Physiological regulation of oral saliva ion composition and flow rate are not coupled in healthy humans-Partial revision of our current knowledge required.

Appropriate composition of oral saliva is essential for a healthy milieu that protects mucosa and teeth. Only few studies, with small sample numbers, investigated physiological saliva ion composition in humans. We determined saliva ion composition in a sufficiently large cohort of healthy adults and analyzed the effect of physiological stimulation. We collected saliva from 102 adults under non-stimulated and physiologically stimulated conditions (chewing). Individual flow rates, pH, osmolality, Na+, K+, Cl-, and HCO3- concentrations under both conditions as well as the individual changes due to stimulation (Δvalues) were determined. Non-stimulated saliva was hypoosmolal and acidic. Na+, Cl-, and HCO3- concentrations remained well below physiological plasma values, whereas K+ concentrations exceeded plasma values more than twofold. Stimulation resulted in a doubling of flow rates and substantial increases in pH, HCO3-, and Na+ concentrations. Overall, stimulation did not considerably affect osmolality nor K+ or Cl- concentrations of saliva. An in-depth analysis of stimulation effects, using individual Δvalues, showed no correlation of Δflow rate with Δion concentrations, indicating independent regulation of acinar volume and ductal ion transport. Stimulation-induced Δ[Na+] correlated with Δ[HCO3-] and Δ[Cl-] but not with Δ[K+], indicating common regulation of ductal Na+, Cl-, and HCO3- transport. We present a robust data set of human oral saliva ion composition in healthy adults and functional insights into physiological stimulation. Our data show (i) that flow-dependence exists for Na+ and HCO3- but not for K+ and Cl- concentrations, (ii) osmolality is flow-independent, (iii) regulation of Na+, Cl-, and HCO3- transport is coupled, (iv) regulation of flow rate and ion concentrations are independent and (v) spatially separated between acini and ducts, respectively.

Association between serum osmolality and deteriorating renal function in patients with acute myocardial infarction: analysis of the MIMIC- IV database.

BACKGROUND: To investigate the association between serum osmolality and deteriorating renal function in patients with acute myocardial infarction (AMI). METHODS: Three thousand eight hundred eighty-five AMI patients from the Medical Information Mart for Intensive Care IV were enrolled for this study. The primary outcome was deteriorating renal function. Secondary outcomes included the new-onset of acute kidney injury (AKI) and progress of AKI. < 293.2725 mmol/L was defined as low serum osmolality, and ≥ 293.2725 mmol/L as high serum osmolality based on upper quartile. Univariate and multivariate logistic regression models were used to explore the associations between serum osmolality and the development of deteriorating renal function, the new-onset of AKI and progress of AKI among AMI patients. Subgroup analysis was also conducted. RESULTS: One thousand three hundred ninety-three AMI patients developed deteriorating renal function. After adjusting all confounding factors, high serum osmolality was associated with increased risk of deteriorating renal function [odds ratio (OR) = 1.47, 95% confidence interval (CI): 1.22-1.78], new-onset of AKI (OR = 1.31, 95% CI: 1.01-1.69), and progress of AKI risk (OR = 1.26, 95% CI: 1.01-1.59) among AMI patients. In addition, when the stratified analysis was performed for age, AMI type, cardiogenic shock, and estimated glomerular filtration rate (eGFR), high serum osmolality was risk factor for the risk of deteriorating renal function among patients aged 65 years or older, without cardiogenic shock, and with an eGFR ≥ 60 mL/min/1.73m2. CONCLUSION: Higher serum osmolality increased the risk of deteriorating renal function among AMI patients.

Unmeasured Osmoles: The Hidden Solutes Obscuring a Hyponatremia Evaluation.

