The comparisons of procalcitonin and age between mild and severe Hand, foot, and mouth disease.

Background: Hand, foot, and mouth disease (HFMD) is an epidemic infectious disease in children, usually associated with fever, mouth lesions, and limb rashes. Although benign and self-limiting, it can be dangerous or even fatal in rare cases. Early identification of severe cases is crucial to ensure optimal care. Procalcitonin (PCT) is an early marker for predicting sepsis. Therefore, in this study, we aimed to investigate the significance of PCT levels, age, lymphocyte subsets, N-terminal pro-brain natriuretic peptide (BNP) in the early diagnosis of severe HFMD. Methods: Using strict inclusion and exclusion criteria, we retrospectively enrolled 183 children with HFMD between January 2020 and August 2021 and divided them into mild (76 cases) and severe (107 cases) groups according to their condition. Data on the patients' PCT levels, lymphocyte subsets, and clinical characteristics at admission were evaluated and compared using the Student's t-test and χ2 test. Results: We found that compared with mild disease forms, the severe disease forms were associated with higher blood PCT levels (P=0.001) and lower ages of onset (P<0.001). The percentages of lymphocyte subsets, including suppressor T cells (CD3+CD8+), T lymphocytes (CD3+), T helper cells (CD3+CD4+), natural killer cells (CD16+56+), and B lymphocytes (CD19+), were identical between the two disease forms in patients under 3 years of age. Conclusions: Age and blood PCT levels play a vital role in the early identification of severe HFMD.

High sodium intake does not worsen low potassium-induced kidney damage.

High sodium and low potassium intake have both been linked to poor cardiovascular health outcomes and increased mortality rates. A combination of the two is thought to be particularly detrimental. While mechanisms are multiple, the kidney is an important target of harmful effects and low potassium influences on both proximal and distal nephron segments are especially potent. We recently reported that a combined high sodium/low potassium diet causes kidney injury and that low potassium in isolation can have similar effects. However, how sodium intake alters this process is not well-understood. Here we tested the hypothesis that a high sodium intake amplifies effects of low dietary potassium on kidney injury. We observed adding high sodium to low potassium caused an expected increase in blood pressure, but did not worsen markers of kidney injury, inflammation, and fibrosis. It also did not increase abundance or phosphorylation of the sodium chloride cotransporter or its regulatory kinases, SPAK and OxSR1, known renal targets of low potassium. Findings support the claim that dietary potassium deficiency, and not high sodium, is a dominant factor affecting kidney injury in animal models of high sodium/low potassium intake. This suggests further investigation is required to identify optimal ranges of sodium and potassium intake in both healthy populations and in those with kidney disease.

Kir4.2 mediates proximal potassium effects on glutaminase activity and kidney injury.

Inadequate potassium (K+) consumption correlates with increased mortality and poor cardiovascular outcomes. Potassium effects on blood pressure have been described previously; however, whether or not low K+ independently affects kidney disease progression remains unclear. Here, we demonstrate that dietary K+ deficiency causes direct kidney injury. Effects depend on reduced blood K+ and are kidney specific. In response to reduced K+, the channel Kir4.2 mediates altered proximal tubule (PT) basolateral K+ flux, causing intracellular acidosis and activation of the enzyme glutaminase and the ammoniagenesis pathway. Deletion of either Kir4.2 or glutaminase protects from low-K+ injury. Reduced K+ also mediates injury and fibrosis in a model of aldosteronism. These results demonstrate that the PT epithelium, like the distal nephron, is K+ sensitive, with reduced blood K+ causing direct PT injury. Kir4.2 and glutaminase are essential mediators of this injury process, and we identify their potential for future targeting in the treatment of chronic kidney disease.

Cyclooxygenase-2 in adipose tissue macrophages limits adipose tissue dysfunction in obese mice.

