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Background and Purpose: In wake-up stroke, CT-based quantitative net water uptake (NWU) might serve as an alternative tool to MRI to guide intravenous thrombolysis with alteplase (IVT). An important complication after IVT is symptomatic intracerebral haemorrhage (sICH). As NWU directly implies ischaemic lesion progression, reflecting blood-brain barrier injury, we hypothesised that NWU predicts sICH in patients who had a ischaemic stroke undergoing thrombectomy with unknown onset., Methods: Consecutive analysis of all patients who had unknown onset anterior circulation ischaemic stroke who underwent CT at baseline and endovascular treatment between December 2016 and October 2020. Quantitative NWU was assessed on baseline CT. The primary endpoint was sICH. The association of NWU and other baseline parameters to sICH was investigated using inverse-probability weighting (IPW) analysis., Results: A total of 88 patients were included, of which 46 patients (52.3%) received IVT. The median NWU was 10.7% (IQR: 5.1-17.7). The proportion of patients with any haemorrhage and sICH were 35.2% and 13.6%. NWU at baseline was significantly higher in patients with sICH (19.1% vs 9.6%, p<0.0001) and the median Alberta Stroke Program Early CT Score (ASPECTS) was lower (5 vs 8, p<0.0001). Following IPW, there was no association between IVT and sICH in unadjusted analysis. However, after adjusting for ASPECTS and NWU, there was a significant association between IVT administration and sICH (14.6%, 95% CI: 3.3% to 25.6%, p<0.01)., Conclusion: In patients with ischaemic stroke with unknown onset, the combination of high NWU with IVT is directly linked to higher rates of sICH. Besides ASPECTS for evaluating the extent of the early infarct lesion, quantitative NWU could be used as an imaging biomarker to assess the degree of blood-brain barrier damage in order to predict the risk of sICH in patients with wake up stroke., Competing Interests: Competing interests: JF: German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions- und Förderbank (IFB). GT: Grants by the European Union (Grant No. 278276 und 634809) and Deutsche Forschungsgemeinschaft (SFB 936, Projekt C2). AK: research collaboration agreement: Siemens Healthcare (company involved in CT/MRI distribution). All other authors reported no relationships with commercial firms whose products could be affected by the present study., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Hemodialysis patient groups have advocated reducing dialysis fatigue and symptoms. We investigated whether compartmental fluid shifts were associated with peri-dialytic fatigue and symptoms., Methods: Sessional dialysis records of patients reporting both a short and delayed recovery (<1 h and ≥1 h) with corresponding bioimpedance measurements were reviewed., Results: One hundred and twenty-four patients reported both short and delayed recovery times, mean age 66.0 ± 14.8 years, 66.1% male. Differences between sessions included higher distress thermometer [4 (1-6) vs. 3 (0-5)], fatigue [4 (0-9) vs. 2 (0-7)], total symptom scores [20.5 (12.3-34.5) vs. 16 (7-28)], change in extracellular water to total body water ratios between body compartments [right leg/left arm 2.36 (1.23-4.19) vs. 1.28 (0.12-2.01), all p < 0.01] with delayed recovery, and more hemodialysis than hemodiafiltration sessions (χ 2 4.6, p = 0.02)., Conclusion: Sessions with prolonged recovery times were associated with more peri-dialytic symptoms, psychological distress, and hemodialysis mode, and greater changes in compartmental fluid shifts., (© 2024 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis and Japanese Society for Apheresis.)

