Refeeding syndrome and psychopharmacological interventions in children and adolescents with Anorexia Nervosa: a focus on olanzapine-related modifications of electrolyte balance.

This study aims to investigate the potential correlation between the use of olanzapine, a psychopharmacological intervention commonly prescribed in Anorexia Nervosa treatment, and the occurrence of Refeeding Syndrome. Despite the acknowledged nutritional and biochemical impacts of olanzapine, the literature lacks information regarding its specific association with Refeeding Syndrome onset in individuals with Anorexia Nervosa. This is a naturalistic, retrospective, observational study, reporting the occurrence of Refeeding Syndrome in children and adolescents with Anorexia Nervosa, treated or untreated with olanzapine. Dosages and serum levels of olanzapine were assessed for potential associations with the occurrence of Refeeding Syndrome and specific variations in Refeeding Syndrome-related electrolytes. Overall, 113 patients were enrolled, including 46 (41%) who developed a Refeeding Syndrome. Mild (87%), moderate (6.5%), and severe (6.5%) Refeeding Syndrome was described, at a current average intake of 1378 ± 289 kcal/day (39 ± 7.7 kcal/kg/die), frequently associated with nasogastric tube (39%) or parenteral (2.2%) nutrition. Individuals receiving olanzapine experienced a more positive phosphorus balance than those who did not (F(1,110) = 4.835, p = 0.030), but no difference in the occurrence of Refeeding Syndrome was documented. The mean prescribed doses and serum concentrations of olanzapine were comparable between Refeeding Syndrome and no-Refeeding Syndrome patients.    Conclusion: The present paper describes the occurrence of Refeeding Syndrome and its association with olanzapine prescriptions in children and adolescents with Anorexia Nervosa. Olanzapine was associated with a more positive phosphorus balance, but not with a different occurrence of Refeeding Syndrome. Further, longitudinal studies are required. What is Known: • Refeeding Syndrome (RS) is a critical complication during refeeding in malnourished patients, marked by electrolyte (phosphorus, magnesium, potassium) imbalances. • Olanzapine, an atypical antipsychotic with nutritional and biochemical impacts, is used in Anorexia Nervosa (AN) treatment, however data concerning its association with RS are lacking. What is New: • The study observed RS in 46/113 (41%) young patients with AN. • Olanzapine-treated individuals showed a higher improvement in serum phosphate levels than untreated ones, although no impact on the occurrence of Refeeding Syndrome was observed.

The effects of a sugar-free amino acid-containing electrolyte beverage on 5-kilometer performance, blood electrolytes, and post-exercise cramping versus a conventional carbohydrate-electrolyte sports beverage and water.

OBJECTIVE: The purpose of this study was to examine the acute effects of a multi-ingredient, low calorie dietary supplement (MIDS, XTEND® Healthy Hydration) on 5-kilometer (5-km) time trial performance and blood electrolyte concentrations compared to a carbohydrate-electrolyte beverage (CE, GATORADE® Thirst Quencher) and distilled water (W). METHODS: During visit 1 (V1), participants (10 men and 10 women, 20-35 years old, BMI ≤ 29 kg/m2, recreationally active) reported to the laboratory whereby the following tests were performed: i) height and weight measurements, ii) body composition analysis, iii) treadmill testing to measure maximal aerobic capacity, and iv) 5-km time trial familiarization. The second visit (V2) was one week after V1 in the morning (0600 - 0900) and participants arrived 12-14 h fasted (no food or drink). The first battery of assessments (V2-T1) included nude body mass, urine specific gravity (USG), a profile of mood states (POMS) questionnaire, and the completion of a visual analogue scale (VAS) questionnaire to quantify cramping. Then heart rate (HR), blood pressure (BP), total body hydration (via bioelectrical impedance spectroscopy [BIS]) were examined. Finally, a measurement of blood markers via finger stick was performed. Participants consumed a randomized beverage (16 fl. oz. of MIDS, 16 fl. oz. of W, or 16 fl. oz. of CE) within 3 min followed by a 45-min rest. Following the rest period, a second battery (V2-T2) was performed whereby participants' USG was assessed and they completed the POMS and VAS questionnaires, and HR, BP, and blood markers were measured. The participants then performed a 5-km treadmill time trial. Immediately following the 5-km time trial, participants completed a third testing battery (V2-T3) that began with blood markers, HR and BP assessments, followed by nude body weight assessment, and the POMS and VAS questionnaires. After 60 min, a fourth battery (V2-T4) was performed that included HR, BP, and blood markers. After sitting quietly for another 60 min a fifth battery assessment was performed (V2-T5) that included participants' USG, POMS and VAS questionnaires, HR, BP, blood markers, and total body hydration. Visits 3 (V3) and 4 (V4) followed the same protocol except a different randomized drink (16 oz. of CE, MIDS, or W) was consumed; all of which were separated by approximately one week. RESULTS: No differences occurred between conditions for 5-km time trial completion, indirect calorimetry outcomes during 5-km time trials, USG, or nude mass measurements (p > 0.05 for all relevant statistical tests). However, blood potassium and the sodium/potassium ratio displayed significant interactions (p < 0.05), and post hoc testing indicated these values were better maintained in the MIDS versus other conditions. Post-exercise cramp prevalence was greater in the CE (p < 0.05) and trended higher with W (p = 0.083) compared to the MIDS condition. Post-exercise cramp severity was also elevated with the W and CE beverages (p < 0.05) but not the MIDS (p = 0.211). CONCLUSIONS: The MIDS did not affect 5-km time trial performance but exhibited favorable effects on blood electrolyte and post-exercise self-reporting cramp outcomes compared to the CE and W drinks.

