.6 mM). Evidently, maltol increased cell viability and inhibited apoptosis after injury by H2O2., Conclusions: Maltol was demonstrated to prevent DPN development and may provide a new alternative for the treatment of DPN.

5-Hexenyl isothiocyanate (5-HeITC) is a naturally derived flavoring substance from Wasabia japonica. To clarify the toxicological profile of 5-HeITC, we performed a subchronic toxicity study of 5-HeITC with intragastric administration at daily doses of 0, 3, 12, or 48 mg/kg body weight (BW) to 6-week-old male and female F344/DuCrj rats for 13 weeks. Body weight gain was decreased in the male 48 mg/kg BW group. Decreased triglycerides were observed in the male over 12 mg/kg BW and female 48 mg/kg BW groups. Decreased total cholesterol was observed in the male 48 mg/kg BW group. Increases in relative liver weights were observed in the male 48 mg/kg BW and female over 12 mg/kg BW groups. Increases in absolute and relative heart weights were observed in the female over 12 mg/kg BW groups. Simple hyperplasia in the urinary bladder was found in the male and female 12 mg/kg BW groups, and nodular hyperplasia was found in the female 48 mg/kg BW group. Based on these findings, the target organs of 5-HeITC were determined to be the urinary bladder, heart, and liver. The no-observed-adverse-effect level of 5-HeITC for both sexes was estimated to be 3 mg/kg BW., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: To assess preferences for e-cigarettes containing nicotine and flavourings among Australian young adult e-cigarette users., Methods: An online survey was administered to 1,116 young adults (18-25 years), 104 of whom had used an e-cigarette in the last 30 days and were the focus of this study. Among users, 53% also smoked tobacco cigarettes, 27% were non-smokers and 20% had never smoked., Results: Nearly two-thirds (64%) of e-cigarette users preferred nicotine-containing e-cigarettes (71% of smokers, 56% of non-smokers, 55% of never smokers). The vast majority (89%) preferred flavoured e-cigarettes (92% of smokers, 82% of non-smokers, 95% of never smokers), with fruit flavours the most popular., Conclusions: E-cigarettes containing nicotine and flavourings were popular among users of these devices in this sample of young adults. Implications for public health: Previous research has documented potential harms associated with e-liquid additives, flavourings, and nicotine. The present results showing strong preferences for nicotine and flavourings among the sampled e-cigarette users suggest that: i) flavourings in e-liquids should be regulated; and ii) existing prohibitions on the unauthorised supply of liquid nicotine should be better enforced. Population-wide monitoring of the use of e-cigarettes with different product characteristics is also warranted., (© 2018 The Authors.)

: media-1vid110.1542/5804914521001PEDS-VA&#95;2018-0260 Video Abstract BACKGROUND: Little is known about the characteristics of electronic cigarettes (e-cigarettes) used by adolescents. Understanding the product landscape of adolescent e-cigarette use may inform counseling and policy strategies., Methods: Results are from 13 651 adolescents in wave 1 and 12 172 adolescents in wave 2 of the Population Assessment of Tobacco and Health Study, a nationally representative longitudinal study. Past 30-day regular e-cigarettes users were asked about the characteristics of the e-cigarette they used most of the time., Results: In waves 1 and 2, 2.1% and 2.8% of adolescents were regular users in the past 30 days, respectively. These adolescents more often used rechargeable rather than disposable devices (wave 1: 76.0%; wave 2: 82.9%) and refillable rather than nonrefillable devices (wave 1: 66.6%; wave 2: 84.4%) and tended not to use cartridge systems (wave 1: 33.7%; wave 2: 30.5%). Most adolescent past 30-day users (wave 1: 87.5%; wave 2: 89.4%) reported using flavored e-cigarettes. An increased frequency of use was associated with the use of rechargeable (wave 1 adjusted odds ratio [aOR]: 2.7; wave 2 aOR: 2.7) and refillable e-cigarettes (wave 1 aOR: 2.0; wave 2 aOR: 2.7; P < .05). Most users in wave 1 did not continue regular use in wave 2 (70.2%). Among those who continued to use and had reported using closed systems (nonrechargeable and/or nonrefillable) in wave 1, most had progressed to open systems (rechargeable and refillable) in wave 2., Conclusions: Most adolescents use open-system e-cigarettes, and frequent users are even more likely to use open-system e-cigarettes. The majority of regular users use rechargeable devices that are refillable. A change in product preferences across waves suggests a starter product phenomenon, with a graduation to products that have weaker quality controls and may increase health risks., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Methyl