Randomized comparison of in vivo performance of TearLab® and I-PEN® osmometry in normal dogs.

OBJECTIVE: To compare tear film (TF) osmolarity measured using TearLab® and I-PEN® osmometers in the same dogs without any ocular surface disease. ANIMAL STUDIED: Fifty-two dogs (98 eyes) of different breeds were evaluated. PROCEDURES: Tear film (TF) osmolarity was evaluated at 2-min intervals. The test was randomly determined, and single measurements were performed using each osmometer. Subsequently, complete ophthalmologic examinations were performed based on Schirmer tear test-1 (STT-1) analysis, tear film breakup time (TFBUT), and slit-lamp biomicroscopy. For each osmometer, the mean ± standard deviation of the TF osmolarity was calculated, and a paired Student's t-test was used to compare the values obtained. Pearson correlation analysis was performed to assess the association between osmolarity and other values such as STT-1, TFBUT, and age. RESULTS: Tear film osmolarity determined using TearLab® (340.42 ± 15.87 mOsm/L) and I-PEN® (321.58 ± 17.39 mOsm/L) were significantly different (p < .001). However, statistical significance could not be confirmed between osmolarity and other values, such as STT-1, TFBUT, and age. CONCLUSIONS: In dogs, the TF osmolarity values obtained using TearLab® tend to be higher than those obtained using I-PEN®, contrary to that observed in humans. These findings can serve as a reference for establishing normal values for each osmometer for clinical use in measuring TF osmolarity in dogs.

Determination of specific and non-specific protein-protein interactions for beta-lactoglobulin by analytical ultracentrifugation and membrane osmometry experiments.

Protein-protein interactions are essential for the understanding of biological processes. Specific protein aggregation is an important aspect for many biological systems. In particular, electrostatic interactions play the key role for protein-protein interactions, as many amino acids have pH-dependent charge states. Moreover, protein dissociation is directly related to the solution pH, ionic strength, temperature and protein concentration. The subtle interplay between different specific and non-specific interactions is demonstrated for beta-lactoglobulin (BLG) with a focus on low salt concentrations, thus mimicking technically relevant processing conditions. BLG is a well-characterized model system, proven to attain its monomer-dimer equilibrium strongly dependent upon the pH of the solution. In this manuscript, we present a unique combination of analytical ultracentrifugation and membrane osmometry experiments, which quantifies specific and non-specific interactions, i.e. in terms of the dimer dissociation constants and the second osmotic virial coefficient, at pH 3 and 7 and sodium chloride concentrations of 10 mM and 100 mM. This provides direct insight to protein-protein interactions for a system with a concentration-dependent monomer-dimer equilibrium. Moreover, using a coarse-grained extended DLVO model in combination with molecular dynamics simulations, we quantify non-specific monomer-monomer, monomer-dimer and dimer-dimer interactions as well as the binding free energy of BLG dimerization from theoretical calculations. The experimentally determined interactions are shown to be mainly governed by electrostatic interactions and further agree with free energy calculations. Our experimental protocol aims to determine non-specific and specific interactions for a dynamically interacting system and provides an understanding of protein-protein interactions for BLG at low salt concentrations.

Evaluation of tear osmolarity measured by I-Pen osmolarity system in patients with dry eye.

This retrospective comparative study was to evaluate tear osmolarity measured by I-Pen osmolarity system (I-MED Pharma Inc, Dollard-des-Ormeaux, Quebec, Canada) in healthy subjects without dry eye disease (DED) and patients with DED, and its association with other ocular surface parameters. This study comprised 65 eyes of 65 patients. The ocular surface parameters including tear osmolarity with I-Pen osmometer of the patients who visited the refractive surgery center of Samsung Medical Center between January 1, 2020 and May 31, 2020 were retrospectively collected. The subjects were divided as asymptomatic normal group and symptomatic dry eye group. The distribution of tear osmolarity and its association with other ocular surface parameters were evaluated. Total thirty-two patients (32 eyes) were included in the control group, and 33 patients (33 eyes) were included in the DED group. Tear osmolarity was significantly higher in the DED group. Tear osmolarity was negatively correlated with tear break-up time, and the Schirmer test, and was positively correlated with Ocular Surface Disease Index symptom score. The cut-off value of 318 mOsm/L showed a sensitivity of 90.9% and specificity of 90.6% for diagnosing DED. The I-Pen osmometer can be considered suitable for use in the clinical setting, with good performance in DED diagnosis.

