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Abstract Serum osmolality is the sum of the osmolalities of every single dissolved particle in the blood such as sodium and associated anions, potassium, glucose, and urea. Under normal conditions, serum sodium concentration is the major determinant of serum osmolality. Effective blood osmolality, so-called blood tonicity, is created by the endogenous (e.g., sodium and glucose) and exogenous (e.g., mannitol) solutes that are capable of creating an osmotic gradient across the membranes. In case of change in effective blood osmolality, water shifts from the compartment with low osmolality into the compartment with high osmolarity in order to restore serum osmolality. The difference between measured osmolality and calculated osmolarity forms the osmolal gap. An increase in serum osmolal gap can stem from the presence of solutes that are not included in the osmolarity calculation, such as hypertonic treatments or toxic alcoholic ingestions. In clinical practice, determination of serum osmolality and osmolal gap is important in the diagnosis of disorders related to sodium, glucose and water balance, kidney diseases, and small molecule poisonings. As blood hypertonicity exerts its main effects on the brain cells, neurologic symptoms varying from mild neurologic signs and symptoms to life-threatening outcomes such as convulsions or even death may occur. Therefore, hypertonic states should be promptly diagnosed and cautiously managed. In this review, the causes and treatment strategies of hyperosmolar conditions including hypernatremia, diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome, hypertonic treatments, or intoxications are discussed in detail to increase awareness of this important topic with significant clinical consequences.

Background Water intake and hydration status have been suggested to impact cognition; however, longitudinal evidence is limited and often inconsistent. This study aimed to longitudinally assess the association between hydration status and water intake based on current recommendations, with changes in cognition in an older Spanish population at high cardiovascular disease risk. Methods A prospective analysis was conducted of a cohort of 1957 adults (aged 55–75) with overweight/obesity (BMI between ≥ 27 and < 40 kg/m 2 ) and metabolic syndrome from the PREDIMED-Plus study. Participants had completed bloodwork and validated, semiquantitative beverage and food frequency questionnaires at baseline, as well as an extensive neuropsychological battery of 8 validated tests at baseline and 2 years of follow-up. Hydration status was determined by serum osmolarity calculation and categorized as < 295 mmol/L (hydrated), 295–299.9 mmol/L (impending dehydration), and ≥ 300 mmol/L (dehydrated). Water intake was assessed as total drinking water intake and total water intake from food and beverages and according to EFSA recommendations. Global cognitive function was determined as a composite z -score summarizing individual participant results from all neuropsychological tests. Multivariable linear regression models were fitted to assess the associations between baseline hydration status and fluid intake, continuously and categorically, with 2-year changes in cognitive performance. Results The mean baseline daily total water intake was 2871 ± 676 mL/day (2889 ± 677 mL/day in men; 2854 ± 674 mL/day in women), and 80.2% of participants met the ESFA reference values for an adequate intake. Serum osmolarity (mean 298 ± 24 mmol/L, range 263 to 347 mmol/L) indicated that 56% of participants were physiologically dehydrated. Lower physiological hydration status (i.e., greater serum osmolarity) was associated with a greater decline in global cognitive function z -score over a 2-year period ( β : − 0.010; 95% CI − 0.017 to − 0.004, p -value = 0.002). No significant associations were observed between water intake from beverages and/or foods with 2-year changes in global cognitive function. Conclusions Reduced physiological hydration status was associated with greater reductions in global cognitive function over a 2-year period in older adults with metabolic syndrome and overweight or obesity. Future research assessing the impact of hydration on cognitive performance over a longer duration is needed. Trial registration International Standard Randomized Controlled Trial Registry, ISRCTN89898870. Retrospectively registered on 24 July 2014

is the best studied eukaryote and a valuable tool for most aspects of basic research on eukaryotic organisms. This is due to its unicellular nature, which often simplifies matters, offering the combination of the facts that nearly all biological functions found in eukaryotes are also present and well conserved in . . In addition, it is also easily amenable to genetic manipulation. Moreover, unlike other model organisms, . is concomitantly of great importance for various biotechnological applications, some of which date back to several thousands of years. . 's biotechnological usefulness resides in its unique biological characteristics, i.e., its fermentation capacity, accompanied by the production of alcohol and CO and its resilience to adverse conditions of osmolarity and low pH. Among the most prominent applications involving the use of . are the ones in food, beverage -especially wine- and biofuel production industries. This review focuses exactly on the function of . in these applications, alone or in conjunction with other useful microorganisms involved in these processes. Furthermore, various aspects of the potential of the reservoir of wild, environmental, . isolates are examined under the perspective of their use for such applications.