Hyponatremia is defined as serum sodium less than 135 mEq/L and is principally a result of water excess relative to total body sodium content. The evaluation of hyponatremia is incomplete without a careful assessment of the patient's volume status, history, and acquisition of both serum and urine osmolality and sodium studies. Many of these studies can be affected by various clinical factors, and these nuances should be considered while interpreting the results. This is because these results guide the etiologic diagnosis of hyponatremia and consequently its management. In this report, we describe a 50-year-old male being evaluated for hyponatremia found to have unusual serum/urine osmolality studies but ultimately found to have an unmeasured serum osmole (ethanol) interfering with the interpretation of these results. Clinical scenarios that interfere with serum and urine studies commonly obtained in a hyponatremia evaluation are reviewed and an equation to correct for ethanol's osmotic contribution is described.

Unraveling the impact of pH, sodium concentration, and medium osmolality on Vibrio natriegens in batch processes.

BACKGROUND: Vibrio natriegens, a halophilic marine γ-proteobacterium, holds immense biotechnological potential due to its remarkably short generation time of under ten minutes. However, the highest growth rates have been primarily observed on complex media, which often suffer from batch-to-batch variability affecting process stability and performance. Consistent bioprocesses necessitate the use of chemically defined media, which are usually optimized for fermenters with pH and dissolved oxygen tension (DOT) regulation, both of which are not applied during early-stage cultivations in shake flasks or microtiter plates. Existing studies on V. natriegens' growth on mineral media report partially conflicting results, and a comprehensive study examining the combined effects of pH buffering, sodium concentration, and medium osmolality is lacking. RESULTS: This study evaluates the influence of sodium concentration, pH buffering, and medium osmolality on the growth of V. natriegens under unregulated small-scale conditions. The maximum growth rate, time of glucose depletion, as well as the onset of stationary phase were observed through online-monitoring the oxygen transfer rate. The results revealed optimal growth conditions at an initial pH of 8.0 with a minimum of 300 mM MOPS buffer for media containing 20 g/L glucose or 180 mM MOPS for media with 10 g/L glucose. Optimal sodium chloride supplementation was found to be between 7.5 and 15 g/L, lower than previously reported ranges. This is advantageous for reducing industrial corrosion issues. Additionally, an osmolality range of 1 to 1.6 Osmol/kg was determined to be optimal for growth. Under these optimized conditions, V. natriegens achieved a growth rate of 1.97 ± 0.13 1/h over a period of 1 h at 37 °C, the highest reported rate for this organism on a mineral medium. CONCLUSION: This study provides guidelines for cultivating V. natriegens in early-stage laboratory settings without pH and DOT regulation. The findings suggest a lower optimal sodium chloride range than previously reported and establish an osmolality window for optimal growth, thereby advancing the understanding of V. natriegens' physiology. In addition, this study offers a foundation for future research into the effects of different ions and carbon sources on V. natriegens.

Evolution of the thirst mechanism in Homo: The need and limitations of thirst and hydration.

There is a view that the perception of thirst and actual body fluid balance may affect cognitive and exercise performance. The evolutionary evidence suggests that our survival was dependent on our ability to sweat profusely when hunting during the heat of the day (persistence hunting), so if water deficits were not tolerated, consequently the thirst mechanism would limit our persistence hunting capability. This also means that hunting and searching for water was undertaken with some extent of water deficit, and in turn suggests that performance; physical and cognitive, was conducted with a degree of dehydration. Given the current views on the maintenance of body water for performance, there is a need to evaluate the evidence relating to tolerance limits for water deficits with respect to both physical and cognitive performance. This review considers the thirst mechanism and the conditions and selective pressures under which this might have evolved. Consideration will be given to how the thirst mechanism influences our physical and cognitive performance. The review suggests that Homo developed appropriate tolerances for water deficits and thirst perception, with a safety margin that prevented detrimental declines in physical and cognitive performance to the point of inhibiting corrective action. This would have offered a selective advantage, enabling the search for water and functioning adequately during periods of water scarcity.

Dying of thirst: Osmoregulation by a hawkmoth pollinator in response to variability in ambient humidity and nectar availability.

