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Research question Is there an influence of maternal lifestyle factors on the incidence of oocyte dimorphisms and the outcomes of intracytoplasmic sperm injection (ICSI) cycles? Design A total of 752 female patients undergoing ICSI cycle, in a private university-affiliated in vitro fertilization center, from January/2015 to December/2019, were included in this historical cohort study. Prior to start of controlled ovarian stimulation (COS), participants answered a questionnaire regarding cigarette smoking habit, consumption of items such as alcoholic beverages, refined sugar, artificial sweetener, soft drinks, fruits, legumes and vegetables, milk and dairy, and meats, and exercise frequency over the past 6 months. Oocyte morphology was evaluated before ICSI. The influence of maternal lifestyle factors on the incidence of oocyte dimorphisms and ICSI outcomes was evaluated by multivariate general linear models and generalized linear models, adjusted for potential confounders. The main outcome measures were the incidence of oocyte dimorphisms per cycle and clinical outcomes. Results Lifestyle factors and nutritional habits such as cigarette smoking, and the consumptions of alcohol, refined sugar, and artificial sweetener were positively associated with incidence of several oocyte dimorphisms and negatively associated with the response to COS and embryo development. Negative relationships were also observed between those habits and pregnancy outcomes, apart from miscarriage rate, in which positive relationships were observed. Significant negative dose-dependent relationships between those habits and implantation rate were noted. The intake of alcoholic beverages also showed inverse dose-dependent relationships with pregnancy and live-birth rates. Live-birth rate was also negatively associated with cigarette smoking, in a dose-dependent manner. Conclusions Bad maternal habits were associated with reduced oocyte quality and ICSI outcomes. Many of those associations were shown to be dose-dependent.

BACKGROUND: Both the incidence of diabetes mellitus and consumption of sugar-sweetened beverages are high in the Hispanic/Latino population in the United States. The associations between consumption of sugar-sweetened beverages, artificially sweetened beverages, and 100% fruit juice with prediabetes and glucose metabolism markers in the diverse Hispanic/Latino population in the United States are unknown. OBJECTIVES: The objective of this study was to examine the cross-sectional associations between consumption of sugar-sweetened beverages, artificially sweetened beverages, and 100% fruit juice with prediabetes and glucose metabolism markers such as fasting glucose and insulin, 2-h oral-glucose-tolerance test, HOMA-IR, HOMA index for β-cell function (HOMA-B), and glycated hemoglobin (HbA1c) among US Hispanic/Latino adults. METHODS: Using baseline data from the Hispanic Community Health Study/Study of Latinos (2008–2011), beverage consumption was ascertained using two 24-h dietary recalls and a food propensity questionnaire. Diabetes/prediabetes status was defined by self-report, antihyperglycemic medication use, and American Diabetes Association laboratory criteria. Among 9965 individuals without diabetes (5194 normoglycemia, 4771 prediabetes) aged 18–74 y, the associations of beverage consumption with prediabetes and glucose metabolism markers were analyzed using logistic and linear regressions, respectively, accounting for complex survey design. RESULTS: Compared with individuals who consumed 2 servings/d (>480 mL/d) had 1.3 times greater odds of having prediabetes (95% CI: 1.06, 1.61) and higher glucose metabolism markers including fasting glucose, fasting insulin, HOMA-IR, and HbA1c. Consumption of artificially sweetened beverages showed an inverse association with β-cell function (HOMA-B). Intake of 100% fruit juice was not significantly associated with prediabetes nor with glucose metabolism markers. CONCLUSIONS: Among US Hispanic/Latino adults, higher sugar-sweetened beverage consumption was associated with increased odds of prediabetes and higher glucose metabolism markers. Public health initiatives to decrease sugar-sweetened beverage consumption could potentially reduce the burden of diabetes among Hispanics/Latinos in the United States.

Objective: The aim of this study is to examine the effect of diet drinks on dental erosion among a representative sample of US adults. Methods: Adult dietary and dental data were analyzed from the 2003–2004 cycle of the National Health and Nutrition Examination Survey. Erosion was measured with a modified tooth wear index and was analyzed as a dichotomous variable. Cluster analysis was performed, and the cluster number was based on having a separate diet drink cluster and the R2 values. Survey procedure and sample weights were used. Results: Most of the population (80%) had some form of dental erosive lesions. When compared with the total sample, people with erosion were more likely to be male (52.5%) and older. People with no erosive lesions were younger (42.3%) and non-Hispanic Black (21.2%). Cluster analysis resulted in 4 distinct clusters: high water, high diet drinks, high coffee/tea, and high soda. The respective percentage of individuals in each cluster who had erosion was 78.9%, 85%, 83.9%, and 76.2%, where the “high diet drinks” cluster showed the highest erosion ( P = 0.28). Logistic regression modeling showed that the “high diet drinks” cluster had increased odds of erosion (odds ratio = 1.27; 95% CI = 0.58 to 2.77) when compared with the “high water” cluster, but the relationship was not statistically significant. Conclusion: High diet drinks consumption slightly increased the odds of dental erosion among US adults, although this relationship was not statistically significant. It is thus not yet clear that dentists should recommend diet drinks, as they might be linked to systemic diseases. Further research is needed to explore more about risk factors of erosion. Knowledge Transfer Statement: The findings of this study are suggestive, though not significantly, that diet drinks may increase risk for dental erosion. While further research is needed, it is not clear that dentists should recommend these drinks as healthy substitutes for sugary drinks.

BACKGROUND/OBJECTIVE The evidence that maternal non-nutritive sweetener (NNS) intake during pregnancy increases childhood obesity risk is conflicting. A potential reason for this is that all prior studies examined childhood body mass index (BMI) at only one timepoint and at different ages. We examined the extent to which NNS intake during pregnancy is associated with offspring BMI z-score and body fat longitudinally from birth to 18 years. SUBJECTS A total of 1683 children from Project Viva, a prospective pre-birth cohort, were recruited from 1999 to 2002 in Massachusetts. METHODS We assessed maternal NNS intake in the first and second trimesters of pregnancy using a semiquantitative food frequency questionnaire. Our outcomes were offspring BMI z-score, (at birth, infancy (median 6.3 months), early childhood (3.2 years), mid-childhood (7.7 years), and early adolescence (12.9 years)), sum of skinfolds (SS), fat mass index (FMI) measured by dual x-ray absorptiometry, and BMI z-score trajectory from birth to 18 years. We adjusted models for maternal pre-pregnancy BMI, age, race/ethnicity, education, parity, pre-pregnancy physical activity, smoking, and paternal BMI and education. RESULTS A total of 70% of mothers were white and pre-pregnancy BMI was 24.6 ± 5.2 kg/m2. The highest quartile of NNS intake (Q4: 0.98 ± 0.91 servings/day) was associated with higher BMI z-score in infancy (β 0.20 units; 95% CI 0.02, 0.38), early childhood (0.21; 0.05, 0.37), mid-childhood (0.21; 0.02, 0.40), and early adolescence (0.14; -0.07, 0.35) compared with Q1 intake (Q1: 0.00 ± 0.00 servings/day). Q4 was also associated with higher SS in early childhood (1.17 mm; 0.47, 1.88), mid-childhood (2.33 mm; 0.80, 3.87), and early adolescence (2.27 mm; -0.06, 4.60) and higher FMI in mid-childhood (0.26 kg/m2; -0.07, 0.59). Associations of maternal NNS intake with offspring BMI z-score became stronger with increasing age from 3 to 18 years (Pinteraction

BackgroundNeonatal hypoglycemia is a common disorder especially in at-risk infants and it can be associated with poor long-term neurological outcomes. Several therapeutic interventions are suggested, from the implementation of breastfeeding to the glucose intravenous administration. Oral dextrose gel massaged into the infant’s inner cheek is a recent treatment option of asymptomatic hypoglycemia, after which oral feeding is encouraged. This approach seems to reduce the admission of infants to neonatal intensive care unit (NICU) so favouring maternal bonding and breastfeeding success at discharge.MethodsIn our ward, we prospectively compared a group of near-term neonates, (Gr2,n = 308) at risk for hypoglycemia, treated with an innovative protocol based on the addition of 40% oral dextrose gel (Destrogel, Orsana®,Italy) administered by massaging gums and cheek with historical matching newborns (Gr1,n = 389) treated with a formerly used protocol, as control group. The primary outcome was occurrence of NICU admission and the requirement of intravenous glucose administration; while discharge with full breastfeeding was the secondary outcome.ResultsIn Gr1, 39/389 (10%) infants presented with asymptomatic hypoglycemia, 19/39 were transferred to the NICU, and 14/39 required intravenous glucose treatment. In Gr2, among the 30/308 infants with asymptomatic hypoglycemia managed according to the new protocol, 3/30 were transferred to the NICU and received intravenous glucose infusion. The mean duration of hospitalization respectively was 6.43 (± 6.36) and 3.73 ± 1.53 days (p p = 0.02). Considering Gr1 vs Gr2, the number of patients that were transferred to NICU was 19 (48.7%) vs 3 (10%) (p = 0.001) and the number of infants that needed intravenous glucose infusion was 14 (35.9%) vs 3 (10%) (p = 0.01), respectively.ConclusionsIn our population of near term infants, the introduction of 40% oral dextrose gel to the protocol, helped in the safe management of asymptomatic hypoglycemia and, at the same time, implemented breastfeeding.