propyl trisulfide is a flavoring substance found in foods such as garlic and onions. At the request of the European Food Safety Authority (EFSA) for additional toxicological data on methyl propyl trisulfide, groups of Sprague-Dawley rats (10/sex/group) were gavaged with 0 (corn oil vehicle control), 0.5, 2, or 6 mg methyl propyl trisulfide/kg bw/day in a 90-day GLP-compliant study. No effects on clinical observations, hematology and clinical chemistry parameters, organ weights, or macroscopic and histopathological examinations were found attributable to ingestion of methyl propyl trisulfide. The oral no-observed-adverse-effect level (NOAEL) for rats of both sexes was the highest dose tested of 6 mg/kg bw/day., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Conditioned flavor preferences (CFP) are elicited by sucrose relative to saccharin in inbred mice with both the robustness of the preferences and sensitivity to pharmacological receptor antagonists sensitive to genetic variance. Dopamine, opioid and N-methyl-d-aspartate receptor antagonists differentially interfere with the acquisition (learning) and expression (maintenance) of sucrose-CFP in BALB/c and SWR inbred mice. Further, the muscarinic cholinergic receptor antagonist, scopolamine (SCOP) more potently reduces both sucrose and saccharin intake in BALB/c and C57BL/6 relative to SWR inbred mice. The present study examined whether SCOP altered the expression and acquisition of sucrose-CFP in BALB/c, C57BL/6 and SWR mice. In expression experiments, food-restricted mice alternately consumed a flavored (CS+, e.g., cherry, 5 sessions) 16% sucrose solution and a differently-flavored (CS-, e.g., grape, 5 sessions) 0.05% saccharin solution. Two-bottle CS choice tests with the two flavors mixed in 0.2% saccharin solutions occurred following vehicle or SCOP at doses of 1 or 5 mg/kg. SCOP significantly reduced the magnitude of the expression of sucrose-CFP in BALB/c, but not either C57BL/6 or SWR mice. In acquisition experiments, separate groups of BALB/c, C57BL/6 and SWR mice were treated prior to acquisition training sessions with vehicle or 2.5 or 5 mg/kg SCOP doses that was followed by six two-bottle CS choice tests without injections. SCOP dose-dependently reduced (1 mg/kg) and eliminated (2.5 mg/kg) the acquisition of sucrose-CFP in BALB/c mice, and reduced the magnitude of acquisition of sucrose-CFP in SWR mice. In contrast, neither SCOP dose affected the acquisition of sucrose-CFP in C57BL/6 mice. Thus, muscarinic cholinergic receptor signaling is essential for the learning of sucrose-CFP in BALB/c mice, to a lesser degree in SWR mice, but not in C57BL/6 mice. Murine genetic variance differentially modulates muscarinic cholinergic receptor control of sweet intake per se relative to learned conditioned flavor preferences of sweets., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: This double-blind, placebo controlled study examined whether menthol inhaled from an electronic cigarette (e-cigarette) would change subjective and withdrawal alleviating effects of intravenous nicotine in young adult smokers., Methods: A total of 32 menthol-preferring smokers and 25 non-menthol-preferring smokers participated in the study that consisted of a random sequence of three different inhaled menthol conditions (0.0%, 0.5%, and 3.2%) across three test sessions (a single menthol condition per session). In each test session (performed at least 24 hours apart), a random order of saline, and two different nicotine infusions of 0.25 mg and 0.5 mg/70 kg of bodyweight were administered, one hour apart, concurrent with menthol inhalation., Results: While menthol did not alter the positive subjective effects of nicotine, menthol significantly enhanced aversive effects of nicotine in non-menthol-preferring smokers and reduced smoking urges in menthol-preferring smokers. In addition, menthol-preferring smokers reported blunted positive subjective responses to nicotine and less severe nicotine withdrawal after overnight nicotine deprivation. Finally, compared to non-menthol-preferring smokers, menthol-preferring smokers had a significantly lower baseline nicotine metabolite ratio indicating slower nicotine metabolism within our sample of menthol-preferring smokers., Conclusions: Our findings did not support an enhancement of nicotine's positive subjective effects from inhaled menthol. However, as compared to non-menthol-preferring smokers, menthol-preferring smokers had blunted positive subjective responses to nicotine and reduced overnight withdrawal severity that may be partly due to inhibition of nicotine metabolism from chronic exposure to inhaled menthol. Collectively, these results reveal a more complex and nuanced role of inhaled menthol in smokers than previously recognized.