Purpose To evaluate the structural changes in corneal sub-basal nerves of dry eye disease (DED) patients with tear hyperosmolarity versus normosmolar tears. Methods A prospective evaluation of the tear film (keratograph 5 M), tear osmolarity, and sub-basal corneal nerves (laser scanning in-vivo confocal microscopy) was performed in a cohort of 53 DED patients (106 eyes) diagnosed as per DEWS II criteria. Patients with tear hyperosmolarity (Group 1, n  = 48 eyes) were compared with DED patients without tear hyperosmolarity (Group 2, n  = 58 eyes). Results Of 53 patients (27 females), 28 had Sjogren’s syndrome, and the rest had meibomian gland dysfunction. There were more SS patients (21 vs 7) and females in Group 1. The two groups were similar in age, TMH, NIBUT, meibomian gland loss, bulbar redness, and corneal staining, except for Schirmer I ( p  < 0.001), and tear osmolarity ( p  < 0.001; worse in group 1). The groups did not differ in dendritic cell density, whether immature (53.8 vs. 38) or mature (2.7 vs. 0). The significantly different corneal nerve parameters were nerve fiber length (p = 0.005), density ( p  = 0.01), and branching density ( p  = 0.04), with lower values observed in group 1. Only tear osmolarity had a weak negative correlation with corneal nerve fiber length (r, -0.38), density (r, -0.32), and branching (r, -0.28). SS patients with hyperosmolar tears had reduced nerve fiber length and branching compared to SS patients with normosmolar tears. Conclusion Tear hyperosmolarity is associated with reduced nerve branching, fiber density, and fiber length despite similar levels of conjunctival congestion, tear film stability, and meibomian gland loss in DED patients. Key messages What is known • Corneal nerves are reduced in density and length in dry eye disease patients. • Laboratory studies have shown fragmentation of corneal nerves on exposure to hyperosmolar solutions. What is new • Tear hyperosmolarity is associated with reduced nerve branching, fiber density, and fiber length in dry eyes compared to normosmolar tears. • The effect is independent of dendritic cell density.

PurposeTo compare tear film osmolarity (TFO) values and matrix metalloproteinase 9 (MMP-9) levels between anophthalmic sockets and healthy fellow eyes and to assess the use of the MMP-9 and TFO as objective biomarkers for the dry anophthalmic socket syndrome (DASS).MethodsIn this prospective single-center study, the anophthalmic sockets and healthy fellow eyes of 98 unilateral anophthalmic patients were assessed using the ocular surface disease index (OSDI) questionnaire, InflammaDry® MMP-9 point-of-care immunoassay, TFO with TearLab™ Osmolarity System, and clinical conjunctival inflammation. MMP-9 concentration and conjunctival inflammation were graded semi-quantitatively. Differences between anophthalmic sockets and the healthy fellow eyes for OSDI scores, MMP-9, TFO values, clinical conjunctival inflammation, and eyelid abnormalities as well as the correlation between these factors and demographic data were evaluated.ResultsPatients had significantly higher OSDI, MMP-9, and TFO values, as well as higher conjunctival inflammation on the anophthalmic side, compared to the healthy side (p ≤ 0.002, respectively). For anophthalmic sockets, there was a significant positive correlation between OSDI scores and TFO values (p = 0.007), between the grade of posterior blepharitis and TFO values (p = 0.026), and between the conjunctival inflammation and MMP-9 values (p < 0.001), as well as between MMP-9 levels and time since eye loss (p = 0.004).ConclusionsMeasuring MMP-9 and TFO may be helpful tools as efficient, quantifiable biomarkers, disease course parameters, or predictors for treatment response in the clinical management of patients with DASS or future therapy studies. Ophthalmologists should consider the updated diagnosis criteria including TFO and the definition for DASS proposed in this study.

Purpose Risks of dehydration and cognitive decline increase with advancing age, yet the relation between dehydration, water intake, and cognitive performance among older adults remains understudied. Methods Using data from the 2011–2014 cycles of the Nutrition and Health Examination Survey (NHANES), we tested if calculated serum osmolarity (Sosm) and adequate intake (AI) of water among women ( n  = 1271) and men ( n  = 1235) ≥ 60 years old were associated with scores of immediate and delayed recall, verbal fluency, and attention/processing speed. Sosm was categorized as < 285 (hyperhydrated), 285–289, 290–294, 295–300, or > 300 (dehydrated) mmol/L. AI of water was defined as ≥ 2 L/day for women and ≥ 2.5 L/day for men. Results Women with Sosm between 285 and 289 mmol/L scored 3.2–5.1 points higher on the Digit Symbol Substitution test (DSST) of attention/processing speed than women in other Sosm categories ( P values < 0.05). There was evidence of a curvilinear relationship between DSST scores and Sosm among women and men ( P values for quadratic terms < 0.02). Meeting an alternative AI on water intake of ≥ 1 mL/kcal and ≥ 1500 mL, but not the sex-specific AI, was associated with scoring one point higher on a verbal fluency test ( P  = 0.02) and two points higher on the DSST ( P  = 0.03) among women. Significant negative associations between dehydration or inadequate water intake and test scores were not observed among men. Conclusion Hydration status and water intake were moderately associated with attention/processing speed among females. Future work should consider the effects of both dehydration and overhydration on cognitive function and investigate potential sex differences in cognitive responses to hydration status.