Climate-induced shifts in flowering phenology can disrupt pollinator-floral resource synchrony, especially in desert ecosystems where rainfall dictates both. However, baseline metrics to gauge pollinator health in the wild amidst rapid climate change are lacking. Our laboratory-based study establishes a baseline for pollinator physiological state by exploring how osmotic conditions influence survivorship in a desert hawkmoth pollinator, Manduca sexta. We sampled hemolymph osmolality from over 1000 lab-grown moths at 20 %, 50 %, and 80 % ambient humidity levels. Starved moths maintained healthy osmolality of 350-400 mmol/kg for 1-3 days after eclosion regardless of ambient humidity, but it sharply rose to 550 mmol/kg after 4-5 days in low and moderate humidity, and after 5 days in high humidity. Starved moths in low humidity conditions perished within 5 days, while those in high humidity survived twice as long. Moths fed synthetic Datura wrightii nectar, synthetic Agave palmeri nectar, or water, maintained osmolality within a healthy range of 350-400mmol/kg. The same was true for moths fed authentic floral nectars from Datura and Agave plants, although moths consumed more synthetic than authentic nectars, possibly due to non-sugar constituents. Simulating a 4-day mismatch between pollinator emergence and nectar availability, a single nectar meal osmotically rescued moths under dry ambient conditions. Our findings highlight hemolymph osmolality as a rapid and accurate biomarker distinguishing dehydrated from hydrated states in insect pollinators.

Enlarged brain perivascular spaces correlate with blood plasma osmolality in the healthy population: a longitudinal study.

Enlarged perivascular spaces (EPVS) are increasingly recognized as an MRI detectable feature of neuroinflammatory processes and age-related neurodegenerative changes. Understanding perivascular characteristics in healthy individuals is crucial for their applicability as a reference for pathological changes. Limited data exists on the EPVS load and interhemispheric asymmetry in distribution among young healthy subjects. Despite the known impact of hydration on brain morphometric studies, blood plasma osmolality's effect on EPVS remains unexplored. This study investigated the influence of age, total intracranial volume (TIV), and blood plasma osmolality on EPVS characteristics in 59 healthy adults, each undergoing MRI and osmolality assessment twice within 14.8 months (mean ± 4 months). EPVS analysis was conducted in the centrum semiovale using high-resolution automated segmentation, followed by an optimization algorithm to enhance EPVS segmentation accuracy. Linear Mixed Effects model was used for the statistical analysis, which unveiled significant inter-individual variability in EPVS load and inter-hemispheric asymmetry. EPVS volume increased with age, higher TIV and lower blood plasma osmolality levels. Our findings offer valuable insights into EPVS characteristics among the healthy population, establishing a foundation to further explore age-related and pathological changes.

The In Vivo Effect of Water-Based Lubricants on the Vaginal Microbiome of Women from Varying Age Groups: Exploratory Analysis of a Randomized Controlled Trial.

Vaginal mucosa undergoes physiological changes across the lifespan, such as increased pH and reduced natural lubrication which are known to impact vaginal commensal microorganisms, hence increasing the chances of vaginal infections. An improved understanding of vaginal microbiome composition in different age groups and the effect of social behaviors, such as the use of personal lubricants, could facilitate the development of new strategies to maintain good vaginal health. The objective of this study was to assess the effect of water-based lubricants on the human vaginal microbiome. Fifty females from three age groups (18-29, 30-44, and 45-65 years) with mild-to-moderate vaginal dryness were randomized to one of five lubricants (four of which were formulated to meet expert guidance on osmolality and pH). Subjects entered the study at tolerance or treatment phase (vaginal intercourse minimum once a week using assigned lubricant). Four vaginal swabs per participant were sampled during pre-("baseline"), post-first ("2 h", "24 h") and post-last ("4 weeks") lubricant application to assess bacterial and fungal diversity via amplicon sequencing. Vaginal pH and relative humidity were measured at baseline, 2 h, and 24 h post-lubricant application. Relative bacteriome abundance was statistically compared between timepoints for each lubricant group. Vaginal moisture, age, BMI, and pH were correlated with bacteriome relative abundance. Lactobacilli and Gardnerella sp. Were predominant across participants. Repeated lubricant application did not significantly alter the vaginal bacteriome during 4 weeks of product use (p > 0.05) when measured by relative abundance and alpha-diversity index. Bacteriome diversity and abundance differed significantly between age groups at baseline whereas lactobacilli relative abundance was negatively associated with age and vaginal pH.

