A Nonorthogonal Configuration Interaction Approach to Singlet Fission in Perylenediimide Compounds.

Perylenediimide molecules constitute a family of chromophores that undergo singlet fission, a process in which an excited singlet state converts into lower energy triplets on two neighboring molecules, potentially increasing the efficiency of organic solar cells. Here, the nonorthogonal configuration interaction method is applied to study the effect of the different crystal packing of various perylenediimide derivatives on the relative energies of the singlet and triplet states, the intermolecular electronic couplings, and the relative rates for singlet fission. The analysis of the wave functions and electronic couplings reveals that charge transfer states play an important role in the singlet fission mechanism. Dimer conformations where the PDI molecules are at large displacements along the long axis and short on the short axis are posed as the most favorable for singlet fission. The role of the substituent at the imide group has been inspected concluding that, although it has no effect in the energies, for some conformations it significantly influences the electronic couplings, and therefore, replacing this substituent with hydrogen may introduce artifacts in the computational modeling of the PDI molecules.

In vivo clonal tracking reveals evidence of haemangioblast and haematomesoblast contribution to yolk sac haematopoiesis.

During embryogenesis, haematopoietic and endothelial lineages emerge closely in time and space. It is thought that the first blood and endothelium derive from a common clonal ancestor, the haemangioblast. However, investigation of candidate haemangioblasts in vitro revealed the capacity for mesenchymal differentiation, a feature more compatible with an earlier mesodermal precursor. To date, no evidence for an in vivo haemangioblast has been discovered. Using single cell RNA-Sequencing and in vivo cellular barcoding, we have unravelled the ancestral relationships that give rise to the haematopoietic lineages of the yolk sac, the endothelium, and the mesenchyme. We show that the mesodermal derivatives of the yolk sac are produced by three distinct precursors with dual-lineage outcomes: the haemangioblast, the mesenchymoangioblast, and a previously undescribed cell type: the haematomesoblast. Between E5.5 and E7.5, this trio of precursors seeds haematopoietic, endothelial, and mesenchymal trajectories.

On the role of dynamic electron correlation in non-orthogonal configuration interaction with fragments.

Two different approaches have been implemented to include the effect of dynamic electron correlation in the Non-Orthogonal Configuration Interaction for Fragments (NOCI-F) method. The first is based on shifting the diagonal matrix elements of the NOCI matrix, while the second incorporates the dynamic correlation explicitly in the fragment wave functions used to construct the many-electron basis functions of the NOCI. The two approaches are illustrated for the calculation of the electronic coupling relevant in singlet fission and the coupling of spin moments in organic radicals. Comparison of the calculated diabatic couplings, the NOCI energies and wave functions shows that dynamic electron correlation is not only efficiently but also effectively incorporated by the shifting approach and can largely affect the coupling between electronic states. Also, it brings the NOCI coupling of the spin moments in close agreement with benchmark calculations.

GronOR: Scalable and Accelerated Nonorthogonal Configuration Interaction for Molecular Fragment Wave Functions.

GronOR is a program package for nonorthogonal configuration interaction calculations. Electronic wave functions are constructed in terms of antisymmetrized products of multiconfiguration molecular fragment wave functions. The computational complexity of the nonorthogonal methodologies implemented in GronOR applied to large molecular assemblies requires a design that takes full advantage of massively parallel supercomputer architectures and accelerator technologies. This work describes the implementation strategy and resulting performance characteristics. In addition to parallelization and acceleration, the software development strategy includes aspects of fault resiliency and heterogeneous computing. The program was designed for large-scale supercomputers but also runs effectively on small clusters and workstations for small molecular systems. GronOR is available as open source to the scientific community.

Chemosensory perception and food preferences in colorectal cancer patients undergoing adjuvant chemotherapy.