The aim of the present study was to apply the Check-all-that-apply (CATA) method in an ambulatory context involving subjects with phenylketonuria (PKU) to obtain a sensory description and to find the drivers of liking of low-phenylalanine products (Glycomacropeptide vs. L-amino acids formulas). 86 subjects with PKU (age range: 8⁻55 years) evaluated 8 samples: 4 L-amino acid formulas and 4 Glycomacropeptide (GMP) formulas, flavored with neutral, chocolate, strawberry and tomato aromas. Participants were asked to indicate which sensory attributes characterized each formulations and to score the overall liking. Significant differences were found regarding liking scores (F = 65.29; p < 0.001). GMP samples flavored with chocolate and strawberry, described as sweets, with a mild and natural taste and odor, were the most appreciated. Overall, GMP formulas obtained higher liking scores compared to L-amino acid formulas. Tomato flavored samples, described as bitter, salty, with artificial color, with strong taste and odor, obtained the lowest scores. In conclusion, CATA questionnaire seems to be a suitable method also in ambulatory context since this approach suggested that different foods and beverages with GMP could be developed to improve dietary treatment compliance of subjects with PKU from school age onwards.

Taste and flavor (retronasal olfaction) interact in the brain. The rules of that interaction are not well understood. This study uses 2 taste modifiers that alter sweet to examine the effects on flavors. Subjects used the Global Sensory Intensity Scale to assess the aroma, sweetness, sourness, and flavor of 10 foods. As previous work had shown, miracle fruit added sweetness to acids, which secondarily reduced sourness (mixture suppression) and Gymnema sylvestre reduced sweetness in sweet foods as well as the sweetness induced by miracle fruit. In this study, multiple regression showed that both sweet and sour contribute to flavor. Gymnema sylvestre reduced the perceived sweet of predominantly sweet foods (chocolate and maple syrup) as expected; reducing the sweet, reduced the flavor. The effects of miracle fruit were complicated by its dual action: intensification of sweet and reduction of sour. Predominantly sour foods (vinegar, lemon, mustard, pickle) were sweetened by miracle fruit but any flavor enhancement associated with the added sweet appears to have been countered by the flavor reduction associated with reduced sourness. Moderately sour foods that are also sweet (tomatoes, strawberries) were sweetened by miracle fruit and thus flavor was enhanced; flavor loss through sour reduction was apparently not sufficient to counter the flavor enhancement due to increased sweet so the net result was that tomato and strawberry flavors were enhanced. The flavors of control foods (not predominantly sweet or sour [sausage, peanuts]) showed only small changes.