Arrhythmogenic Potential of Myocardial Edema: The Interstitial Osmolality Induces Spiral Waves and Multiple Excitation Wavelets.

Myocardial edema is a common symptom of pathological processes in the heart, causing aggravation of cardiovascular diseases and leading to irreversible myocardial remodeling. Patient-based studies show that myocardial edema is associated with arrhythmias. Currently, there are no studies that have examined how edema may influence changes in calcium dynamics in the functional syncytium. We performed optical mapping of calcium dynamics on a monolayer of neonatal rat cardiomyocytes with Fluo-4. The osmolality of the solutions was adjusted using the NaCl content. The initial Tyrode solution contained 140 mM NaCl (1T) and the hypoosmotic solutions contained 105 (0.75T) and 70 mM NaCl (0.5T). This study demonstrated a sharp decrease in the calcium wave propagation speed with a decrease in the solution osmolality. The successive decrease in osmolality also showed a transition from a normal wavefront to spiral wave and multiple wavelets of excitation with wave break. Our study demonstrated that, in a cellular model, hypoosmolality and, as a consequence, myocardial edema, could potentially lead to fatal ventricular arrhythmias, which to our knowledge has not been studied before. At 0.75T spiral waves appeared, whereas multiple wavelets of excitation occurred in 0.5T, which had not been recorded previously in a two-dimensional monolayer under conditions of cell edema without changes in the pacing protocol.

Pain related syndrome of inappropriate antidiuretic hormone secretion in a kitten.

A 2-month-old domestic shorthair kitten was presented for evaluation of weakness, gait abnormalities, and signs of pain after trauma. On admission, the patient was found laterally recumbent with obvious gait abnormalities: difficulty rising from sitting and marked unilateral left hind limb lameness. On orthopedic examination, severe pain, crepitations, and swelling of the left hind limb were detected. Results of the first diagnostic work-up were all consistent with hyponatremia, hypochloremia and a Salter-Harris type I fracture. The kitten initially received isotonic fluids, analgesia, and antiemetic treatment. Twelve hours after admission, the analgesic plan was considered insufficient, and the general patient's condition worsened, showing severe mental depression. Blood and urine samples were collected for a more in-depth diagnostic evaluation; the patient showed worsening hyponatremia (113 mmol/L; [RR: 146,2-156,2]), severe plasma hypoosmolality (218.2 mOsm/kg; [RR: 287-307 mOsm/kg]), high natriuresis (Na: 74.9 mmol/L; [RR: <40 mmol/L]), and urinary hyperosmolality (630 mOsm/kg; [RR: <150 mOsm/kg]). Based on these new clinical findings syndrome of inappropriate antidiuretic hormone (SIADH) secretion was diagnosed. Emergency treatment with hypertonic saline was then instituted, a constant rate infusion of 3% hypertonic saline infusion to increase plasma sodium was initiated and a loop diuretic, furosemide (1 mg/kg/IV), was administered at 12-hour intervals to induce diuresis. Discharge occurred 4 days after admission as the patient was clinically stable and the hyponatremia progressively resolved. To the author's knowledge this is the first report of a kitten developing pain related SIADH associated to orthopedic trauma.

Approach to the patient with suspected hypotonic polyuria.