BACKGROUND AND AIM: Cancer is one of the major public health problems, with colorectal cancer being one of the most occurring types of cancer. During treatment, patients may experience changes in their dietary intake due to side-effects of treatment, like changes in chemosensory perception, i.e. smell and taste function. This study investigated alterations in chemosensory perception and food preferences in colorectal cancer patients during and after adjuvant chemotherapy. METHODS: Objective olfactory and gustatory function were measured by the Sniffin' Sticks and the Taste Strips test. Subjective smell and taste perception were determined with a questionnaire, while food preferences were assessed with a computer-based ranking task. To investigate changes during chemotherapy, patients undergoing adjuvant chemotherapy were measured before the start, halfway through (approximately 3 months after the start of adjuvant chemotherapy), and within one month after finishing chemotherapy (longitudinal measurements, n = 15 patients). As a comparison group, colorectal cancer patients not undergoing chemotherapy (n = 20), underwent the same measurements at similar time points. To measure changes after treatment, chemosensory perception and food preferences of patients who had undergone chemotherapy treatment were measured once, either at 6, 12 or 24 months after diagnosis (cross-sectional measurements; n = 20 for all time points). Changes during treatment were assessed using linear mixed model analyses, and changes after treatment were assessed with a one-way ANOVA or a Kruskal Wallis test. RESULTS: Objective olfactory and gustatory function did not differ statistically significantly between any of the groups and at any time point during or after treatment (all p > 0.05). In contrast, subjective smell (F(1,84) = 8.17, p = 0.005) and taste (F(1,99) = 4.08, p = 0.046) perception were rated statistically significantly lower by patients undergoing chemotherapy than the comparison group during treatment. At 6 months after diagnosis, patients who underwent chemotherapy rated their subjective taste perception significantly lower than patients at 12 and 24 months after treatment (F(2,57) = 12.05, p = 0.002). Food preferences did not change during treatment, or thereafter (all p > 0.05). Preference for protein-rich foods was positively correlated with objective gustatory function (r = 0.36, p < 0.001), while the preference for low-energy foods showed a negative correlation with objective gustatory function (r = -0.28, p = 0.004). CONCLUSIONS: Similar to other cancer patient populations, mainly subjective smell and taste perception are affected in colorectal cancer patients undergoing adjuvant chemotherapy. Changes in objective olfactory and gustatory function in relation to chemotherapy were not detected by the tests used in our study nor did food preferences change. However, it should be noted that subjective changes in smell and taste perception can affect subsequent flavor perception and food enjoyment, which might negatively impact eating behavior and nutritional intake.

GronOR: Massively parallel and GPU-accelerated non-orthogonal configuration interaction for large molecular systems.

GronOR is a program package for non-orthogonal configuration interaction calculations for an electronic wave function built in terms of anti-symmetrized products of multi-configuration molecular fragment wave functions. The two-electron integrals that have to be processed may be expressed in terms of atomic orbitals or in terms of an orbital basis determined from the molecular orbitals of the fragments. The code has been specifically designed for execution on distributed memory massively parallel and Graphics Processing Unit (GPU)-accelerated computer architectures, using an MPI+OpenACC/OpenMP programming approach. The task-based execution model used in the implementation allows for linear scaling with the number of nodes on the largest pre-exascale architectures available, provides hardware fault resiliency, and enables effective execution on systems with distinct central processing unit-only and GPU-accelerated partitions. The code interfaces with existing multi-configuration electronic structure codes that provide optimized molecular fragment orbitals, configuration interaction coefficients, and the required integrals. Algorithm and implementation details, parallel and accelerated performance benchmarks, and an analysis of the sensitivity of the accuracy of results and computational performance to thresholds used in the calculations are presented.

Baby's first bites: a randomized controlled trial to assess the effects of vegetable-exposure and sensitive feeding on vegetable acceptance, eating behavior and weight gain in infants and toddlers.