Background: Menthol cigarettes are disproportionately used by young people and have been called smoking starter products. However, limited qualitative research exists on young adults' perceptions of and experiences with these products, with much of it based on document reviews of the tobacco industry's research., Methods: We conducted six focus groups with young adult (ages 18-24) menthol smokers in New Jersey (half with black smokers) between December 2014 and March 2015. Participants were asked open-ended questions about their menthol smoking initiation, preference reasons, substitution behaviors, and perceptions of menthol cigarette risks and regulation., Results: Participants' menthol cigarette initiation and preference were influenced by their perceived popularity, brand recognition, taste, smoothness, satisfaction and access (including as "loosies," typically available for Newport). Some believed menthol cigarettes were less harmful than non-menthol cigarettes when initiating smoking. Many currently believed menthol cigarettes were more harmful because they contained extra "additives," were stronger (ie, requiring fewer cigarettes to feel satisfied), and/or based on hearsay. Many had tried new brand Camel Crush, which was perceived to be especially minty, fun, and attractive for newer smokers. While some used non-menthol cigarettes when menthols were unavailable, many said they would never or almost never substitute. Many acknowledged a menthol cigarettes ban would likely help them quit smoking, even though they did not support the idea., Conclusions: Menthol cigarette initiation is influenced by an interplay of multiple factors including their sensory properties, marketing, perceived popularity and availability. The FDA should continue to pursue closing this flavored cigarette loophole., Implications: In this first qualitative study of menthol cigarette use among young adults, we found further evidence that menthol cigarettes can act as starter products because they are perceived as easier to smoke and taste and smell better than non-menthol cigarettes. We also add to the literature in finding that menthol cigarettes are perceived by young people who smoke menthol cigarettes as delivering satisfaction with fewer cigarettes, being accessible as "loosies", and being popular among their peers. Many did not understand the reasons behind a potential menthol ban. Any future regulation of menthol cigarettes should include a public educational campaign to support buy-in.

Introduction: Since being brought to market in 2007, cigarettes with capsules in the filter that can be burst to change the flavor have had remarkable global success, highlighting the importance of product innovation for tobacco companies. Very few studies have explored how these products are perceived by smokers however. This paper sought to address this gap by exploring smokers' awareness of cigarettes with one or two flavor-changing capsules in the filter and the appeal of these products., Methods: Twenty focus groups were conducted in Glasgow and Edinburgh in 2015 with current smokers (N = 120), segmented by age (16-17, 18-24, 25-35, 36-50, >50), gender, and social grade., Results: Awareness, use and appeal of capsule cigarettes was greater among younger adults (16-35 years), who showed most interest in these products. Those who perceived capsules positively mentioned multiple benefits: the ability to burst the capsule, convenience of being able to share cigarettes among menthol and nonmenthol smokers, better taste, fresher breath, reduced smell, and greater discretion. It was suggested that capsule cigarettes, particularly the double capsule cigarette (which had two differently flavored capsules in the filter), would encourage nonsmokers to experiment with smoking and discourage smokers from quitting., Conclusions: The findings offer some reasons behind the global growth of the capsule cigarette segment., Implications: Cigarettes with flavor-changing capsules in the filter have been one of the most successful product innovations of the last decade for tobacco companies. They have received very little academic attention however. Employing focus groups with 120 smokers aged 16 and over, we found that capsule cigarettes held most appeal to, and were considered to be targeted at, younger people, with it suggested that these products would encourage initiation and discourage cessation. This study provides some understanding of how these products are viewed by smokers.