Objectives: To determine the relationship between bioelectrical impedance analysis (BIA) parameters, including the extracellular water-to-total body water ratio (ECW/TBW), and the activities of daily living (ADL) improvement, in patients who experienced acute stroke., Materials and Methods: This retrospective cohort study included 307 patients (mean age, 72 years; 39 % female) who experienced acute stroke and were admitted to the stroke unit of the Nippon Medical School Hospital (Bunkyo-ku, Tokyo, Japan) between April 2021 and March 2022. The Functional Independence Measure (FIM) was assessed at initial rehabilitation and discharge, and FIM effectiveness was calculated as ADL improvement in the participating acute care hospitals. BIA markers included the skeletal muscle mass index (SMI), phase angle (PhA), and ECW/TBW. Multiple linear regression models were used to estimate the relationship between the FIM effectiveness and each BIA marker., Results: The mean (±SD) FIM effectiveness was 0.45 ± 0.36. The proportions of low SMI (male, <7.0 kg/m 2 ; female, <5.7 kg/m 2 ) and low PhA (male <5.36 degrees, female <3.85 degrees), were 48.9 % and 43.3 %, respectively. In addition, the proportions of of low (<0.36), normal (0.36-0.40), and high (>0.4) ECW/TBW ratios were 1.3 %, 78.5 %, and 20.2 %, respectively. After adjustments for demographic and clinical variables, low PhA, low ECW/TBW, and high ECW/TBW were all significantly associated with FIM effectiveness (P < 0.05), with β coefficients of -0.126, -0.089, and -0.117, respectively., Conclusions: Low and High ECW/TBW and low PhA levels were negatively correlated with improvements in ADL. The ECW/TBW ratio may be an additional indicator of rehabilitation trainability in patients who experience acute stroke., Competing Interests: Declaration of competing interest The authors have no financial disclosures or conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Our goal was to investigate linkages between skin color parameters and skin hydration. Since most prior studies focused on stratum corneum hydration, we focused on epidermal and dermal hydration in relation to skin color parameters in both sexes., Materials and Methods: Thirty adults (16 female) with an age ± SD of 24.3 ± 0.6 years participated. Three sites on both volar forearms were evaluated for melanin index (MI), erythema index (EI), Individual Typology Angle (ITA), tissue dielectric constant (TDC) values to depths of 0.5 mm (TDC 0.5 ) and 2.5 mm (TDC 2.5 ), and Fitzpatrick skin type (FST)., Results: MI and EI were highly correlated (r = 0.800, p < 0.001) with maximum differences in MI and ITA along the arm of 3% and 6.3% with no difference between arms. Male MI was greater than females (p < 0.01). Male TDC 2.5 was 36.1 ± 5.4 and correlated with EI (r = 0.231, p = 0.035). Contrastingly, female TDC 25 was 28.5 ± 3.6 with no correlation with EI but was correlated with MI (r = -0.301, p = 0.003). These differential patterns held true for TDC 0.5 . For both sexes, FST and ITA were highly correlated (r = -0.756, p < 0.001)., Conclusions: The findings revealed several correlations between skin color parameters and hydration that differed between males in females in some cases. The observed correlations may indicate that melanin may differentially impact water-holding capacity between sexes and provides a future research target. Further, these initial findings also may hold significance for dermatological assessments and the customization of skincare treatments tailored to individual skin types and demographics., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

In the present study, we examined the inter-relationships between body water balance, nutritional risk, sarcopenia, and outcome after acute ischemic stroke (AIS) in patients who were living independently. We defined abnormal body water balance as overhydration, with an extracellular fluid/total body water ratio > 0.390. A geriatric nutritional risk index (GNRI) < 98 was considered low GNRI. Sarcopenia was defined according to the 2019 Asian Working Group for sarcopenia criteria. Poor outcome was defined as a modified Rankin scale (mRS) score ≥ 3 at discharge. Among 111 eligible patients (40 females, median age: 77 years), 43 had a poor prognosis, 31 exhibited overhydration, 25 had low GNRI, and 44 experienced sarcopenia. Patients with poor outcomes had significantly higher National Institutes of Health Stroke Scale (NIHSS) scores, which were significantly more common with overhydration, low GNRI, and sarcopenia ( p < 0.001 for all). Concomitant overhydration, low GNRI, and sarcopenia were associated with poorer outcomes. In multivariate analysis, overhydration [odds ratio (OR) 5.504, 95% confidence interval (CI) 1.717-17.648; p = 0.004], age (OR 1.062, 95%CI 1.010-1.117; p = 0.020), and NIHSS score (OR 1.790, 95%CI 1.307-2.451; p < 0.001) were independent prognostic factors for poor outcome. The results indicated that the combination of overhydration, low GNRI, and sarcopenia predict poor outcomes following AIS. Overhydration was particularly associated with poor outcomes.