Obesity-associated complications are causing increasing morbidity and mortality worldwide. Expansion of adipose tissue in obesity leads to a state of low-grade chronic inflammation and dysregulated metabolism, resulting in insulin resistance and metabolic syndrome. Adipose tissue macrophages (ATMs) accumulate in obesity and are a source of proinflammatory cytokines that further aggravate adipocyte dysfunction. Macrophages are rich sources of cyclooxygenase (COX), the rate limiting enzyme for prostaglandin E2 (PGE2) production. When mice were fed a high-fat diet (HFD), ATMs increased expression of COX-2. Selective myeloid cell COX-2 deletion resulted in increased monocyte recruitment and proliferation of ATMs, leading to increased proinflammatory ATMs with decreased phagocytic ability. There were increased weight gain and adiposity, decreased peripheral insulin sensitivity and glucose utilization, increased adipose tissue inflammation and fibrosis, and abnormal adipose tissue angiogenesis. HFD pair-feeding led to similar increases in body weight, but mice with selective myeloid cell COX-2 still exhibited decreased peripheral insulin sensitivity and glucose utilization. Selective myeloid deletion of the macrophage PGE2 receptor subtype, EP4, produced a similar phenotype, and a selective EP4 agonist ameliorated the metabolic abnormalities seen with ATM COX-2 deletion. Therefore, these studies demonstrated that an ATM COX-2/PGE2/EP4 axis plays an important role in inhibiting adipose tissue dysfunction.

An analysis of the Chinese scheduled freighter network during the first year of the COVID-19 pandemic.

COVID-19 caused the vast majority of passenger flights to be grounded, but the crisis raised the importance of the network of dedicated cargo flights and, therefore, interest in its development. This paper aims to evaluate the Chinese scheduled freighter network (CSFN) via its topological properties and to explore its changes following the COVID-19 pandemic. Using spatial analysis with the complex network theory (CNT), the paper found that the CSFN displays small-world and scale-free network properties, similar to that of air passenger network. Hangzhou, Shenzhen and Nanjing are the dominant national hubs in the CSFN because they host the headquarters of many e-commerce giant enterprises and have relatively underutilized airport capacities. The CSFN has improved since the COVID-19 pandemic, with increased network average degree, clustering coefficient, and closeness, and reduced average path. These improvements were mainly driven by major hub cities whose centralities had been strengthened with more route connections. Since China's air passenger traffic had quickly restored in the second half of 2020, we argue that the changes in the CSFN during COVID-19 were unlikely to be a result of the substitution effect between freighter and passenger aircraft. It was more likely a result of the higher air cargo demand during the pandemic and airlines' realisation of the importance of freighter operations in China.

Macrophage interferon regulatory factor 4 deletion ameliorates aristolochic acid nephropathy via reduced migration and increased apoptosis.

Aristolochic acid (AA) is the causative nephrotoxic alkaloid in AA nephropathy, which results in a tubulointerstitial fibrosis. AA causes direct proximal tubule damage as well as an influx of macrophages, although the role of macrophages in pathogenesis is poorly understood. Here, we demonstrate that AA directly stimulates migration, inflammation, and ROS production in macrophages ex vivo. Cells lacking interferon regulatory factor 4 (IRF4), a known regulator of macrophage migration and phenotype, had a reduced migratory response, though effects on ROS production and inflammation were preserved or increased relative to WT cells. Macrophage-specific IRF4-knockout mice were protected from both acute and chronic kidney effects of AA administration based on functional and histological analysis. Renal macrophages from kidneys of AA-treated macrophage-specific IRF4-knockout mice demonstrated increased apoptosis and ROS production compared with WT controls, indicating that AA directly polarizes macrophages to a promigratory and proinflammatory phenotype. However, knockout mice had reduced renal macrophage abundance following AA administration. While macrophages lacking IRF4 can adopt a proinflammatory phenotype upon AA exposure, their inability to migrate to the kidney and increased rates of apoptosis upon infiltration provide protection from AA in vivo. These results provide evidence of direct AA effects on macrophages in AA nephropathy and add to the growing body of evidence that supports a key role of IRF4 in modulating macrophage function in kidney injury.

COVID-19 and bailout policy: The case of Virgin Australia.

The impact of COVID-19 on air transport is unprecedented and some well-known airline brands may disappear as a result. Governments around the world have responded swiftly to cushion the financial impact by offering direct wage subsidies, tax relief, loans, etc. This paper explores the government's appropriate responses to failing airlines' bailout request by examining the case of Virgin Australia. Following the bailout policy principles established in the literature, we suggest that bankruptcy protection should be considered as the first solution to a failing carrier. A bailout decision should be guided by a set of principles and procedures, which should not be taken lightly. Our analysis also shows that the government cannot take a hands-off approach in the absence of private lenders and investors, as the costs to consumers and regional residents would be huge if the carrier could not get through the COVID-19 pandemic. A minimum level of assistance with conditions might be needed to maintain market competition.