Investigation and management of hypotonic polyura is a common challenge in clinical endocrinology. The three main causes, recently renamed to arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus), AVP-resistance (AVP-R, formerly nephrogenic diabetes insipidus), and primary polydipsia (PP) require accurate diagnosis as management differs for each. This new nomenclature more accurately reflects pathophysiology, and has now been adopted by the Systemised Nomenclature of Medicine (SNOMED). Advances in diagnosis over the last few years have centered around the use of copeptin measurement. Here, we use three patient case histories to highlight the use of this approach, and to demonstrate how it can succeed where other approaches, such as the water deprivation test, sometimes fail. We discuss the overall approach to each type of patient and the strengths and limitations of diagnostic strategies, illustrating the use of the new nomenclature.

Effects of Total Parenteral Nutrition on Serum Osmolality and Patent Ductus Arteriosus.

BACKGROUND: The persistence of high serum osmolality in the early postnatal period is a risk for developing patent ductus arteriosus (PDA). Early aggressive nutrition (EAN), involving total parenteral nutrition (TPN), by which enough concentrations of glucose and amino acids are administered intravenously, is recommended postnatally to improve the neurological prognosis in preterm infants. However, the effects of EAN involving TPN on serum osmolality and the development of a PDA have not been adequately studied. OBJECTIVES: Thus, in this study, we aimed to investigate the impact of TPN on serum osmolality and determine whether increased serum osmolality could be associated with a higher incidence of PDA in preterm infants. METHODS: In this single-center retrospective observational study, preterm infants born at <28 weeks of gestation who had been admitted to our neonatal intensive care unit (NICU) before (pre-TPN period) and after the introduction of TPN (post-TPN) were included. We reviewed the medical records of these patients, compared the changes in serum osmolality from birth to five days after birth, the clinical background, and the incidence of PDA between these two periods, and analyzed the risk factors. Additionally, the factors affecting the serum osmolality in very preterm infants were examined. The patients who met the intervention criteria of our NICU and received a cyclooxygenase (COX) inhibitor, Indacin® (Nobelpharma, Tokyo, Japan), within seven days after birth were classified as PDA+; those who could not be identified to have PDA flow by echo and did not receive a COX inhibitor were classified as PDA-. RESULTS: The postnatal day and serum sodium (Na+) were statistically significantly correlated with a higher serum osmolality. Serum osmolality remained statistically significantly higher in the PDA+ cohort compared with the PDA- cohort after the first day of life. However, no statistically significant differences were observed in serum osmolality after 24 hours of age, weeks of gestational age, birth weight, or incidence of PDA between the pre- and post-TPN periods. The results of the multiple logistic regression analyses revealed that the increased serum osmolality correlated with PDA development. CONCLUSIONS: In this study, the serum Na+ statistically significantly correlated with a higher serum osmolality. Moreover, the increased serum osmolality correlated with PDA development. Thus, the prevention of hypernatremia might reduce the incidence of PDA. Nonetheless, the findings in this study revealed that no statistically significant differences in serum osmolality were observed between the pre-and post-TPN periods, indicating that TPN had little effect on serum osmolality.

Association between serum osmolality and risk of in-hospital mortality in patients with intracerebral hemorrhage.

Aim: This study aimed to analyze the association between serum osmolality and the risk of in-hospital mortality in intracerebral hemorrhage (ICH) patients. Methods: In this retrospective cohort study, data of a total of 1,837 ICH patients aged ≥18 years were extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV). Serum osmolality and blood urea nitrogen (BUN)-to-creatinine (Cr) ratio (BCR) were used as the main variables to assess their association with the risk of in-hospital mortality in ICH patients after first intensive care unit (ICU) admission using a univariable Cox model. Univariable and multivariable Cox regression analyses were applied to explore the associations between serum osmolality, BCR, and in-hospital mortality of ICH patients. Hazard ratio (HR) and 95% confidence intervals (CIs) were calculated. Results: The median survival duration of all participants was 8.29 (4.61-15.24) days. Serum osmolality of ≥295 mmol/L was correlated with an increased risk of in-hospital mortality in patients with ICH (HR = 1.43, 95%CI: 1.14-1.78). BCR of >20 was not significantly associated with the risk of in-hospital mortality in ICH patients. A subgroup analysis indicated an increased risk of in-hospital mortality among ICH patients who were women, belonged to white or Black race, or had complications with acute kidney injury (AKI). Conclusion: High serum osmolality was associated with an increased risk of in-hospital mortality among ICH patients.