Left atrial (LA) dysfunction has been linked to cognitive impairment and cerebrovascular dysfunction. Higher brain free-water (FW) derived from diffusion-MRI was associated with early and subtle cerebrovascular dysfunction and more severe cognitive impairment. We hypothesized that LA dysfunction would correlate with higher brain free-water (FW) among healthy older adults. 56 community older adults (73.13 ± 3.56 years; 24 female) with normal cognition and without known cardiovascular disease who had undergone cardiac-MRI, brain-MRI, and neuropsychological assessments were included. Whole-brain voxel-level general linear models were constructed to correlate brain FW measures with LA indices. We found lower scores in LA function measures were related to higher grey matter (GM) FW in regions including orbital frontal and right temporal regions (p < 0.01, family-wise error corrected). In parallel, LA dysfunction was associated with higher FW in white matter (WM) fibres including superior longitudinal fasciculus, internal capsule, and superior corona radiata. However, LA dysfunction was not related to WM tissue reduction and GM cortical thinning. Moreover, these cardiac-related higher brain FW were associated with lower executive function and higher serum B-type natriuretic peptide (p < 0.05, Holm-Bonferroni corrected). These findings may have implications for anti-ageing preventive strategies targeting cardiac and cerebral vascular functions to improve heart and brain outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The fluid transport of cerebrospinal fluid (CSF) and interstitial fluid in surrounding tissues plays an important role in the drainage pathway that facilitates waste clearance from the brain. This pathway is known as the glymphatic or perivascular system, and its functions are dependent on aquaporin-4 (AQP4). Recently, magnetization transfer indirect spin labeling (MISL) magnetic resonance imaging (MRI) has been proposed as a noninvasive and noncontrast-enhanced method for detecting water exchange between CSF and brain tissue. In this study, we first optimized the MISL sequence at preclinical 3 T MRI, and then studied the correlation of MISL in CSF with magnetization transfer (MT) in brain tissue, as well as the altered water exchange under AQP4 inhibition, using C57BL/6 mice. Results showed a strong correlation of MISL signal with MT signal. With the AQP4 inhibitor, we observed a significant decrease in MISL value (P < 0.05), suggesting that the hampered AQP4 activity led to decreased water exchange between CSF and brain tissue or the impairment of the glymphatic function. Overall, our findings demonstrate the potential application of MISL in assessing brain water exchange at 3 T MRI and its potential clinical translation., (© 2024 John Wiley & Sons Ltd.)

The skin is a vital organ in the human body, providing essential functions such as protection, sensation, and metabolism. Skin hydration is one of the crucial factors in maintaining normal skin function. Insufficient skin hydration can lead to dryness, shedding of the stratum corneum, a decrease in skin barrier function, and may cause skin inflammation. Therefore, maintaining or improving skin hydration is critical in promoting healthy skin. Currently, the commonly used method for measuring skin hydration is bioelectrical capacitance analysis, which is often affected by environmental humidity and can only provide limited information. To overcome these limitations, this study used diffuse reflectance spectroscopy (DRS) in the wavelength range of 400-1000 nm to quantify skin absorption and scattering modulation caused by changes in skin hydration states. The advantages of this technique include rapid measurements, non-invasiveness, a straightforward optical setup, and suitability for prolonged skin monitoring. We found that DRS-derived skin absorption coefficients had a correlation coefficient of 0.93 with the skin capacitance at various skin hydration states. In addition, our findings reveal that absorption and scattering coefficients may be useful in discerning skin hydration enhancement induced by applying soaked cotton pads or cosmeceutical facial masks, as well as evaluating skin sensation. This study verifies that the DRS method could be a convenient and effective tool for evaluating skin hydration related information., (© 2023. The Author(s).)

Purpose: Biophysical models of diffusion MRI have been developed to characterize microstructure in various tissues, but existing models are not suitable for tissue composed of permeable spherical cells. In this study we introduce Cellular Exchange Imaging (CEXI), a model tailored for permeable spherical cells, and compares its performance to a related Ball & Sphere (BS) model that neglects permeability., Methods: We generated DW-MRI signals using Monte-Carlo simulations with a PGSE sequence in numerical substrates made of spherical cells and their extracellular space for a range of membrane permeability. From these signals, the properties of the substrates were inferred using both BS and CEXI models., Results: CEXI outperformed the impermeable model by providing more stable estimates cell size and intracellular volume fraction that were diffusion time-independent. Notably, CEXI accurately estimated the exchange time for low to moderate permeability levels previously reported in other studies ( κ < 25 μ m / s $$ \kappa <25\kern0.3em \mu \mathrm{m}/\mathrm{s} $$ ). However, in highly permeable substrates ( κ = 50 μ m / s $$ \kappa =50\kern0.3em \mu \mathrm{m}/\mathrm{s} $$ ), the estimated parameters were less stable, particularly the diffusion coefficients., Conclusion: This study highlights the importance of modeling the exchange time to accurately quantify microstructure properties in permeable cellular substrates. Future studies should evaluate CEXI in clinical applications such as lymph nodes, investigate exchange time as a potential biomarker of tumor severity, and develop more appropriate tissue models that account for anisotropic diffusion and highly permeable membranes., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Aquaporin (AQP) water channels are pivotal to renal water handling and therefore in the regulation of body water homeostasis. However, beyond the kidney, AQPs facilitate water reabsorption and secretion in other cells and tissues, including sweat and salivary glands and the gastrointestinal tract. A growing body of evidence has also revealed that AQPs not only facilitate the transport of water but also the transport of several small molecules and gases such as glycerol, H 2 O 2 , ions and CO 2 . Moreover, AQPs are increasingly understood to contribute to various cellular processes, including cellular migration, adhesion and polarity, and to act upstream of several intracellular and intercellular signalling pathways to regulate processes such as cell proliferation, apoptosis and cell invasiveness. Of note, several AQPs are highly expressed in multiple cancers, where their expression can correlate with the spread of cancerous cells to lymph nodes and alter the response of cancers to conventional chemotherapeutics. These data suggest that AQPs have diverse roles in various homeostatic and physiological systems and may be exploited for prognostics and therapeutic interventions., (© 2023. Springer Nature Limited.)