Utility of Tear Osmolarity Measurement in Diagnosis of Dry Eye Disease.

The prevalence of dry eye disease is high worldwide and poses a great burden on patients' daily lives. Accurate diagnosis of the disease is important, and it requires application of various methods. Hyperosmolarity is believed to be the disease marker and thus measuring it provides useful information. In this study we investigated utility of tear osmolarity measured with TearLab osmometer, along with other diagnostic tests (Ocular Surface Disease Index questionnaire, Tear film break-up time, Ocular Protection Index, Ocular Surface Staining, Schirmer I test, Meibomian gland functionality in 757 patients (1514 eyes) with dry eye disease and 29 healthy controls (58 eyes). Statistical differences between the patient group and the control group were observed for all the tests apart from tear osmolarity, regardless of cut-off value (>308 mOsm/L, >316 mOsm/L, and inter-eye difference >8 mOsm/L). Moreover, in the receiver operating characteristics curve analyses tear osmolarity measurement could not discriminate dry eye disease pathological scores. Therefore, our study suggests that tear osmolarity measured with TearLab osmometer cannot be used as a key indicator of DED.

Comparison of measured and calculated osmolality levels.

BACKGROUND: Serum osmolality levels are measured to determine acid-base and electrolyte imbalance in serum. In cases where measurement is not possible, the serum osmolality value can be calculated by various calculation methods. In this study, we compared the Worthley osmolality calculation method which is used most frequently mentioned in literature and the measurements made with vapor pressure osmometer used in our laboratory. We compared whether there was a difference between the results obtained by measurement and calculation method in different age groups. METHODS: 221 serum samples of patients who were admitted to the Eskisehir Osmangazi University Hospital Biochemistry Laboratory between December 2016 and May 2018 were included in this study. Glucose, blood urea nitrogen and sodium values were recorded to determine the calculated osmolality values of the patients. RESULTS: There was a statistically significant difference between the measured osmolality values and the calculated osmolality values of the patients (p < 0.001). When compared according to age groups, there was a significant difference between calculated osmolality values (p = 0.006), but there was no difference in measured osmolality values (p = 0.787) in different age groups. It has been observed that this difference in the calculated osmolality values between the age groups is derived from the adult group (18-65, p < 0.001). CONCLUSION: Our results showed that it is not reliable to calculate serum osmolality values, especially in the adult age group. According to our results the calculated osmolality values are higher than our measured osmolality values.

Physicochemical characterization of micafungin and anidulafungin for its nebulized administration.

OBJECTIVE: To determine by experimentation whether micafungin and  anidulafungin possess physicochemical properties suitable for  nebulization. METHOD: PH, osmolality, viscosity, density and chloride content were  determined by pH monitoring, osmometry, viscometry, densitometry  and potentiometry in two samples of different concentrations, 5 and 10  mg/mL each echinocandin. Results: The results obtained for micafungin solution were: pH 5.80 (0.14), osmolality 293.33 (1.53) mOsm/kg, chloride content  134.67 (0.58) mmol/L and density 1,009.4 (0,1) kg/m3; while for 10  mg/mL solution: osmolality 342.00 (1.00) mOsm/kg, chloride content  139.67 (0.58) mmol/L and density 1,014.5 (0.2) kg/m3. The results  obtained for 5 mg/mL anidulafungin were: pH 4.22 (0.01), osmolality  464.67 (2.52) mOsm/kg, chloride content 137.00 (0.00) mmol/L and  density 1,016.5 (0,2) kg/m3; while for 10 mg/mL solution: osmolality  656.33 (1.15) mOsm/kg, chloride content 132.00 (0.00) mmol/L and  density 1,029.8 (0.4) kg/m3. Conclusions: PH, osmolality, chloride content and density values  proved to be suitable for proper tolerability by nebulization.