High blood glucose has long been established as a risk factor for tumor metastasis, yet the molecular mechanisms underlying this association have not been elucidated. Here we describe that hyperglycemia promotes tumor metastasis via increased platelet activity. Administration of glucose, but not fructose, reprogrammed the metabolism of megakaryocytes to indirectly prime platelets into a prometastatic phenotype with increased adherence to tumor cells. In megakaryocytes, a glucose metabolism-related gene array identified the mitochondrial molecular chaperone glucose-regulated protein 75 (GRP75) as a trigger for platelet activation and aggregation by stimulating the Ca2+-PKCα pathway. Genetic depletion of Glut1 in megakaryocytes blocked MYC-induced GRP75 expression. Pharmacologic blockade of platelet GRP75 compromised tumor-induced platelet activation and reduced metastasis. Moreover, in a pilot clinical study, drinking a 5% glucose solution elevated platelet GRP75 expression and activated platelets in healthy volunteers. Platelets from these volunteers promoted tumor metastasis in a platelet-adoptive transfer mouse model. Together, under hyperglycemic conditions, MYC-induced upregulation of GRP75 in megakaryocytes increases platelet activation via the Ca2+-PKCα pathway to promote cancer metastasis, providing a potential new therapeutic target for preventing metastasis. Significance: This study provides mechanistic insights into a glucose–megakaryocyte–platelet axis that promotes metastasis and proposes an antimetastatic therapeutic approach by targeting the mitochondrial protein GRP75.

The association between artificial sweetener (AS) consumption and the risk of organ-specific cancers has been debated for decades. We hypothesized that AS consumption is associated with reduced risk of gastrointestinal (GI) cancers. We aimed to test this hypothesis by conducting a systematic review and meta-analysis of the association between AS and GI cancers. We searched 4 databases for comparative studies of AS consumption (exposed) versus no consumption (nonexposed) and the odds or risk of GI luminal or non-luminal cancer (primary outcome). Estimates were pooled using a random-effects model. Studies were evaluated for quality, bias, and heterogeneity. We analyzed 8 (4 prospective, 4 case-control) studies comprising data on 1,043,496 individuals, among whom 3271 pancreatic, 395 gastric, 304 esophageal, 3008 colorectal, and 598 oropharyngeal cancers occurred. While there was no significant association between AS consumption and odds of GI cancer overall, AS consumption was associated with 19% reduced likelihood of luminal GI cancer (OR 0.81, 95% CI:0.68-0.97). There was no association between AS consumption and non-luminal GI cancer. Meta-regression demonstrated no difference in effect estimates based on study type. Based on this first meta-analysis of AS and GI cancer, we demonstrated that AS consumption is associated with a significantly lower likelihood of luminal, but not non-luminal, GI cancer.

Resumen Introducción. Los edulcorantes son aditivos que se consumen en los alimentos. Pueden ser naturales (sacarosa y estevia) o artificiales (sucralosa). Actualmente, se consumen rutinariamente en múltiples productos, y sus efectos en la mucosa y la microbiota del intestino delgado aún son controversiales Objetivo. Relacionar el consumo de edulcorantes y su efecto en el sistema inmunitario y la microbiota del intestino delgado en ratones CD1. Materiales y métodos. Se utilizaron 54 ratones CD1 de tres semanas de edad divididos en tres grupos: un grupo de tres semanas sin tratamiento, un grupo tratado durante seis semanas y un grupo tratado durante 12 semanas. Se les administró sacarosa, sucralosa y estevia. A partir del intestino delgado, se obtuvieron linfocitos B CD19+ y células IgA+, TGF-β (Transforming Growth Factor-beta) o el factor de crecimiento transformador beta (TGF-beta), IL-12 e IL-17 de las placas de Peyer y de la lámina propia. De los sólidos intestinales se obtuvo el ADN para identificar las especies bacterianas. Resultados. Después del consumo de sacarosa y sucralosa durante 12 semanas, se redujeron las comunidades bacterianas, la IgA+ y el TGF-beta, se aumentó el CD19+, y además, se incrementaron la IL-12 y la IL-17 en las placas de Peyer; en la lámina propia, aumentaron todos estos valores. En cambio, con la estevia mejoraron la diversidad bacteriana y el porcentaje de linfocitos CD19+, y hubo poco incremento de IgA+, TGF- β e IL-17, pero con disminución de la IL-17. Conclusión. La sacarosa y la sucralosa alteraron negativamente la diversidad bacteriana y los parámetros inmunitarios después de 12 semanas, en contraste con la estevia que resultó benéfica para la mucosa intestinal. Abstract Introduction: Sweeteners are additives used in different foods. They can be natural (sucrose and stevia) or artificial (sucralose). Currently, they are routinely consumed in multiple products and their effects on the mucosa of the small intestine and its microbiota are still controversial. Objective: To relate the consumption of sweeteners and their effect on the immune system and the microbiota of the small intestine in CD1 mice. Materials and methods: We used 54 three-week-old CD1 mice divided into three groups in the experiments: 1) A group of three weeks without treatment, 2) a group treated for six weeks, and 3) a group treated for 12 weeks using sucrose, sucralose, and stevia. We obtained CD19+ B lymphocytes, IgA+ antibodies, transforming growth factor-beta (TGF-b), and interleukins 12 and 17 (IL-12 and -17) from Peyer's patches and lamina propria cells while DNA was obtained from intestinal solids to identify bacterial species. Results: After 12 weeks, sucrose and sucralose consumption caused a reduction in bacterial communities with an increase in CD19+, a decrease in IgA+ and TGF-b, and an increase in IL-12 and -17 in the Peyer's patches while in the lamina propria there was an increase in all parameters. In contrast, stevia led to an improvement in bacterial diversity and percentage of CD19+ lymphocytes with minimal increase in IgA+, TGF-b, and IL-12, and a decrease in IL-17. Conclusion: Sucrose and sucralose caused negative alterations in bacterial diversity and immune parameters after 12 weeks; in contrast, stevia was beneficial for the intestinal mucosa.

BACKGROUND AND AIM The artificial sweetener acesulfame potassium (ACK) is officially approved as safe for intake and has been used in processed foods. However, ACKs have been reported to induce metabolic syndrome, along with alteration of the gut microbiota in mice. In recent years, studies have suggested that this artificial sweetener promotes myeloperoxidase reactivity in Crohn's disease-like ileitis. We aimed to investigate the effect of ACK on the intestinal mucosa and gut microbiota of normal mice. METHODS Acesulfame potassium was administered to C57BL/6J mice (8 weeks old) via free drinking. Intestinal damage was evaluated histologically, and messenger RNA (mRNA) levels of TNF-α, IFN-γ, IL1-β, MAdCAM-1, GLP1R, and GLP2R were determined with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Immunohistochemistry was performed to examine the expression of MAdCAM-1 in the small intestine. The composition of gut microbiota was assessed using high-throughput sequencing. We performed intravital microscopic observation to examine if ACK altered lymphocyte migration to the intestinal microvessels. RESULTS Acesulfame potassium increased the expression of proinflammatory cytokines, decreased the expression of GLP-1R and GLP-2R, and induced small intestinal injury with an increase in intestinal permeability, and ACK treatment induced microbial changes, but the transfer of feces alone from ACK mice did not reproduce intestinal damage in recipient mice. ACK treatment significantly increased the migration of lymphocytes to intestinal microvessels. CONCLUSION Acesulfame potassium induces dysbiosis and intestinal injury with enhanced lymphocyte migration to intestinal mucosa. Massive use of non-caloric artificial sweeteners may not be as safe as we think.

BACKGROUND The brief-access taste aversion (BATA) model has been used as an alternative taste assessment tool to human taste panels and became an important element of pharmaceutical drug development, especially regarding pediatric patient's compliance. This model has been validated, demonstrating a concentration-dependent sensitivity to drug aversiveness, as well as the capacity to evaluate the taste-masking effects of cyclodextrins. In the BATA model, samples are presented randomly to rodents in numerous sipper tubes and a lickometer is used for the electronic record of licks in a sophisticated approach. OBJECTIVES The aim of this study was to test possible drug taste-masking strategies. Additionally, we have used an alternative approach to measure the animal lick number in the presence of different compounds, non-simultaneously. RESULTS In the present work we show for the first time the licking profile of different compounds during the time course of the experiment, with each animal being exposed to only one bottle of testing product. To validate the experiments, quinine hydrochloride dihydrate (QHD) was used as a bitter reference compound. CONCLUSION The results obtained using this simple approach showed that aversiveness is dependent on the assay duration, and that it is possible to predict the aversiveness just by measuring the mass of the tested substance consumption. Moreover, some taste-masking strategies, such as those used in pediatric formulations and corresponding to the addition of sweeteners or flavors, cannot be predicted from rodents BATA model.