The effects of betaine supplementation on fluid balance and heat tolerance during passive heat stress in men.

INTRODUCTION: Consuming intracellular osmolytes, like betaine (BET), may attenuate symptoms of heat stress. The purpose of this study was to examine the effects of BET supplementation on fluid balance and heat tolerance after a 7-day loading period and during passive heat exposure. METHODS: A double-blind, placebo controlled, crossover study compared BET or placebo consumption (50 mg·kg-1 , twice daily) for 7 days in young, recreationally active men (N = 11). RESULTS: During the loading period, no significant interactions were found for any marker of fluid balance between or within conditions. During heat exposure, significant time effects but no condition x time interactions, were found for plasma characteristics (i.e., volume, osmolality, sodium, albumin, and total protein). Plasma volume was significantly increased by min 30 in both conditions (PLA: +6.9. ± 5.0%, BET: +10.2 ± 7.4%) and remained elevated for the remainder of the experimental trial, but was not significantly different between conditions. After 60 min of passive heat exposure, both conditions experienced a similar increase in core temperature (PLA: +0.32 ± 0.22°C, BET: +0.31 ± 0.21°C; p = 0.912). CONCLUSIONS: Supplemental BET did not improve markers of fluid balance or heat tolerance during 7 days of loading or during passive heat exposure.

Effect of fluid replacement with green tea on body fluid balance and renal responses under mild thermal hypohydration: a randomized crossover study.

PURPOSE: Maintaining an appropriate hydration level by ingesting fluid in a hot environment is a measure to prevent heat-related illness. Caffeine-containing beverages, including green tea (GT), have been avoided as inappropriate rehydration beverages to prevent heat-related illness because caffeine has been assumed to exert diuretic/natriuretic action. However, the influence of caffeine intake on urine output in dehydrated individuals is not well documented. The aim of the present study was to examine the effect of fluid replacement with GT on body fluid balance and renal water and electrolyte handling in mildly dehydrated individuals. METHODS: Subjects were dehydrated by performing three bouts of stepping exercise for 20 min separated by 10 min of rest. They were asked to ingest an amount of water (H2O), GT, or caffeinated H2O (20 mg/100 ml; Caf-H2O) that was equal to the volume of fluid loss during the dehydration protocol; fluid balance was measured for 2 h after fluid ingestion. RESULTS: The dehydration protocol induced hypohydration by ~ 10 g/kg body weight (~ 1% of body weight). Fluid balance 2 h after fluid ingestion was significantly less negative in all trials, and the fluid retention ratio was 52.2 ± 4.2% with H2O, 51.0 ± 5.0% with GT, and 47.9 ± 6.2% with Caf-H2O; those values did not differ among the trials. After rehydration, urine output, urine osmolality, and urinary excretions of osmotically active substances, sodium, potassium and chloride were not different among the trials. CONCLUSION: The data indicate that ingestion of GT or an equivalent caffeine amount does not worsen the hydration level 2 h after ingestion and can be effective in reducing the negative fluid balance for acute recovery from mild hypohydration. TRIAL REGISTRATION: ISRCTN53057185; retrospectively registered.

Dopamine subsystems that track internal states.

Food and water are rewarding in part because they satisfy our internal needs1,2. Dopaminergic neurons in the ventral tegmental area (VTA) are activated by gustatory rewards3-5, but how animals learn to associate these oral cues with the delayed physiological effects of ingestion is unknown. Here we show that individual dopaminergic neurons in the VTA respond to detection of nutrients or water at specific stages of ingestion. A major subset of dopaminergic neurons tracks changes in systemic hydration that occur tens of minutes after thirsty mice drink water, whereas different dopaminergic neurons respond to nutrients in the gastrointestinal tract. We show that information about fluid balance is transmitted to the VTA by a hypothalamic pathway and then re-routed to downstream circuits that track the oral, gastrointestinal and post-absorptive stages of ingestion. To investigate the function of these signals, we used a paradigm in which a fluid's oral and post-absorptive effects can be independently manipulated and temporally separated. We show that mice rapidly learn to prefer one fluid over another based solely on its rehydrating ability and that this post-ingestive learning is prevented if dopaminergic neurons in the VTA are selectively silenced after consumption. These findings reveal that the midbrain dopamine system contains subsystems that track different modalities and stages of ingestion, on timescales from seconds to tens of minutes, and that this information is used to drive learning about the consequences of ingestion.