Copeptin as a surrogate marker for arginine vasopressin: analytical insights, current utility, and emerging applications.

Copeptin is a 39-amino-acid long glycosylated peptide with a leucine-rich core segment in the C-terminal part of pre-pro-vasopressin. It exhibits a rapid response comparable to arginine vasopressin (AVP) in response to osmotic, hemodynamic, and nonspecific stress-related stimuli. This similarity can be attributed to equimolar production of copeptin alongside AVP. However, there are markedly different decay kinetics for both peptides, with an estimated initial half-life of copeptin being approximately two times longer than that of AVP. Like AVP, copeptin correlates strongly over a wide osmolality range in healthy individuals, making it a useful alternative to AVP measurement. While copeptin does not appear to be significantly affected by food intake, small amounts of oral fluid intake may result in a significant decrease in copeptin levels. Compared to AVP, copeptin is considerably more stable in vitro. An automated immunofluorescent assay is now available and has been used in recent landmark trials. However, separate validation studies are required before copeptin thresholds from these studies are applied to other assays. The biological variation of copeptin in presumably healthy subjects has been recently reported, which could assist in defining analytical performance specifications for this measurand. An established diagnostic utility of copeptin is in the investigation of polyuria-polydipsia syndrome and copeptin-based testing protocols have been explored in recent years. A single baseline plasma copeptin >21.4 pmol/L differentiates AVP resistance (formerly known as nephrogenic diabetes insipidus) from other causes with 100% sensitivity and specificity, rendering water deprivation testing unnecessary in such cases. In a recent study among adult patients with polyuria-polydipsia syndrome, AVP deficiency (formerly known as central diabetes insipidus) was more accurately diagnosed with hypertonic saline-stimulated copeptin than with arginine-stimulated copeptin. Glucagon-stimulated copeptin has been proposed as a potentially safe and precise test in the investigation of polyuria-polydipsia syndrome. Furthermore, copeptin could reliably identify those with AVP deficiency among patients with severe hypernatremia, though its diagnostic utility is reportedly limited in the differential diagnosis of profound hyponatremia. Copeptin measurement may be a useful tool for early goal-directed management of post-operative AVP deficiency. Additionally, the potential prognostic utility of copeptin has been explored in other diseases. There is an interest in examining the role of the AVP system (with copeptin as a marker) in the pathogenesis of insulin resistance and diabetes mellitus. Copeptin has been found to be independently associated with an increased risk of incident stroke and cardiovascular disease mortality in men with diabetes mellitus. Increased levels of copeptin have been reported to be independently predictive of a decline in estimated glomerular filtration rate and a greater risk of new-onset chronic kidney disease. Furthermore, copeptin is associated with disease severity in patients with autosomal dominant polycystic kidney disease. Copeptin predicts the development of coronary artery disease and cardiovascular mortality in the older population. Moreover, the predictive value of copeptin was found to be comparable with that of N-terminal pro-brain natriuretic peptide for all-cause mortality in patients with heart failure. Whether the measurement of copeptin in these conditions alters clinical management remains to be demonstrated in future studies.

The association between renal medullary and cortical fibrosis, stiffness, and concentrating capacity: an observational, single-center cross-sectional study.