The purpose of the current study was to investigate the feasibility of simultaneously estimating the cellular water efflux rate ( k ie ), intracellular longitudinal relaxation rate ( R 10 i ), and intracellular volume fraction ( v i ) of a cell suspension using multiple samples with different gadolinium concentrations. Numerical simulation studies were conducted to assess the uncertainty in the estimation of k ie , R 10 i , and v i from saturation recovery data using single (SC) or multiple concentrations (MC) of gadolinium-based contrast agent (GBCA). In vitro experiments with 4 T1 murine breast cancer and SCCVII squamous cell cancer models were conducted at 11 T to compare parameter estimation using the SC protocol with that using the MC protocol. The cell lines were challenged with a Na + /K + -ATPase inhibitor, digoxin, to assess the treatment response in terms of k ie , R 10 i , and v i . Data analysis was conducted using the two-compartment exchange model for parameter estimation. The simulation study data demonstrate that the MC method, compared with the SC method, reduces the uncertainty of the estimated k ie by decreasing the interquartile ranges from 27.3% ± 3.7% to 18.8% ± 5.1% and the median differences from ground truth from 15.0% ± 6.3% to 7.2% ± 4.2%, while estimating R 10 i and v i simultaneously. In the cell studies, the MC method demonstrated reduced uncertainty in overall parameter estimation compared with the SC approach. MC method-measured parameter changes in cells treated with digoxin increased R 10 i by 11.7% (p = 0.218) and k ie by 5.9% (p = 0.234) for 4 T1 cells, respectively, and decreased R 10 i by 28.8% (p = 0.226) and k ie by 1.6% (p = 0.751) for SCCVII cells, respectively. v i did not change noticeably by the treatment. The results of this study substantiate the feasibility of using saturation recovery data of multiple samples with different GBCA concentrations for simultaneous measurement of the cellular water efflux rate, intracellular volume fraction, and intracellular longitudinal relaxation rate in cancer cells., (© 2023 John Wiley & Sons Ltd.)