Fluid and Electrolyte Management in the Neonate: Potassium and Phosphorus.

Maintenance of electrolyte balance in the neonate is challenging in the context of illness or prematurity. Imbalances in potassium and phosphorus can occur in neonates, ranging from benign and clinically insignificant to those that can be life-threatening. An individualized approach to fluid and electrolyte management is based on the neonate's gestational age, day of life, maintenance needs, deficits, and ongoing losses. This article reviews normal and abnormal potassium and phosphorus values along with management strategies. Using a case scenario, the reader can apply concepts outlined in this article to management of critically ill neonates with electrolyte disturbances.

Effects of dietary electrolyte balance on performance, energy balance, and expression of genes related to acid-basic balance, absorption, and transport of nutrients in broilers.

The objective of this study was to evaluate the effect of dietary electrolyte balance (DEB) levels on performance characteristics (feed intake, FI; body weight gain, BWG; and feed efficiency, FE), energy balance (retained energy, RE; metabolizable energy ingested, MEI; heat production, HP; and energy retention efficiency, ERE), and the expression of genes related to acid-base balance, nutrient absorption, and transport in broilers from 1 to 21 days of age. A total of 245 male Cobb chickens were used in a completely randomized design with five DEB levels (110, 175, 240, 305, and 370 mEq/kg) and seven replicates of seven birds each. The inclusion of DEB levels influenced FE; 110 mEq/kg provided the better values for this characteristic both in the pre-initial phase and in the initial phase but was different only concerning 175 mEq/kg (1-7 days) and 240 mEq/kg (1-21 days). Birds that ingested diets with a level of 240 mEq/kg of DEB had a higher MEI and HP. This DEB level caused a lesser and greater expression of the SLC12A2 gene in the liver and the ATP1A1 gene in the intestine, respectively. On the other hand, the ATP1A1 gene was less expressed in the liver and kidney of broilers supplemented with 370 mEq/kg compared to a level of 110 mEq/kg. In general, a level of 110 mEq/kg DEB in the ration seems to be the most suitable for good performance, energy balance, and gene expression of broilers from 1 to 21 days of age.

Hepatocellular carcinoma induces body mass loss in parallel with osmolyte and water retention in rats.

AIMS: The number of cancer survivors with cardiovascular disease is increasing. However, the effect of cancer on body fluid regulation remains to be clarified. In this study, we evaluated body osmolyte and water imbalance in rats with hepatocellular carcinoma. MAIN METHODS: Wistar rats were administered diethylnitrosamine, a carcinogenic drug, to establish liver cancer. We analyzed tissue osmolyte and water content, and their associations with aldosterone secretion. KEY FINDINGS: Hepatocellular carcinoma rats had significantly reduced body mass and the amount of total body sodium, potassium, and water. However, these rats had significantly increased relative tissue sodium, potassium, and water content per tissue dry weight. Furthermore, these changes in sodium and water balance in hepatocellular carcinoma rats were significantly associated with increased 24-h urinary aldosterone excretion. Supplementation with 0.25% salt in drinking water improved body weight reduction associated with sodium and water retention in hepatocellular carcinoma rats, which was suppressed by treatment with spironolactone, a mineralocorticoid receptor antagonist. Additionally, the urea-driven water conservation system was activated in hepatocellular carcinoma rats. SIGNIFICANCE: These findings suggest that hepatocellular carcinoma induces body mass loss in parallel with activation of the water conservation system including aldosterone secretion and urea accumulation to retain osmolyte and water. The osmolyte and water retention at the tissue level may be a causative factor for ascites and edema formation in liver failure rats.

Low variability of plant protein intake in the CKiD cohort does not demonstrate changes in estimated GFR nor electrolyte balance.

BACKGROUND: Vegetable or plant-based sources of protein may confer health benefits in children with progressive kidney disease. Our aims were to understand the effect of the proportion of vegetable protein intake on changes in estimated GFR and to understand the effect of the proportion of vegetable protein intake on serum levels of bicarbonate, phosphorus, and potassium. METHODS: Children with baseline eGFR between 30 and 90 mL/min/1.73 m2 were recruited from 59 centers across North America as part of the chronic kidney disease in children (CKiD) study. The percentage of dietary vegetable protein (VP%) was gathered from annual Food Frequency Questionnaires. We performed longitudinal linear mixed models to determine the effect of VP% on eGFR and longitudinal logistic mixed models to determine the effect of VP% on electrolyte balance (potassium, phosphorus, bicarbonate). RESULTS: Two thousand visits from 631 subjects. Across all dichotomized groups of children (sex, African American race, Hispanic ethnicity, glomerular etiology of CKD, hypertension, anemia, hyperkalemia, hyperphosphatemia, acidosis, BMI < 95th percentile), the median VP% was 32-35%. The longitudinal mixed model analysis did not show any effect of VP% on eGFR electrolyte (bicarbonate, phosphorus, and potassium) abnormalities (p > 0.1). CONCLUSIONS: A diverse cohort of children with CKD has a narrow and homogeneous intake of vegetable protein. Due to the low variability of plant-based protein in the cohort, there were no associations between the percentage of plant protein intake and changes in eGFR nor electrolyte balance. A higher resolution version of the Graphical abstract is available as Supplementary information.