Objetivo: Determinar experimentalmente si micafungina y  nidulafungina poseen propiedades fisicoquímicas adecuadas para su  nebulización.Método: Se determinó el pH, la osmolalidad, la viscosidad, la densidad y el contenido en cloruros mediante pH-metría, osmometría,  viscosimetría, densitometría y potenciometría, respectivamente, en dos  muestras de diferente concentración, 5 y 10 mg/ml, de cada  equinocandina.Resultados: Para la solución de micafungina 5 mg/ml los resultados  obtenidos fueron: pH 5,80 (0,14), osmolalidad 293,33 (1,53) mOsm/kg,  contenido en cloruros 134,67 (0,58) mmol/l y densidad  1.009,4 (0,1) kg/m3; y para la solución de 10 mg/ml: osmolalidad  342,00 (1,00) mOsm/kg, contenido en cloruros 139,67 (0,58) mmol/l y  densidad 1.014,5 (0,2) kg/m3. Para la solución de anidulafungina 5  mg/ml los resultados obtenidos fueron: pH 4,22 (0,01), osmolalidad  464,67 (2,52) mOsm/kg, contenido en cloruros 137,00 (0,00) mmol/l y  densidad 1.016,5 (0,2) kg/m3; y para la solución de 10 mg/ml:  osmolalidad 656,33 (1,15) mOsm/kg, contenido en cloruros 132,00  (0,00) mmol/l y densidad 1.029,8 (0,4) kg/m3. Conclusiones: Los valores de pH, osmolalidad, contenido en cloruros y densidad resultaron adecuados para una correcta tolerabilidad  ediante nebulización.

Calculated Versus Measured Urine Osmolarity: Accuracy of Estimated Urine Density.

BACKGROUND: Urine osmolarity (OsmU) is the gold standard for the evaluation of the kidney's urine concentration capacity; nevertheless, urinary density (UD) is often used as a surrogate for its estimation. OBJECTIVE: The objective of this study was to analyze the accuracy of UD in estimating OsmU. MATERIALS AND METHODS: A transversal study including patients with simultaneous determination of UD measured with refractometry and OsmU measured by osmometer (OsmUm). We multiplied the last two digits of the UD by 35, 30, 32, 33.5, and 40 to estimate OsmU; the estimates were considered precise if the value was ± 30 mOsm/kg from the OsmUm. A Bland-Altman analysis was conducted. RESULTS: Among 205 patients, there was no difference between OsmUm and the estimated form when using a factor of 33.5 (p = 0.578). When analyzing by the absence or presence of proteinuria and/or glycosuria, there were no differences when using the factors 35 (p = 0.844) and 32 with adjusted UD (p = 0.898). In the linear correlation analysis, values for Pearson's r = 0.788 and r2 = 0.621 were obtained (p < 0.001). The areas under the curve obtained by the receiver operating characteristics curves to estimate urine osmolarity values < 100 and > 600 mOsm/kg were > 0.90. CONCLUSION: The estimation of the OsmU from UD showed adequate performance. If an osmometer is unavailable, we recommend using the factor 35 for clean samples and 32 with adjusted UD for samples with proteinuria and/or glycosuria.

Validity and Reliability of a Novel Handheld Osmolarity System for Measurement of a National Institute of Standards Traceable Solution.

PURPOSE: To evaluate the validity and reliability of a novel handheld osmolarity system (I-PEN Osmolarity System; I-MED Pharma Inc, Dollard-des-Ormeaux, Quebec, Canada) for measurement of the osmolarity of a National Institute of Standards and Technology (NIST) traceable solution at a variety of ambient temperatures. METHODS: A total of 65 measurements of an NIST solution with a verified osmolarity of 290 ± 2 mOsmol/L were taken using 3 separate handheld osmolarity systems, 65 unique single-use sensors (SUSs) from 3 different lots, and 2 adaptors. Mean values were calculated using the device, SUS, and adaptor. Measurements were taken using a handheld osmolarity system, an adaptor, and 56 individual SUSs at 6 different ambient temperatures ranging from 17.7 to 26.5°C. RESULTS: Overall, the mean osmolarity measured was 294.06 mOsmol/L (SD ±2.29; percent coefficient of variation 0.78), ranging from 286.60 to 298.18 mOsmol/L. This fell within a prespecified acceptable variability of ±4 mOsmol/L (SD ±7). Mean values did not vary across devices, adaptors, or single-use sensors used. Mean osmolarity measurements increased with rising ambient temperatures, with an R = 0.88. The temperature correction factor was calculated to be 2.01 mOsmol/L per °C. CONCLUSIONS: The osmolarity system reliably and accurately measured the osmolarity of an NIST solution in a laboratory setting, using an adaptor to correct for differences in resistance between a laboratory NIST solution measurement and direct measurements on the palpebral conjunctiva of the eyelid. The handheld osmolarity system represents a rapid and accurate instrument for measurement of tear osmolarity in a simulated testing setting.