Aims: We explored the predictive utility of baseline neutrophil/lymphocyte ratio (NLR), which reflects a systemic inflammatory tone, in kidney impairment in type 2 diabetes mellitus (T2DM); and investigated the effect of extracellular water/total body water (ECW/TBW) ratio on the relationship., Methods: This longitudinal study included 1,224 T2DM adults recruited from a single centre. Cox regression analyses examined the association between NLR and progressive kidney function decline or albuminuria progression. Improvements in risk discrimination were assessed using Harrell's concordance-statistics. The mediatory role of ECW/TBW ratio estimated by bioelectrical impedance was evaluated., Results: Higher baseline NLR levels were observed in cases with kidney function decline or albuminuria progression over a median 2-year follow-up. NLR independently predicted progressive kidney function decline (hazard ratio:1.39, 95% CI:1.21-1.60, P < 0.001) or albuminuria progression (hazard ratio:1.34, 95% CI:1.08-1.68, P = 0.009). Addition of NLR to a base model comprising demographics, T2DM duration, metabolic and renal parameters, and medications significantly improved the risk discrimination of kidney function decline (P = 0.022) but not albuminuria progression. ECW/TBW ratio accounted for 19.7% of the total effect between NLR and kidney function loss., Conclusions: Increased NLR reflecting systemic inflammation is associated with progressive kidney function decline in T2DM, partially explained by dysregulated body fluid balance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Muscle glycogen is a crucial energy source for exercise, and assessment of muscle glycogen storage contributes to the adequate manipulation of muscle glycogen levels in athletes before and after training and competition. Muscle biopsy is the traditional and gold standard method for measuring muscle glycogen; alternatively, 13 C magnetic resonance spectroscopy (MRS) has been developed as a reliable and non-invasive method. Furthermore, outcomes of ultrasound and bioimpedance methods have been reported to change in association with muscle glycogen conditions. The physiological mechanisms underlying this activity are assumed to involve a change in water content bound to glycogen; however, the relationship between body water and stored muscle glycogen is inconclusive. In this review, we discuss currently available muscle glycogen assessment methods, focusing on 13 C MRS. In addition, we consider the involvement of muscle glycogen in changes in body water content and discuss the feasibility of ultrasound and bioimpedance outcomes as indicators of muscle glycogen levels. In relation to changes in body water content associated with muscle glycogen, this review broadens the discussion on changes in body weight and body components other than body water, including fat, during carbohydrate loading. From these discussions, we highlight practical issues regarding muscle glycogen assessment and manipulation in the sports field.

The goal of the current study is to include transcytolemmal water exchange in MR cell size imaging using the IMPULSED model for more accurate characterization of tissue cellular properties (e.g., apparent volume fraction of intracellular space v in ) and quantification of indicators of transcytolemmal water exchange. We propose a heuristic model that incorporates transcytolemmal water exchange into a multicompartment diffusion-based method (IMPULSED) that was developed previously to extract microstructural parameters (e.g., mean cell size d and apparent volume fraction of intracellular space v in ) assuming no water exchange. For t diff ≤ 5 ms, the water exchange can be ignored, and the signal model is the same as the IMPULSED model. For t diff ≥ 30 ms, we incorporated the modified Kärger model that includes both restricted diffusion and exchange between compartments. Using simulations and previously published in vitro cell data, we evaluated the accuracy and precision of model-derived parameters and determined how they are dependent on SNR and imaging parameters. The joint model provides more accurate d values for cell sizes ranging from 10 to 12 microns when water exchange is fast (e.g., intracellular water pre-exchange lifetime τ in ≤ 100 ms) than IMPULSED, and reduces the bias of IMPULSED-derived estimates of v in , especially when water exchange is relatively slow (e.g., τ in &gt; 200 ms). Indicators of transcytolemmal water exchange derived from the proposed joint model are linearly correlated with ground truth τ in values and can detect changes in cell membrane permeability induced by saponin treatment in murine erythroleukemia cancer cells. Our results suggest this joint model not only improves the accuracy of IMPULSED-derived microstructural parameters, but also provides indicators of water exchange that are usually ignored in diffusion models of tissues., (© 2022 John Wiley & Sons Ltd.)

Introduction: Plasma albumins as protein nanoparticles (PNs) exert essential functions in the control of biological osmotic pressure (OP), being involved in regulating water metabolism, cell morphology and cell tension. Understanding how plasma albumins and different electrolytes co-determine biological OP effects is crucial for correct interpretation of hemodynamic disorders, and practical treatment of hypo/hyper-proteinemia., Methods: Optical measurement based on intermediate filament (IF) tension probe was used for real-time evaluation of transmembrane osmotic effects in live cells. Ion fluorescent probes were employed to evaluate intracellular ion levels, and a current clamp was used to measure membrane potential, thus exploring association of electrochemical and osmotic effects., Results: Albumins are involved in regulation of intracellular osmolarity by a quantitative relationship. Extracellular PNs can alter membrane potentials by adsorbing counterions, induce production of intracellular PNs and further control the opening of ion channels and ion flow, contributing to electrochemical and osmotic re-equilibrium. Furthermore, various ions interplay with extracellular PNs, showing different osmotic effects: increased levels of calcium ions result in a hypotonic effect, whereas potassium ions induce hyper-osmolarity., Conclusion: Extracellular PNs and Ca 2+ /K + display antagonistic or synergetic effects in regulating biological OP. Live cells can spontaneously regulate osmotic effects through changing membrane potential and controlling intracellular ion content. Various plasma components need to be comprehensively analyzed, further developing a diagnostic index that considers the biological OP effects of various blood components and improves the evaluation of symptoms and diseases, such as calcium/potassium-hemodynamic disorders and edema., Competing Interests: Dr Jun Guo reports a patent 2021103033666 issued to Nanjing University of Chinese Medicine. The author reports no other conflicts of interest in this work., (© 2022 Zheng et al.)

