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The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk., (© 2023. Springer Nature Limited.)

Rationale & Objective: Increased interdialytic weight gain (IDWG) has been associated with increased morbidity and mortality. We evaluated the usefulness and safety of a mobile application (app) that allows patients receiving maintenance hemodialysis to self-monitor their daily fluid intake., Study Design: Within group comparison before or during intervention., Setting & Participants: Patients receiving maintenance hemodialysis with mean IDWG of <4%., Exposure: Participants were trained to use a smartphone-based app, FiApp that allowed them to record fluid intake and compare with individual targeted daily fluid intake determined by the nephrologist., Outcomes: The primary study outcome was the association between IDWG and fluid intake recorded in the FiApp. Secondary outcomes included FiApp safety and usage. Patient interviews were performed at weeks 1 and 4 to collect information regarding FiApp usability and recommendations for app improvements., Analytical Approach: Mean, median, and standard deviation., Results: Eighteen of 25 patients completed the full 4-week study, provided all app data, and completed 2 patient interviews. The mean 4-week IDWG during app use was similar to the baseline mean 4-week IDWG before app use; however, 61% of the participants had a decrease in IDWG when using the app compared with IDWG at baseline. Of the 18 participants who completed the study, only 1 had a mean 4-week IDWG that was 20% higher than that at baseline. The app was used on ≥80% of the days by 13 (72%) of 18 participants, and was used every day in 7 (39%) of 18 participants. The mean relationship between fluid reported in the app and fluid consumed was 40%., Limitations: This safety study recruited patients who had IDWG of <4%., Conclusions: A smartphone-based app can be safely used to help patients receiving maintenance hemodialysis track and control fluid intake. Motivated patients were able to decrease IDWG despite baseline IDWG being <4% of the body weight., Trial Registration: NCT03759847., Plain-Language Summary: Patients receiving maintenance hemodialysis struggle to limit fluid intake. Excess fluid intake can lead to adverse cardiovascular events. We developed a smartphone app to help patients receiving dialysis self-monitor their fluid intake. In this safety study in patients receiving dialysis with an interdialytic weight gain of <4% of the body weight, more than half of the patients were able to decrease their interdialytic fluid intake while using the app, and only 1 patient had an increase in interdialytic weight gain of >20% while using the app. Information gleaned from structured patient interviews will be used to refine this app., (© 2023 The Authors.)

Purpose: Recent studies suggest that 24-h urine osmolality (UOsm) for optimal water intake should be maintained < 500 mmol·kg -1 . The purpose of this study was to determine the total water intake (TWI) requirement for healthy adults to maintain optimal hydration as indicated by 24-h urine osmolality < 500 mmol·kg -1 ., Methods: Twenty-four-hour UOsm was assessed in 49 men and 50 women residing in the United States (age: 41 ± 14 y, body mass index: 26.3 ± 5.2 kg·m -2 ). TWI was assessed from 7-day water turnover, using a dilution of deuterium oxide, corrected for metabolic water production. The diagnostic accuracy of TWI to identify UOsm < 500 mmol·kg -1 was evaluated using receiver operating characteristic (ROC) analysis in men and women separately., Results: Twenty-four-hour UOsm was 482 ± 229 and 346 ± 182 mmol·kg -1 and TWI was 3.57 ± 1.10 L·d -1 and 3.20 ± 1.27 L·d -1 in men and women, respectively. ROC analysis for TWI detecting 24-h UOsm < 500 mmol·kg -1 in men yielded an area under the curve (AUC) of 77.4% with sensitivity, specificity, and threshold values of 83.3%, 64.5%, and 3.39 L·d -1 , respectively. The AUC was 82.4% in women with sensitivity, specificity, and threshold values of 85.7%, 72.1%, and 2.61 L·d -1 ., Conclusion: Considering threshold values in men and women of 3.4 L·d -1 and 2.6 L·d -1 , respectively, maintaining TWI in line with National Academy of Medicine guidelines of 3.7 L·d -1 in men and 2.7 L·d -1 in women should be sufficient for most individuals in the United States to maintain 24-h UOsm < 500 mmol·kg -1 ., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: The microbiome of the digestive tract exerts fundamental roles in host physiology. Extrinsic factors including lifestyle and diet are widely recognized as key drivers of gut and oral microbiome compositions. Although drinking water is among the food items consumed in the largest amount, little is known about its potential impact on the microbiome., Objectives: We explored the associations of plain drinking water source and intake with gut and oral microbiota compositions in a population-based cohort., Methods: Microbiota, health, lifestyle, and food intake data were extracted from the American Gut Project public database. Associations of drinking water source (bottled, tap, filtered, or well water) and intake with global microbiota composition were evaluated using linear and logistic models adjusted for anthropometric, diet, and lifestyle factors in 3413 and 3794 individuals, respectively (fecal samples; 56% female, median [IQR] age: 48 [36-59] y; median [IQR] BMI: 23.3 [20.9-26.3] kg/m2), and in 283 and 309 individuals, respectively (oral samples)., Results: Drinking water source ranked among the key contributing factors explaining the gut microbiota variation, accounting for 13% [Faith's phylogenetic diversity (Faith's PD)] and 47% (Bray-Curtis dissimilarity) of the age effect size. Drinking water source was associated with differences in gut microbiota signatures, as revealed by β diversity analyses (P < 0.05; Bray-Curtis dissimilarity, weighted UniFrac distance). Subjects drinking mostly well water had higher fecal α diversity (P < 0.05; Faith's PD, observed amplicon sequence variants), higher Dorea, and lower Bacteroides, Odoribacter, and Streptococcus than the other groups. Low water drinkers also exhibited gut microbiota differences compared with high water drinkers (P < 0.05; Bray-Curtis dissimilarity, unweighted UniFrac distance) and a higher abundance of Campylobacter. No associations were found between oral microbiota composition and drinking water consumption., Conclusions: Our results indicate that drinking water may be an important factor in shaping the human gut microbiome and that integrating drinking water source and intake as covariates in future microbiome analyses is warranted., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Emerging evidence links underhydration and habitual low water intake to higher cardiometabolic risk, but evidence is limited in community-dwelling older adults., Objectives: The objective is to examine if higher water intake and better hydration are associated with better cardiometabolic health., Methods: This cross-sectional analysis using general linear models included 2238 participants from the Framingham Heart Study Second Generation and First Generation Omni cohorts with an estimated glomerular filtration rate >30 mL·min-1·1.73 m-2 and a valid FFQ for assessment of water intake. Of these participants, 2219 had fasting spot urinary creatinine data and 950 had 24-h urine creatinine data to assess hydration. Cardiometabolic risk factors included fasting glucose, triglycerides (TGs), total cholesterol (TC), HDL cholesterol, and calculated LDL cholesterol; glycated hemoglobin (HbA1c); C-reactive protein (CRP); and systolic (SBP) and diastolic (DBP) blood pressure., Results: The combined cohorts were on average aged 70 y; 55% were women. Mean (95% CI) daily total water intakes were 2098 (2048, 2150) mL for men and 2109 (2063, 2156) mL for women. Total daily water, beverage (including plain water), and plain water intakes demonstrated significant positive trends with HDL cholesterol (P < 0.01). TG concentrations were significantly lower among the highest plain water consumers (P < 0.05). The 24-h urine concentration, as measured by creatinine, was positively associated with LDL cholesterol and TG concentrations ( P < 0.01) and inversely associated with HDL cholesterol concentrations (P < 0.002). Neither water intake nor urine concentration was associated with glucose or HbA1c (P > 0.05)., Conclusions: Our findings of a consistent pattern between circulating lipid concentrations and different water sources and hydration markers support an association between hydration and lipid metabolism in older adults and add to the growing evidence that inadequate water intake and underhydration may lead to higher cardiometabolic risk., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Our aim was to investigate the validity of osmolality from 24-h urine collection in examining the risk for calcium-oxalate (CaOx) kidney stone formation in patients with recurrent urolithiasis. Three hundred and twelve subjects (males/females: 184/128) from France with a history of recurrent kidney stones from confirmed or putative CaOx origin were retrospectively included in the study (46 ± 14 years, BMI: 25.3 ± 5.0 kg·m -2 ). Tiselius' crystallization risk index (CRI) was calculated based on urinary calcium, oxalate, citrate, magnesium, and volume from 24-h samples. The diagnostic ability of 24-h urine osmolality to classify patients as high risk for kidney stone crystallization was examined through the receivers operating characteristics analysis. High risk for CaOx crystallization was defined as CRI > 1.61 and > 1.18, for males and females, respectively. The accuracy of urine osmolality to diagnose risk of CaOx stone formation (AUC, area under the curve) for females was 84.6%, with cut-off point of 501 mmol·kg -1 (sensitivity: 83.3%, specificity: 76.0%). Males had AUC of 85.8% with threshold of 577 mmo·kg -1 (sensitivity: 85.5%, specificity: 77.6%). A negative association was found between 24-h urine volume and osmolality (r = - 0.63, P < 0.001). Also, a positive association was found between 24-h urine osmolality and CRI (r = 0.65, P < 0.001), as well as urea excretion with CRI (r = 0.37, P < 0.001). In conclusion, urine osmolality > 501 and > 577 mmol·kg -1 , in female and in male, respectively, was associated with a risk for CaOx kidney stone formation in patients with a history of recurrent urolithiasis. Thus, when CaOx origin is confirmed or suspected, 24-h urine osmolality provides a simple way to define individualized target of urine dilution to prevent urine crystallization and stone formation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background/objectives: To test the diagnostic ability of two combined practical markers for elevated urine osmolality (underhydration) in free-living adults and children., Subjects/methods: One hundred and one healthy adults (females n = 52, 40 ± 14 y, 1.70 ± 0.95 m, 76.7 ± 17.4 kg, 26.5 ± 5.5 kg/m 2 ) and 210 children (females = 105, 1.49 ± 0.13 m, 43.4 ± 12.6 kg, 19.2 ± 3.2 kg m -2 ) collected urine for 24-h. Urine was analyzed for urine osmolality (UOsm), color (UC), while the number of voids (void) was also recorded. Receiver Operating Characteristic (ROC) analysis was performed for UC, void, and combination of UC and void, to determine markers' diagnostic ability for detecting underhydration based on elevated UOsm (UOsm ≥ 800 mmol kg -1 )., Results: Linear regression analysis revealed that UC was significantly associated with UOsm in both adults (R 2  = 0.38; P < 0.001) and children (R 2  = 0.45; P < 0.001). Void was significantly associated with UOsm in both adults (R 2  = 0.13; P < 0.001) and children (R 2  = 0.15; P < 0.001). In adults, when UC > 3 and void <7 were combined, the overall diagnostic ability for underhydration was 97% with sensitivity and specificity of 100% and 88%, respectively. In children, UC > 3 and void <5 had an overall diagnostic ability for underhydration of 89% with sensitivity and specificity of 100% and 62%, respectively., Conclusions: Urine color alone and the combination of urine color with void number can a valid and simple field-measure to detect underhydration based on elevated urine osmolality., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Bariatric surgery before pregnancy can result in improved maternal fertility. However, long-term data on the consequences at childhood age are currently lacking., Methods: EFFECTOR is a prospective cohort study of children (aged 4 to 11 years) born to mothers who underwent bariatric surgery (BS) before pregnancy (n = 36), controls with overweight/obesity (OW/OB) matched on pre-pregnancy BMI (n = 36) and normal weight controls (NL) (n = 35). We performed prospective collection of anthropometric data, data on psychomotor development, school functioning and behaviour (Strengths and Difficulties Questionnaire (SDQ), Child Behaviour Checklist (CBCL))., Results: The children born after bariatric surgery (BS) presented with the highest body-weight SDS (0.70 vs 0.14 in OW/OB and -0.09 in NL; P = .006) and BMI SDS (0.47 vs -0.02 in OW/OB and -0.42 in NL; P = .01). A higher excess in body fat percentage and waist circumference SDS were found in the BS group (5.7 vs 1.4 in OW/OB and -0.1 in NL; P < .001 and 0.61 vs 0.16 in OW/OB and -0.15 in NL; P = .04). The SDQ questionnaires revealed a higher amount of overall problems in the BS offspring (11.1 vs 7.5 in OW/OB and 8.1 in NL; P = .03), with a higher externalizing score at the CBCL (52.0 vs 44.2 in OW/OB and 47.0 in NL; P = .03)., Conclusion: Maternal bariatric surgery does not appear to protect the offspring for childhood overweight and obesity. Parents reported more behaviour problems in these children, especially externally of nature., (© 2020 World Obesity Federation.)