Electrochemical Investigation of the Interaction between Catecholamines and ATP.

The study of the colligative properties of adenosine 5'-triphosphate (ATP) and catecholamines has received the attention of scientists for decades, as they could explain the capabilities of secretory vesicles (SVs) to accumulate neurotransmitters. In this Article, we have applied electrochemical methods to detect such interactions in vitro, at the acidic pH of SVs (pH 5.5) and examined the effect of compounds having structural similarities that correlate with functional groups of ATP (adenosine, phosphoric acid and sodium phosphate salts) and catecholamines (catechol). Chronoamperometry and fast scan cyclic voltammetry (FSCV) provide evidence compatible with an interaction of the catechol and adenine rings. This interaction is also reinforced by an electrostatic interaction between the phosphate group of ATP and the protonated ammonium group of catecholamines. Furthermore, chronoamperometry data suggest that the presence of ATP subtlety reduces the apparent diffusion coefficient of epinephrine in aqueous media that adds an additional factor leading to a slower rate of catecholamine exocytosis. This adds another plausible mechanism to regulate individual exocytosis events to alter communication.

Analytical validation and reference intervals for freezing point depression osmometer measurements of urine osmolality in dogs.

Urine osmolality (UOsm) is considered the most accurate measure of urine concentration and is used to assess body fluid homeostasis and renal function. We performed analytical validation of freezing point depression measurement of canine UOsm, to establish reference intervals (RIs) and to determine the effect of age, sex, and reproductive status on UOsm in dogs. Clinically healthy dogs ( n = 1,991) were retrospectively selected and stratified in groups by age (young [0-12 mo], adults [13-84 mo], and seniors [>84 mo]), sex (females and males), and reproductive status (intact and neutered). RIs were calculated for each age group. Intra- and inter-assay coefficients of variation were <1% in all cases. Good linearity ( r2 = 1, p < 0.001) and recovery (89-98%) were observed. The limit of detection and limit of quantification were zero. Urine specific gravity and UOsm had a highly significant positive correlation ( r = 0.96, p < 0.001) but had inconsistent agreement. The 95% RI for canine UOsm was 369-2,416 mOsm/kg in young and adult dogs, and 366-2,178 mOsm/kg in seniors. Senior dogs had a significantly lower UOsm than young and adult dogs ( p < 0.000). Neutered females had a significantly lower UOsm than intact female dogs ( p < 0.002). These results indicate that the method evaluated is adequate for UOsm measurement and that RIs based on age and reproductive status should be used in dogs.

Preferential interactions of trehalose, L-arginine.HCl and sodium chloride with therapeutically relevant IgG1 monoclonal antibodies.

Preferential interactions of weakly interacting formulation excipients govern their effect on the equilibrium and kinetics of several reactions of protein molecules in solution. Using vapor pressure osmometry, we characterized the preferential interactions of commonly used excipients trehalose, L-arginine.HCl and NaCl with three therapeutically-relevant, IgG1 monoclonal antibodies that have similar size and shape, but differ in their surface hydrophobicity and net charge. We further characterized the effect of these excipients on the reversible self-association, aggregation and viscosity behavior of these antibody molecules. We report that trehalose, L-arginine.HCl and NaCl are all excluded from the surface of the three IgG1 monoclonal antibodies, and that the exclusion behavior is linearly related to the excipient molality in the case of trehalose and NaCl, whereas a non-linear behavior is observed for L-arginine.HCl. Interestingly, we find that the magnitude of trehalose exclusion depends upon the nature of the protein surface. Such behavior is not observed in case of NaCl and L-arginine.HCl as they are excluded to the same extent from the surface of all three antibody molecules tested in this study. Analysis of data presented in this study provides further insight into the mechanisms governing excipient-mediated stabilization of mAb formulations.

How Osmolytes Counteract Pressure Denaturation on a Molecular Scale.