Activation of hypoxia-sensing pathways promotes renal ischemic preconditioning following myocardial infarction.

Ischemic heart disease is the leading cause of death worldwide and is frequently comorbid with chronic kidney disease. Physiological communication is known to occur between the heart and the kidney. Although primary dysfunction in either organ can induce dysfunction in the other, a clinical entity known as cardiorenal syndrome, mechanistic details are lacking. Here, we used a model of experimental myocardial infarction (MI) to test effects of chronic cardiac ischemia on acute and chronic kidney injury. Surprisingly, chronic cardiac damage protected animals from subsequent acute ischemic renal injury, an effect that was accompanied by evidence of chronic kidney hypoxia. The protection observed post-MI was similar to protection observed in a separate group of healthy animals housed in ambient hypoxic conditions prior to kidney injury, suggesting a common mechanism. There was evidence that chronic cardiac injury activates renal hypoxia-sensing pathways. Increased renal abundance of several glycolytic enzymes following MI suggested that a shift toward glycolysis may confer renal ischemic preconditioning. In contrast, effects on chronic renal injury followed a different pattern, with post-MI animals displaying worsened chronic renal injury and fibrosis. These data show that although chronic cardiac injury following MI protected against acute kidney injury via activation of hypoxia-sensing pathways, it worsened chronic kidney injury. The results further our understanding of cardiorenal signaling mechanisms and have implications for the treatment of heart failure patients with associated renal disease.NEW & NOTEWORTHY Experimental myocardial infarction (MI) protects from subsequent ischemic acute kidney injury but worsens chronic kidney injury. Observed protection from ischemic acute kidney injury after MI was accompanied by chronic kidney hypoxia and increased renal abundance of hypoxia-inducible transcripts. These data support the idea that MI confers protection from renal ischemic injury via chronic renal hypoxia and activation of downstream hypoxia-inducible signaling pathways.

COVID-19 impacts on general aviation - Comparative experiences, governmental responses and policy imperatives.

This article catalogues experiences of the general aviation sector as it progressively encountered the challenges of COVID-19 in the early part of 2020. The article focuses primarily on the Australian marketplace as a contribution to the body of knowledge in an under-researched industry sector. The article draws on literature pertaining to prior pandemic experience to enquire about the level of precursory preparedness in the sector, and then utilises data from 12 semi-structured interviews with experienced industry participants locally and internationally. The key findings suggest that there has been a lack of applied learning by policy makers in the past, and that generic support on offer now does not address the long term resilience of the sector nor does it address a pathway for future sudden moments of dislocation. Policies which purport to support aviation should be crafted in a way that engages all levels of industry rather than be airline centric.

The impact of the COVID-19 pandemic on current tertiary aviation education and future careers: Students' perspective.

This study investigates Australian undergraduate tertiary aviation students' perceptions of the aviation industry and skills required to succeed following the COVID-19 pandemic. By developing an understanding of the skills students perceive to be necessary for their careers following the COVID-19 pandemic, comparisons can be drawn with industry perspectives to determine whether these perspectives align and, more importantly, support students' successful development of skills as sought by the industry. An online survey of current undergraduate tertiary aviation students at Australian universities was conducted to determine the perceived impediments, additional skills required, post-graduation plans and how university courses should evolve post-COVID-19. The results show that students are cognisant of the current oversupply of aviation professionals due to the downturn in the industry and are seeking further support with the development of non-technical skills to better prepare themselves to be competitive following graduation. These findings have implications for both undergraduate aviation students and universities offering an undergraduate aviation program. By considering these findings universities can adapt their programs to better prepare students and support the development of skilled aviation professionals, equipped to deal with challenges of the post-COVID-19 aviation industry.

Preparing for 'COVID-27': Lessons in management focus - An Australian general aviation perspective.

This paper considers the observed impacts of COVID-19 on the behaviour of a cross-section of the general aviation (GA) community in Australia. It specifically observes the nature of management decision making observed in the sector, and the financial impacts of such choices. This paper highlights a lack of financial acumen in the Australian GA community which is likely to inhibit resilience in the sector and limit its ability to learn from the economic shock COVID-19 represents. Finally, the paper proposes several initiatives to improve the quality of management decision making in the sector's leadership, with a view to improving its financial outlook and visibility to policy makers.

Exploring the roles of high-speed train, air and coach services in the spread of COVID-19 in China.