Background/aims: Accurate stool consistency classification of non-toilet-trained children remains challenging. This study evaluated the feasibility of automated classification of stool consistencies from diaper photos using machine learning (ML)., Methods: In total, 2687 usable smartphone photos of diapers with stool from 96 children younger than 24 months were obtained after independent ethical study approval. Stool consistency was assessed from each photo according to the original 7 types of the Brussels Infant and Toddler Stool Scale independently by study participants and 2 researchers. A health care professional assigned a final score in case of scoring disagreement between the researchers. A proof-of-concept ML model was built upon this collected photo database, using transfer learning to re-train the classification layer of a pretrained deep convolutional neural network model. The model was built on random training (n = 2478) and test (n = 209) subsets., Results: Agreements between study participants and both researchers were 58.0% and 48.5%, respectively, and between researchers 77.5% (assessable n = 2366). The model classified 60.3% of the test photos in exact agreement with the final score. With respect to the 4-class grouping of the 7 Brussels Infant and Toddler Stool Scale types, the agreement between model-based and researcher classification was 77.0%., Conclusion: The automated and objective scoring of stool consistency from diaper photos by the ML model shows robust agreement with human raters and overcomes limitations of other methods relying on caregiver reporting. Integrated with a smartphone application, this new framework for photo database construction and ML classification has numerous potential applications in clinical studies and home assessment., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Eating behaviour of older adults is influenced by a complex interaction of determinants. Understanding the determinants of a specific target group is important when developing targeted health-promoting strategies. The aim of this study was to explore interpersonal determinants of eating behaviours in older adults living independently in a specific neighbourhood in the Netherlands., Methods: In the neighbourhood of interest, populated by relatively many older adults, fifteen semi-structured interviews were conducted with independently living older adults (aged 76.9 ± 6.4y). Interviews were complemented with observations among the target group: three occasions of grocery shopping and three collective eating occasions in the neighbourhood. A thematic approach was used to analyse the qualitative data., Results: When we asked the older adults unprompted why they eat what they eat, the influence of interpersonal determinants did not appear directly; respondents rather mentioned individual (e.g. habits) and environmental factors (e.g. food accessibility). Key findings regarding interpersonal factors were: 1) Behaviours are shaped by someone's context; 2) Living alone influences (determinants of) eating behaviour via multiple ways; 3) There is a salient norm that people do not interfere with others' eating behaviour; 4) Older adults make limited use of social support (both formal and informal) for grocery shopping and cooking, except for organised eating activities in the neighbourhood. In this particular neighbourhood, many facilities (e.g. shops at walking distance) are present, and events (e.g. dinners) are organised with and for the target group, which likely impact (determinants of) their behaviours., Conclusions: The study showed that older adults do not directly think of interpersonal factors influencing their eating behaviour, but rather of individual or environmental factors. However, multiple interpersonal factors did appear in the interviews and observations. Moreover, neighbourhood-specific factors seem to play a role, which underlines the need to understand the specific (social) setting when developing and implementing intervention programmes. Insights from this study can assist in developing health-promoting strategies for older adults, taking into account the context of the specific neighbourhood.