Effects of isocaloric (sweetness differences but constant calories) preloads and isosweet (caloric differences but constant sweetness) preloads, as well as preloads that were neither isosweet nor isocaloric (sweetness and caloric differences) on subsequent ad libitum meal and total (preload + ad libitum) energy intakes were investigated. Thirty-five crossover studies were eligible for inclusion, representing 116 comparisons (41, isocaloric; 41, isosweet; and 34, neither isosweet nor isocaloric). References of existing reviews and literature from 4 databases were searched. The calculated raw mean differences in ad libitum and total energy intakes were pooled in meta-analyses using a random-effects model and the inverse of the variance as the weighting factor. Energy intakes at an ad libitum meal were significantly lower for low-/no-calorie sweetener (LNCS)–sweetened compared with unsweetened preloads in the isocaloric comparison (−55.5 kcal; 95% CI: −82.9, −28.0 kcal; P

Skyr yogurts have been gaining prominence because of their different sensory characteristics. Due to their healthy appeal, the use of natural sweeteners to replace sucrose in this type of yogurt can be an alternative for incorporating a sweet taste, in addition to increasing the functionality of the product through the incorporation of prebiotics. This study aimed to determine whether the addition of fructooligosaccharide (FOS), sucrose, stevia, and thaumatin affects the sensory profile of the skyr yogurt with mango pulp and its acceptance in two Brazilian regions. Eight formulations of skyr with mango pulp were developed. The compositional parameters evaluated were moisture, protein, lipids, ash, and carbohydrate. The tests performed were ideal sweetness and mango flavor, sweetness equivalence for each sweetener used, Quantitative Descriptive Analysis (QDA), and consumer testing in the Southeast and Northeast regions of Brazil. In general, the addition of FOS did not impact the characteristics of the formulated skyr yogurt. The type of sweetener had an impact on the sensory profile and acceptance of the skyr yogurt, affected characteristics such as mango flavor, sweet taste, sweet aftertaste, bitter taste, bitter aftertaste, and metallic flavor. The results of the affective test demonstrated that, for consumers in the Southeast, mango flavor is a positive attribute in this yogurt, and for Northeastern consumers, in addition to mango flavor, sweetness must also be taken into consideration. PRACTICAL APPLICATION: This study may be useful for the dairy industry because in the literature, there is still a lack of sensory studies of skyr yogurt, especially when sucrose substitutes are used. The results of the consumer test in this work reinforce the importance of studies related to consumer preferences with cultural differences.

Background The activation of insulin pathways is hypothesized to promote tumor growth and worsen breast cancer survival. Sugar-sweetened beverages (SSBs) can lead to a higher risk of insulin resistance and may affect survival. The authors prospectively evaluated the relation of postdiagnostic SSB and artificially sweetened beverage (ASB) consumption with mortality among women with breast cancer. Methods In total, 8863 women with stage I through III breast cancer were identified during follow-up of the Nurses' Health Study (NHS; 1980-2010) and Nurses' Health Study II (NHSII; 1991-2011). Women completed a validated food frequency questionnaire every 4 years after diagnosis and were followed until death or the end of follow-up (2014 for the NHS and 2015 for the NHSII). Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer-specific and all-cause mortality after adjusting for measures of adiposity and other potential predictors of cancer survival. Results With a median follow-up of 11.5 years, 2482 deaths were prospectively documented, including 1050 deaths from breast cancer. Compared with women who had no consumption, women who had SSB consumption after diagnosis had higher breast cancer-specific mortality (>1 to 3 servings per week: HR, 1.31 [95% CI, 1.09-1.58]; >3 servings per week: HR, 1.35 [95% CI, 1.12-1.62]; Ptrend = .001) and all-cause mortality (>1 to 3 servings per week: HR, 1.21 [95% CI, 1.07-1.37]; >3 servings per week: HR, 1.28 [95% CI, 1.13-1.45]; Ptrend = .0001). In contrast, ASB consumption was not associated with higher breast cancer-specific or all-cause mortality. Furthermore, replacing 1 serving per day of SSB consumption with 1 serving per day of ASB consumption was not associated with a lower risk of mortality. Conclusions Higher postdiagnostic SSB consumption among breast cancer survivors was associated with higher breast cancer-specific mortality and death from all causes.

Type 2 diabetes mellitus (T2DM) leads to monocyte dysfunction associated with atherogenesis and defective arteriogenesis. Transforming growth factor (TGF)‐β1, placenta growth factor (PlGF)‐1 and vascular endothelial growth factor (VEGF)A play important roles in atherogenesis and arteriogenesis. VEGF‐receptor (VEGFR)‐mediated monocyte migration is inhibited in T2DM (VEGFA resistance), while TGF‐β1‐induced monocyte migration is fully functional. Therefore, we hypothesize that TGF‐β antagonises the VEGFA responses in human monocytes. We demonstrate that monocytes from T2DM patients have an increased migratory response towards low concentrations of TGF‐β1, while PlGF‐1/VEGFA responses are mitigated. Mechanistically, this is due to increased expression of type II TGF‐β receptor in monocytes under high‐glucose conditions and increased expression of soluble (s)VEGFR1, which is known to interfere with VEGFA signalling. VEGFA resistance in monocytes from T2DM patients can be rescued by either experimental down‐regulation of TGF‐β receptor expression in vitro or by functional blocking of TGF‐β signalling using either a TGF‐β receptor kinase inhibitor or a TGF‐β neutralizing antibody. Our data demonstrate that both T2DM and high‐glucose potentiate the TGF‐β pathway. TGF‐β signalling impairs VEGFR‐mediated responses in T2DM monocytes and in this way contributes to mononuclear cell dysfunction, provide novel insights into T2DM vascular dysfunction.

Metabolic syndrome is a multifactorial disorder originating from central obesity through a high caloric intake and a sedentary lifestyle. Metabolic syndrome increases the risk of type 2 diabetes (T2D) disease, converting it to one of the costliest chronic diseases, which reduces life quality. A strategy proposed by the food industry to reduce this problem is the generation of low-caloric products using sweeteners, which are compounds that can substitute sucrose, given their sweet taste. For many years, it was assumed that sweeteners did not have a relevant interaction in metabolism. However, recent studies have demonstrated that sweeteners interact either with metabolism or with gut microbiota, in which sweet-taste receptors play an essential role. This review presents an overview of the industrial application of most commonly consumed sweeteners. In addition, the interaction of sweeteners within the body, including their absorption, distribution, metabolism, gut microbiota metabolism, and excretion is also reviewed. Furthermore, the complex relationship between metabolic syndrome and sweeteners is also discussed, presenting results from in vivo and clinical trials. Findings from this review indicate that, in order to formulate sugar-free or noncaloric food products for the metabolic syndrome market, several factors need to be considered, including the dose, proportions, human metabolism, and interaction of sweeteners with gut microbiota and sweet-taste receptors. More clinical studies, including the metabolic syndrome, are needed to better understand the interaction of sweeteners with the human body, as well as their possible effect on the generation of dysbiosis.

[EN] This article analyses, the replacement of sucrose in muffins with nine different combinations of isomaltulose and oligofructose. Being a structural isomer of sucrose with approx. 50% of sucrose sweetness, isomaltulose is non-cariogenic and with a low glycemic profile but having the same calories as sucrose. Oligofructose is composed of fructose polymers, with a reduced caloric value and prebiotic effect. Specifically, height, percentage of alveoli, water content, A(w), mechanical, and optical properties have been measured along with a sensory evaluation. The results showed that all combinations of sweeteners gave place to softer muffins than control ones. Moreover, isomaltulose caused a darkening of the products likely due to an enhancement of the Maillard reactions. The highest amount of isomaltulose and the absence of sucrose meant the worst score in sweetness and flavor due to the low sweetening powder of isomaltulose., GENERALITAT VALENCIANA, Grant/Award Number: AICO/2017/043

Background Conclusions remain controversial between the consumption of sugar and artificially sweetened beverages (SSBs and ASBs) and mortality. Methods We systematically searched the PubMed, Embase, Cochrane Library and Web of Science databases from their inception date to 1st January 2020, prospective cohort studies researching the mortality risk and SSBs or ASBs consumption were included. Random effects meta-analyses and dose–response analyses were performed to measure the association. Subgroup analyses and sensitivity analyses were further performed to explore the source of heterogeneity. Publication bias was assessed by Funnel plots and Egger’s regression test. Results Across all 15 cohorts, 1211 470 participants were included. High SSB consumption was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.06–1.19, P Conclusions High consumption of both ASBs and SSBs showed significant associations with a higher risk of CVD mortality and all-cause mortality. This information may provide ideas for decreasing the global burden of diseases by reducing sweetened beverage intake.