Analysis of performance, bone characteristics, and expression of genes involved in the balance of ionic concentrations in broilers subjected to dietary electrolyte balance levels.

1. Sodium bicarbonate (NaHCO3), potassium carbonate (K2CO3), and ammonium chloride (NH4Cl) are commonly used to correct dietary electrolyte balance (DEB) in birds. However, there are many gaps in the knowledge of their effects when used simultaneously. This study investigated the effect of DEB levels on performance, femur bone characteristics and the expression of genes related to the balance of ionic concentrations in broilers at 21 days of age.2. Male Cobb broiler chickens (n = 245), aged 1-21 d, were divided into groups based on a completely randomised design with five DEB levels (110 mEq/kg, 175 mEq/kg, 240 mEq/kg, 305 mEq/kg, and 370 mEq/kg).3. The performance characteristics measured included body weight (BW), body weight gain (BWG), feed intake (FI), feed conversion (FCR) and body weight birds slaughtered (BWS).4. The bone variables assessed in the femur were weight (WE), relative bone weight (RBWE), length (L), width (WI), maximum load supported (MLS), bone-breaking resistance (BR), and Seedor index (SI). In addition, the expression of CHP1, SLC9A1, and SLC24A3 in the livers, intestines and kidneys of birds was evaluated.5. The DEB level of 370 mEq/kg, at Na+ content of 0.48%, resulted in the highest averages for L, MLS, and BR of the femur. This DEB level increased the expression of SLC9A1 in the liver and SLC24A3 in the intestine. A 240 mEq/kg DEB level decreased the expression of CHP1 in the liver, while supplementation with 110 mEq/kg increased the expression of SLC24A3 in the kidney.6. In conclusion, 370 mEq/kg DEB improved FCR and increased the mean bone characteristics of the femur (L, MLS, and BR) and the expression of SLC9A1 and SLC24A3 in the liver and intestine, respectively. These findings should be considered in future assessments of the effects of DEB levels on broilers.

Apelin and Vasopressin: The Yin and Yang of Water Balance.

Apelin, a (neuro)vasoactive peptide, plays a prominent role in controlling body fluid homeostasis and cardiovascular functions. Experimental data performed in rodents have shown that apelin has an aquaretic effect via its central and renal actions. In the brain, apelin inhibits the phasic electrical activity of vasopressinergic neurons and the release of vasopressin from the posterior pituitary into the bloodstream and in the kidney, apelin regulates renal microcirculation and counteracts in the collecting duct, the antidiuretic effect of vasopressin occurring via the vasopressin receptor type 2. In humans and rodents, if plasma osmolality is increased by hypertonic saline infusion/water deprivation or decreased by water loading, plasma vasopressin and apelin are conversely regulated to maintain body fluid homeostasis. In patients with the syndrome of inappropriate antidiuresis, in which vasopressin hypersecretion leads to hyponatremia, the balance between apelin and vasopressin is significantly altered. In order to re-establish the correct balance, a metabolically stable apelin-17 analog, LIT01-196, was developed, to overcome the problem of the very short half-life (in the minute range) of apelin in vivo. In a rat experimental model of vasopressin-induced hyponatremia, subcutaneously (s.c.) administered LIT01-196 blocks the antidiuretic effect of vasopressin and the vasopressin-induced increase in urinary osmolality, and induces a progressive improvement in hyponatremia, suggesting that apelin receptor activation constitutes an original approach for hyponatremia treatment.

Molecular Basis, Diagnostic Challenges and Therapeutic Approaches of Bartter and Gitelman Syndromes: A Primer for Clinicians.

Gitelman and Bartter syndromes are rare inherited diseases that belong to the category of renal tubulopathies. The genes associated with these pathologies encode electrolyte transport proteins located in the nephron, particularly in the Distal Convoluted Tubule and Ascending Loop of Henle. Therefore, both syndromes are characterized by alterations in the secretion and reabsorption processes that occur in these regions. Patients suffer from deficiencies in the concentration of electrolytes in the blood and urine, which leads to different systemic consequences related to these salt-wasting processes. The main clinical features of both syndromes are hypokalemia, hypochloremia, metabolic alkalosis, hyperreninemia and hyperaldosteronism. Despite having a different molecular etiology, Gitelman and Bartter syndromes share a relevant number of clinical symptoms, and they have similar therapeutic approaches. The main basis of their treatment consists of electrolytes supplements accompanied by dietary changes. Specifically for Bartter syndrome, the use of non-steroidal anti-inflammatory drugs is also strongly supported. This review aims to address the latest diagnostic challenges and therapeutic approaches, as well as relevant recent research on the biology of the proteins involved in disease. Finally, we highlight several objectives to continue advancing in the characterization of both etiologies.