To understand the roles of different transport modes in the spread of COVID-19 pandemic across Chinese cities, this paper looks at the factors influencing the number of imported cases from Wuhan and the spread speed and pattern of the pandemic. We find that frequencies of air flights and high-speed train (HST) services out of Wuhan are significantly associated with the number of COVID-19 cases in the destination cities. The presence of an airport or HST station at a city is significantly related to the speed of the pandemic spread, but its link with the total number of confirmed cases is weak. The farther the distance from Wuhan, the lower number of cases in a city and the slower the dissemination of the pandemic. The longitude and latitude coordinates do not have a significant relationship with the number of total cases but can increase the speed of the COVID-19 spread. Specifically, cities in the higher longitudinal region tended to record a COVID-19 case earlier than their counterparties in the west. Cities in the north were more likely to report the first case later than those in the south. The pandemic may emerge in large cities earlier than in small cities as GDP is a factor positively associated with the spread speed.

Lipopolysaccharide induces filtrate leakage from renal tubular lumina into the interstitial space via a proximal tubular Toll-like receptor 4-dependent pathway and limits sensitivity to fluid therapy in mice.

Sustained oliguria during fluid resuscitation represents a perplexing problem in patients undergoing therapy for septic acute kidney injury. Here, we tested whether lipopolysaccharide induces filtrate leakage from the proximal tubular lumen into the interstitium, thus disturbing the recovery of urine output during therapy, such as fluid resuscitation, aiming to restore the glomerular filtration rate. Intravital imaging of the tubular flow rate in the proximal tubules in mice showed that lipopolysaccharide did not change the inflow rate of proximal tubule filtrate, reflecting an unchanged glomerular filtration rate, but significantly reduced the outflow rate, resulting in oliguria. Lipopolysaccharide disrupted tight junctions in proximal tubules and induced both paracellular leakage of filtered molecules and interstitial accumulation of extracellular fluid. These changes were diminished by conditional knockout of Toll-like receptor 4 in the proximal tubules. Importantly, these conditional knockout mice showed increased sensitivity to fluid resuscitation and attenuated acute kidney injury. Thus, lipopolysaccharide induced paracellular leakage of filtrate into the interstitium via a Toll-like receptor 4-dependent mechanism in the proximal tubules of endotoxemic mice. Hence, this leakage might diminish the efficacy of fluid resuscitation aiming to maintain renal hemodynamics and glomerular filtration rate.

Abnormal sodium and water homeostasis in mice with defective heparan sulfate polymerization.

Glycosaminoglycans in the skin interstitium and endothelial surface layer have been shown to be involved in local sodium accumulation without commensurate water retention. Dysfunction of heparan sulfate glycosaminoglycans may therefore disrupt sodium and water homeostasis. In this study, we investigated the effects of combined heterozygous loss of heparan sulfate polymerization genes (exostosin glycosyltransferase 1 and 2; Ext1+/-Ext2+/-) on sodium and water homeostasis. Sodium storage capacity was decreased in Ext1+/-Ext2+/- mice as reflected by a 77% reduction in endothelial surface layer thickness and a lower skin sodium-to-glycosaminoglycan ratio. Also, these mice were characterized by a higher heart rate, increased fluid intake, increased plasma osmolality and a decreased skin water and sodium content, suggesting volume depletion. Upon chronic high sodium intake, the initial volume depletion was restored but no blood pressure increase was observed. Acute hypertonic saline infusion resulted in a distinct blood pressure response: we observed a significant 15% decrease in control mice whereas blood pressure did not change in Ext1+/-Ext2+/- mice. This differential blood pressure response may be explained by the reduced capacity for sodium storage and/or the impaired vasodilation response, as measured by wire myography, which was observed in Ext1+/-Ext2+/- mice. Together, these data demonstrate that defective heparan sulfate glycosaminoglycan synthesis leads to abnormal sodium and water homeostasis and an abnormal response to sodium loading, most likely caused by inadequate capacity for local sodium storage.

Noninvasive quantitative magnetization transfer MRI reveals tubulointerstitial fibrosis in murine kidney.