BACKGROUND: Fibrosis is a common final pathway leading to end-stage renal failure. As the renal medulla and cortex contain different nephron segments, we analyzed the factors associated with the progression of renal medullary and cortical fibrosis. METHODS: A total of 120 patients who underwent renal biopsy at Kawashima Hospital between May 2019 and October 2022 were enrolled in this retrospective study. Renal medullary and cortical fibrosis and stiffness were evaluated using Masson's trichrome staining and shear wave elastography, respectively. Maximum urine osmolality in the Fishberg concentration test was also examined. RESULTS: Medullary fibrosis was positively correlated with cortical fibrosis (p < 0.0001) and log-converted urinary ß2-microglobulin (MG) (log urinary ß2-MG) (p = 0.022) and negatively correlated with estimated glomerular filtration rate (eGFR) (p = 0.0002). Cortical fibrosis also correlated with log urinary ß2-MG, eGFR, and maximum urine osmolality. Multivariate analysis revealed that cortical fibrosis levels (odds ratio [OR]: 1.063) and medullary stiffness (OR: 1.089) were significantly associated with medullar fibrosis (≧45%). The severe fibrosis group with both medullary fibrosis (≧45%) and cortical fibrosis (≧25%) had lower eGFR and maximum urine osmolality values and higher urinary ß2-MG levels than the other groups. CONCLUSIONS: Patients with disorders involving both renal medullary and cortical fibrosis had decreased maximum urine osmolality but had no abnormalities in the urinary concentrating capacities with either condition. Renal medullary and cortical fibrosis were positively correlated with urinary ß2-MG, but not with urinary N-acetyl-beta-D-glucosaminidase.

Heart failure related fatigue: An exploratory analysis of serum osmolality from the national health and nutrition examination survey.

BACKGROUND: Fatigue is a prominent symptom of heart failure (HF). However, underlying mechanisms remain poorly understood. Fluid volume status has been suggested as a physiologic mechanism of HF-related fatigue. Serum osmolality may fluctuate with changes in volume status associated with neurohormonal dysregulation. The relationship of fatigue to serum osmolality has not been assessed in adults with HF. OBJECTIVES: Describe the relationship between serum osmolality and fatigue in adults with HF. METHODS: We analyzed two waves of cross-sectional data from the National Health and Nutrition Examination Survey (2015-2016 and 2017-2018). Adults who self-reported having HF without select co-morbid conditions known to contribute to fatigue were included. Data were weighted to provide US national estimates, and complex sample design used for analyses. Sequential logistic regression was used to isolate the effect of serum osmolality on the odds of having fatigue. RESULTS: Data from the sample represented 1.4 million Americans with HF (58.5 % male; median age 68 years), of whom 1,001,589 (67.9 %) reported fatigue. Participants with fatigue had lower serum osmolality compared to those without fatigue (t = -3.04, p = .009). Higher serum osmolality was associated with 8.8 % lower odds of experiencing fatigue when controlling for sex and body mass index (OR = 0.912, p = .007, CI 0.857 - 0.972). CONCLUSIONS: HF-related fatigue is associated with lower serum osmolality. Low serum osmolality may indicate excess volume and the presence of a heightened neurohormonal response, both of which may influence fatigue. Alternatively, serum osmolality may directly affect other physiologic changes that may contribute to fatigue.

PEG 300 Promotes Mesodermal Differentiation in iPSC-Derived Embryoid Body Formation In Vitro.

Embryoid bodies (EB) are sensitive to changes in the culture conditions. Recent studies show that the addition of PEG 300 to culture medium affects cell growth and differentiation; however, its effect on the embryoid body is unclear. This study aims to understand the role of PEG 300 in the process of EB formation and germ layer differentiation. EBs formed more efficiently and differentiated toward the mesoderm when cultured in a medium supplemented with appropriate concentrations of PEG 300. The expression of T/Bry, a marker of mesodermal differentiation, increases in EBs in the PEG group, and the expression of TUBB3 generally decreases, showing a quantitative relationship with PEG. Furthermore, further differentiation of PEG-pretreated EB into vascular smooth muscle cells (VSMCs) by directional induction shows that PEG 300-pretreated induced VSMCs have higher expression of phenotypic markers and greater secretory and contractile functions. This study highlights the role of PEG 300 in the culture medium during EB differentiation, which can significantly enhance mesodermal gene expression and the efficiency of subsequent differentiation into smooth muscle cells and other target cells.