Objective: The primary objective of this pilot study was to describe the impact of e-cigarette liquid flavors on experienced e-cigarette users' vaping behavior., Methods: 11 males and 3 females participated in a 3-day inpatient crossover study using e-cigarettes with strawberry, tobacco, and their usual brand e-liquid. Nicotine levels were nominally 18 mg/mL in the strawberry and tobacco e-liquids and ranged between 3-18 mg/mL in the usual brands. On each day, participants had access to the study e-cigarette (KangerTech mini ProTank 3, 1.5 Ohms, 3.7 V) and the assigned e-liquid during a 90-minute videotaped ad libitum session., Results: Average puff duration was significantly longer when using the strawberry e-liquid (3.2 ± 1.3 s, mean ± SD) compared to the tobacco e-liquid (2.8 ± 1.1 s) but the average number of puffs was not significantly different (strawberry, 73 ± 35; tobacco, 69 ± 46). Compared to the strawberry- and tobacco-flavored e-liquids, average puff duration was significantly longer (4.3 ± 1.6 s) and the average number of puffs was significantly higher (106 ± 67 puffs) when participants used their usual brand of e-liquid. Participants generally puffed more frequently in small groups of puffs (1-5 puffs) with the strawberry compared to the tobacco e-liquid and more frequently in larger groups (>10 puffs) with their usual brand. The strength of the relationship between vaping topography and nicotine intake and exposure were not consistent across e-liquids., Conclusion: Vaping behavior changes across e-liquids and influences nicotine intake. Research is needed to understand the mechanisms that underlie these behavioral changes, including e-liquid pH and related sensory effects, subjective liking, and nicotine effects., (Copyright © 2018. Published by Elsevier B.V.)

Introduction: Nicotine replacement therapy (NRT) benefits smokers who wish to quit; nicotine gum represents one NRT. New formulations of nicotine gum have been developed to consider consumer preferences and needs. A new mint-flavored nicotine gum with a different texture was developed that may provide a more appealing taste and chewing experience. This study evaluated this new nicotine gum (2 and 4 mg strengths) for bioequivalence versus the original flavor sugar-free nicotine gum at corresponding dosages., Methods: All subjects randomized in this crossover study received a single dose of all treatments, i.e., 2 and 4 mg doses of test and reference gums, separated by 2-7 days of washout between treatments. Subjects' maximal plasma nicotine concentration (C max ) and extent of nicotine absorption (AUC 0-t ) following the administration of each treatment were calculated from plasma nicotine concentrations. Ratios of test/reference for C max and AUC 0-t were calculated to evaluate bioequivalence between the two products., Results: Both 2 and 4 mg doses of the new mint-flavored nicotine gum were bioequivalent to the dose-matched reference product as determined by the ratio of the geometric means and their 90% confidence intervals for C max and AUC 0-t as well as secondary pharmacokinetic parameters. The safety profiles of the test and reference gums were similar; all treatments were well tolerated., Conclusions: A new mint-flavored nicotine gum with modified taste and texture is bioequivalent to the original flavor sugar-free nicotine gum at both the 2 and 4 mg dosage strengths and has a similar safety profile., Funding: GlaxoSmithKline., Trial Registration: ClinicalTrials.gov identifier NCT01847443.

To understand whether flavor enhancers pose potential risks to the environment, it is important to assess its effects on insects. Therefore, the objective of this study was to evaluate the toxicity of flavor enhancers on the survival and behaviors of the red imported fire ant, Solenopsis invicta. In this study, we found that the mortality of S. invicta workers that were fed glutamic acid monosodium salt hydrate, glycine, L-alanine, succinic acid, succinic acid disodium, inosinate 5'-monophosphate disodium salt hydrate, and GMP were significantly higher than the mortality rates of workers fed sucrose. Moreover, glycine and GMP exhibited the strongest toxicities and caused 100% mortality in workers after 84 h. LC 50 values were 0.004 g/ml and 0.02 g/ml for GMP and glycine, respectively. Additionally, at sublethal doses, both GMP and glycine solutions decreased foraging and digging behaviors. Our results suggest that flavor enhancers are toxic to insects and also likely to have a negative impact at sublethal concentrations.