Protein kinase A (PKA) directly phosphorylates aquaporin-2 (AQP2) water channels in renal collecting ducts to reabsorb water from urine for the maintenance of systemic water homeostasis. More than 50 functionally distinct PKA-anchoring proteins (AKAPs) respectively create compartmentalized PKA signaling to determine the substrate specificity of PKA. Identification of an AKAP responsible for AQP2 phosphorylation is an essential step toward elucidating the molecular mechanisms of urinary concentration. PKA activation by several compounds is a novel screening strategy to uncover PKA substrates whose phosphorylation levels were nearly perfectly correlated with that of AQP2. The leading candidate in this assay proved to be an AKAP termed lipopolysaccharide-responsive and beige-like anchor protein (LRBA). We found that LRBA colocalized with AQP2 in vivo, and Lrba knockout mice displayed a polyuric phenotype with severely impaired AQP2 phosphorylation. Most of the PKA substrates other than AQP2 were adequately phosphorylated by PKA in the absence of LRBA, demonstrating that LRBA-anchored PKA preferentially phosphorylated AQP2 in renal collecting ducts. Furthermore, the LRBA-PKA interaction, rather than other AKAP-PKA interactions, was robustly dissociated by PKA activation. AKAP-PKA interaction inhibitors have attracted attention for their ability to directly phosphorylate AQP2. Therefore, the LRBA-PKA interaction is a promising drug target for the development of anti-aquaretics.

Objectives: The importance of muscle wasting as a predictor of mortality in the hemodialysis population is not clear. Lack of association of muscle mass with survival in some studies could be related to reliance on single measures or to incorporation of excess extracellular water (ECW) into estimates of muscle mass. We examined changes in body composition over a 2-year period and the association of body composition with survival., Design and Methods: We analyzed data from 325 adults receiving hemodialysis in the Bay Area. We estimated ECW, intracellular water (ICW), and fat mass by whole-body bioimpedance spectroscopy (BIS) at 0, 12, and 24 months from enrollment. We used linear mixed modeling to examine changes in body mass index and BIS-derived estimates of body composition and Cox modeling with BIS-derived estimates as time-varying independent variables to examine associations between body composition and survival in multivariable analyses., Results: Body mass index declined over time. Considering individual components of body composition, ICW declined (-0.09 kg/m 2 per year, 95% confidence interval -0.14 to -0.04), but fat mass and ECW did not change significantly. There were 120 deaths over a median of 5.2 years. The relationship between ICW and mortality was not linear such that the association was steeper at low values of ICW, whereas higher ICW was associated with better survival that was relatively stable above 9 kg/m2. Higher ECW was associated with higher mortality, and fat mass was not associated with survival. These associations were independent of markers of inflammation and nutritional status., Conclusions: ICW declined over 2 years in this cohort, whereas fat mass and ECW remained relatively stable. Higher ICW was associated with better survival, but higher fat mass was not. Higher ECW was associated with worse survival. These results suggest that muscle mass may predict survival among patients on hemodialysis., (Published by Elsevier Inc.)