Excessive tissue scarring, or fibrosis, is a critical contributor to end stage renal disease, but current clinical tests are not sufficient for assessing renal fibrosis. Quantitative magnetization transfer (qMT) MRI provides indirect information about the macromolecular composition of tissues. We evaluated measurements of the pool size ratio (PSR, the ratio of immobilized macromolecular to free water protons) obtained by qMT as a biomarker of tubulointerstitial fibrosis in a well-established murine model with progressive renal disease. MR images were acquired from 16-week-old fibrotic hHB-EGFTg/Tg mice and normal wild-type (WT) mice (N = 12) at 7 T. QMT parameters were derived using a two-pool five-parameter fitting model. A normal range of PSR values in the cortex and outer stripe of outer medulla (CR + OSOM) was determined by averaging across voxels within WT kidneys (mean ± 2SD). Regions in diseased mice whose PSR values exceeded the normal range above a threshold value (tPSR) were identified and measured. The spatial distribution of fibrosis was confirmed using picrosirius red stains. Compared with normal WT mice, scattered clusters of high PSR regions were observed in the OSOM of hHB-EGFTg/Tg mouse kidneys. Moderate increases in mean PSR (mPSR) of CR + OSOM regions were observed across fibrotic kidneys. The abnormally high PSR regions (% area) detected by the tPSR were significantly increased in hHB-EGFTg/Tg mice, and were highly correlated with regions of fibrosis detected by histological fibrosis indices measured from picrosirius red staining. Renal tubulointerstitial fibrosis in OSOM can thus be assessed by qMT MRI using an appropriate analysis of PSR. This technique may be used as an imaging biomarker for chronic kidney diseases.

Renal Medullary Interstitial COX-2 (Cyclooxygenase-2) Is Essential in Preventing Salt-Sensitive Hypertension and Maintaining Renal Inner Medulla/Papilla Structural Integrity.

COX (cyclooxygenase)-derived prostaglandins regulate renal hemodynamics and salt and water homeostasis. Inhibition of COX activity causes blood pressure elevation. In addition, chronic analgesic abuse can induce renal injury, including papillary necrosis. COX-2 is highly expressed in the kidney papilla in renal medullary interstitial cells (RMICs). However, its role in blood pressure and papillary integrity in vivo has not been definitively studied. In mice with selective, inducible RMIC COX-2 deletion, a high-salt diet led to an increase in blood pressure that peaked at 4 to 5 weeks and was associated with increased papillary expression of AQP2 (aquaporin 2) and ENac (epithelial sodium channel) and decreased expression of cystic fibrosis transmembrane conductance regulator. With continued high-salt feeding, the mice with RMIC COX-2 deletion had progressive decreases in blood pressure from its peak. After return to a normal-salt diet for 3 weeks, blood pressure remained low and was associated with a persistent urinary concentrating defect. Within 2 weeks of institution of a high-salt diet, increased apoptotic RMICs and collecting duct cells could be detected in papillae with RMIC deletion of COX-2, and by 9 weeks of high salt, there was a striking loss of the papillae. Therefore, RMIC COX-2 expression plays a crucial role in renal handling water and sodium homeostasis, preventing salt-sensitive hypertension and maintaining structural integrity of papilla.

Association between urinary sodium and potassium excretion and blood pressure and inflammation in patients with rheumatoid arthritis.

Hypertension is highly prevalent in patients with rheumatoid arthritis (RA). In other populations, high sodium (Na+) and low potassium (K+) intake are associated with an increased risk of hypertension, and in animal models, a high salt intake exacerbated arthritis. Patients with RA have many comorbidities associated with salt sensitivity, but their salt intake and its relationship to blood pressure and inflammation is unknown. Using the Kawasaki formula, Na+ and K+ urinary excretion (reflecting intake) was estimated in 166 patients with RA and 92 controls, frequency matched for age, sex, and race. Inflammatory markers and disease activity were measured in RA patients. We tested the associations between blood pressure and Na+ and K+ excretion. Estimated 24-h Na+ excretion was similarly high in both RA (median [IQR] 5.1 g, [3.9-6.6 g]) and controls (4.9 g, [4.0-6.5 g]), p = 0.9, despite higher rates of hypertension in RA (54 vs. 39%, p = 0.03). The Na+:K+ excretion ratio was significantly higher in RA (2.0 [1.6-2.4]) vs. 1.7 [1.5-2.1]), p = 0.02] compared to controls. In RA, a lower K+ excretion was inversely correlated with diastolic blood pressure (adjusted ß = - 1.79, p = 0.04). There was no significant association between Na+ or K+ excretion and inflammatory markers. Despite a similar Na+ excretion, patients with RA had higher rates of hypertension than controls, a finding compatible with increased salt sensitivity. Patients with RA had a lower Na+:K+ excretion ratio than controls, and lower K+ excretion was associated with higher diastolic blood pressure in RA.