Background: Coverage of e-cigarettes in the news media may shape public perceptions about them but little is known about such news content. This content analysis characterized discussion of e-cigarettes in leading print and online US news sources in 2015., Methods: We searched Access World News and Factiva databases for e-cigarette-related news articles appearing in the top 30 circulating newspapers, 4 newswires, and 4 online news sources in the United States in 2015 (n = 295). Coders identified the presence of various e-cigarette topics (e.g. regulation), and benefit and risk statements., Results: Nearly half of articles (45.1%) focused primarily on e-cigarette policy/regulatory issues, although e-cigarette prevalence (21.0%) and health effects (21.7%) were common main topics. Concerns about youth were frequently mentioned, including the rise in youth e-cigarette use (45.4%), gateway to smoking potential (33.9%) and appeal of flavors (22.4%). Youth e-cigarette prevalence was more frequently mentioned than adult prevalence in articles discussing FDA regulation (61% vs. 13.5%, respectively). News articles more frequently discussed potential e-cigarette risks or concerns (80%) than benefits (45.4%), such as smoking harm-reduction. Quoted physicians, researchers, and government representatives were more likely to refer to e-cigarette risks than benefits., Conclusions: In 2015, rising rates of e-cigarette use among youth and policy strategies to address e-cigarettes dominated US e-cigarette news stories, leading up to their FDA regulation in 2016. Statements about e-cigarettes' potential risks were frequently attributed to trusted sources such as physicians, and outnumbered claims about their harm-reduction benefits. Such coverage may impact e-cigarette risk perceptions, use intentions and policy support., Implications: In the year leading up to the FDA's Deeming Rule, concerns about youth use or potential use were frequently discussed in e-cigarette news. News articles more frequently discussed potential e-cigarette risks/concerns compared to potential harm-reduction benefits relative to tobacco cigarettes. While such coverage may inform the public about potential e-cigarette risks, they may also contribute to increasing perceptions that e-cigarettes are as harmful as tobacco cigarettes. E-cigarette risk and benefit statements were most frequently made by or attributed to researchers and physicians in articles, which is significant given that they may be particularly trusted sources of e-cigarette risk information.

We used an umami substance, monosodium glutamate (MSG), as a simple stimulant to clarify the mechanism of the formation of emotional behavior. A 60 mM MSG solution was fed to spontaneously hypertensive rats (SHR), used as a model of attention-deficit hyperactivity disorder, from postnatal day 25 for 5 weeks kept in isolation. Emotional behaviors (anxiety and aggression) were then assessed by the open-field test, cylinder test and social interaction test. MSG ingestion during the developmental period resulted in a significant reduction in aggressive behavior but had few effects on anxiety-like behavior. Several experiments were performed to identify the reason for the reduced aggression with MSG intake. Blood pressure in the MSG-treated SHR was comparable to that of the controls during development. Argyrophil III staining to detect the very early phase of neuronal damage revealed no evidence of injury by MSG in aggression-related brain areas. Assessment of plasma amino acids revealed that glutamate levels remained constant (∼80 μM) with MSG ingestion, except for a transient increase after fasting (∼700 μM). However, lactate dehydrogenase assay in an in vitro blood-brain barrier model showed that cell toxicity was not induced by indirect MSG application even at 700 μM, confirming that MSG ingestion caused minimal neuronal damage. Finally, vagotomy at the sub-diaphragmatic level before MSG ingestion blocked its effect on aggressive behavior in the isolated SHR. The data suggest that MSG ingestion during the developmental period can reduce aggressive behavior in an attention deficit-hyperactivity disorder model rat, mediated by gut-brain interaction., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Patients who are malnourished or at-risk for malnutrition often benefit from the consumption of oral nutritional supplements (ONS). ONS supply a range of micro- and macro-nutrients, and they can be used to supplement a diet or provide total nutrition. Since ONS are specially formulated products, all ONS ingredients&mdash;including carbohydrates&mdash;are added ingredients. This may seem to be at odds with the growing public health discourse on the need to reduce &ldquo;added sugars&rdquo; in the diet. However, carbohydrate is an essential nutrient for human health and is a critical ingredient in ONS. Helping to educate patients on the value of &ldquo;added sugars&rdquo; in ONS may be useful to improve compliance with nutritional recommendations when ONS are indicated. This perspective paper reviews the important roles of &ldquo;added sugars&rdquo; in ONS, in terms of flavor, function, and product formulation.