BACKGROUND: The start of complementary feeding in infancy plays an essential role in promoting healthy eating habits. Evidence shows that it is important what infants are offered during this first introduction of solid foods: e.g. starting exclusively with vegetables is more successful for vegetable acceptance than starting with fruits. How infants are introduced to solid foods also matters: if parents are sensitive and responsive to infant cues during feeding, this may promote self-regulation of energy intake and a healthy weight. However, the effectiveness of the what and the how of complementary feeding has never been experimentally tested in the same study. In the current project the what and how (and their combination) are tested in one study to determine their relative importance for fostering vegetable acceptance and self-regulation of energy intake in infants. METHODS: A four-arm randomized controlled trial (Baby's First Bites (BFB)) was designed for 240 first-time Dutch mothers and their infants, 60 per arm. In this trial, we compare the effectiveness of (a) a vegetable-exposure intervention focusing on the what in complementary feeding; (b) a sensitive feeding intervention focusing on the how in complementary feeding, (c) a combined intervention focusing on the what and how in complementary feeding; (d) an attention-control group. All mothers participate in five sessions spread over the first year of eating solid foods (child age 4-16 months). Primary outcomes are vegetable consumption, vegetable liking and self-regulation of energy intake. Secondary outcomes are child eating behaviors, child anthropometrics and maternal feeding behavior. Outcomes are assessed before, during and directly after the interventions (child age 18 months), and when children are 24 and 36 months old. DISCUSSION: The outcomes are expected to assess the impact of the interventions and provide new insights into the mechanisms underlying the development of vegetable acceptance, self-regulation and healthy eating patterns in infants and toddlers, as well as the prevention of overweight. The results may be used to improve current dietary advice given to parents of their young children on complementary feeding. TRIAL REGISTRATION: The trial was retrospectively registered during inclusion of participants at the Netherlands National Trial Register (identifier NTR6572 ) and at ClinicalTrials.gov ( NCT03348176 ). Protocol issue date: 1 April 2018; version number 1.

Low reported taste function is associated with low preference for high protein products in advanced oesophagogastric cancer patients undergoing palliative chemotherapy.

BACKGROUND & AIMS: Cancer patients undergoing palliative chemotherapy can experience a variety of chemosensory and food preference changes which may impact their nutritional status and quality of life. However, evidence of these changes in oesophagogastric cancer (OGC) patients is currently mostly qualitative and not supported by quantitative data. The aim of this study was to assess how self-reported and objective taste and smell function and food preferences change over time during chemotherapy in OGC patients. METHODS: This observational study included 15 advanced OGC patients planned for first line treatment with capecitabine and oxaliplatin. Participants completed two test sessions scheduled before start of cytotoxic treatment and after two cycles. Self-reported and objective taste and smell function and the macronutrient and taste preference ranking task were conducted at each test session. RESULTS: Self-reported taste and smell did not change upon chemotherapy. Objective taste function decreased during chemotherapy, although this was not statistically significant (p = 0.06), objective smell function did not change. Before and during chemotherapy, high protein foods were preferred over high carbohydrate and over low energy products, but food preferences did not change over time. A lower self-reported taste function correlated with a lower preference for high-protein products (ρ = 0.526, p = 0.003). CONCLUSION: This study suggests that objective taste function decreases during chemotherapy in OGC patients, but not smell function. A low reported taste function was related to a lower preference for high-protein products.

Sensory analysis of characterising flavours: evaluating tobacco product odours using an expert panel.

OBJECTIVES: Tobacco flavours are an important regulatory concept in several jurisdictions, for example in the USA, Canada and Europe. The European Tobacco Products Directive 2014/40/EU prohibits cigarettes and roll-your-own tobacco having a characterising flavour. This directive defines characterising flavour as 'a clearly noticeable smell or taste other than one of tobacco […]'. To distinguish between products with and without a characterising flavour, we trained an expert panel to identify characterising flavours by smelling. METHODS: An expert panel (n=18) evaluated the smell of 20 tobacco products using self-defined odour attributes, following Quantitative Descriptive Analysis. The panel was trained during 14 attribute training, consensus training and performance monitoring sessions. Products were assessed during six test sessions. Principal component analysis, hierarchical clustering (four and six clusters) and Hotelling's T-tests (95% and 99% CIs) were used to determine differences and similarities between tobacco products based on odour attributes. RESULTS: The final attribute list contained 13 odour descriptors. Panel performance was sufficient after 14 training sessions. Products marketed as unflavoured that formed a cluster were considered reference products. A four-cluster method distinguished cherry-flavoured, vanilla-flavoured and menthol-flavoured products from reference products. Six clusters subdivided reference products into tobacco leaves, roll-your-own and commercial products. CONCLUSIONS: An expert panel was successfully trained to assess characterising odours in cigarettes and roll-your-own tobacco. This method could be applied to other product types such as e-cigarettes. Regulatory decisions on the choice of reference products and significance level are needed which directly influences the products being assessed as having a characterising odour.