Crystal structures of the solid solutions Na3Zn0.912Cd0.088B5O10 and Na3Zn0.845Mg0.155B5O10.

Two new penta-borates, tris-odium zinc cadmium penta-borate, Na3Zn0.912Cd0.088B5O10, and tris-odium zinc magnesium penta-borate, Na3Zn0.845Mg0.155B5O10, have been synthesized by high-temperature solution reactions at 1023 K. Their crystal structures were determined by single-crystal X-ray diffraction. Both solid solutions crystallize in the ortho-rhom-bic form of the parent compound Na3ZnB5O10 (space group type Pbca, Z = 8) and contain the double ring [B5O10]5- anion composed of one BO4 tetra-hedron and four BO3 triangles as the basic structural motif. The anions are bridged by tetra-hedrally coordinated and occupationally disordered M2+ (M = Zn/Cd, Zn/Mg) cations via common O atoms to form [MB5O10] n3n- layers. The intra-layer inter-secting channels and the inter-layer voids are occupied by Na+ cations to balance the charge.

High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation.

Natriuretic regulation of extracellular fluid volume homeostasis includes suppression of the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion and lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed to control the extracellular volume. Here, we have demonstrated that urine concentration, and therefore regulation of water conservation, is an important control system for urine formation and extracellular volume homeostasis in mice and humans across various levels of salt intake. We observed that the renal concentration mechanism couples natriuresis with correspondent renal water reabsorption, limits natriuretic osmotic diuresis, and results in concurrent extracellular volume conservation and concentration of salt excreted into urine. This water-conserving mechanism of dietary salt excretion relies on urea transporter-driven urea recycling by the kidneys and on urea production by liver and skeletal muscle. The energy-intense nature of hepatic and extrahepatic urea osmolyte production for renal water conservation requires reprioritization of energy and substrate metabolism in liver and skeletal muscle, resulting in hepatic ketogenesis and glucocorticoid-driven muscle catabolism, which are prevented by increasing food intake. This natriuretic-ureotelic, water-conserving principle relies on metabolism-driven extracellular volume control and is regulated by concerted liver, muscle, and renal actions.

Increased salt consumption induces body water conservation and decreases fluid intake.

BACKGROUND: The idea that increasing salt intake increases drinking and urine volume is widely accepted. We tested the hypothesis that an increase in salt intake of 6 g/d would change fluid balance in men living under ultra-long-term controlled conditions. METHODS: Over the course of 2 separate space flight simulation studies of 105 and 205 days' duration, we exposed 10 healthy men to 3 salt intake levels (12, 9, or 6 g/d). All other nutrients were maintained constant. We studied the effect of salt-driven changes in mineralocorticoid and glucocorticoid urinary excretion on day-to-day osmolyte and water balance. RESULTS: A 6-g/d increase in salt intake increased urine osmolyte excretion, but reduced free-water clearance, indicating endogenous free water accrual by urine concentration. The resulting endogenous water surplus reduced fluid intake at the 12-g/d salt intake level. Across all 3 levels of salt intake, half-weekly and weekly rhythmical mineralocorticoid release promoted free water reabsorption via the renal concentration mechanism. Mineralocorticoid-coupled increases in free water reabsorption were counterbalanced by rhythmical glucocorticoid release, with excretion of endogenous osmolyte and water surplus by relative urine dilution. A 6-g/d increase in salt intake decreased the level of rhythmical mineralocorticoid release and elevated rhythmical glucocorticoid release. The projected effect of salt-driven hormone rhythm modulation corresponded well with the measured decrease in water intake and an increase in urine volume with surplus osmolyte excretion. CONCLUSION: Humans regulate osmolyte and water balance by rhythmical mineralocorticoid and glucocorticoid release, endogenous accrual of surplus body water, and precise surplus excretion. FUNDING: Federal Ministry for Economics and Technology/DLR; the Interdisciplinary Centre for Clinical Research; the NIH; the American Heart Association (AHA); the Renal Research Institute; and the TOYOBO Biotechnology Foundation. Food products were donated by APETITO, Coppenrath und Wiese, ENERVIT, HIPP, Katadyn, Kellogg, Molda, and Unilever.