Purpose: This investigation had three purposes: (a) to evaluate changes in hydration biomarkers in response to a graded rehydration intervention (GRHI) following 3 days of water restriction (WR), (b) assess within-day variation in urine concentrations, and (c) quantify the volume of fluid needed to return to euhydration as demonstrated by change in U col ., Methods: 115 adult males and females were observed during 1 week of habitual fluid intake, 3 days of fluid restriction (1000 mL day -1 ), and a fourth day in which the sample was randomized into five different GRHI groups: no additional water, CON; additional 500 mL, G +0.50 ; additional 1000 mL, G +1.00 ; additional 1500 mL, G +1.50 ; additional 2250 mL, G +2.25 . All urine was collected on 1 day of the baseline week, during the final 2 days of the WR, and during the day of GRHI, and evaluated for urine osmolality, color, and specific gravity., Results: Following the GRHI, only G +1.50 and G +2.25 resulted in all urinary values being significantly different from CON. The mean volume of water increase was significantly greater for those whose U col changed from > 4 to < 4 (+ 1435 ± 812 mL) than those whose U col remained ≥ 4 (+ 667 ± 722 mL, p < 0.001)., Conclusions: An additional 500 mL of water is not sufficient, while approximately 1500 mL of additional water (for a total intake between 2990 and 3515 mL day -1 ) is required to return to a urine color associated with adequate water intake, following 3 days of WR.

Background/objectives: While daily hydration is best assessed in 24-h urine sample, spot sample is often used by health care professionals and researchers due to its practicality. However, urine output is subject to circadian variation, with urine being more concentrated in the morning. It has been demonstrated that afternoon spot urine samples are most likely to provide equivalent urine concentration to 24-h urine samples in adults. The aim of the present study was to examine whether urine osmolality (UOsm) assessed from a spot urine sample in specific time-windows was equivalent to 24-h UOsm in free-living healthy children., Subjects/methods: Among 541 healthy children (age: 3-13 years, female: 45%, 77% non-Hispanic white, BMI:17.7 ± 4.0 kg m -2 ), UOsm at specific time-windows [morning (0600-1159), early afternoon (1200-1559), late afternoon (1600-1959), evening (2000-2359), overnight (2400-0559), and first morning] was compared with UOsm from the corresponding pooled 24-h urine sample using an equivalence test., Results: Late afternoon (1600-1959) spot urine sample UOsm value was equivalent to the 24-h UOsm value in children (P < 0.05; mean difference: 62 mmol kg -1 ; 95% CI: 45-78 mmol kg -1 ). The overall diagnostic ability of urine osmolality assessed at late afternoon (1600-1959) to diagnose elevated urine osmolality on the 24-h sample was good for both cutoffs of 800 mmol kg -1 [area under the curve (AUC): 87.4%; sensitivity: 72.6%; specificity: 90.5%; threshold: 814 mmol kg -1 ] and 500 mmol kg -1 (AUC: 83.5%; sensitivity: 75.0%; specificity: 80.0%; threshold: 633 mmol kg -1 )., Conclusion: These data suggest that in free-living healthy children, 24-h urine concentration may be approximated from a late afternoon spot urine sample. This data will have practical implication for health care professionals and researchers.

The idea that water intake or hydration may play an intrinsic, independent role in modulating metabolic disease risk is relatively recent. Here, we outline the journey from early experimental works to more recent evidence linking water and hydration to metabolic health. It has been known for decades that individuals with existing metabolic dysfunction experience challenges to body water balance and have elevated arginine vasopressin (AVP), a key hormone regulating body fluid homeostasis. Later, intervention studies demonstrated that altering fluid balance in these individuals could worsen their condition, suggesting that hydration played a role in modulating glycemic control. More recently, observational and interventional studies in healthy individuals have implicated the hydration-vasopressin axis in the pathophysiology of metabolic diseases. Individuals with higher AVP (or its surrogate, copeptin) are at higher risk for developing type 2 diabetes and components of the metabolic syndrome, an association that remains even when controlling for known risk factors. Supporting preclinical work also suggests a causal role for AVP in metabolic dysfunction. It is known that individuals who habitually drink less fluids tend to have higher circulating AVP, which may be lowered by increasing water intake. In the short term, water supplementation in habitual low drinkers with high copeptin may reduce fasting glucose or glucagon, generating a proof of concept for the role of water supplementation in reducing incident metabolic disease. A large randomized trial is ongoing to determine whether water supplementation for 1 year in subjects with low water intake can meaningfully reduce fasting glucose, risk of new-onset diabetes, and other cardiometabolic risk factors., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Adults consuming sugar-sweetened beverages (SSBs) are at increased risk of becoming overweight/obese and developing lifestyle-related diseases. Furthermore, a low water intake is associated with increased health risks, such as CKD. These issues are especially pressing in Mexico where SSB intake is high. The present research aimed to describe the attitudes of Mexican adults who are considered high sugar-low water drinkers (HS-LWDs). HS-LWDs were defined as adults aged 18-45 years, drinking at least 2 servings (500 mL) of SSB/day and maximum 3 servings (750 mL) of water/day. The study included 2.858 HS-LWD (58% males) living in the urban area of Mexico City. Data were collected using an online, self-administered questionnaire. Bayesian approach was applied to analyze attitudes in life and towards drinking. Results showed that social aspects, such as sharing with friends and family and self-image, were the dominant attitudes in life. The main reason to choose a beverage was to get sensations, resulting in 2 axes, one was pleasure oriented and one was health oriented. Getting sensations was also a main driver to drink linked to a moment, together with self-image. The Bayesian network analysis demonstrated 5 attitude profiles, based on the most important attitudes defining each profile: mood and pleasure, self-image and body image, sharing and restoring, pleasure and energy, and health and success. This study allowed describing HS-LWD attitudes, in life and towards drinking. It constitutes a first step in understanding this target group's attitudes and behavior, offering potential recommendations for tailored interventions to promote the adoption of healthier drinking habits., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Background: Hydration effects on cognition remain understudied in children. This is concerning since a large proportion of US children exhibit insufficient hydration., Objective: This study investigated the effects of water intake on urinary markers of hydration and cognition among preadolescents., Methods: A 3-intervention crossover design was used among 9- to 11-y-olds [n = 75 (43 males, 32 females); 58.2 ± 28.5 BMI percentile]. Participants maintained their water intake [ad libitum (AL)] or consumed high (2.5 L/d) or low (0.5 L/d) water for 4 d. The primary outcomes were performance on cognitive tasks requiring inhibition, working memory, and cognitive flexibility assessed using a modified flanker, go/no-go, and color-shape switch tasks, respectively. Secondary outcomes included urine hydration indices [i.e., color, urine specific gravity (USG), osmolality] assessed using 24-h urine collected during day 4 of each intervention. Repeated-measures ANOVAs were used to assess intervention effects., Results: There was a significant difference in hydration across all 3 interventions. Urine color during the low intervention [median (IQR): 6 (2)] was greater than during AL [5 (2)], and both were greater than during the high intervention [18 (0)] (all P ≤ 0.01). Similarly, osmolality [low (mean ± SD): 912 ± 199 mOsmol/kg, AL: 790 ± 257.0 mOsmol/kg, high: 260 ± 115 mOsmol/kg] and USG [low (mean ± SD): 1.023 ± 0.005, AL: 1.020 ± 0.007, high: 1.005 ± 0.004] during the low intervention were greater during AL, and both were greater than during the high intervention (all P ≤ 0.01). USG and osmolality AL values were related to switch task measures (β: 0.21 to -0.31, P < 0.05). Benefits of the high intervention were observed during the switch task, whereby participants exhibited 34% lower working memory cost relative to the low intervention. No significant changes in cognition were observed for the flanker and go/no-go tasks., Conclusions: The water intervention improved urinary markers of hydration and had selective benefits during task switching. Furthermore, children's cognitive flexibility selectively benefits from greater habitual hydration and water intake. This study is registered at clinicaltrials.gov as NCT02816450., (Copyright © American Society for Nutrition 2019.)