The relationship between serum osmolarity and cognitive function has not been fully characterized. This study aimed to examine the cross-sectional association between repeated high serum osmolarity and cognitive performance among elderly community residents. We performed a subanalysis of the Kobe Orthopedic and Biomedical Epidemiological Study, including residents aged ≥ 75 years who completed the Japanese Montreal Cognitive Assessment (MoCA-J) in 2016–2017 ( n  = 127), 2018–2019 ( n  = 71), and 2020 ( n  = 16). Serum osmolarity was obtained from the data in the 2012–2013 survey and in the 2016–2017 survey. MoCA-J scores were dichotomized at ≤ 22 versus > 22. Multivariate logistic regression adjusted for demographic, lifestyle including daily non-alcohol drink intake, seasonal, and clinical covariates to assess associations between osmolarity status and cognitive group. Among 214 participants (mean age 76.2 ± 1.3 years; 56% female), high osmolarity (≥ 300 mOsm/L) in 2012–2013 was associated with MoCA-J ≤ 22 (OR 2.67, 95% CI 1.29–5.53, p  = 0.008). A similar association emerged for 2016–2017 measurements (OR 6.12, 95% CI 1.46–25.61, p  = 0.013). Participants with high serum osmolarity at both time points showed a stronger cross-sectional association with lower MoCA-J scores (OR 17.64, 95% CI = 1.8–184.83, p  = 0.017). No significant association was observed between daily non-alcoholic drink (NAD) intake and either MoCA-J scores or serum osmotic pressure. Repeated high serum osmolarity was cross-sectionally associated with lower cognitive performance in Japanese community-dwelling older adults. While NAD intake showed no significant association, further research is needed to explore the potential role of serum osmolarity in cognitive health. These findings warrant confirmation in larger prospective studies.

To compare the in vivo precision of two commercially available point-of-care osmometers among normal subjects with no dry eye disease. Twenty healthy adults with healthy ocular surfaces were evaluated by licensed eye care practitioners. All subjects had low Ocular Surface Disease Index score (<5), normal tear breakup time (>10 seconds), and no evidence of corneal fluorescein staining. Five consecutive measurements of tear osmolarity were measured on each eye using each of the two osmometers: the TearLab Osmolarity System (TearLab) and the I-Med i-Pen (i-Pen), for a total of 200 measurements per device. Performance of the osmometers was determined by specificity, estimated by the percentage of osmolarity data at or below the clinical cutoff (308 mOsm/L) and precision, and represented by the standard deviation per subject. In addition, to assess analytical performance, on each day of patient testing, standardized osmolarity quality control solutions (338 mOsm/L) were tested on the TearLab per manufacturer instructions. i-Pen manufacturer instructions do not neither provide for, nor recommend quality control procedures. The mean age of the 20 subjects was 27±8 years (range: 19-48 years, 16 females, four males). Over 2 months of testing, the TearLab reported analytical performance on quality control solutions of 335.8±4.2 mOsm/L with a coefficient of variation of 1.3%. In the subject cohort, 90.9% of TearLab measurements were in the normal range ≤308 mOsm/L. The i-Pen reported 37.5% of all measurements in the normal range. The average intra-subject osmolarity of the TearLab was 295.4±8.6 mOsm/L, which was significantly lower and less variable than the i-Pen, which reported an average of 319.4±20.3 mOsm/L ( <0.001). When the measurements were grouped by subject, the TearLab accurately identified 100% of subjects as normal while the i-Pen accurately identified only 15% of subjects as normal. In this randomized comparative study of two point-of-care osmometers among normal, healthy non-dry eye subjects, the TearLab Osmolarity System demonstrated accuracy, precision, and agreement with clinical interpretation in line with the manufacturer claims. The i-Pen lacked sufficient performance to delineate subjects with and without dry eye disease.

Osmotic stress imposed by drought and high salinity inhibits plant growth and crop yield. However, our current knowledge on the mechanism by which plants sense osmotic stress is still limited. Here, we identify the transcriptional regulator SEUSS (SEU) as a key player in hyperosmotic stress response in Arabidopsis. SEU rapidly coalesces into liquid-like nuclear condensates when extracellular osmolarity increases. The intrinsically disordered region 1 (IDR1) of SEU is responsible for its condensation. IDR1 undergoes conformational changes to adopt more compact states after an increase in molecular crowding both in vitro and in cells, and two predicted α-helical peptides are required. SEU condensation is indispensable for osmotic stress tolerance, and loss of SEU dramatically compromises the expression of stress tolerance genes. Our work uncovers a critical role of biomolecular condensates in cellular stress perception and response and expands our understanding of the osmotic stress pathway.SEUSS is a transcriptional adaptor that undergoes condensation after hyperosmotic stress-induced increase of molecular crowding. The SEUSS condensates are indispensable for stress tolerance via facilitating the expression of stress-related genes.