Objectives: Brain white matter (WM) microstructural changes evaluated by diffusion MRI are well documented in patients with SLE. Yet, the conventional diffusion tensor imaging technique fails to differentiate WM changes that originate from tissue alterations from those due to increased extracellular free water (FW) related to neuroinflammation, microvascular disruption, atrophy, or other extracellular processes. Here, we sought to delineate changes in WM tissue microstructure and extracellular FW volume and examine their relationships with neurocognitive function in SLE patients., Methods: Twenty SLE patients [16 females, aged 36.0 (10.6)] without clinically overt neuropsychiatric manifestation and 61 healthy controls (HCs) [29 females, aged 29.2 (9.4)] underwent diffusion MRI and computerized neuropsychological assessments cross-sectionally. The FW imaging method was applied to compare microstructural tissue changes and extracellular FW volume of the brain WM between SLE patients and HCs. Association between extracellular FW changes and neurocognitive performance was studied., Results: SLE patients had higher WM extracellular FW compared with HCs (family-wise-error-corrected P < 0.05), while no group difference was found in FW-corrected tissue compartment and structural connectivity metrics. Extracellular FW increases in SLE patients were associated with poorer neurocognitive performance that probed sustained attention (P = 0.022) and higher cumulative glucocorticoid dose (P = 0.0041). Such findings remained robust after controlling for age, gender, intelligence quotient, and total WM volume., Conclusion: The association between WM extracellular FW increases and reduced neurocognitive performance suggest possible microvascular degradation and/or neuroinflammation in SLE patients with clinically inactive disease. The mechanistic impact of cumulative glucocorticoids on WM FW deserves further evaluation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Transmembrane water exchange is a potential biomarker in the diagnosis and understanding of cancers, brain disorders, and other diseases. Filter-exchange imaging (FEXI), a special case of diffusion exchange spectroscopy adapted for clinical applications, has the potential to reveal different physiological water exchange processes. However, it is still controversial whether modulating the diffusion encoding gradient direction can affect the apparent exchange rate (AXR) measurements of FEXI in white matter (WM) where water diffusion shows strong anisotropy. In this study, we explored the diffusion-encoding direction dependence of FEXI in human brain white matter by performing FEXI with 20 diffusion-encoding directions on a clinical 3T scanner in-vivo. The results show that the AXR values measured when the gradients are perpendicular to the fiber orientation (0.77 ± 0.13 s  -   1 , mean ± standard deviation of all the subjects) are significantly larger than the AXR estimates when the gradients are parallel to the fiber orientation (0.33 ± 0.14 s  -   1 , p < 0.001) in WM voxels with coherently-orientated fibers. In addition, no significant correlation is found between AXRs measured along these two directions, indicating that they are measuring different water exchange processes. What's more, only the perpendicular AXR rather than the parallel AXR shows dependence on axonal diameter, indicating that the perpendicular AXR might reflect transmembrane water exchange between intra-axonal and extra-cellular spaces. Further finite difference (FD) simulations having three water compartments (intra-axonal, intra-glial, and extra-cellular spaces) to mimic WM micro-environments also suggest that the perpendicular AXR is more sensitive to the axonal water transmembrane exchange than parallel AXR. Taken together, our results show that AXR measured along different directions could be utilized to probe different water exchange processes in WM., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)

Background & Aims: Doubly labelled water (DLW) is considered the reference standard method of measuring total energy expenditure (TEE), but there is limited information on its use in the Intensive Care Unit (ICU) and acute care setting. This scoping review aims to systematically summarize the available literature on TEE measured using DLW in these contexts., Methods: Four online databases (MEDLINE, Embase, Emcare and CINAHL) were searched up to Dec 12, 2020. Studies in English were included if they measured TEE using DLW in adults in the ICU and/or acute care setting. Key considerations, concerns and practical recommendations were identified and qualitatively synthesized., Results: The search retrieved 7582 studies and nine studies were included; one in the ICU and eight in the acute care setting. TEE was measured over 7-15-days, in predominantly clinically stable patients. DLW measurements were not commenced until four days post admission or surgery in one study and following a 10-14-day stabilization period on parenteral nutrition (PN) in three studies. Variable dosages of isotopes were administered, and several equations used to calculate TEE. Four main considerations were identified with the use of DLW in these settings: variation in background isotopic abundance; excess isotopes leaving body water as carbon dioxide or water; fluctuations in rates of isotope elimination and costs., Conclusion: A stabilization period on intravenous fluid and PN regimens is recommended prior to DLW measurement. The DLW technique can be utilized in medically stable ICU and acute care patients, with careful considerations given to protocol design., Competing Interests: Conflict of Interest EJR has received honorarium from Baxter Healthcare (United States and Australia), Nestle and Nutricia (Australia). EJR is supported by a National Health and Medical Research Council (NHMRC) Emerging Leadership