Background: Epidemiological studies in humans show increased concentrations of copeptin, a surrogate marker of arginine vasopressin (AVP), to be associated with increased risk for type 2 diabetes., Objectives: To examine the acute and independent effect of osmotically stimulated AVP, measured via the surrogate marker copeptin, on glucose regulation in healthy adults., Methods: Sixty subjects (30 females) participated in this crossover design study. On 2 trial days, separated by ≥7 d (males) or 1 menstrual cycle (females), subjects were infused for 120 min with either 0.9% NaCl [isotonic (ISO)] or 3.0% NaCl [hypertonic (HYPER)]. Postinfusion, a 240-min oral-glucose-tolerance test (OGTT; 75 g) was administered., Results: During HYPER, plasma osmolality and copeptin increased (P < 0.05) and remained elevated during the entire 6-h protocol, whereas renin-angiotensin-aldosterone system hormones were within the lower normal physiological range at the beginning of the protocol and declined following infusion. Fasting plasma glucose did not differ between trials (P > 0.05) at baseline and during the 120 min of infusion. During the OGTT the incremental AUC for glucose from postinfusion baseline (positive integer) was greater during HYPER (401.5 ± 190.5 mmol/L·min) compared with the ISO trial (354.0 ± 205.8 mmol/L·min; P < 0.05). The positive integer of the AUC for insulin during OGTT did not differ between trials (HYPER 55,850 ± 36,488 pmol/L·min compared with ISO 57,205 ± 31,119 pmol/L·min). Baseline values of serum glucagon were not different between the 2 trials; however, the AUC of glucagon during the OGTT was also significantly greater in HYPER (19,303 ± 3939 ng/L·min) compared with the ISO trial (18,600 ± 3755 ng/L·min; P < 0.05)., Conclusions: The present data indicate that acute osmotic stimulation of copeptin induced greater hyperglycemic responses during the oral glucose challenge, possibly due to greater glucagon concentrations.This study was registered at clinicaltrials.gov as NCT02761434., (Copyright © American Society for Nutrition 2019.)

Recently repeated heat stress and dehydration have been reported to cause oxidative stress and kidney damage that is enhanced by rehydrating with fructose solutions. We hypothesized that antioxidants might provide a novel way to prevent kidney damage. To test this hypothesis, mild heat stress was induced by exposing rats to 37 °C during 1 h in a closed chamber. The supplementation with water-soluble antioxidants (Antiox), ascorbic acid 1% plus N-acetyl cysteine 600 mg/L was done either in the 10% fructose 2 h rehydration fluid immediately after heat stress (Fructose 10% + Antiox), and/or in the tap water (Water + Antiox) for the remainder of the day, or in both fluids. After 4 weeks, control rats exposed to heat with fructose rehydration developed impaired renal function, tubular injury, intrarenal oxidative stress, a reduction in Nrf2-Keap1 antioxidant pathway, stimulation of vasopressin and the intrarenal polyol-fructokinase pathway. In contrast, dosing the antioxidants in the tap water (i.e., before the heat exposure and rehydration with fructose) preserved renal function, prevented renal tubule dysfunction and avoided the increase in systemic blood pressure. These effects were likely due to the amplification of the antioxidant defenses through increased Nrf2 nuclear translocation stimulated by the antioxidants and by the prevention of polyol fructokinase pathway overactivation. More studies to understand the mechanisms implicated in this pathology are warranted as there is recent evidence that they may be operating in humans as well., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Up to 50% of the adult population fail to meet the recommended total water intake despite the adverse health outcomes associated with chronic low fluid intake. Total fluid intake plays an important role in the energy and nutrient intake of individuals. Dietitians' role is to advise and guide the population toward a healthier diet. However, based on existing evidence, dietitians' current knowledge and practices regarding healthy hydration is an area for improvement. The European Healthy Hydration Awareness Campaign (EuHHAC) is an initiative between the European Federation of the Associations of Dietitians (EFAD) and the Hydration and Health Department of Danone Research, which aims to increase knowledge and awareness of healthy hydration and provide dietitians with evidence-based resources to use in practice. Since 2016, a series of tasks were undertaken by the EuHHAC group targeting dietitians across Europe. These tasks included an online survey addressing gaps in hydration knowledge, a webinar providing information on the terminology and impact of hydration on health, an interactive session addressing facilitators and barriers to healthy hydration, and a tutorial summarizing key hydration information and take-home messages. Dietitians were actively engaged in each aspect. Based on the feedback received, awareness of hydration was increased among dietitians. To further enhance understanding, an online Hydration Resource Center, including the resources of EuHHAC, will be created and uploaded on the EFAD website. Once completed an evaluation study will be undertaken to assess the usefulness of the resources in practice. The deliverables will be cascaded across Europe and worldwide via social media, conferences, and publications., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

In children, maintaining adequate fluid intake and hydration is important for physiological reasons and for the adoption of healthy, sustainable drinking habits. In the Liq.In7 cross-sectional surveys involving 6,469 children (4-17 years) from 13 countries, 60% of children did not meet the European Food Safety Authority (EFSA) adequate intake for water from fluids. Beyond fluid quantity, the quality of what children drink is important for health. In these surveys, the contribution of sugar-sweetened beverages and fruit juices to total fluid intake (TFI) in children exceeded that of water in 6 out of 13 countries. To assess the adequacy of children's fluid intake, urinary biomarkers of hydration such as urine osmolality, urine specific gravity, and urine color may be used. To date, while there are no widely accepted specific threshold values for urine concentration to define adequate hydration in children, the available literature suggests that many children have highly concentrated urine, indicating insufficient fluid intake. This is worrisome since studies have demonstrated a relationship between low fluid intake or insufficient hydration and cognitive performance in children. Furthermore, results of the Liq.In7 surveys showed that at school - where children spend a significant amount of time and require optimal cognitive performance - children drink only 14% of their TFI. Consequently, it is pertinent to better understand the barriers to drinking water at school and encourage the promotion of water intake through multicomponent interventions that combine educational, environmental, and behavioral aspects to support adequate hydration as well as optimal cognition in children., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Background: The comparative effectiveness of treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or their combination in people with albuminuria and cardiovascular risk factors is unclear., Methods: In a multicenter, randomized, open label, blinded end point trial, we evaluated the effectiveness on cardiovascular events of ACE or ARB monotherapy or combination therapy, targeting BP<130/80 in patients with moderate or severe albuminuria and diabetes or other cardiovascular risk factors. End points included a primary composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for cardiovascular causes and a revised end point of all-cause mortality. Additional end points included ESRD, doubling of serum creatinine, albuminuria, eGFR, BP, and adverse events., Results: Because of slow enrollment, the trial was modified and stopped 41% short of targeted enrollment of 2100 participants, corresponding to 35% power to detect a 25% reduced risk in the primary outcome. Our analysis included 1243 adults, with median follow-up of 2.7 years. Efficacy outcomes were similar between groups (ACE inhibitor versus ARB, ACE inhibitor versus combination, ARB versus combination) as were rates of serious adverse events. The rate of permanent discontinuation for ARB monotherapy (6.3%) was significantly lower than for ACE inhibitor monotherapy (15.7%) or combined therapy (18.3%)., Conclusions: Patients may tolerate ARB monotherapy better than ACE inhibitor monotherapy. However, data from this trial and similar trials, although as yet inconclusive, show no trend suggesting differences in mortality and renal outcomes with ACE inhibitors or ARBs as dual or monotherapy in patients with albuminuria and diabetes or other cardiovascular risk factors., (Copyright © 2018 by the American Society of Nephrology.)