Background: E-cigarettes are sold in flavors such as "skittles," "strawberrylicious," and "juicy fruit," and no restrictions are in place on marketing e-cigarettes to youth. Sweets/fruits depicted in e-cigarette advertisements may increase their appeal to youth and interfere with health warnings. This study tested a brain biomarker of product preference for sweet/fruit versus tobacco flavor e-cigarettes, and whether advertising for flavors interfered with warning labels., Methods: Participants (N = 26) were college-age young adults who had tried an e-cigarette and were susceptible to future e-cigarette use. They viewed advertisements in fMRI for sweet/fruit and tobacco flavor e-cigarettes, menthol and regular cigarettes, and control images of sweets/fruits/mints with no tobacco product. Cue-reactivity was measured in the nucleus accumbens, a brain biomarker of product preference. Advertisements randomly contained warning labels, and recognition of health warnings was tested post-scan. Visual attention was measured using eye-tracking., Results: There was a significant effect of e-cigarette condition (sweet/tobacco/control) on nucleus accumbens activity, that was not found for cigarette condition (menthol/regular/control). Nucleus accumbens activity was greater for sweet/fruit versus tobacco flavor e-cigarette advertisements and did not differ compared with control images of sweets and fruits. Greater nucleus accumbens activity was correlated with poorer memory for health warnings., Conclusions: These and exploratory eye-tracking findings suggest that advertising for sweet/fruit flavors may increase positive associations with e-cigarettes and/or override negative associations with tobacco, and interfere with health warnings, suggesting that one way to reduce the appeal of e-cigarettes to youth and educate youth about e-cigarette health risks is to regulate advertising for flavors., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: This open-label study sought to evaluate the warming sensation produced by IFF flavor 316282 in an acetylcysteine oral solution in subjects with productive cough., Materials: 2% ace-tylcysteine oral solution (200 mg per 10 mL) containing IFF flavor 316282., Methods: Subjects (N = 57; mean age 38.7 years; 58% female) with a productive cough lasting < 7 days and rated as mild to moderate in severity received 10 mL of study product. Warming sensation intensity was assessed using a 100-mm visual analog scale, its onset and duration using stopwatches, its acceptability using a 9-point scale (from "dislike extremely" to "like extremely") and the taste, texture, and overall acceptability of the solution using 5-point scales (from "unacceptable" to "excellent")., Results: 53 (93.0%) subjects perceived a warming sensation within 10 minutes of swallowing the solution; median onset was ~ 14 seconds, and median duration was ~ 2.8 minutes. Warming sensation intensity increased from baseline by a mean of 29.2 mm when evaluated 60 seconds after ingestion. 30 subjects (52.6%) thought the warming sensation was "just about right"; 25 (43.9%) considered it "too weak" or "much too weak." Most subjects had positive overall ratings ("fair," "good," or "excellent") of the taste (79.0%), texture (96.5%), and solution (91.2%). No treatment-emergent adverse events were reported, and no evidence of oral mucosal irritation was found., Conclusion: The addition of IFF flavor 316282 to a 2% acetylcysteine oral solution produced a warming sensation with rapid onset and relatively short duration, which the majority of subjects found acceptable.
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We have recently developed a Tobacco Heating Product (THP) comprising an electrical heating device, commercially known as Glo™, and consumable tobacco rods, commercially known as Kent Neostiks™. We refer to this system as THP1.0; Bright tobacco-flavoured variant THP1.0(T), or THP1.0(M) Menthol-flavoured variant. In this issue, we present a series of seven pre-clinical studies conducted on THP1.0,covering the following aspects of its design, development, safety and toxicological assessment, and a paper on placing THPs on an emissions continuum., (Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.)