Objective:There remain inconclusive findings from previous observational epidemiological studies on whether consumption of artificially sweetened soft drinks (ASSD) increases the risk of gastrointestinal (GI) cancer. We investigated the associations between the consumption of ASSD and the risk of GI cancer using a meta-analysis.Design:Systematic review and meta-analysis.Setting:PubMed and EMBASE were searched using keywords until May 2020 to identify observational epidemiological studies on the association between the consumption of ASSD and the risk of GI cancer.Subjects:Twenty-one case–control studies and seventeen cohort studies with 12 397 cancer cases and 2 474 452 controls.Results:In the random-effects meta-analysis of all the studies, consumption of ASSD was not significantly associated with the risk of overall GI cancer (OR/relative risk (RR), 1·02; 95 % CI, 0·92, 1·14). There was no significant association between the consumption of ASSD and the risk of overall GI cancer in the subgroup meta-analyses by study design (case–control studies: OR, 0·95; 95 % CI, 0·82, 1·11; cohort studies: RR, 1·14; 95 % CI, 0·97, 1·33). In the subgroup meta-analysis by type of cancer, consumption of ASSD was significantly associated with the increased risk of liver cancer (OR/RR, 1·28; 95 % CI, 1·03, 1·58).Conclusions:The current meta-analysis of observational epidemiological studies suggests that overall, there is no significant association between the consumption of ASSD and the risk of GI cancer.

Sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) intakes have been reported to be associated with mortality; however, conclusions have been inconsistent. This review synthesized the evidence on the associations of SSB and ASB intakes with mortality from all causes, cardiovascular disease (CVD), and cancer among all populations (including general, diseased, or occupational populations, etc.). PubMed, EMBASE, Web of Science, Cochrane Library, ProQuest, ClinicalTrials.gov, and the International Clinical Trials Registry Platform were searched up to March 2020. Fifteen studies including 17 cohorts were included in meta-analyses. Each serving (12 fluid ounces or 355 mL) increase in daily SSB consumption was associated with higher risks of all-cause (HR: 1.08; 95% CI: 1.04, 1.12; 11 cohorts with 965,851 participants) and CVD (HR: 1.08; 95% CI: 1.04, 1.12; 13 cohorts with 898,005 participants) mortality. The associations of ASB intakes with all-cause and CVD mortality were J-shaped, and HRs (95% CI) across different doses (0, 1, 1.5, 2, and 2.5 servings/d) were 1.00, 1.01 (0.99, 1.03), 1.04 (1.02, 1.07), 1.08 (1.05, 1.11), and 1.13 (1.09, 1.18) for all-cause mortality and 1.00, 1.01 (0.96, 1.07), 1.07 (1.01, 1.13), 1.15 (1.08, 1.23), and 1.25 (1.14, 1.37) for CVD mortality. No significant association was found for cancer mortality. According to the NutriGrade scoring system, the quality of evidence on the associations of SSB intakes with all-cause and CVD mortality was high, and the quality of evidence on other associations was low to moderate. In summary, higher SSB and ASB intakes were associated with higher risks of all-cause mortality and CVD mortality. Given the limited evidence, future studies should further investigate the association between ASB intakes and cause-specific mortality.

Hyperglycemia-induced podocyte damage contributes to the onset of diabetic nephropathy, a severe complication of diabetes. Perilipin 5 (Plin5) exerts a vital role in numerous pathological conditions via affecting cell apoptosis, oxidative stress, and inflammation. However, whether Plin5 plays a role in regulating podocyte damage of diabetic nephropathy has not been fully determined. This work aimed to explore the role of Plin5 in mediating high glucose (HG)-induced injury of podocytes in vitro. Our results demonstrated that Plin5 expression was markedly decreased in mouse podocytes challenged with HG. Plin5 overexpression markedly suppressed HG-induced apoptosis, reactive oxygen species (ROS) production, and the pro-inflammatory response in podocytes. On the contrary, Plin5 silencing produced the opposite effects. Further mechanistic analysis demonstrated that Plin5 upregulation remarkably increased the levels of phospho-Akt and phospho-glycogen synthase kinase-3β (GSK-3β) in HG-exposed podocytes. Moreover, Plin5 overexpression increased the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and enhanced the activation of Nrf2 signaling. Akt inhibition markedly blocked Plin5-mediated activation of Nrf2, while GSK-3β inhibition reversed Plin5-silencing-induced suppressive effects on Nrf2 activation. Notably, Nrf2 suppression significantly blocked Plin5-mediated protective effects against HG-induced podocyte injury. In summary, our work indicates a vital role for Plin5 in protecting against HG-induced apoptosis, oxidative stress, and inflammation in podocytes via modulation of Akt/GSK-3β/Nrf2 signaling. This study suggests that Plin5 may participate in modulating podocyte damage in diabetic nephropathy.

The consumption of non-nutritive sweeteners has increased in the last decades. However, there are doubts about its consumption and its impact on body mass and metabolic alterations. For this reason, this study investigates the effects of the consumption of nutritive and non-nutritive sweeteners on body mass in different life stages of male and female Wistar rats: Childhood, adolescence, young adult, adulthood, and aged. For this purpose, 8 groups of male and female rats were used (10 per group/gender): sucrose 10%, glucose 14%, fructose 7%, acesulfame K 0.05%, aspartame:acesulfame mixture 1.55%, sucralose 0.017%, saccharin 0.033%, and a control group. Only in aged male rats (504 days) there were significant differences in body mass. In both genders, there were differences in food, drink, and energy intake along all life stage. It is concluded that non-nutritive sweeteners when consumed together with a balanced diet did not cause a greater body mass gain.

Artificial sweeteners (ASs) have generally been applied as food additives to improve the taste of sweetness. Thus, their potential toxic effects have received extensive attention. Saccharin (SAC), discovered more than a century ago, has been used as the first noncaloric AS in foods and beverages for over 100 years. Although the toxicological effects such as carcinogenicity of SAC have been controversial for a long time, there is a paucity of knowledge covering its potential behavioral toxicity and neurotoxicity. Methodologically, in current research, adult zebrafish neurobehavioral phenotypic screening approaches were introduced to systematically delineate the potential behavioral and neural toxicity of SAC by phenotyping the comprehensive neuro-behavioral profiles of adult zebrafish, which were chronically (2 months) subject to SAC (0, 1, 10, and 50 mg/L) exposure. Subsequently, a cohort of standard neurobehavioral tests including the light/dark preference (LDP) test, novel tank diving (NTD) test, novel object recognition (NOR) test, social interaction test (SIT), color-associated learning and memory test, and conditional place preference test were applied to delineate the general adverse effect of SAC. Specifically, in a concentration-dependent manner, SAC significantly increased the preference toward the dark side in the LDP test, inhibited exploratory behavior to the top arena in the NTD test, dampened the motivation to explore the novel object in the NOR test, weakened social preference in the SIT, and interfered in the color-based associative learning and memory ability. For example, in the LDP test, SAC remarkably increased the swimming distance of zebrafish in the dark part from 222 ± 34.6 (control group) to 675 ± 35.0 (50 mg/L group). Finally, the quantity of certain key neurotransmitters was further measured to determine the alteration induced by SAC on the brain chemistry. In total, the current research would provide a versatile neurobehavioral phenomics-based strategy to phenotypically screen the neurotoxicity of food additives at the overall animal level and provide a reference for further neurotoxicity exploration at the tissue and molecular level.

Consumption of sugar or artificially-sweetened beverages (SASBs) has been linked to albuminuria, decline in kidney function, and risk of chronic kidney disease (CKD). However, the results are controversial. We therefore aim to evaluate the effects of sugar or artificially-sweetened beverage consumption on CKD risk. Original observational studies reporting relative risks (RRs) with 95% confidence intervals (CIs) for the association between sugar or artificially-sweetened beverage consumption and impaired renal function or CKD risk in adults were identified using a systematic search of PubMed and EMBASE from inception to 20 February, 2019. Random effects model was applied to derive summary RRs and 95% CIs. Linear and non-linear dose–response relationships were estimated using data from sugar or artificially-sweetened beverage consumption categories in each study. The summary RR of CKD for high versus low sugar-sweetened beverage consumption was 1.30 (95% CI 0.88–1.94) according to six included studies with a total of 25,455 participants, while the pooled RR of CKD for high versus low artificially sweetened beverage consumption was 1.40 (95% CI 0.65–3.02) according to three studies with a total of 19,995 participants. For dose–response analysis, a significant, increased risk of CKD was observed with the sugar or artificially-sweetened beverage consumption above seven servings per week (P

Objective:To examine the influence of prenatal artificial sweetener (AS) consumption on birth outcomes.Design:Systematic review and meta-analysis.Setting:Online databases (Medline, CINAHL, Embase, Cochrane Library, Scopus, Web of Science, FSTA – the food resource database, and ClinicalTrials.gov) were searched up to 9 April 2020. Studies of all designs (except case studies and reviews) were eligible, which contained information on the relevant population (pregnant women), intervention/exposure (any AS consumption), comparator (no AS consumption) and birth outcomes (preterm delivery, gestational age, birth weight).Results:From 677 citations, ten cohort studies and one randomised controlled trial (n 138 007 women) were included. ‘Low’ to ‘very low’ certainty evidence revealed that daily consumption of AS was associated with an increased risk of preterm delivery (three studies, n 129 009; risk ratio = 1·18, 95 % CI 1·09, 1·28, I2 = 9 %), a 24 g increase in birth weight (three studies, n 64 417; mean difference (MD): 23·74 g, 95 % CI 0·89, 45·58, I2 = 0 %) and a 0·11 week decrease in gestational age (three studies, n 64 417; MD: –0·11 weeks, 95 % CI –0·19, –0·03, I2 = 0 %).Conclusions:‘Low’ to ‘very low’ certainty evidence suggests daily AS consumption during pregnancy is associated with an increased risk of preterm delivery, increased birth weight and decreased gestational age. Additional ‘high’-quality research is urgently needed to further assess these relationships.PROSPERO registration number: CRD42019136728.