Background: Basophil activation contributes to inflammatory reactions, especially in allergy. It is controlled, both positively and negatively, by several mechanisms. High-affinity IgE receptors (FcεRI) generate a mixture of activation and inhibition signals when aggregated, the ratio of which depends on the concentration of allergen recognized by receptor-bound IgE. Low-affinity IgG receptors (FcγRIIA/B) generate inhibition signals when coengaged with FcεRI by allergen-antibody immune complexes. Commensal and probiotic bacteria, such as Lactobacillus paracasei, generate inhibition signals through still unclear mechanisms., Objective: We sought to investigate whether mechanisms that control, both positively and negatively, basophil activation, which were unraveled and studied in basophils from healthy donors, are functional in allergic patients., Methods: FcεRI and FcγRIIA/B expression, FcεRI-dependent activation, FcεRI-dependent inhibition, and FcγRIIB-dependent inhibition were examined in blood basophils incubated overnight with or without L paracasei and challenged under 10 experimental conditions. Basophils from healthy donors were compared with basophils from patients who consulted an allergology outpatient clinic over a period of 3 months with respiratory allergy, anaphylaxis antecedents, chronic urticaria, and/or atopic dermatitis., Results: Patients' basophils expressed neither more FcεRI nor less FcγRIIB than basophils from healthy donors. They were neither hyperreactive to positive regulation nor hyporeactive to negative regulation, irrespective of the receptors or mechanisms involved and the allergic manifestations of the patients., Conclusion: Regulatory mechanisms that control basophil activation are fully functional in allergic patients. Intrinsic defects in these mechanisms do not explain allergic manifestations. Based on these mechanisms, immune checkpoint modifiers can be developed as novel therapeutic tools for allergy., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe total fluid intake (TFI) and types of fluid consumed in urban China by age, gender, regions and city socioeconomic status relative to the adequate intakes (AI) set by the Chinese Nutrition Society., Methods: In 2016, participants aged 4-9, 10-17 and 18-55 years were recruited via a door-to-door approach in 27 cities in China. In total, 2233 participants were included. The volumes and sources of TFI were collected using the Liq.In 7 record, assisted by a photographic booklet of standard fluid containers., Results: The mean daily TFI among children, adolescents and adults were 966, 1177 and 1387 mL, respectively. In each age group, TFI was significantly higher in male vs female (981 vs 949, 1240 vs 1113, 1442 vs 1332; mL). Approximately 45, 36 and 28% of children, adolescents and adults reached the AI. Although plain water was the highest contributor to TFI, the contribution of sugar sweetened beverages (SSB) was ranked in the top three together with water and milk and derivatives. Approximately 27, 48 and 47% of children, adolescents and adults consumed more than one serving of SSB per day, respectively., Conclusions: A relatively large proportion of participants did not drink enough to meet the AI in urban China. Many children, adolescents and adults consumed more than one serving of SSB per day. A majority of children, adolescents and adults in the study population do not meet both quantitative and qualitative fluid intake requirements, and signal socioeconomic disparities.

Purpose: This study aimed to identify and characterize patterns of fluid intake in children and adolescents from six countries: Argentina, Brazil, China, Indonesia, Mexico and Uruguay., Methods: Data on fluid intake volume and type amongst children (4-9 years; N = 1400) and adolescents (10-17 years; N = 1781) were collected using the validated 7-day fluid-specific record (Liq.In 7 record). To identify relatively distinct clusters of subjects based on eight fluid types (water, milk and its derivatives, hot beverages, sugar-sweetened beverages (SSB), 100% fruit juices, artificial/non-nutritive sweetened beverages, alcoholic beverages, other beverages), a cluster analysis (partitioning around k-medoids algorithm) was used. Clusters were then characterized according to their socio-demographics and lifestyle indicators., Results: The six interpretable clusters identified were: low drinkers-SSB (n 523), low drinkers-water and milk (n 615), medium mixed drinkers (n 914), high drinkers-SSB (n 513), high drinkers-water (n 352) and very high drinkers-water (n 264). Country of residence was the dominant characteristic, followed by socioeconomic level, in all six patterns., Conclusions: This analysis showed that consumption of water and SSB were the primary drivers of the clusters. In addition to country, socio-demographic and lifestyle factors played a role in determining the characteristics of each cluster. This information highlights the need to target interventions in particular populations aimed at changing fluid intake behavior and improving health in children and adolescents.

Background: Mean daily water intake from fluids (WATER-FL) has proven to be difficult to measure because of a range of nonvalidated data collection techniques. Few questionnaires have been validated to estimate WATER-FL against self-reported diaries or urinary hydration markers, which may limit their objectivity. Objectives: The goals of this investigation were 1 ) to assess the validity of a 7-d fluid record (7dFLR) to measure WATER-FL (WATER-FL-7dFLR) through comparison with WATER-FL as calculated by measuring deuterium oxide (D 2 O) disappearance (WATER-FL-D 2 O), and 2 ) to evaluate the reliability of the 7dFLR in measuring WATER-FL. Methods: Participants [ n = 96; 51% female; mean ± SD age: 41 ± 14 y; mean ± SD body mass index (in kg/m 2 ): 26.2 ± 5.1] completed body water turnover analysis over 3 consecutive weeks. They completed the 7dFLR and food diaries during weeks 2 and 4 of the observation. The records were entered into nutritional software to determine the water content of all foods and fluids consumed. WATER-FL-D 2 O was calculated from water turnover (via the D 2 O dilution method), minus water from food and metabolic water. The agreement between the 2 methods of determining WATER-FL were compared according to a Bland-Altman plot at week 2. The test-retest reliability of 7dFLR between weeks 2 and 4 was assessed via intraclass correlation (ICC). Results: The mean ± SD difference between WATER-FL-7dFLR and WATER-FL-D 2 O was -131 ± 845 mL/d. In addition, no bias was observed ( F [1,94] = 0.484; R 2 = 0.006; P = 0.488). When comparing WATER-FL-7dFLR from weeks 2 and 4, no significant difference (mean ± SD difference: 71 ± 75 mL/d; t [79] = 0.954; P = 0.343) and an ICC of 0.85 (95% CI: 0.77, 0.90) was observed. Conclusions: The main findings of this study were that the use of the 7dFLR is an effective and reliable method to estimate WATER-FL in adults. This style of questionnaire may be extremely helpful for collecting water intake data for large-scale epidemiologic studies., Competing Interests: Author disclosures: LTJ, CC-J, AM, and JDA, no conflicts of interest. ECJ has an active grant with Danone Research. FP is a scientific consultant for Danone Research. IG and LJ are employees of Danone Research. SAK is a scientific consultant for Quest Diagnostics and has active grants with Danone Research., (© 2017 American Society for Nutrition.)

Objective: We investigated the effect of three interventions to increase the plain water consumption of children with unhealthy drinking habits, with an innovative approach combining the three layers of Installation Theory: embodied competences, affordances and social regulation., Methods: 334 preschool children and their carers were allocated to three interventions: Control (control): no intervention, Information (info): online coaching sessions on water health benefits aiming at modifying embodied competences (knowledge), Information + Water Affordance (info + w): the same plus home delivery of small bottles of water. After three months, half of the info and info + w subjects were allocated to Social Regulation (+social) (on-line discussion forum) or no further intervention (-social). Intake of plain water and all other fluid types of the children were recorded by the carers 6 times over a year using an online 7-day fluid-specific dietary record., Results: Over 1 year, all groups significantly increased daily water consumption by 3.0-7.8 times (+118 to +222 mL). Info + w + social and Info-social generated the highest increase in plain water intake after one year compared to baseline, by 7.8 times (+216 mL) and 6.7 times (+222 mL) respectively; both significantly exceeded the control (3.0 times, +118 mL), whilst the effect of info + w-social (5.0 times, +158 mL) and info + social (5.3 times, +198 mL) did not differ from that of control. All groups saw a decrease of sweetened beverages intake, again with info + w + social generating the largest decrease (-27%; -172 mL). No changes in other fluids or total fluid intake were observed., Conclusions: Sustainable increased water consumption can be achieved in children with unhealthy drinking habits by influencing representations, changing material affordances, and providing social regulation. Combining the three provided the strongest effect as predicted by Installation Theory., (Copyright © 2017. Published by Elsevier Ltd.)

The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine. A healthy microbiota plays a key role influencing epithelial barrier functions through the production of short-chain fatty acids (SCFAs) and interactions with innate pattern recognition receptors in the mucosa, driving the steady-state expression of mucus and antimicrobial factors. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability, and dysbiosis of the microbiota, which are recognized to play a role in the pathophysiology of a variety of gastrointestinal disorders. Additionally, gut-brain signaling may be affected by prolonged mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the hypothalamus-pituitary-adrenal axis and both mast cell-dependent and mast cell-independent mechanisms. The modulation of gut barrier function through nutritional interventions, including strategies to manipulate the microbiota, is considered a relevant target for novel therapeutic and preventive treatments against a range of diseases. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in intestinal diseases, but there remains a need to explore their use in assessing the effect of nutritional factors on gut barrier function. Future studies should aim to establish normal ranges of available biomarkers and their predictive value for gut health in human cohorts., (Copyright © 2017 the American Physiological Society.)