Physical properties of soft contact lens multipurpose solutions commercially available in Ghana.

Purpose: To investigate the physical properties of commercially available multipurpose soft contact lens solutions in Ghana. Methods: pH (Kelilong ICL-099 pH meter, China), osmolality (OSMOMAT 3000, GONOTEC, Germany), surface tension (Sigma 700 Tensiometer, Sweden), and viscosity (CFOC-200 Viscometer, Cannon Company, USA) of various soft contact lens multipurpose solutions (MPS) were measured in triplicates at room temperature. Viscosity measurements were also taken at 34 °C ocular surface temperature. The solutions examined were Opti-Free Replenish (OFR), Trufresh (TF), Avizor (AV), Freshlook (FL), and Refresh (RF). Results: Several solutions were largely hypo-osmotic in the range of 108-231 mOsm/kg, the exception being Avizor, which had osmolality values that were closer to human tears (301 ± 0.58 mOsm/kg). The range of pH values of the solutions (6.33-8.24, mean (SD) = 7.53 ± 0.18) fell within the reported tolerable range for the ocular surface (6.20-9.00). Surface tension values ranged from 35.86 to 42.27 mNm with a mean of 38.49 ± 2.32 mNm. The average viscosity of most solutions at room temperature (25 °C) was 1.44 ± 0.49 cP with a range of 1.04-2.15 cP. Significantly lower values ranging from 0.79 to 1.58 cP were obtained at ocular surface temperature (34 °C), p = 0.0001). Conclusions: The physical properties of many of the solutions used as MPS in Ghana are markedly variable. Nevertheless, pH, surface tension, and viscosity fall within the acceptable limits of ocular physiological tolerance; except for osmolality, which majority were outside the reported tolerable range for the ocular surface. This information may partly explain the reason some patients exhibit strong preferences for certain care systems and should aid clinical decision-making when prescribing eye care systems to patients.

Increased water intake dilutes protective uromodulin levels in urine and results in increased rates of pyelonephritis in a murine model.

AIM: Urinary tract infections (UTIs) rank among the most prevalent infections in humans, carrying substantial implications for public health. Women experiencing recurrent UTIs are often advised to boost their fluid intake to help eliminate bacteria. In this study, we explored the impact of elevated fluid consumption during UTIs using a mouse model of pyelonephritis. METHODS: UTI was induced in 8-10 w female BALB/cJ-mice by surgically injecting Escherichia coli (O6:K13:H1) into the bladder whereafter mice were randomized to gel food (GF) or regular chow. Immune response and infection severity were determined 24-h post-infection. In vitro bacterial growth (OD600) was determined in urine from mice or from human volunteers. RESULTS: Gel feeding increased urine output (1.40 ± 0.77 µL min-1, p < 0.01) and diluted the urine (668.7 ± 177 mOsmol kg-1, p < 0.0001) compared to controls on regular chow (urine output: 0.34 ± 0.27 µL min-1, osmolality: 1439 ± 473.5 mOsmol kg-1). Mice on GF had a higher risk of pyelonephritis (87.5%) and more severe infections (26.22 ± 9.88 CFU mg-1 tissue) compared to controls (43.75%; 3.87 ± 3.56 CFU mg-1, p < 0.01). Correspondingly, the growth of E. coli was markedly reduced at osmolalities above 1200 mOsmol kg-1 compared to 600 mOsmol kg-1 and GF mice had lower urine levels of uromodulin (13.70 ± 1.89 µg mL-1, p < 0.01) compared to controls (24.65 ± 2.70 µg mL-1). CONCLUSION: Increased water intake and urine flow in mice will markedly increase the risk of pyelonephritis. The increased risk may reflect reduced urine uromodulin combined with optimized growth conditions for E. coli. The study does not immediately support the notion that established UTIs can be eliminated by increased water intake.