Background: In the last few years there has been emerging interest in substituting added sugars from juices with other sweeteners to make them healthier. But their long-term effects have been poorly evaluated. The aim of this study is to evaluate the effect of the addition of stevia, sucralose and sucrose (control) to maqui-citrus beverages on antioxidant and inflammatory status. Methods: a 3-arm parallel, randomized and triple blind clinical trial was performed in overweight subjects (n = 138), who consumed the test beverage (330 mL day-1) for 60 days. The following markers were determined: antioxidant status (ORAC, homocysteine, and oxidized LDL), safety parameters (ALP, AST, ALT, and total bilirubin), lipid profile (total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides) and inflammatory biomarkers (IL-6, TNF-a, and IL-10). Results: The homocysteine levels significantly increased after consumption of sucralose (27%, p = 0.001) and sucrose (40%, p = 0.006). A significant increase in the IL-10 concentration after consumption of the stevia sweetened beverage, and in ORAC values (21%) in subjects with lower basal antioxidant status were observed. The HDL and total cholesterol levels significantly increased after consumption of sucralose (p = 0.039) and sucrose (p = 0.001), respectively. No changes in triglycerides, LDL or oxidized LDL were observed. Conclusions: Oxidative stress and an inflammatory response were observed after consumption of these sweetened beverages, with the exception of stevia, which produced an anti-inflammatory response. The possible antioxidative effects of this polyphenol-rich beverage may only benefit those individuals with poorer antioxidant status. Many randomized controlled trials at normal levels of consumption using commonly consumed sweeteners are necessary to clarify their roles in health., The authors acknowledge the financial support from Comisión Interministerial de Ciencia y Tecnología (CICYT)

Sucralose is a widely consumed non-nutritive sweetener (NNS). Studies have shown that some NNS can favor weight gain by altering the intestinal microbiota, satiety hormone production, or aspects related to glucose homeostasis. In this study, we investigated the effects of ad libitum sucralose consumption in mice fed with normal or high-fat diet (HFD) for an extended period (16 weeks). Weight gain, final body composition, energy expenditure, intestinal and pancreatic hormone production, and endotoxemia during a voracity test, as well as liver and skeletal muscles were evaluated after 16 weeks. We observed that sucralose supplementation reduced weight gain in HFD-fed mice but did not change weight gain in mice fed with normal diet. The evaluation of HFD mice showed that sucralose supplementation resulted in improvements in glycemic homeostasis, hepatic steatosis, and increased energy expenditure. Our results suggest that sucralose consumption promotes different outcomes in relation to weight gain when combined with different diets, which may explain the controversial data in previous studies, and can be considered in future clinical research aimed at clarifying the impact of NNS consumption on human health.

The long-term associations between the consumption of sugar-sweetened beverages (SSBs) and low-calorie sweetened beverages (LCSBs) with cardiovascular diseases (CVDs) remains inconsistent. To synthesize the evidence, we conducted a meta-analysis of prospective cohort studies published up to 1 December, 2019 on the associations between SSB and LCSB intake and the risk of CVD incidence and mortality. Out of 5301 articles retrieved from our literature search, 11 articles evaluating the consumption of SSBs (16,915 incident CVD cases, 18,042 CVD deaths) and 8 articles evaluating the consumption of LCSBs (18,077 incident CVD cases, 14,114 CVD deaths) were included in the meta-analysis. A 1 serving/d increment of SSBs was associated with an 8% (RR: 1.08; 95% CI: 1.02, 1.14, I2 = 43.0%) and 8% (RR: 1.08; 95% CI: 1.04, 1.13, I2 = 40.6%) higher risk of CVD incidence and CVD mortality, respectively. A 1 serving/d increment of LCSBs was associated with a 7% (RR: 1.07; 95% CI: 1.05, 1.10, I2 = 0.0%) higher risk of CVD incidence. The association between LCSBs and CVD mortality appeared to be nonlinear (P = 0.003 for nonlinearity) with significant associations observed at high intake levels (>2 servings/d). Under an assumption of causality, the consumption of SSBs may be linked to 9.3% (95% CI: 6.6%, 11.9%) of predicted CVD incidence in the USA from 2015 to 2025, among men and nonpregnant women, who were aged 40–79 y in 2015–2016. The habitual consumption of SSBs was associated with a higher risk of CVD morbidity and mortality in a dose-response manner. LCSBs were also associated with a higher risk of these outcomes, however, the interpretation of these findings may be complicated by reverse causation and residual confounding., Habitual consumption of SSBs/LCSBs were associated with higher risk of CVD morbidity and mortality. However, potential reverse causation and residual confounding complicate interpretation of findings related to LCSBs.

Sucralose is one of the most widely used artificial sweeteners, free of nutrients and calories. Its approval and uses correlate with many of the worldwide epidemiological changes in inflammatory bowel disease (IBD). Multiple animal studies by us and others showed that sucralose exacerbated ileitis in SAMP1/YitFc mice and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. In this study, we further investigated the effect of sucralose on dextran sulfate sodium (DSS)-induced colitis in mice and the associated mechanisms. Male C57BL/6 mice received 1.5 mg ml-1 sucralose in drinking water for 6 weeks. Then, 2.5% DSS was added to drinking water for 7 days to induce ulcerative colitis (UC). The results showed that, compared with the DSS group, administration of sucralose exacerbated the severity of colitis as indicated by the further decrease in body weight, increase in disease activity index (DAI) and the expression of pro-inflammatory cytokines, as well as the activation of the TLR5-MyD88-NF-κB signaling pathway, and the disturbances of intestinal barrier function, along with changes in the intestinal microbiota. Our findings indicate that sucralose may increase the susceptibility to DSS-induced colitis through causing dysbiosis of intestinal microbiota and damage to the intestinal barrier.

While numerous techniques can be used to measure and analyze insulin secretion in isolated islets in culture, assessments of insulin secretion in vivo are typically indirect and only semiquantitative. The CpepSfGFP reporter mouse line allows the in vivo imaging of insulin secretion from individual islets after a glucose stimulation, in live, anesthetized mice. Imaging the whole pancreas at high resolution in live mice to track the response of each individual islet over time includes numerous technical challenges and previous reports were only limited in scope and non-quantitative. Elaborating on this previous model—through the development of an improved methodology addressing anesthesia, temperature control and motion blur—we were able to track and quantify longitudinally insulin content throughout a glucose challenge in up to two hundred individual islets simultaneously. Through this approach we demonstrate quantitatively for the first time that while isolated islets respond homogeneously to glucose in culture, their profiles differ significantly in vivo. Independent of size or location, some islets respond sharply to a glucose stimulation while others barely secrete at all. This platform therefore provides a powerful approach to study the impact of disease, diet, surgery or pharmacological treatments on insulin secretion in the intact pancreas in vivo.

ObjectiveTo determine the effect of prophylactic dextrose gel for prevention of neonatal hypoglycaemia on neurodevelopment and executive function at 2 years’ corrected age.DesignProspective follow-up of a randomised trial.SettingNew Zealand.PatientsParticipants from the pre-hypoglycaemia Prevention with Oral Dextrose (pre-hPOD) trial randomised to one of four dose regimes of buccal 40% dextrose gel or equivolume placebo.Main outcome measuresCoprimary outcomes were neurosensory impairment and executive function. Secondary outcomes were components of the primary outcomes, neurology, anthropometry and health measures.ResultsWe assessed 360 of 401 eligible children (90%) at 2 years’ corrected age. There were no differences between dextrose gel dose groups, single or multiple dose groups, or any dextrose and any placebo groups in the risk of neurosensory impairment or low executive function (any dextrose vs any placebo neurosensory impairment: relative risk (RR) 0.77, 95% CI 0.50 to 1.19, p=0.23; low executive function: RR 0.50, 95% CI 0.24 to 1.06, p=0.07). There were also no differences between groups in any secondary outcomes. There was no difference between children who did or did not develop neonatal hypoglycaemia in the risk of neurosensory impairment (RR 1.05, 95% CI 0.68 to 1.64, p=0.81) or low executive function (RR 0.73, 95% CI 0.34 to 1.59, p=0.43).ConclusionProphylactic dextrose gel did not alter neurodevelopment or executive function and had no adverse effects to 2 years’ corrected age, but this study was underpowered to detect potentially clinically important effects on neurosensory outcomes.