Background: Pregnant and breastfeeding women experience great changes in their total body water content and water dynamics. To support the accretion of total body water during pregnancy and compensate for the water lost through breast milk during breastfeeding, increased adequate intakes (AI) for total water have been established by various health authorities. Despite this widespread advice, several studies suggest that pregnant and breastfeeding women do not meet the AI for total water, suggesting the need to raise women's awareness on the importance of adequate water intake, particularly during pregnancy and breastfeeding, as well as to provide them with a simple means of monitoring their hydration on a day-to-day basis. A urine color (UC) scale recently has been validated for hydration monitoring in pregnant and breastfeeding women., Summary: We sought to develop a version of a tool based on the UC scale, using only images or illustrations, which could be understood by users of various nationalities and spoken languages. Pregnant and breastfeeding women (n = 1,275) from Brazil, Mexico, and Poland were shown 3 versions of the tool. Understanding, appreciation, simplicity and intent to use were evaluated using a questionnaire consisting of 26 items. Key Messages: Among the 3 versions tested, one tool emerged as the most highly understood (88% spontaneous understanding) and was highly appreciated by users (mean [SD]: 8.40 [2.20] out of 10). There were no differences between countries. Furthermore, 83% reported being very likely to use the tool daily. These results suggest that a simple tool based on the UC scale will help pregnant and breastfeeding women meet the AI for total water., (© 2017 The Author(s) Published by S. Karger AG, Basel.)

Suboptimal fluid intake may require enhanced release of antidiuretic hormone (ADH) or vasopressin for the maintenance of adequate hydration. Enhanced copeptin levels (reflecting enhanced vasopressin levels) in 25% of the common population are associated with enhanced risk of metabolic syndrome with abdominal obesity, type 2 diabetes, hypertension, coronary artery disease, heart failure, vascular dementia, cognitive impairment, microalbuminuria, chronic kidney disease, inflammatory bowel disease, cancer, and premature mortality. Vasopressin stimulates the release of glucocorticoids which in turn up-regulate the serum- and glucocorticoid-inducible kinase 1 (SGK1). Moreover, dehydration upregulates the transcription factor NFAT5, which in turn stimulates SGK1 expression. SGK1 is activated by insulin, growth factors and oxidative stress via phosphatidylinositide-3-kinase, 3-phosphoinositide-dependent kinase PDK1 and mTOR. SGK1 is a powerful stimulator of Na+/K+-ATPase, carriers (e.g. the Na+,K+,2Cl- cotransporter NKCC, the NaCl cotransporter NCC, the Na+/H+ exchanger NHE3, and the Na+ coupled glucose transporter SGLT1), and ion channels (e.g. the epithelial Na+ channel ENaC, the Ca2+ release activated Ca2+ channel Orai1 with its stimulator STIM1, and diverse K+ channels). SGK1 further participates in the regulation of the transcription factors nuclear factor kappa-B NFκB, p53, cAMP responsive element binding protein (CREB), activator protein-1, and forkhead transcription factor FKHR-L1 (FOXO3a). Enhanced SGK1 activity fosters the development of hypertension, obesity, diabetes, thrombosis, stroke, inflammation including inflammatory bowel disease and autoimmune disease, cardiac fibrosis, proteinuria, renal failure as well as tumor growth. The present brief review makes the case that suboptimal fluid intake in the common population may enhance vasopressin and glucocorticoid levels thus up-regulating SGK1 expression and favouring the development of SGK1 related pathologies., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Background/objectives: Urinary biomarkers of hydration (urine osmolality, UOsm; urine specific gravity, USG) follow circadian variations. For individuals, researchers and health-care professionals, there is value in identifying time frames during which spot values of UOsm and USG are representative of 24-h values in healthy young adults., Subjects/methods: Eighty-two free-living adults (22.3±2.9 years, 22.2±1.5 kg/m(2)) collected individual urine voids over a 24-h period. UOsm and USG were measured on each void and on the pooled 24-h sample. To determine the time of day when a spot sample was likely to be equivalent to the 24-h value, daytime voids were binned by time and equivalence was tested for each 2-h window. Equivalence was a priori defined as being within 100 mOsm/kg (UOsm) and within 0.003 units (USG) of 24-h values., Results: For both UOsm and USG, voids between 1400 and 2000 hours produced values that were equivalent to the 24-h sample, whereas earlier voids tended to overestimate 24-h UOsm and USG. For windows 1401-1600 hours, 1601-1800 hours and 1801-2000 hours, the mean difference (95% confidence interval) between spot and 24-h UOsm (mOsm/kg) was -25 (-72; 22), 28 (-35; 92) and 12 (-41; 66), respectively, whereas for USG the difference was 0.0014 (-0.0028; -0.0001), 0.0001 (-0.0017; 0.0019) and 0.0005 (-0.0018; 0.0009), respectively., Conclusions: In free-living healthy French adults, 24-h urine concentration can be approximated from a mid- to late-afternoon spot urine sample. This finding suggests that an afternoon sample may be an accurate and practical tool for hydration monitoring, useful to individuals and health-care practitioners.

Background: Ingestion of water has been associated with general wellbeing. When water intake is insufficient, symptoms such as thirst, fatigue and impaired memory result. Currently there are no instruments to assess water consumption associated with wellbeing. The objective of our study was to develop and validate such an instrument in urban, low socioeconomic, adult Mexican population., Methods: To construct the Water Ingestion-Related Wellbeing Instrument (WIRWI), a qualitative study in which wellbeing related to everyday practices and experiences in water consumption were investigated. To validate the WIRWI a formal, five-process procedure was used. Face and content validation were addressed, consistency was assessed by exploratory and confirmatory psychometric factor analyses, repeatability, reproducibility and concurrent validity were assessed by conducting correlation tests with other measures of wellbeing such as a quality of life instrument, the SF-36, and objective parameters such as urine osmolality, 24-hour urine total volume and others., Results: The final WIRWI is composed of 17 items assessing physical and mental dimensions. Items were selected based on their content and face validity. Exploratory and confirmatory factor analyses yielded Cronbach's alpha of 0.87 and 0.86, respectively. The final confirmatory factor analysis demonstrated that the model estimates were satisfactory for the constructs. Statistically significant correlations with the SF-36, total liquid consumption and simple water consumption were observed., Conclusion: The resulting WIRWI is a reliable tool for assessing wellbeing associated with consumption of plain water in Mexican adults and could be useful for similar groups.

Lactobacillus rhamnosus is a diverse Gram-positive species with strains isolated from different ecological niches. Here, we report the genome sequence analysis of 40 diverse strains of L. rhamnosus and their genomic comparison, with a focus on the variable genome. Genomic comparison of 40 L. rhamnosus strains discriminated the conserved genes (core genome) and regions of plasticity involving frequent rearrangements and horizontal transfer (variome). The L. rhamnosus core genome encompasses 2,164 genes, out of 4,711 genes in total (the pan-genome). The accessory genome is dominated by genes encoding carbohydrate transport and metabolism, extracellular polysaccharides (EPS) biosynthesis, bacteriocin production, pili production, the cas system, and the associated clustered regularly interspaced short palindromic repeat (CRISPR) loci, and more than 100 transporter functions and mobile genetic elements like phages, plasmid genes, and transposons. A clade distribution based on amino acid differences between core (shared) proteins matched with the clade distribution obtained from the presence-absence of variable genes. The phylogenetic and variome tree overlap indicated that frequent events of gene acquisition and loss dominated the evolutionary segregation of the strains within this species, which is paralleled by evolutionary diversification of core gene functions. The CRISPR-Cas system could have contributed to this evolutionary segregation. Lactobacillus rhamnosus strains contain the genetic and metabolic machinery with strain-specific gene functions required to adapt to a large range of environments. A remarkable congruency of the evolutionary relatedness of the strains' core and variome functions, possibly favoring interspecies genetic exchanges, underlines the importance of gene-acquisition and loss within the L. rhamnosus strain diversification., (© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Aim: Urine color (UC) is a practical tool for hydration assessment. The technique has been validated in adults, but has not been tested in children., Purpose: The purpose of the study was to test the validity of the urine color scale in young, healthy boys and girls, as a marker of urine concentration, investigate its diagnostic ability of detecting hypohydration and examine the ability of children to self-assess UC., Methods: A total of 210 children participated (age: 8-14 years, body mass: 43.4 ± 12.6 kg, height: 1.49 ± 0.13 m, body fat: 25.2 ± 7.8 %). Data collection included: two single urine samples (first morning and before lunch) and 24-h sampling. Hydration status was assessed via urine osmolality (UOsmo) and UC via the eight-point color scale., Results: Mean UC was 3 ± 1 and UOsmo 686 ± 223 mmol kg(-1). UC displayed a positive relationship as a predictor of UOsmo (R (2): 0.45, P < 0.001). Based on the receiver operating curve, UC has good overall classification ability for the three samples (area under the curve 85-92 %), with good sensitivity (92-98 %) and specificity (55-68 %) for detecting hypohydration. The overall accuracy of the self-assessment of UC in the morning or the noon samples ranged from 67 to 78 %. Further threshold analysis indicated that the optimal self-assessed UC threshold for hypohydration was ≥4., Conclusions: The classical eight-point urine color scale is a valid method to assess hydration in children of age 8-14 years, either by researchers or self-assessment.