Structure-based exploration and pharmacological evaluation of N-substituted piperidin-4-yl-methanamine CXCR4 chemokine receptor antagonists.

Using the available structural information of the chemokine receptor CXCR4, we present hit finding and hit exploration studies that make use of virtual fragment screening, design, synthesis and structure-activity relationship (SAR) studies. Fragment 2 was identified as virtual screening hit and used as a starting point for the exploration of 31 N-substituted piperidin-4-yl-methanamine derivatives to investigate and improve the interactions with the CXCR4 binding site. Additionally, subtle structural ligand changes lead to distinct interactions with CXCR4 resulting in a full to partial displacement of CXCL12 binding and competitive and/or non-competitive antagonism. Three-dimensional quantitative structure-activity relationship (3D-QSAR) and binding model studies were used to identify important hydrophobic interactions that determine binding affinity and indicate key ligand-receptor interactions.

Sweetness but not sourness enhancement increases acceptance of cucumber and green capsicum purees in children.

For children it is important to consume enough vegetables to establish healthy dietary patterns. Taste acceptance is an important factor contributing to food choice and consumption. Sweetness and sourness enhancement can increase acceptance of specific foods in children. The aim of this study was to determine the effect of sweetness and sourness enhancement on acceptance of cucumber and green capsicum purees in 5-6-year-old children. Three concentrations of sucrose (2, 5 and 10%) and citric acid (0.05, 0.08 and 0.15%) were added to cucumber and green capsicum purees. Children (n = 70, 5.7 ±â€¯0.5 yrs) assessed acceptance of the vegetable purees using a 5-point hedonic facial scale. Sweetness enhancement significantly increased acceptance of cucumber purees (5 and 10% sucrose) and green capsicum purees (2 and 10% sucrose) compared to unmodified purees. Sourness enhancement (0.05, 0.08 and 0.15% citric acid) did not significantly influence acceptance of cucumber and green capsicum purees compared to unmodified purees. Children differed in acceptance of vegetable purees with added sucrose and citric acid. Sweetness likers (cucumber 77.1%, green capsicum 58.6%) accepted sucrose concentrations better than sweetness non-likers in both vegetables. Sourness likers (cucumber 50.0%, green capsicum 44.3%) accepted medium and high concentrations of citric acid better than sourness non-likers in cucumber and all citric acid concentrations in green capsicum. We conclude that enhancement of sweetness increases acceptance of cucumber and green capsicum purees in most children whereas enhancement of sourness is better accepted by only a few children. This study highlights the challenge to get children to better accept vegetables, since only sweetness enhancement improved acceptance while addition of sucrose is undesirable. For a small subset of children enhancing sourness might be an alternative strategy to increase acceptance of vegetables.

Altered neural inhibition responses to food cues after Roux-en-Y Gastric Bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery is a highly effective weight-loss intervention that often reduces preference and intake of high-energy foods. Research into the neural mechanisms behind this shift has mainly focused on reward processing of food cues. However, the ability to successfully control food intake and thereby weight-loss also depends on inhibitory control capacity. We investigated whether RYGB leads to alterations in neural inhibitory control in response to food cues. METHODS: A food-specific go/no-go task with pictures of high-energy (desserts) and low-energy foods (vegetables), was used to assess neural inhibition responses before and after RYGB with functional magnetic resonance imaging. Data from 18 morbidly obese patients (15 females; age 41 ±â€¯11 years; BMI 42 ±â€¯4 kg/m2 before; BMI 36 ±â€¯4 kg/m2 after) were analysed. Pre- and post-RYGB BOLD fMRI responses were compared for response inhibition towards high- and low-energy foods. Participants were tested in a satiated state. RESULTS: Response inhibition to high-energy foods was associated with increased activation of the right lateral prefrontal cortex (PFC), right medial PFC, dorsolateral PFC, right middle cingulate cortex and the right inferior frontal operculum (involved in inhibitory control), after compared to before surgery. Response inhibition to low-energy foods elicited diminished post- compared to pre-surgery responses in the left superior temporal pole, right parahippocampal gyrus and right hypothalamus (involved in metabolic control). CONCLUSION: Neural changes indicate improved response inhibition towards high-energy food cues, altered influence of metabolic control during response inhibition towards low-energy food cues and a more positive attitude to both high-energy and low-energy food after RYGB. Alterations in neural circuits involved in inhibitory control, satiety signalling and reward processing may contribute to effective weight-loss after RYGB.