Neural basis for regulation of vasopressin secretion by anticipated disturbances in osmolality.

Water balance, tracked by extracellular osmolality, is regulated by feedback and feedforward mechanisms. Feedback regulation is reactive, occurring as deviations in osmolality are detected. Feedforward or presystemic regulation is proactive, occurring when disturbances in osmolality are anticipated. Vasopressin (AVP) is a key hormone regulating water balance and is released during hyperosmolality to limit renal water excretion. AVP neurons are under feedback and feedforward regulation. Not only do they respond to disturbances in blood osmolality, but they are also rapidly suppressed and stimulated, respectively, by drinking and eating, which will ultimately decrease and increase osmolality. Here, we demonstrate that AVP neuron activity is regulated by multiple anatomically and functionally distinct neural circuits. Notably, presystemic regulation during drinking and eating are mediated by non-overlapping circuits that involve the lamina terminalis and hypothalamic arcuate nucleus, respectively. These findings reveal neural mechanisms that support differential regulation of AVP release by diverse behavioral and physiological stimuli.

Fine-tuning the amount of water present in the body at any given time is a tight balancing act. The hormone vasopressin helps to ensure that organisms do not get too dehydrated by allowing water in the urine to be reabsorbed into the bloodstream. A group of vasopressin neurons in the brain trigger the release of the hormone if water levels get too low (as reflected by an increase in osmolality, the level of substances dissolved in a unit of blood). However, these cells also receive additional information that allows them to predict and respond to upcoming changes in water levels. For example, drinking water while dehydrated 'switches off' the neurons, even before osmolality is restored in the blood to normal levels. Eating, on the other hand, rapidly activates vasopressin neurons before the food is digested and blood osmolality increases as a result. How vasopressin neurons receive this 'anticipatory' information remains unclear. Kim et al. explored this question in mice by inhibiting different sets of brain cells one by one, and then examining whether the neurons could still exhibit anticipatory responses. This revealed a remarkable division of labor in the neural circuits that regulate vasopressin neurons: two completely different sets of neurons from distinct areas of the brain are dedicated to relaying anticipatory information about either water or food intake. These findings help to understand how healthy levels of water can be maintained in the body. Overall, they give a glimpse into the neural mechanisms that underlie anticipatory forms of regulation, which can also take place when hunger or thirst neurons 'foresee' that food or water will be consumed.

The subfornical organ and organum vasculosum of the lamina terminalis: Critical roles in cardiovascular regulation and the control of fluid balance.

In this chapter, we review the extensive literature describing the roles of the subfornical organ (SFO), the organum vasculosum of the terminalis (OVLT), and the median preoptic nucleus (MnPO), comprising the lamina terminalis, in cardiovascular regulation and the control of fluid balance. We present this information in the context of both historical and technological developments which can effectively be overlaid upon each other. We describe intrinsic anatomy and connectivity and then discuss early work which described how circulating angiotensin II acts at the SFO to stimulate drinking and increase blood pressure. Extensive studies using direct administration and lesion approaches to highlight the roles of all regions of the lamina terminalis are then discussed. At the cellular level we describe c-Fos and electrophysiological work, which has highlighted an extensive group of circulating hormones which appear to influence the activity of specific neurons in the SFO, OVLT, and MnPO. We highlight optogenetic studies that have begun to unravel the complexities of circuitries underlying physiological outcomes, especially those related to different components of drinking. Finally, we describe the somewhat limited human literature supporting conclusions that these structures play similar and potentially important roles in human physiology.

Pre-loading large volume oral electrolytes: tracing fluid and ion fluxes in horses during rest, exercise and recovery.