Aims/Introduction Gut dysbiosis is generally associated with type 2 diabetes mellitus. However, the effect of habitual dietary intake on gut dysbiosis in Japanese patients with type 2 diabetes mellitus has not yet been explicated. This study investigated whether alteration of the gut microbiota was influenced by dietary intake of sucrose in Japanese patients with type 2 diabetes mellitus. Materials and Methods In this cross‐sectional study, 97 patients with type 2 diabetes mellitus and 97 healthy individuals were matched by age and sex, and then, fecal samples were obtained. Next‐generation sequencing of the 16S ribosomal ribonucleic acid gene was carried out, and functional profiles for the gut microbiota were analyzed. We selected the top 30 gut microbial genera and top 20 functional profiles for the gut microbiota specified by the weighted average difference method. The association between gut microbial genera or functional profiles and habitual dietary intake was investigated by Spearman’s rank correlation coefficient, and then, clustering analysis was carried out to clarify the impact of habitual dietary intake. Results The Actinobacteria phylum was highly abundant in patients with type 2 diabetes mellitus, whereas the Bacteroidetes phylum was less abundant. Diabetic‐type gut microbes, specifically Bacteroides and Bifidobacterium, were altered by sucrose intake at the genus level. Furthermore, sucrose intake was associated with glycolysis/gluconeogenesis in the diabetic‐type functional profiles of the gut microbiota. Conclusions The gut microbiota and functional profiles for the gut microbiota in patients with type 2 diabetes mellitus were significantly different from those in healthy individuals. Furthermore, we showed that sucrose intake was closely associated with these differences., Gut dysbiosis and change of functional profiles of the gut microbiota exist in Japanese patients with type 2 diabetes mellitus. Diet habit, especially sucrose intake, has a close association with these changes.

This article examines, using an organ-systems based approach, rapid diagnosis, resuscitation, and critical care management of the crashing poisoned patient in the emergency department. The topics discussed in this article include seizures and status epilepticus, respiratory failure, cardiovascular collapse and mechanical circulatory support, antidotes and drug-specific therapies, acute liver failure, and extracorporeal toxin removal.

Objective:The associations between sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) consumption and the risk of metabolic syndrome (MetS) remain controversial. A quantitative assessment of dose–response associations has not been reported. This study aims to assess the associations between the risk of MetS and SSB, ASB, and total sweetened beverage (TSB, the combination of SSB and ASB) consumption by reviewing population-based epidemiological studies.Design:Meta-analysis.Setting:We searched PubMed, Embase and Web of Science databases prior to 4 November 2019, for relevant studies investigating the SSB–MetS and ASB–MetS associations. A random effects model was used to estimate pooled relative risks (RR) and 95 % CI. Dose–response association was assessed using a restricted cubic splines model.Participants:We identified seventeen articles (twenty-four studies, including 93 095 participants and 20 749 MetS patients).Results:The pooled RR for the risk of MetS were 1·51 (95 % CI 1·34, 1·69), 1·56 (1·32, 1·83) and 1·44 (1·19, 1·75) in high consumption group of TSB, SSB and ASB, respectively; and 1·20 (1·13, 1·28), 1·19 (1·11, 1·28) and 1·31 (1·05, 1·65) per 250 ml/d increase in TSB, SSB and ASB consumption, respectively. Additionally, we found evidence of non-linear, TSB–MetS and SSB–MetS dose–response associations and a linear ASB–MetS dose–response association.Conclusions:TSB, SSB and ASB consumption was associated with the risk of MetS. The present findings provide evidence that supports reducing intake of these beverages to lower the TSB-, SSB- and ASB-related risk of MetS.

BACKGROUND/AIMS: Excessive consumption of dietary fat and sugar is associated with an elevated risk of nonalcoholic fatty liver disease (NAFLD). Hepatocytes exposed to saturated fat or sugar exert effects on nearby hepatic stellate cells (HSCs); however, the mechanisms by which this occurs are poorly understood. We sought to determine whether paracrine effects of hepatocytes exposed to palmitate and fructose produced profibrotic transcriptional responses in HSCs. METHODS: We performed expression profiling of mRNA and lncRNA from HSCs treated with conditioned media (CM) from human hepatocytes treated with palmitate (P), fructose (F), or both (PF). RESULTS: In HSCs exposed to CM from palmitate-treated hepatocytes, we identified 374 mRNAs and 607 lncRNAs showing significant differential expression (log2 foldchange ≥ |1|; FDR ≤0.05) compared to control cells. In HSCs exposed to CM from PF-treated hepatocytes, the number of differentially expressed genes was much higher (1198 mRNAs and 3348 lncRNAs); however, CM from fructose-treated hepatocytes elicited no significant changes in gene expression. Pathway analysis of differentially expressed genes showed enrichment for hepatic fibrosis and hepatic stellate cell activation in P- (FDR =1.30E-04) and PF-(FDR =9.24E-06) groups. We observed 71 lncRNA/nearby mRNA pairs showing differential expression under PF conditions. There were 90 mRNAs and 264 lncRNAs strongly correlated between the PF group and differentially expressed transcripts from a comparison of activated and quiescent HSCs, suggesting that some of the transcriptomic changes occurring in response to PF overlap with HSC activation. CONCLUSION: The results reported here have implications for dietary modifications in the prevention and treatment of NAFLD.

Sweet taste perception is a key factor in the establishment of the food pattern with nonstatic thresholds. Indeed, taste sensitivity can be influenced by physiological factors (age and sex), pathologies (obesity and type 2 diabetes mellitus), and acquired habits (tobacco and alcohol consumption). In order to elucidate how these variables influence the sucrose detection threshold (DT) and recognition threshold (RT), a systematic review and meta-analysis of the relevant literature were performed. After a comprehensive search in the PubMed and Scopus databases, a total of 48 studies were qualitatively considered, and 44 were meta-analyzed. The factors of aging (standard mean difference [SMD]: -0.46; 95% confidence interval (CI), -0.74 to -0.19; I2 : 73%; Tau2 : 0.18) and type 2 diabetes mellitus (SMD: 0.30; 95% CI, 0.06 to 0.55; I2 : 0%; Tau2 : 0.00) were found to significantly increase the sucrose RT, whereas the DT only increased in subjects with a higher body mass index (SMD: 0.58; 95% CI, 0.35 to 0.82; I2 : 0%; Tau2 : 0.00). No effects of sex and tobacco smoking were found, and associations with alcohol consumption could not be assessed, as it was included as a variable in only one study. Feasible mechanisms underlying changes in sucrose thresholds include the modulation of hormones involved in energy and body weight homeostasis, taste bud abundance, taste brain signaling, and the gut-brain axis. The present work provides insights into the variables that should be considered when assessing sweet taste sensitivity, discusses the mechanisms underlying differences in sweet taste, and highlights the need for further research in the field of personalized nutrition.

Objective: This study focused on describing local trends in sugar‐sweetened beverage (SSB) consumption, including variations between subgroups, to inform equitable health policy to curb soft drink consumption. Methods: Weighted data were obtained from the South Australian Monitoring and Surveillance System, a state‐based population health survey that monitors trends in health risk factors and chronic disease via computer‐assisted telephone interviewing. From 2008 onwards, participants provided an estimate of the average amount of soft drink they consumed per day. Results: From 2008–2017, there were significant decreases in the proportion of adults who consumed any SSBs, but the mean consumption per consumer increased. High‐risk dietary and lifestyle behaviours are the strongest predictors for consumption of soft drink, but there is also a significant association with socioeconomic status. Conclusions: Population trends mask increasing inequity. There is a societal trend away from the consumption of SSBs across all subgroups, but at‐risk groups who engage in clusters of unhealthy behaviours remain high consumers. Implications for public health: The identification of at‐risk populations allows research to focus more precisely on the structural barriers, beliefs, attitudes and facilitators of ongoing consumption of SSB in order to inform future health promotion efforts.

Background: It has been suggested that low-energy sweeteners (LES) may be associated with an increased risk of metabolic diseases, possibly due to stimulation of glucose-responsive mechanisms.Objective: We conducted a systematic review and meta-analysis of human intervention studies examining the acute effect of LES intake on postprandial glucose (PPG) and postprandial insulin (PPI) responses, in order to comprehensively and objectively quantify these relations.Methods: We systematically searched the Medline, OVID FSTA, and SCOPUS databases until January 2020. Randomized controlled trials comparing acute postprandial effects on PPG and/or PPI after exposure to LES, either alone, with a meal, or with other nutrient-containing preloads to the same intervention without LES were eligible for inclusion. PPG and PPI responses were calculated as mean incremental area under the curve divided by time. Meta-analyses were performed using random effects models with inverse variance weighing.Results: Twenty-six papers (34 PPG trials and 29 PPI trials) were included. There were no reports of statistically significant differences in the effects of LES on PPG and PPI responses compared with control interventions. Pooled effects of LES intake on the mean change difference in PPG and PPI were -0.02 mmol/L (95% CI: -0.09, 0.05) and -2.39 pmol/L (95% CI: -11.83, 7.05), respectively. The results did not appreciably differ by the type or dose of LES consumed, cointervention type, or fasting glucose and insulin levels. Among patients with type 2 diabetes, the mean change difference indicated a smaller PPG response after exposure to LES compared with the control (-0.3 mmol/L; 95% CI: -0.53, -0.07).Conclusions: Ingestion of LES, administered alone or in combination with a nutrient-containing preload, has no acute effects on the mean change in postprandial glycemic or insulinemic responses compared with a control intervention. Apart from a small beneficial effect on PPG (-0.3 mmol/L) in studies enrolling patients with type 2 diabetes, the effects did not differ by type or dose of LES, or fasting glucose or insulin levels. This review and meta-analysis was registered at PROSPERO as CRD42018099608.