Life in the deep sea exposes enzymes to high hydrostatic pressure, which decreases their stability. For survival, deep sea organisms tend to accumulate various osmolytes, most notably trimethylamine N-oxide used by fish, to counteract pressure denaturation. However, exactly how these osmolytes work remains unclear. Here, a rigorous statistical thermodynamics approach is used to clarify the mechanism of osmoprotection. It is shown that the weak, nonspecific, and dynamic interactions of water and osmolytes with proteins can be characterized only statistically, and that the competition between protein-osmolyte and protein-water interactions is crucial in determining conformational stability. Osmoprotection is driven by a stronger exclusion of osmolytes from the denatured protein than from the native conformation, and water distribution has no significant effect on these changes at low osmolyte concentrations.

Coherent Experimental and Simulation Approach To Explore the Underlying Mechanism of Denaturation of Stem Bromelain in Osmolytes.

Characterization of a protein in the context of its environment is of crucial importance for a complete understanding of its function. Although biophysical techniques provide powerful tools for studying the stability and activity of the enzyme in the presence of various cosolvents, an approach of combining both experimental techniques and molecular dynamic (MD) simulations may lead to the mechanistic insight into the interactions governing the stability of an enzyme. The knowledge of these interactions can be further utilized for range of modifications in the wild form of an enzyme for various pharmaceutical applications. Herein, we employed florescence, UV-visible, circular dichroism (CD), dynamic light scattering (DLS) study, and MD simulations for comprehensive understanding of stem bromelain (BM) in the presence of betaine, sarcosine, arginine, and proline. The thermal stability of BM in the presence of 1 M of osmolytes is found to be in order: proline > betaine > buffer > arginine > sarcosine. BM gets more preferentially hydrated in the presence of betaine and proline than in sarcosine and arginine. Nonetheless, MD simulations suggest that betaine, sarcosine, and arginine at 1 M interact with the active site of BM through H-bonding except proline which are responsible for more disruption of active site. The distances between the catalytic site residues are 1.6, 1.9, 4.3, 5.0, and 6.2 Å for BM in proline, buffer, betaine, arginine, and sarcosine at 1 M, respectively. To the best of our knowledge, this is the first report on detailed unequivocal evidence of denaturation and deactivation of BM in the presence of methylamines and amino acids.

[New approaches to the treatment of keratoconjunctivitis sicca]. / Novye podkhody k lecheniiu sukhogo keratokon''iunktivita.

A new method has been developed for the treatment of severe forms of keratoconjunctivitis sicca (KCS) that involves the use of an original cyclosporine A (CyA) saturated soft contact lens (SCL) together with preservative-free artificial tears therapy. AIM: to evaluate the effectiveness of the newly developed treatment for KCS based on the use of medical SCL saturated with 0.05% CyA. MATERIAL AND METHODS: The patients (43 men, 60 eyes) with severe KCS were divided into 2 groups. Group 1 included 21 patients (30 eyes), who received artificial tears and wore 0.05% CyA-saturated silicone-hydrogel SCLs. Group 2 included 22 patients (30 eyes), who wore unsaturated original SCLs and received CyA instillations 2 times daily and, also, artificial tears. Apart from a standard ophthalmic examination, the assessment included Schirmer's test, Norn's test, vital eye stain tests, tear osmometry, laser confocal tomography of the cornea, optical coherence tomography of the anterior segment with meniscometry, impression cytology of the conjunctiva, tear pH measurement, plating of the content of the conjunctival cavity, measurement of the width of the palpebral fissure, and calculation of the ocular surface disease index. Treatment results were followed up at 1, 3, 6, and 12 months. RESULTS: The use of 0.05% CyA-saturated SCLs allows to halve treatment time for patients with severe KSC (down to 1 week - 1 month) as compared to unsaturated original SCLs in combination with 0.05% CyA instillations and to reduce it 5 times as compared to 0.05% CyA instillations only. CONCLUSION: The new method of KSC treatment that involves the use of medical SCL of original design (ensures even distribution of 0.05% CyA across the ocular surface) and preservative-free artificial tears has demonstrated high therapeutic effectiveness as compared to existing methods.

Calculating osmotic pressure of glucose solutions according to ASOG model and measuring it with air humidity osmometry.

The osmotic pressure of glucose solution at a wide concentration range was calculated using ASOG model and experimentally determined by our newly reported air humidity osmometry. The measurements from air humidity osmometry were compared with the well-established freezing point osmometry and ASOG model calculations at low concentrations and with only ASOG model calculations at high concentrations where no standard experimental method could serve as a reference for comparison. Results indicate that air humidity osmometry measurements are comparable to ASOG model calculations at a wide concentration range, while at low concentrations freezing point osmometry measurements provide better comparability with ASOG model calculations.