KEY POINTS: Exercise results in rapid and large extracellular to intracellular fluid shifts, as well as significant sweating losses of water and ions. It is unknown whether ions within oral electrolyte supplements are taken up by muscle (and other soft tissues) and whether oral supplementation can effectively offset sweating losses. Pre-loading with 8 L of a balanced hypotonic electrolyte supplement attenuated extracellular fluid losses, increased exercise duration and increased sweating fluid and ion losses during submaximal exercise. Supplemented electrolytes appear in skeletal muscle within 1 h after administration. Electrolyte supplementation increased exercise performance, improved maintenance of extracellular fluid volumes, and attenuated body fluid losses while maintaining sweating rates. ABSTRACT: This study used radioactive sodium (24 Na) and potassium (42 K) in a balanced, hypotonic electrolyte supplement to trace their appearance in skeletal muscle, and also quantified extracellular and whole-body fluid and ion changes during electrolyte supplementation, exercise and recovery. In a randomized crossover design, 1 h after administration of 1 to 3 L of water or electrolyte supplement with 24 Na, horses were exercised at 35% VO2max to voluntary fatigue or, after administration of 8 L of water or electrolyte supplement with 42 K were exercised at 50% peak VO2 for 45 min (n = 4 in each trial). Pre-exercise electrolyte supplementation was associated with decreased loss of fluid and electrolytes from the extracellular fluid compartments during exercise and recovery compared with water alone. The improved fluid and ion balance during prolonged exercise was associated with increased exercise duration, despite continuing sweating losses of fluid and ions. Nasogastric administration of radiotracer 24 Na+ and 42 K+ showed rapid absorption into the blood with plasma levels peaking 45 min after administration, followed by distribution into the extracellular space and intracellular fluid of muscle within 1 h. Following exercise, virtually all Na+ remained within the extracellular compartment, while the majority of K+ underwent intracellular uptake by 2 h of recovery. It is concluded that pre-loading with a large volume, balanced electrolyte supplement helps maintain whole-body fluid and ion balance and support muscle function during periods of prolonged sweat ion losses.

Association of Positive Fluid Balance at Discharge After Sepsis Management With 30-Day Readmission.

Importance: Although early fluid administration has been shown to lower sepsis mortality, positive fluid balance has been associated with adverse outcomes. Little is known about associations in non-intensive care unit settings, with growing concern about readmission from excess fluid accumulation in patients with sepsis. Objective: To evaluate whether positive fluid balance among non-critically ill patients with sepsis was associated with increased readmission risk, including readmission for heart failure. Design, Setting, and Participants: This multicenter retrospective cohort study was conducted between January 1, 2012, and December 31, 2017, among 57 032 non-critically ill adults hospitalized for sepsis at 21 hospitals across Northern California. Kaiser Permanente Northern California is an integrated health care system with a community-based population of more than 4.4 million members. Statistical analysis was performed from January 1 to December 31, 2019. Exposures: Intake and output net fluid balance (I/O) measured daily and cumulatively at discharge (positive vs negative). Main Outcomes and Measures: The primary outcome was 30-day readmission. The secondary outcomes were readmission stratified by category and mortality after living discharge. Results: The cohort included 57 032 patients who were hospitalized for sepsis (28 779 women [50.5%]; mean [SD] age, 73.7 [15.5] years). Compared with patients with positive I/O (40 940 [71.8%]), those with negative I/O (16 092 [28.2%]) were older, with increased comorbidity, acute illness severity, preexisting heart failure or chronic kidney disease, diuretic use, and decreased fluid administration volume. During 30-day follow-up, 8719 patients (15.3%) were readmitted and 3639 patients (6.4%) died. There was no difference in readmission between patients with positive vs negative I/O (HR, 1.00; 95% CI, 0.95-1.05). No association was detected between readmission and I/O using continuous, splined, and quadratic function transformations. Positive I/O was associated with decreased heart failure-related readmission (HR, 0.80 [95% CI, 0.71-0.91]) and increased 30-day mortality (HR, 1.23 [95% CI, 1.15-1.31]). Conclusions and Relevance: In this large observational study of non-critically ill patients hospitalized with sepsis, there was no association between positive fluid balance at the time of discharge and readmission. However, these findings may have been limited by variable recording and documentation of fluid intake and output; additional studies are needed to examine the association of fluid status with outcomes in patients with sepsis to reduce readmission risk.

Twenty six-week repeat dose oral rat toxicity study of cizolirtine, a substance-P and calcitonin gene-related peptide release modulator.

Cizolirtine, a substance-P and calcitonin gene-related peptide release modulator developed for the treatment of pain and urinary incontinence, was orally administered for 26-weeks to rats at dosages of 20, 60 and 200 mg/kg/day. Clinical signs were limited to post-dosing salivation and brown staining on head and muzzle. There were slight decreases in bodyweight gain and slight increases in water consumption among cizolirtine-treated animals. Slight increases in plasma alkaline phosphatase activity, and cholesterol and phospholipid concentrations were observed in mid- and/or high-dose animals. Low urinary volume, pH and sodium and potassium outputs were observed after 12-weeks, and low urinary pH, low sodium and high potassium outputs at end of treatment. Increased relative (to bodyweight) liver weight was observed in high-dose animals. Treated males and high-dose females showed a dose-related increase in the incidence and severity of periacinar hepatocytic hypertrophy and midzonal/periacinar hepatocytic fat vacuolization. Increased incidences of hepatic clear cell foci were observed in all cizolirtine-treated male groups and, to a lesser extent, in treated females. Ovaries of treated females showed a dose-dependent increased incidence of absent corpora lutea and, occasionally, follicular cysts. The dosages of 20 and 60 mg/kg/day were considered as the No-Observed-Adverse-Effect Levels for males and females, respectively.