BACKGROUND: Male Kunming mice were divided into the normal diet group (control group) and the high-fat diet group (HF group, 185 g·kg-1 protein, 600 g·kg-1 fat and 205 g·kg-1 carbohydrate). After eight weeks' feeding, the behavioral and biochemical indicators in serum were determined. The double bottle preference experiment was used to study the preference of mice for five sweeteners. The contents of monoamine neurotransmitters and genes expression related to dopamine (DA) and opioid receptor were also determined. RESULTS: The body weight of the mice in HF group increased significantly (p < 0.05) after 36 days compared with the control group. While the feed intake of HF group increased sharply in the first 12 days, and then it became basically unchanged. The preference of the HF group for all the five sweeteners was very significantly lower (p < 0.01) than that of the control group. The depression-related behavior was observed in the HF group mice. The contents of TG, TC and LDLC in the HF group were extremely higher (p < 0.01) than that of the control group. The genes expression related to DA and opioid receptor in the HF group was significantly lower than that of the control group, except for the preproenkephalin (PENK). CONCLUSIONS: In summary, this study suggested that a long-term high-fat diet could result in the decrease of the preference for sweeteners on mice due to the long-term consumption of high-fat diet could result in a state of reward hypofunction on mice. This article is protected by copyright. All rights reserved.

Podocyte pyroptosis, characterized by inflammasome activation, plays an important role in inflammation-mediated diabetic nephropathy (DN). Our study aimed to investigate whether miR-21-5p in macrophage-derived extracellular vesicles (EVs) could affect podocyte injury in DN. EVs were extracted after the treatment of RAW 264.7 (mouse macrophage line) with high glucose (HG). The podocyte pyroptosis was determined using the flow cytometry and the western blot. After the knockdown of miR-21-5p in HG-induced RAW264.7 cells, we injected the extracted EVs into DN model mice. The level of miR-21-5p was higher in HG-stimulated macrophage-derived EVs than in normal glucose-cultured macrophage-derived EVs. The co-culture of EVs and podocytes promoted reactive oxygen species (ROS) production and activation of inflammatory in MPC5 cells (mouse podocyte line). However, restraint of miR-21-5p in EVs reduced ROS production and inhibit inflammasome activation in MPC5 cells, thereby reducing podocytes injury. Meanwhile, we found that miR-21-5p inhibited the A20 expression through binding with its 3′-untranslated regions in MPC5 cells. Further studies showed that A20 was also involved in the regulation of miR-21-5p of RAW 264.7-derived EVs on MPC5 injury. At the same time, it was also proved in the DN model mice that miR-21-5p in macrophage-derived EVs could regulate podocyte injury. MiR-21-5p in macrophage-derived EVs can regulate pyroptosis-mediated podocyte injury by A20 in DN.

Consumption of sugar-sweetened beverages (SSBs) during pregnancy has been associated with childhood obesity. Research in which rodent dams have been given high-fat/high-sugar diets has consistently found metabolic alterations in their offspring. However, what remains unclear is the potential impact on the developing fetus of giving sugar in isolation at concentrations similar to SSBs to the mothers. Therefore, we conducted a systematic review and meta-analysis (Protocol No: 127115 on Prospero) to identify potential relationships between maternal sucrose consumption and metabolic outcomes in offspring of rodent (rat or mouse) models. We analysed studies that provided rodent mothers dams with access to sucrose solutions (8–20% w/v) prior to conception, during pregnancy and/or lactation and that reported offspring outcomes of body weight (BW), body composition and glycaemic control. Following a systematic search of four databases (PubMed, EMBASE, Web of Science and Scopus) performed on 15 January 2019, maternal and offspring data from 15 papers were identified for inclusion. Only rat studies were identified. Meta-analyses were performed on standardised mean differences for maternal and offspring BW and fasting glucose levels, with subgroup analyses of strain, sucrose concentration, exposure period and sex of offspring. A bias towards the inclusion of only data from male offspring was identified and this limited interpretation of potential sexually dimorphic outcomes. Maternal sucrose exposure was associated with an increased risk of obesity and poor glucose disposal in adult and aged offspring.

The prostate development has an important postnatal period where cell proliferation begins at the first days after birth and is related to gland growth and ramification. Any metabolic and/or hormonal changes occurring during the postnatal period can interfere with prostate branching. Hyperglycemia is a common condition in low-weight preterm babies at neonatal period and also a disorder found in the offspring of obese mothers. Thus, this study aimed to investigate the in vitro effects of a glucose-rich environment during prostate postnatal development. Wistar rats prostate were removed at birth and cultured for 1, 2 and 3 days in DMEM under normal (5.5 mM) or elevated (7 and 25 mM) glucose concentrations. Samples were processed for morphological analysis, PCNA and smooth muscle α-actin immunohistochemistry, evaluation of active caspase-3, ERK1/2 and Wnt5a gene expression. High glucose concentrations reduced the number of prostatic buds and proliferating cells. The natural increase in smooth muscle cells and collagen deposition observed in control prostates during the first 3 days of development was reduced by elevated glucose concentrations. The amount of active caspase-3 was higher in prostates incubated at 7 mM and TGF-β levels also increased sharply after both glucose concentrations. Additionally, high glucose environment decreased ERK 1/2 activation and increased Wnt5a expression. These data show that high levels of glucose during the first postnatal days affected prostate development by inhibiting cell proliferation which impairs bud branching and this was associated with anti-proliferative signals such as decreased ERK1/2 activation and increased Wnt5a expression.

Elektronik sigaralar, geliştirildiğinden beri, tüm dünyada her geçen gün artan bir pazara sahiptir. Günümüzde e-sigara, tütün kullanımı insidansını azaltabilecek yeni bir “tütün” endüstrisini temsil etmektedir. Elektronik nikotin verme sistemi olarak da bilinen elektronik sigaralar minimal bir araçla aerosol haline getirilmiş nikotini vermek üzere tasarlanan cihazlardır. Elektronik sigaraların asıl amacı kullanıcıya sigara içiyor hissini tütün kullanmadan vermektir. E-sigara üreticileri elektronik sigaraları, sigarayı azaltmanın ya da tamamıyla bırakmanın bir yolu olarak pazarlamakla birlikte pek çok kullanıcı, özellikle gençler, e-sigarayı tütün sigarasından daha güvenli olduklarını düşündükleri için tercih etmektedirler. Birçok e-sigara markası marketlerde satılmakta ve bunlara her gün yeni bir tanesi eklenmektedir. Ek olarak, e-sigaralar için birçok farklı tatlandırıcı madde içeren ve birbirinden farklı aromalara sahip çeşitli e-likitler vardır. Bu e-likitlerin ana içerikleri; nikotin, propilen glikol ve bitkisel gliserindir. Çeşitli e-likit içerikleri nedeniyle, e-sigaranın inhalasyondan sonra insan sağlığı üzerindeki etkisi hala belirsizdir. Bu derlemede, e-sigaranın tarihi, çalışma mekanizması, gelişimi ve pazarlaması, bölümleri ve özellikleri, içerdiği maddeler, nikotin ve nikotinin farmakokinetiği, ülkelerin getirdiği düzenlemeler hakkında genel bilgiler ele alınmıştır., Electronic cigarettes (e-cig), since it developed, have very big market all over the world, and which increases day by day. Nowadays e-cigarette represents a new “tobacco” industry that could reduce the incidence of tobacco smoking. Electronic cigarettes are electronic delivery system are devices designed to deliver aerosolized nicotine with at least one vehicle. The main purpose of electronic cigarettes is to give the user the feeling of smoking without using tobacco. E-cigarette suppliers are marketed e-cigs as a way to reduce or completely quit smoking, and many users, especially young, prefer e-cigarettes because they thought it was safer than tobacco cigarettes in general. Many e-cigarette brands are currently sold in the markets and a new one is added every day. In addition to this there are various e-liquids with distinctive aromas which contain many different types of sweetening agents for e-cigarettes. Main ingredients of these e-liquids are nicotine, propylene glycol and vegetable glycerin. Due to various e-liquid ingredients, e-cigarette's effect on human health after inhalation is still undetermined. In this review is focused on general information about the e-cigarette history, its working mechanism, development and marketing, parts and feature of it, ingredients, nicotine and nicotine's pharmacokinetics, regulation of the countries.