Rapid identification of osmolytes in tropical microalgae and cyanobacteria by (1)H HR-MAS NMR spectroscopy.

In this study, we report the chemical characterization of 47 tropical microalgae and cyanobacteria by HR-MAS. The generated data confirm the interest of HR-MAS as a rapid screening technique with the major advantage of its easiness. The sample is used as powder of freeze-dried microalgae without any extraction process before acquisition. The spectral fingerprints of strains are then tested as variables for a chemotaxonomy study to discriminate cyanobacteria and dinoflagellates. The individual factor map generated by PCA analysis succeeds in separating the two groups, essentially thanks to the presence of specific carbohydrates. Furthermore, more resolved signals enable to identify many osmolytes. More precisely the characteristics δ of 2-O-alpha-D-glucosylglycerol (GG) are observed in all 21 h-MAS spectra of tropical cyanobacteria. After specific extraction, complementary analysis by 1D and 2D-NMR spectroscopies validates the identification of this osmolyte.

Lack of Agreement among Electrical Impedance and Freezing-Point Osmometers.

PURPOSE: To assess the interchangeability of tear osmolarity measurements between electrical impedance and freezing-point depression osmometers and to analyze inter-eye tear osmolarity variability measured with these osmometers in healthy subjects. METHODS: Tear osmolarity was measured using the TearLab osmometer (OcuSense Inc., San Diego, CA) and the Fiske 210 microsample osmometer (Advanced Instruments Inc., Norwood, MA). We randomly selected one eye in 50 subjects (29 women, 21 men; mean age, 33.16 ± 6.11 years) to analyze whether osmolarity measurements by these osmometers were interchangeable. Both eyes of 25 patients (15 women, 10 men; mean age, 34.32 ± 6.37 years) were included to analyze inter-eye osmolarity variability. RESULTS: The mean tear osmolarity values measured with the TearLab osmometer were higher (305.22 ± 16.06 mOsm/L) than those with the Fiske 210 osmometer (293.40 ± 12.22 mOsm/L), with the intraclass correlation coefficient being 0.23 (p = 0.051). A Bland-Altman plot showed that the systems were not interchangeable because there was a systematic difference, with the limits of agreement being -17.93 to 41.57 mOsm/L. There were no statistically significant differences (p = 0.5006 and p = 0.6533, respectively) between an individual's eyes measured with either osmometer. CONCLUSIONS: Because the TearLab tear osmolarity measurements were higher than those of the Fiske 210 measurements and the limits of agreement were too wide, the two osmolarity values cannot be used interchangeably. In healthy subjects, there is no difference in tear osmolarity between right and left eyes of the same individual measured with both instruments.

Effects of maternal hydration status on the osmolality of maternal milk

Background: It has been demonstrated that human milk osmolality (Mosm) is regulated within an established range, typically 290 to 300 mOsm/kg, and appears to be resistant to effects of maternal dehydration, as reflected by high urinary osmolality (Uosm). Objective: To determine the degree of association between Mosm and Uosm at a common point in time, as well as the reproducibility of both measures over a one-week interval of sampling. Methods: Mosm and Uosm were measured with a Vogel Löser 450 osmometer on samples of the respective biological fluids collected concurrently in 31 lactating women, with infants aged between 30 and 340 days. In the first 15 women recruited, collections were repeated 7 days after the initial ones. Results: The median Mosm for the 46 samples collected was 308 mOsm/kg with a range from 288 to 448 mOsm/kg. The corresponding values for Uosm were 598 mOsm/kg with a range from 93 to 1,678 mOsm/kg. The Spearman rank-order correlation coefficient for within-individual association of Mosm and Uosm was r = 0.214 (p = 0.153). The median Mosm for the 15 repeat-subjects was 309 mOsm/kg on both occasions, with a within-individual Spearman coefficient of r = 0.326 (p = 0.118). By contrast, for the Uosm, the within-subject association was much stronger, with r = 0.699 (p = 0.002). Conclusions: The osmometry technique proved to be a highly stable and reproducible measurement technique. Mosm and Uosm are not significantly associated at a point in time. Intra-subject Mosm varies more across time than intra-subject Uosm (AU)

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