Introduction: This study examined the association of sociodemographic characteristics, tobacco and substance use behaviors, and reasons to use cigars in young adults' flavored and non-flavored cigar use., Methods: Participants were 523, 18- to 29- year-old young adult college students (60.4% male; 40.9% non-Hispanic white) who reported current (past 30-day) cigar use., Results: Almost 75% of the sample regularly chose flavored cigar products. Multilevel logistic regression analyses indicated that younger, female, and racial/ethnic minority cigar users had significantly greater odds of using flavored cigars than their counterparts. Current marijuana smokers, ever-blunt smokers, and students who reported using cigars because they were affordable and/or available in flavors they liked had a greater odds of flavored cigar use compared to their counterparts. Moreover, among dual users of cigars and cigarettes, those who cited using cigars because they were cheaper than cigarettes and because cigars felt like smoking regular cigarettes had greater odds of using flavored cigars compared to their peers. Number of days cigars were smoked and current use of other tobacco products were not associated with flavored cigar use., Conclusions: Appealing attributes of flavored cigars have the potential to contribute to the tobacco use and subsequent nicotine addiction of younger, female, and racial/ethnic minority young adults. The wide variety of cigar flavors, their attractive price, and similarity to cigarette smoking underscore the need for additional research that links these unique traits to sustained tobacco use, and underscore the need for regulation of flavored products., Implications: This study extends the current literature by finding that younger, female, and racial/ethnic minorities have greater odds of flavored cigar use than their peers. Flavored cigars have characteristics that appeal to members of these populations, which can contribute to their long-term use and potential for addiction., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Various factors need to be taken into account when reformulating a food or beverage. The food components, not only macronutrients but also minor ingredients such as flavoring agents, could affect the perception of the sensory sensations, importantly their dynamic aspects, as rising and duration, which are not normally considered. The novelty of this approach is the study of the effects of the addition of several ingredients (fiber, extra milk powder, and strawberry flavoring) on the dynamic perception of a food item (strawberry shakes) using the temporal dominance of sensations (TDS) technique. The occurrence and duration of the key sensory sensations (acid, natural strawberry flavor, thick, sweet, candy strawberry flavor, and milk flavor) extracted from the TDS curves were analyzed and linked to the composition factors and liking and expectations of satiety scores. For example, the addition of flavoring increased the liking scores (increments ranging from 0.3 to 1.1) that was linked to the attenuation of acid sensation; and the addition of extra milk powder increased the expectation of satiety scores (increments ranging from 0.5 to 0.7) that was linked to the perception of early thick sensation in the mouth. In general, the more complex sensory profiles the higher liking and expectations of satiety., Practical Application: This work is a case study on how temporal sensory methods can contribute important information on the actual perception of food during consumption. Depending on the ingredients added these sensory properties appear at different times and with different dominance during evaluation affecting liking or fullness expectations. In consequence, the temporal sensory properties should be taken into account when designing or reformulating food., (© 2017 Institute of Food Technologists®.)

Background: Monosodium Glutamate (MSG) is one of the most commonly used food additives for the enhancement of food taste and flavour. There are several conflicting reports of toxicity or otherwise safety of the compound, which raises a growing concern regarding the safety of monosodium glutamate as a food additive., Objective: In the present study, we sought to investigate the effect of monosodium glutamate on body weight, feed consumption, body temperature and some haematological parameters., Methodology: Twenty adult Wistar rats divided into four groups of five rats each were used for the study. Rats in groups 1, 2 and 3 were given feed thoroughly mixed with 3, 6 and 9 g of monosodium glutamate respectively for 14 days, while rats in group 4 (Control) were given only the feed for the same period of time. Body weight, temperature, feed consumption, and some haematological parameters were measured before the addition of the compound to the feed and thereafter for every 2 days for a period of 14 days., Results: Our findings indicated significant changes (P < 0.05) in the red blood cells (RBC) count, packed cell volume (PCV), as well as body temperature in all the treated groups compared to the control group. The result also revealed a significant dose-dependent increase in body weight in the groups treated with 6 and 9 g of monosodium glutamate compared to the control, the body weight correlated positively with the duration of monosodium glutamate consumption., Conclusion: The current data suggest that consumption of high doses/quantity of monosodium glutamate for a long duration of time could lead to anaemia due to a decrease in red blood cell count and packed cell volume and obesity resulting from an increase in body weight gain., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)