Background Knowledge of the bioactive content of sweet sorghum syrups compared to other common food-grade syrups will expand their utilisation as a food source. Total phenolic content (TPC), phenolics evaluated by high-performance liquid chromatography, antioxidant 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging activities and oxygen radical absorbance capacity (ORAC), as well as colour of high-fructose corn syrup (HFCS), corn, honey, maple, agave, rice and grain sorghum syrups, were compared to 10 commercial sweet sorghum syrups. Results Sweet sorghum syrups contained markedly higher (P ≤ 0.05) TPC (6471 ± 1823 mg L-1 ) compared to the other syrups (596 ± 497 mg L-1 ). HFCS, corn, white grain sorghum and rice syrups had negligible and low DPPH radical scavenging activities and ORAC values, respectively. DPPH activities, ORAC and colour values of the sweet sorghum syrups were also markedly (P ≤ 0.05) higher than other syrups and highly related. The predominant phenolic components identified in sweet sorghum syrups were phenolic acids. Ellagic acid and protocatechuic acid were found in sorghum syrups ranging in concentration from 335-1177 and 53-485 μg g-1 , respectively. Sinapic acid was detected in several sorghum syrups, ranging in concentrations between 21 and 3654 μg g-1 . Conclusion HFCS, corn, white grain sorghum and rice syrups demonstrated low bioactivity with negligible and low DPPH activities and ORAC values, respectively. The TPC, DPPH, ORAC and colour values of the sweet sorghum syrups were related to each other and markedly (P ≤ 0.05) higher compared to the other syrups. Phenolic acids were the predominant phenolic compounds identified in sorghum syrups and represent potential for health benefits. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.

The objective of this study was to investigate the effects of dietary 3 kinds of sweeteners supplementation on growth performance, serum biochemicals, and jejunal physiological functions of broiler chickens for 21 D. A total of one hundred ninety-two 1-day-old male Ross 308 broiler chicks were randomly divided into 4 treatments with 6 replicates for each treatment. The treatments were basal diet (CON), a basal diet supplemented with 250 mg/kg stevioside (STE), a basal diet supplemented with 100 mg/kg sucralose (SUC), and a basal diet supplemented with 600 mg/kg saccharin sodium (SAC). All birds were housed in 3-level battery cages. The results showed that dietary STE supplementation increased (P

The use of in vitro embryo production in the horse is increasing in clinical and research settings; however, protocols are yet to be optimised. Notably, the two most commonly used base media for in vitro maturation (IVM) supply glucose at markedly different concentrations: physiological (5.6 mM, M199) or supraphysiological (17 mM, DMEM/F-12). Exposure to high glucose has detrimental effects on oocytes and early embryos in many mammalian species, but the impact has not yet been examined in the horse. To address this, we compared the energy metabolism of equine COCs matured in M199-based maturation medium containing either 5.6 or 17 mM glucose, as well as expression of key genes in oocytes and cumulus cells. Oocytes were fertilised by ICSI and cultured. Analysis of spent medium revealed that COC glucose consumption and production of lactate and pyruvate were similar between treatments. However, the glycolytic index was decreased at 17 mM and analysis of mitochondrial function of COCs revealed that IVM in 17 mM glucose was associated with decreased ATP-coupled respiration and increased non-mitochondrial respiration compared to that for 5.6 mM glucose. We also found that the metabolic enzyme lactate dehydrogenase-A (LDHA) was downregulated in cumulus cells of oocytes that completed IVM in 17 mM glucose. There was no difference in maturation or blastocyst rates. These data indicate that COC mitochondrial function and gene expression are altered by high glucose concentration during IVM. Further work is needed to determine if these changes are associated with developmental changes in the resulting offspring.

Many older adults suffer from difficulty swallowing thin beverages like water or coffee. To improve swallowing safety, beverages are typically thickened. This creates a new problem: the thickened beverages can be disgusting. New research suggests chemesthesis, particularly spiciness, carbonation, or intense sourness, could improve swallowing without the need for thickeners. Yet, whether such beverages would be liked by older adults is unknown. We thus conducted this experiment to establish older adults' sensory perception and liking/disliking of commercially available chemesthetic beverages. We recruited participants to rate sweetness, sourness, fizziness, stinging, and liking/disliking of unsweetened carbonated waters (1 plain, 5 flavored), sour orange juice, spicy ginger beer, and colas (sugar or aspartame-sweetened). Initial tests (N = 30 older adults) indicated sour orange juice, spicy ginger beer, and two of the flavored waters were not well-liked, so other beverages were selected for a second test (N = 94, 30 younger adults, 64 older adults). Sweetened, carbonated colas were the best-liked of the beverages. The unsweetened, flavored carbonated waters were in general not liked. Regarding comparisons of sensory ratings between older and younger adults, only sweetness differed between age groups. In particular, intensity ratings for the chemesthetic aspects of the beverages (stinging/burning/spiciness, fizziness) and the sour taste did not differ by age. As the chemesthetic properties are the most likely reason the beverages could aid in swallowing safety, observing no suppression of these sensations in older adults is encouraging for the potential of these products as a treatment option.

Background The orbitofrontal cortex (OFC) encodes internal representations of outcomes and subjective value to facilitate flexible reward seeking. OFC activation is associated with drug seeking in both human subjects and animal models. OFC plays a role in alcohol use, but studies in animal models have produced conflicting results with some showing decreased seeking after OFC inactivation but others showing increased seeking or no changes. In part, this may be due to the different measures of alcohol seeking used (e.g., homecage drinking vs. operant seeking). Methods We characterized the impact of transient inactivation of OFC (primarily lateral and, to a lesser extent, ventral subregions) using inhibitory hM4Di designer receptors exclusively activated by designer drugs (DREADDs). OFC neurons were transiently inhibited during 10% and 20% alcohol (ethanol, EtOH) and sucrose homecage consumption, fixed ratio (FR1) operant self-administration, and cue-induced reinstatement of either 10% EtOH or sucrose in male and female rats. Results OFC inactivation did not affect sucrose or EtOH consumption in the homecage, nor did it influence seeking or consumption under FR1 operant conditions. In contrast, OFC inactivation suppressed cued-induced reinstatement for both EtOH and sucrose in both male and female rats. Conclusions Our results are aligned with previous work indicating a selective suppressive effect of OFC inactivation on reinstatement for alcohol and other drugs of abuse. They extend these findings to demonstrate no effect on homecage consumption or FR1 seeking as well as showing an impact of sucrose reinstatement. These data indicate that OFC plays a uniquely important role when reward seeking is driven by associations between external stimuli and internal representations of reward value, both for natural and drug rewards. They further implicate the OFC as a key structure driving relapse-associated seeking and potentially contributing to alcohol use disorder and other diseases of compulsive reward seeking.

Neonatal hypoglycemia is a common diagnosis for which management strategies vary. Our goal was to implement hypoglycemia algorithms (HGA) to streamline management of neonatal hypoglycemia within our hospital system and improve outcomes related to promoting the mother-infant dyad and decreasing hospital costs.A retrospective cohort study analyzed data on 4,666 asymptomatic infants at risk for hypoglycemia and born at two, large, community hospitals between 2010 and 2016. The first algorithm (HGA1) was created in 2012 and subsequently updated (HGA2) in 2014 to include the use of dextrose gel. Infants were separated into three groups by epoch: pre-HGA (2010-2011), HGA1 (2012-2013), and HGA2 (2014-2016). Outcomes between groups were then analyzed. Cost savings were calculated using linear regression.Compared with the pre-HGA group, the HGA1 group had decreased intravenous dextrose use (3.9 vs. 2.5%,By implementing HGA1 and providing resources to unify care for asymptomatic infants at risk for hypoglycemia, short-term outcomes in our hospital system improved. By updating HGA2 to include the use of dextrose gel, the advantages gained by HGA1 were maintained and further enhanced. Overall cost of care was reduced.

Background Artificial sweeteners have been used widely as substitutes for sugar for several decades. In recent years they have been reported to be harmful to human health - especially to glucose absorption. However, as conclusions from previous studies using a single Caco-2 cell model were not consistent, further studies with a more suitable cell model are needed. Results We established a co-culture model with enterocyte Caco-2 and enteroendocrine NCI-H716 cell lines cultured in transwell inserts. The effects of artificial sweeteners, enhancing the glucose transport rate, lasted for 60 min and then began to diminish. Most importantly, different artificial sweeteners with the same sweetness intensity had similar effects on glucose transport. The sodium / glucose co-transporter member 1 (SGLT1) mRNA expression levels increased significantly with an initial glucose concentration of 20 mM, while glucose transporter 2 (GLUT2) mRNA expression significantly increased with initial glucose concentrations of 20 mM and 60 mM. Conclusion Based on the Caco-2/NCI-H716 co-culture model, SGLT1 and GLUT2 mediated the enhancing effects of artificial sweeteners on glucose transport, depending on the sweetness intensity and initial glucose concentration.