Scope: The ability of different plant sterols/stanols (PS) mixtures, which differed in the degree of B-ring saturation and aliphatic side chain structure and saturation, to reduce cholesterol (CH) micellarization was explored., Methods and Results: Experiments were performed using an in vitro digestion model, synthetic mixed micelles, and pure porcine pancreatic lipases. Sterols were measured by GC-FID. The ability of PS to reduce CH micellarization was dependent on the form of PS and on the type of delivery matrix (low-fat yogurt or olive oil). Long-chain PS esters delivered in the yogurt matrix, and medium chain PS esters delivered in olive oil provided the greatest reduction in CH micellarization. In yogurt, the ability to impair CH micellarization was inversely related (rho = -0.41, p < 0.0005) to PS melting point. In olive oil, the more hydrophobic PS mixtures, i.e. those rich in long-chain PS esters, had the lower ability to impair CH micellarization., Conclusions: Different forms of PS have a different ability to impair CH micellarization. This ability depends on the transfer efficiency of PS from the food matrix to the micelle, which in turn depends on the melting point and the hydrophobicity of PS and on the delivery food matrix., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In the last decade, cross-sectional and multiple cohort studies have associated total fluid intake or water intake with the risk for chronic kidney disease (CKD) and even the risk of developing hyperglycemia. Urine biomarkers have also been linked to the risk of CKD and lithiasis, and these biomarkers respond quickly to variations in fluid intake. High circulating copeptin levels, a surrogate marker of arginine vasopressin, have been associated with metabolic syndrome, renal dysfunction and increased risk for diabetes mellitus, cardiovascular disease and death. The aim of this paper was to explore how the various findings on water intake, hydration and health are interconnected, to highlight current gaps in our understanding and to propose a model that links water intake, homeostatic mechanisms to maintain water balance and health outcomes. Since plasma copeptin and vasopressin have been demonstrated to be sensitive to changes in water intake, inversely associated with 24-hour urine volume, and associated with urine biomarkers and fluid intake, vasopressin is proposed as the central player in this theoretical physiological model., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Purpose: To describe the intake of water and all other beverages in children and adolescents in 13 countries of three continents., Methods: Data of 3611 children (4-9 years) and 8109 adolescents (10-17 years) were retrieved from 13 cross-sectional surveys (47 % males). In three countries, stratified cluster sampling design was applied to randomly recruit schools classes. A quota method was applied in the other countries to randomly recruit participants. Details on the intake of all fluid types were obtained with a fluid-specific record over 7 consecutive days., Results: In the total sample, the highest mean intakes were observed for water (738 ± 567 mL/day), followed by milk (212 ± 209 mL/day), regular soft beverages (RSB) (168 ± 290 mL/day) and juices (128 ± 228 mL/day). Patterns characterized by a high contribution of water, RSB or hot beverages to total fluid intake were identified among the countries with close geographical location. Adolescents had a significantly lower milk intake and higher intake of RSB and hot beverages than children in most countries. The most consistent gender difference observed was that in both age groups males reported a significantly higher RSB consumption than females., Conclusion: On average, water was the fluid consumed in the largest volume by children and adolescents, but the intake of the different fluid types varied substantially between countries. Since the RSB intake was as large, or even larger, than water intake in some countries, undertaking actions to improve fluid intake habits of children and adolescents are warranted.

Purpose: To describe the intake of water and all other fluids and to evaluate the proportion of adults exceeding the World Health Organisation (WHO) recommendations on energy intake from free sugar, solely from fluids., Methods: A total of 16,276 adults (46 % men, mean age 39.8 years) were recruited in 13 countries from 3 continents. A 24-h fluid-specific record over 7 days was used for fluid assessment., Results: In Spain, France, Turkey, Iran, Indonesia and China, fluid intake was characterised by a high contribution of water (47-78 %) to total fluid intake (TFI), with a mean water intake between 0.76 and 1.78 L/day, and a mean energy intake from fluids from 182 to 428 kcal/day. Between 11 and 49 % of adults exceeded the free sugar WHO recommendations, considering solely fluids. In Germany, UK, Poland and Japan, the largest contributors to TFI were hot beverages (28-50 %) and water (18-32 %). Mean energy intake from fluids ranged from 415 to 817 kcal/day, and 48-62 % of adults exceeded free sugar WHO recommendations. In Mexico, Brazil and Argentina, the contribution of juices and regular sugar beverages (28-41 %) was as important as the water contribution to TFI (17-39 %). Mean energy intake from fluids ranged 565-694 kcal/day, and 60-66 % of the adults exceeded the free sugar WHO recommendation., Conclusions: The highest volumes recorded in most of the countries were for water, mean energy intake from fluids was up to 694 kcal/day, and 66 % of adults exceeded the free sugar WHO recommendation solely by fluids. Actions to create an environment in favour of water consumption and reduce sugar intake from fluids therefore are warranted.

Background: Data on the characteristics of consumers of phytosterol-enriched products and modalities of consumption are rare. An observational study evaluating the lifestyle characteristics and cardiovascular risk (CVR) profile of phytosterol-enriched yogurt consumers was performed in France., Methods: Subjects were recruited from general practitioners via electronic medical records. Data were obtained from 358 consumers and 422 nonconsumers with 519 subject questionnaires (243 consumers, 276 nonconsumers; 67% response)., Results: Consumers had more cardiovascular risk factors than nonconsumers (2.0 ± 1.5 versus 1.6 ± 1.4; P < 0.001) and a higher 10-year SCORE cardiovascular risk (1.8 ± 2.0% versus 1.6 ± 2.2%; P = 0.008); they were older (P = 0.030) and had a higher incidence of hypercholesterolaemia (P < 0.001) and family or personal history of heart disease (P = 0.023/P = 0.026, respectively). Among consumers not on cholesterol-lowering medication, 99% were eligible for lifestyle interventions and 56% were eligible for lipid-lowering drug according to European guidelines. Consumers had a healthier lifestyle, with a higher (fruit/vegetable - saturated fatty acid) score than nonconsumers (P = 0.035), focused more on low-intensity leisure activity (P = 0.023), spent more time travelling by foot or bicycle (P = 0.012) and were more likely to act to reduce CVR. Phytosterol-enriched yogurt intake conformed to recommendations in two-thirds of consumers and was mainly consumed because of concerns over cholesterol levels and CVR., Conclusions: The higher cardiovascular disease risk profile of phytosterol-enriched yogurt consumers corresponds to a population for whom European guidelines recommend lifestyle changes to manage cholesterol. The coherence of the data in terms of risk factors, adherence to lifestyle recommendations and the consumption of phytosterol-enriched yogurt conforming to recommendations reflects a health-conscious consumer population., (© 2014 The British Dietetic Association Ltd.)