Effects and interaction of dietary electrolyte balance and citric acid on growth performance, intestinal histomorphology, digestive enzyme activity and nutrient transporters expression of weaned piglets.

Fifty-six piglets were weaned at 21 days and randomly assigned to 1 of 8 dietary treatments with 7 replicate pens for a 14-day experimental period. The eight experimental diets were prepared via a 2 × 4 factorial arrangement with citric acid (CA; 0 and 0.3%) and dietary electrolyte balance (dEB, Na +K - Cl mEq/kg of the diet; -50, 100, 250, and 400 mEq/kg). Varying dEB values were obtained by altering calcium chloride and sodium bicarbonate contents. Dietary CA significantly increased (p < .05) villus height (VH) and villus height:crypt depth (VH:CD) in the jejunum. Piglets fed a 250 mEq/kg diet increased (p < .05) VH and VH:CD values in the duodenum. Jejunal VH and VH:CD increased (quadratic; p < .05), and ileal VH:CD (liner and quadratic; p < .05) decreased as dEB was increased in diets without CA, but no such effect was observed on the diets containing CA (dEB ×CA; p < .05). The CD in jejunum (quadratic; p < .05) increased as dEB was increased in diets containing CA, whereas it was decreased (linear; p < .05) in the diets without CA (dEB ×CA; p < .001). Dietary CA increased maltase activity and reduced the number of Ki67-positive cells (p < .05). Increasing dEB values in diets without CA increased sucrose and lactase activities (quadratic; p < .05), but no such effect was observed in the diets with CA (dEB ×CA; p < .05). An interaction effect between dEB and CA on the number of Ki67-positive cells was observed (p < .001). In conclusion, 250 mEq/kg dEB diet with CA improved piglet intestinal digestion and absorption function by improving intestinal morphology and increasing digestive enzyme activities. However, these improvements were also observed in piglets fed the 100 mEq/kg dEB diet without CA.

Fluid balance during taekwondo training / Equilíbrio hídrico durante treinamento de taekwondo / Equilibrio hídrico durante entrenamiento de taekwondo

ABSTRACT Introduction Dehydration has been described as one of the main factors of reduced performance in combat sports activities, leading to death in extreme cases. Objective To investigate the pre-training hydration status and changes in fluid homeostasis during two taekwondo training sessions. Methods Eighteen male college athletes (age 22.6 ± 3.37 years) were assessed. The study design aimed to reproduce the conditions of a 90-minute taekwondo training session, divided into three stages: a) warm-up exercises (20 min); b) poomsae (30 min) and c) technical training (40 min). The athletes had ad libitum water intake during training. To assess the hydration status we considered body mass (BM), the amount of liquid consumed and urine output, which enabled us to establish absolute and relative fluid loss in kg and percentage as well as the sweating rate. We also considered urine specific gravity (USG), urine color (U-COL), and subjective sensation of thirst (Sthirst) before and after the training session. Pre- and post-training results were compared separately in each session and between sessions. Results There was a significant difference (P<0.05) in pre-training BM between the two days of training. There was a significant difference (P<0.05) in the final BM on both days of the experiment. Most subjects had relative dehydration below 2%. A significant difference (P<0.05) was recorded pre and post training for U-COL and Sthirst, with the highest rates obtained at the end of each session. Participants always started training at a low dehydration status (USG >1,020g.ml-1). Conclusions The athletes tended to start the training sessions in dehydration status, which increases over the course of the training. Ad libitum water intake was not sufficient to balance fluid loss. Changes in fluid levels between sessions were similar. Level of Evidence II; Therapeutic Studies Investigating the Results Level of Treatment.