Sweet taste exposure and the subsequent acceptance and preference for sweet taste in the diet: systematic review of the published literature.

Background: There are consistent, evidence-based global public health recommendations to reduce intakes of free sugars. However, the corresponding evidence for recommending reduced exposure to sweetness is less clear. Objective: Our aim was to identify and review the published evidence investigating the impact of dietary exposure to sweet-tasting foods or beverages on the subsequent generalized acceptance, preference, or choice of sweet foods and beverages in the diet. Design: Systematic searches were conducted to identify all studies testing relations of variation in exposure to sweetness through foods and beverages with subsequent variation in the generalized acceptance, preference, or choice of sweetened foods or beverages, in humans aged >6 mo. Results: Twenty-one studies met our inclusion criteria, comprising 7 population cohort studies involving 2320 children and 14 controlled trials involving 1113 individuals. These studies were heterogeneous in study design, population, exposure, and outcomes measured, and few were explicitly designed to address our research question. The findings from these were inconsistent. We found equivocal evidence from population cohort studies. The evidence from controlled studies suggests that a higher sweet taste exposure tends to lead to reduced preferences for sweetness in the shorter term, but very limited effects were found in the longer term. Conclusions: A small and heterogeneous body of research currently has considered the impact of varying exposure to sweet taste on subsequent generalized sweet taste preferences, and this evidence is equivocal regarding the presence and possible direction of a relation. Future work should focus on adequately powered studies with well-characterized exposures of sufficient duration. This review was registered with PROSPERO as CRD42016051840, 24 November 2016.

Indirect vs direct assessment of gastric emptying: A randomized crossover trial comparing C-isotope breath analysis and MRI.

BACKGROUND: Indirect methods to assess gastric emptying (GE), such as 13 C breath tests (BT), are commonly used. However, BT usually use a sampling time of 4+ hours. The current study aims to assess the validity of BT for four liquid meals differing in physicochemical properties. To this aim, we compared them to MRI GE-measurements. METHODS: Fifteen healthy males (age 22.6 ± 2.4 years, BMI 22.6 ± 1.8 kg/m2 ) participated in a randomized 2 × 2 crossover experiment. Test foods were liquid meals, which were either thin/thick and 100/500 kcal, labeled with 100 mg of 13 C-octanoate. GE was measured with MRI and assessed by 13 C recovery from breath. Participants were scanned every 10 minutes and at six time points breath samples were collected up to t = 90 minutes. Two curves were fitted to the data to estimate emptying halftime (t50 Ghoos and t50 Bluck ). T50 times were ranked per participant and compared between methods. KEY RESULTS: On average, MRI and BT showed similar t50 rankings for the four liquid meals. In comparison to MRI, t50 Ghoos overestimated, while t50 Bluck underestimated GE time. Moreover, more viscous foods were overestimated. In most participants individual t50 time rankings differed significantly between methods. CONCLUSIONS & INFERENCES: BT can assess relative emptying differences on group level and collecting breath data for 90 minutes constitutes a lower burden for participants and the research facility. However, BT has severe shortcomings compared to MRI for individual GE assessment. Notably, food matrix effects should be considered when interpreting the results of BT.

Taste and smell perception and quality of life during and after systemic therapy for breast cancer.