Raising children's awareness about their hydration status could be done through a noninvasive biomarker. Urine color (UC) has been validated as a biomarker of hydration in adults and children aged 8-14 years. The aim of this survey was to design and to evaluate the level of understanding and attractiveness of a self-assessment, UC-based hydration tool for children aged 6-11 years. The first phase of the survey consisted of face-to-face interviews during which 84 children identified those graphical elements necessary to understand the hydration message from 6 illustration-based designs containing the UC chart. The graphic elements selected were the basis to create 3 new designs. During the 2nd phase, the level of understanding and attractiveness of these 3 new designs was then evaluated via an online questionnaire by a total of 1,231 children in 3 countries. The design with the highest level of understanding was totally or partially understood by 76% of the participants, independent of age and gender. The levels of understanding, however, differed in the countries. In Indonesia, the levels of understanding of the 3 designs were comparable; whereas in both France (74%) and Mexico (78%), significantly more participants totally and partially understood one of the 3 designs. The levels of attractiveness of the 3 designs were comparable, independent of country, age, and gender. On average, 80% of all participants liked the 3 designs a bit or a lot. Only 14% did not like the designs, and 5% of participants had no opinion regarding attractiveness. These results indicated that three out of four children like and understand the correct hydration message from a strictly illustration-based tool containing the eight-point UC scale., (© 2015 S. Karger AG, Basel.)

Structural disruption of gut microbiota and associated inflammation are considered important etiological factors in high fat diet (HFD)-induced metabolic syndrome (MS). Three candidate probiotic strains, Lactobacillus paracasei CNCM I-4270 (LC), L. rhamnosus I-3690 (LR) and Bifidobacterium animalis subsp. lactis I-2494 (BA), were individually administered to HFD-fed mice (10(8) cells day(-1)) for 12 weeks. Each strain attenuated weight gain and macrophage infiltration into epididymal adipose tissue and markedly improved glucose-insulin homeostasis and hepatic steatosis. Weighted UniFrac principal coordinate analysis based on 454 pyrosequencing of fecal bacterial 16S rRNA genes showed that the probiotic strains shifted the overall structure of the HFD-disrupted gut microbiota toward that of lean mice fed a normal (chow) diet. Redundancy analysis revealed that abundances of 83 operational taxonomic units (OTUs) were altered by probiotics. Forty-nine altered OTUs were significantly correlated with one or more host MS parameters and were designated 'functionally relevant phylotypes'. Thirteen of the 15 functionally relevant OTUs that were negatively correlated with MS phenotypes were promoted, and 26 of the 34 functionally relevant OTUs that were positively correlated with MS were reduced by at least one of the probiotics, but each strain changed a distinct set of functionally relevant OTUs. LC and LR increased cecal acetate but did not affect circulating lipopolysaccharide-binding protein; in contrast, BA did not increase acetate but significantly decreased adipose and hepatic tumor necrosis factor-α gene expression. These results suggest that Lactobacillus and Bifidobacterium differentially attenuate obesity comorbidities in part through strain-specific impacts on MS-associated phylotypes of gut microbiota in mice.

Background: A carbon footprint is the sum of greenhouse gas emissions (GHGEs) associated with food production, processing, transporting, and retailing., Objective: We examined the relation between the energy and nutrient content of foods and associated GHGEs as expressed as g CO2 equivalents., Design: GHGE values, which were calculated and provided by a French supermarket chain, were merged with the Composition Nutritionnelle des Aliments (French food-composition table) nutrient-composition data for 483 foods and beverages from the French Agency for Food, Environmental and Occupational Health and Safety. Foods were aggregated into 34 food categories and 5 major food groups as follows: meat and meat products, milk and dairy products, frozen and processed fruit and vegetables, grains, and sweets. Energy density was expressed as kcal/100 g. Nutrient density was determined by using 2 alternative nutrient-density scores, each based on the sum of the percentage of daily values for 6 or 15 nutrients, respectively. The energy and nutrient densities of foods were linked to log-transformed GHGE values expressed per 100 g or 100 kcal., Results: Grains and sweets had lowest GHGEs (per 100 g and 100 kcal) but had high energy density and a low nutrient content. The more-nutrient-dense animal products, including meat and dairy, had higher GHGE values per 100 g but much lower values per 100 kcal. In general, a higher nutrient density of foods was associated with higher GHGEs per 100 kcal, although the slopes of fitted lines varied for meat and dairy compared with fats and sweets., Conclusions: Considerations of the environmental impact of foods need to be linked to concerns about nutrient density and health. The point at which the higher carbon footprint of some nutrient-dense foods is offset by their higher nutritional value is a priority area for additional research., (© 2015 American Society for Nutrition.)

Our aim was to compare and combine 3 nutritional strategies to slow down the age-related loss of muscle mass in healthy old rats: 1) increase protein intake, which is likely to stimulate muscle protein anabolism; 2) use leucine rich, rapidly digested whey proteins as protein source (whey proteins are recognized as the most effective proteins to stimulate muscle protein anabolism). 3) Supplement animals with a mixture of chamomile extract, vitamin E, vitamin D (reducing inflammation and oxidative stress is also effective to improve muscle anabolism). Such comparisons and combinations were never tested before. Nutritional groups were: casein 12% protein, whey 12% protein, whey 18% protein and each of these groups were supplemented or not with polyphenols/antioxidants. During 6 months, we followed changes of weight, food intake, inflammation (plasma fibrinogen and alpha-2-macroglobulin) and body composition (DXA). After 6 months, we measured muscle mass, in vivo and ex-vivo fed and post-absorptive muscle protein synthesis, ex-vivo muscle proteolysis, and oxidative stress parameters (liver and muscle glutathione, SOD and total antioxidant activities, muscle carbonyls and TBARS). We showed that although micronutrient supplementation reduced inflammation and oxidative stress, the only factor that significantly reduced the loss of lean body mass was the increase in whey protein intake, with no detectable effect on muscle protein synthesis, and a tendency to reduce muscle proteolysis. We conclude that in healthy rats, increasing protein intake is an effective way to delay sarcopenia.

Background: Oral administration of oxygenated water has been shown to improve blood oxygenation and could be an alternate way for oxygen (O2) supply. In this experiment, tissue oxygenation was compared in anesthetized pigs receiving a placebo or water enriched in O2 by injection or a new electrolytic process., Methods: Forty-two pigs randomized in three groups received either mineral water as placebo or water enriched in O2 by injection or the electrolytic process (10 mL/kg in the stomach). Hemodynamic parameters, partial pressure of oxygen in the arterial blood (PaO2), skin blood flow, and tissue oxygenation (transcutaneous oxygen pressure, or TcPO2) were monitored during 90 minutes of general anesthesia. Absorption and tissue distribution of the three waters administered were assessed using dilution of deuterium oxide., Results: Mean arterial pressure, heart rate, PaO2, arteriovenous oxygen difference, and water absorption from the gut were not significantly different among the three groups. The deuterium to protium ratio was also similar in the plasma, skin, and muscle at the end of the protocol. Skin blood flow decreased in the three groups. TcPO2 slowly decreased over the last 60 minutes of the experiment in the three groups, but when compared to the control group, the values remained significantly higher in animals that received the water enriched in O2 by electrolysis., Conclusions: In this protocol, water enriched in O2 by electrolysis lessened the decline of peripheral tissue oxygenation. This observation is compatible with the claim that the electrolytic process generates water clathrates which trap O2 and facilitate O2 diffusion along pressure gradients. Potential applications of O2-enriched water include an alternate method of oxygen supply.

Dysregulated immune responses to gut microbes are central to inflammatory bowel disease (IBD), and gut microbial activity can fuel chronic inflammation. Examining how IBD-directed therapies influence gut microbiomes may identify microbial community features integral to mitigating disease and maintaining health. However, IBD patients often receive multiple treatments during disease flares, confounding such analyses. Preclinical models of IBD with well-defined disease courses and opportunities for controlled treatment exposures provide a valuable solution. Here, we surveyed the gut microbiome of the T-bet(-/-) Rag2(-/-) mouse model of colitis during active disease and treatment-induced remission. Microbial features modified among these conditions included altered potential for carbohydrate and energy metabolism and bacterial pathogenesis, specifically cell motility and signal transduction pathways. We also observed an increased capacity for xenobiotics metabolism, including benzoate degradation, a pathway linking host adrenergic stress with enhanced bacterial virulence, and found decreased levels of fecal dopamine in active colitis. When transferred to gnotobiotic mice, gut microbiomes from mice with active disease versus treatment-induced remission elicited varying degrees of colitis. Thus, our study provides insight into specific microbial clades and pathways associated with health, active disease and treatment interventions in a mouse model of colitis.