RESUMO Introdução A desidratação tem sido descrita como um dos principais fatores de redução de desempenho em atividades de luta, levando, em casos extremos, à morte. Objetivos Investigar o estado da hidratação antes do treino e as alterações no balanço hídrico corporal durante dois treinamentos de taekwondo. Métodos Foram avaliados 18 atletas universitários do sexo masculino (22,6 ± 3,37 anos). O desenho do estudo procurou reproduzir uma condição de treinamento de taekwondo com duração de 90 minutos, dividido em três etapas: a) aquecimento (20 min.), b) poomsae (30 min.) e c) treino técnico (40 min.). Durante o treino, adotou-se o consumo de água ad libitum. Para avaliar o estado de hidratação, considerou-se a massa corporal (MC), a quantidade de líquido consumido e o volume de urina produzido, o que permitiu estabelecer a perda hídrica absoluta e relativa em kg e porcentagem, além da taxa de sudorese. Foi considerada ainda a gravidade específica da urina (GEU), bem como sua coloração (COL-U), além da sensação subjetiva de sede (SSede) antes e depois do treino. Os resultados antes e depois do treino foram comparados de forma isolada em cada sessão, assim como entre as sessões. Resultados Houve diferença significativa (P < 0,05) da MC pré-treinamento entre os dois dias de treino. Houve redução significativa (P < 0,05) da MC final em ambos os dias de experimento. A maior parte dos avaliados apresentou desidratação relativa inferior a 2%. Registrou-se diferença significativa (P < 0,05) antes e depois do treino para COL-U e para SSede, com os maiores índices obtidos ao final de cada sessão. Os participantes sempre iniciaram o comparados de forma isolada em cada sessão, assim como entre as sessões. Resultados Houve diferença significativa (P < 0,05) da MC pré-treinamento entre os dois dias de treino. Houve redução significativa (P < 0,05) da MC final em ambos os dias de experimento. A maior parte dos avaliados apresentou desidratação relativa inferior a 2%. Registrou-se diferença significativa (P < 0,05) antes e depois do treino para COL-U e para SSede, com os maiores índices obtidos ao final de cada sessão. Os participantes sempre iniciaram o treinamento em leve estado de desidratação (GEU > 1.020 g.ml-1). Conclusões Os atletas tendem a iniciar os treinamentos em estado de desidratação, que se amplia durante o treino. O consumo de líquidos ad libitum não foi suficiente para equilibrar a perda hídrica. As alterações hídricas entre as sessões foram semelhantes. Nível de Evidência II; Estudos terapêuticos- Investigação dos resultados do tratamento.

RESUMEN Introducción La deshidratación ha sido descrita como uno de los principales factores de reducción del desempeño en actividades de lucha, llevando, en casos extremos, a la muerte. Objetivos Investigar el estado de la hidratación antes del entrenamiento y las alteraciones en el balance hídrico corporal durante dos entrenamientos de taekwondo. Métodos Se evaluaron 18 atletas universitarios del sexo masculino (22,6 ± 3,37 años). El diseño del estudio intentó reproducir una condición de entrenamiento de taekwondo con duración de 90 minutos, dividido en tres etapas: a) calentamiento (20 min); b) poomsae (30 min); y c) entrenamiento técnico (40 min). Durante el entrenamiento, se adoptó el consumo de agua ad libitum. Para evaluar el estado de hidratación, se consideró la masa corporal (MC), la cantidad de líquido consumido y el volumen de orina producido, lo que permitió establecer la pérdida hídrica absoluta y relativa en kg y porcentaje, además de la tasa de sudoración. Fue considerada además la gravedad específica de la orina (GEO), así como su coloración (COL-O), además de la sensación subjetiva de sed (SSed), antes y después del entrenamiento. Los resultados antes y después del entrenamiento fueron comparados de forma aislada en cada sesión, así como entre las sesiones. Resultados Hubo diferencia significativa (P<0,05) de la MC preentrenamiento entre los dos días de entrenamiento. Hubo reducción significativa (P<0,05) de la MC final en ambos días de experimento. La mayor parte de los evaluados presentó deshidratación relativa inferior a 2%. Se registró diferencia significativa (P<0,05) antes y después del entrenamiento para COL-O y para SSed, con los mayores índices obtenidos al final de cada sesión. Los participantes siempre iniciaron el entrenamiento en leve estado de deshidratación (GEO > 1.020 g.ml-1). Conclusiones Los atletas tienden a iniciar los entrenamientos en estado de deshidratación, que se amplía durante el entrenamiento. El consumo de líquidos ad libitum no fue suficiente para equilibrar la pérdida hídrica. Las alteraciones hídricas entre las sesiones fueron semejantes. Nivel de Evidencia II; Estudios terapéuticos - Investigación de los resultados del tratamiento.

Evaluation of Diuretic and Antioxidant Properties in Aqueous Bark and Fruit Extracts of Pine.

OBJECTIVE: The present study has been carried out to evaluate the diuretic and antioxidant properties of pine herb in an animal model. MATERIALS AND METHODS: 45 adult male rats were randomly divided into nine groups including: groups I (the negative control), groups II (positive control, furosemide 10 mg/kg), groups III to VIII (treatment groups received 100, 200, 400 mg/kg of the aqueous extracts of bark and fruit) and group IX received the combination of aqueous extract of bark (100 mg/kg) and the fruit (100 mg/kg). The urine output, glomerular filtration rate (GFR), electrolytes, urea, and creatinine levels were evaluated. Furthermore, the phenolic content and antioxidant activity of both extracts were also assessed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and Folin-Ciocalteu methods. RESULTS: The aqueous extracts of the pine bark and fruit increased the urinary output in a dosedependent manner. The combination of the two extracts compared to the other extracts alone significantly increased the serum potassium level. This study also showed each extract increase creatinine clearance in a dose-dependent manner (p<0.01 and p<0.05). The increase of GFR in the combination group was not significant. The current data showed a significant increase in the total phenolic content in pine bark extract in compared with the fruit extract. CONCLUSION: The pine bark and fruit can be useful in the prevention and treatment of kidney stones due to the high diuretic properties and antioxidant activity.