PURPOSE: The purpose of the study was to assess self-reported taste and smell perception after chemotherapy in breast cancer patients compared with women without cancer, and to assess whether taste and smell perception is associated with quality of life after the end of chemotherapy. METHODS: We included 135 newly diagnosed breast cancer patients who completed chemotherapy and 114 women without cancer. Questionnaires on taste, smell, and quality of life were completed shortly after and 6 months after chemotherapy (patients) or at two moments with 6 months' time window in between (comparisons). RESULTS: Self-reported taste and smell perception were significantly lower in patients shortly after chemotherapy compared to the comparison group. Most patients recovered 6 months after chemotherapy, although patients who were still receiving trastuzumab then reported a lower taste and smell perception compared to patients who were not. A lower self-reported taste and smell were statistically significantly associated with a worse quality of life, social, emotional, and role functioning shortly after chemotherapy. Six months after chemotherapy, taste and smell were statistically significantly associated with quality of life, social and role functioning, but only in patients receiving trastuzumab. CONCLUSIONS: Most taste and smell alterations recovered within 6 months after the end of chemotherapy for breast cancer, but not for patients receiving trastuzumab. These results highlight the importance of monitoring taste and smell alterations during and after treatment with chemotherapy and trastuzumab, as they may impact quality of life.

The role of smell, taste, flavour and texture cues in the identification of vegetables.

It has been shown that the identification of many foods including vegetables based on flavour cues is often difficult. The effect of providing texture cues in addition to flavour cues on the identification of foods and the effect of providing taste cues only on the identification of foods have not been studied. The aim of this study was to assess the role of smell, taste, flavour and texture cues in the identification of ten vegetables commonly consumed in The Netherlands (broccoli, cauliflower, French bean, leek, bell pepper, carrot, cucumber, iceberg lettuce, onion and tomato). Subjects (n = 194) were randomly assigned to one of four test conditions which differed in the sensory cues available for vegetable identification: taste, smell (orthonasal), flavour (taste and smell) and flavour-texture (taste, smell and texture). Blindfolded subjects were asked to identify the vegetable from a list of 24 vegetables. Identification was the highest in the flavour-texture condition (87.5%). Identification was significantly lower in the flavour condition (62.8%). Identification was the lowest when only taste cues (38.3%) or only smell cues (39.4%) were provided. For four raw vegetables (carrot, cucumber, onion and tomato) providing texture cues in addition to flavour cues did not significantly change identification suggesting that flavour cues were sufficient to identify these vegetables. Identification frequency increased for all vegetables when perceived intensity of the smell, taste or flavour cue increased. We conclude that providing flavour cues (taste and smell) increases identification compared to only taste or only smell cues, combined flavour and texture cues are needed for the identification of many vegetables commonly consumed in The Netherlands.

Backbone flexibility of extended metal atom chains. Ab initio molecular dynamics for Cr3(dpa)4X2 (X = NCS, CN, NO3) in gas and crystalline phases.

Recently published static DFT and CASSCF/CASPT2 calculations depicted extremely flat Potential Energy Surfaces (PESs) for the Cr-Cr flexibility of Cr3(dpa)4X2 (X = NCS-, CN-, NO3-) extended metal atom chains (EMACs) (M. Spivak, et al., Dalton Trans., 2017, 46, 6202). We herein explore the thermal and crystal packing effects on the structure of EMACs using ab initio molecular dynamics (MD). Car-Parrinello DFT-based simulations of the isolated molecules show that thermal energy favors asymmetric arrangements of the Cr3 chain due, in part, to the bending of the axial ligands (X) and the increased X-Cr distance, both of which weaken X → Cr σ-donation. This effect is even more prominent in the crystalline phase due to the interaction between the axial ligands of neighboring molecules in the unit cell. This could explain the typical discrepancies between the experimental and theoretical characterization of Cr3 EMACs observed in the literature.

A multiconfigurational approach to the electronic structure of trichromium extended metal atom chains.

Density functional theory, Complete Active Space Self-Consistent Field (CASSCF) and perturbation theory (CASPT2) methodologies have been used to explore the electronic structure of a series of trichromium Extended Metal Atom Chains (EMACS) with different capping ligands. The study is motivated by the very different structural properties of these systems observed in X-ray experiments: the CN--capped example has a symmetric Cr3 unit while for the NO3--capped analogue the same unit has two very different Cr-Cr bond lengths. Density functional theory fails to locate an unsymmetric minimum for any of the systems studied, although the surface corresponding to the asymmetric stretch is very flat. CASPT2, in contrast, does locate an unsymmetric minimum only for the NO3--capped system, although again the surface is very flat. We use the Generalized active space (GASSCF) technique and effective Hamiltonian theory to interrogate the multi-configurational wavefunctions of these systems, and show that the increase in the σ-σ* separation as the chain becomes unsymmetric plays a defining role in the stability of the ground state and its expansion in terms of configuration state functions.

Comparison of oro-sensory exposure duration and intensity manipulations on satiation.

Oro-sensory exposure (OSE) is an important factor in the regulation of food intake with increasing OSE leading to lower food intake. Oral processing time and taste intensity both play an important role in OSE but their individual contribution to satiation is unknown. We aimed to determine the independent and combined effects of oral processing time and taste intensity on satiation. Fifty eight participants (23±9y, BMI 22±2kg/m2) participated in a 2×2 factorial randomized crossover study in which they consumed one of four gel-based model foods until satiation during four sessions. Model foods were offered ad libitum and differed in texture (soft or hard texture, yielding shorter and longer oral processing time) and sweetness (low or high intensity). Model foods were isocaloric and were matched for flavor and palatability. Outcome measures were intake of the model food and the microstructure of eating behavior, such as number of chews and eating rate. There was an overall significant effect of texture (p<0.001) but not sweetness (p=0.33) on intake with a 29.2% higher intake of the soft model foods compared to the hard model foods. After correction for palatability the difference in intake between the soft and hard model foods was 21.5% (p<0.001). The number of chews was significantly lower for the soft (10.1±6.2) than for the hard (26.9±6.2) model foods (p<0.001), which resulted in a significantly lower eating rate (soft, 26.3±10.2 and hard, 15.3±7.1g/min, p<0.001). These results show that increasing texture hardness of gel model foods decreases food intake independent of sweet taste intensity. The higher number of chews and faster eating rate may cause this effect. In conclusion, oro-sensory exposure duration rather than taste intensity appears to be the main determinant of food intake.

Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies.

By reducing energy density, low-energy sweeteners (LES) might be expected to reduce energy intake (EI) and body weight (BW). To assess the totality of the evidence testing the null hypothesis that LES exposure (versus sugars or unsweetened alternatives) has no effect on EI or BW, we conducted a systematic review of relevant studies in animals and humans consuming LES with ad libitum access to food energy. In 62 of 90 animal studies exposure to LES did not affect or decreased BW. Of 28 reporting increased BW, 19 compared LES with glucose exposure using a specific 'learning' paradigm. Twelve prospective cohort studies in humans reported inconsistent associations between LES use and body mass index (-0.002 kg m(-)(2) per year, 95% confidence interval (CI) -0.009 to 0.005). Meta-analysis of short-term randomized controlled trials (129 comparisons) showed reduced total EI for LES versus sugar-sweetened food or beverage consumption before an ad libitum meal (-94 kcal, 95% CI -122 to -66), with no difference versus water (-2 kcal, 95% CI -30 to 26). This was consistent with EI results from sustained intervention randomized controlled trials (10 comparisons). Meta-analysis of sustained intervention randomized controlled trials (4 weeks to 40 months) showed that consumption of LES versus sugar led to relatively reduced BW (nine comparisons; -1.35 kg, 95% CI -2.28 to -0.42), and a similar relative reduction in BW versus water (three comparisons; -1.24 kg, 95% CI -2.22 to -0.26). Most animal studies did not mimic LES consumption by humans, and reverse causation may influence the results of prospective cohort studies. The preponderance of evidence from all human randomized controlled trials indicates that LES do not increase EI or BW, whether compared with caloric or non-caloric (for example, water) control conditions. Overall, the balance of evidence indicates that use of LES in place of sugar, in children and adults, leads to reduced EI and BW, and possibly also when compared with water.