Fellowship and has unrestricted research funding from Baxter Healthcare (United States), Nutricia (Australia) and Fresenius Kabi (Australia)., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The study of brain clearance mechanisms is an active area of research. While we know that the cerebrospinal fluid (CSF) plays a central role in one of the main existing clearance pathways, the exact processes for the secretion of CSF and the removal of waste products from tissue are under debate. CSF is thought to be created by the exchange of water and ions from the blood, which is believed to mainly occur in the choroid plexus. This exchange has not been thoroughly studied in vivo. We propose a modified arterial spin labeling (ASL) MRI sequence and image analysis to track blood water as it is transported to the CSF, and to characterize its exchange from blood to CSF. We acquired six pseudo-continuous ASL sequences with varying labeling duration (LD) and post-labeling delay (PLD) and a segmented 3D-GRASE readout with a long echo train (8 echo times (TE)) which allowed separation of the very long-T 2 CSF signal. ASL signal was observed at long TEs (793 ms and higher), indicating presence of labeled water transported from blood to CSF. This signal appeared both in the CSF proximal to the choroid plexus and in the subarachnoid space surrounding the cortex. ASL signal was separated into its blood, gray matter and CSF components by fitting a triexponential function with T 2 s taken from literature. A two-compartment dynamic model was introduced to describe the exchange of water through time and TE. From this, a water exchange time from the blood to the CSF (T bl->CSF ) was mapped, with an order of magnitude of approximately 60 s., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The stratum corneum (SC) is the outermost layer of the epidermis and plays an important role in maintaining skin moisture and protecting the skin from the external environment. Ceramide and natural moisturizing factor (NMF) are the major SC components that maintain skin moisture. In this study, we investigated whether the oral intake of enzymatically decomposed AP collagen peptides (APCPs) can improve skin moisture and barrier function by assessing changes in the ceramide and NMF contents in the SC after APCP ingestion with the aim to develop a skin functional food. Fifty participants orally ingested APCP (1000 mg) or placebo for 12 weeks, and then, skin hydration and skin texture were evaluated. SC samples were collected to analyze skin scaling, ceramide, and NMF contents. Participants in the APCP group exhibited improved skin moisture content by 7.33% ( p = 0.031) and roughness by -4.09% ( p = 0.036) when compared with those in the placebo group. NMF content; the amounts of amino acids (AA), including glycine and proline; and AA derivatives were significantly increased in the APCP group (31.98 μg/mg protein) compared to those in the placebo group (-16.01 μg/mg protein) ( p = 0.006). The amounts of total ceramides and ceramide subclasses were significantly higher in the APCP group than in the placebo group ( p = 0.014). In conclusion, our results demonstrate that APCP intake improves skin moisture and increase the ceramide and NMF contents in the SC, thereby enhancing the skin barrier function.

Doxorubicin (Dox), an effective antineoplastic drug, was limited use for cardiotoxicity. Xinshuitong Capsule (XST), a patented herbal formula, showed desirable beneficial effects in the treatment of chronic heart failure (CHF) patients. However, the drug on Dox-induced cardiotoxicity remains unclear. Ninety male Sprague-Dawley rats were randomized into two groups: 15 rats were selected as the normal group and 75 rats were injected intraperitoneally with Dox to establish CHF rat models, the success ones were randomly divided into five groups: low XST (LXST), medium XST (MXST) or high XST (HXST) (4.9, 9.8, or 19.6 g/kg d) administrated intragastrically twice a day for 4 weeks, with the captopril-treated group and the model group as comparison. The model group showed the cardiac functions generally impaired, and CHF mortality rate higher (47%) than those in the XST-treated groups (averaged 24%, P < 0.05). Compared with XST-treated groups, myocardial remodeling, inflammation and desarcomerization, and higher water content more severe in the cardiac tissue in the model group (P < 0.05), which was associated with higher expressions of mRNA or protein levels of AQP1, 4 and 7. Dox-impaired cardiac functions, cardiac remodeling and myocardial edema could be dose-dependently reverted by XST treatment. XST could inhibit AQP1, 4 and 7 at mRNA levels or at protein levels, which was associated with the attenuation of myocardial edema and cardiac remodeling, decreasing the ventricular stiffness and improving the cardiac functions and rats' survival. AQPs is involved in cardiac edema composed one of the mechanisms of Dox-induced cardiotoxicity, XSTvia inhibition of AQPs relieved the Dox-induced side effects., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Ensuring the proper amount of water inside the body is essential for survival. One of the key factors in the maintenance of body water balance is water reabsorption in the collecting ducts of the kidney, a process that is regulated by aquaporin-2 (AQP2). AQP2 is a channel that is exclusively selective for water molecules and impermeable to ions or other small molecules. Impairments of AQP2 result in various water balance disorders, including nephrogenic diabetes insipidus (NDI), which is a disease characterized by a massive loss of water through the kidney and consequent severe dehydration. Dysregulation of AQP2 is also a cause of water retention with hyponatremia in heart failure, hepatic cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Antidiuretic hormone vasopressin is an upstream regulator of AQP2. Its binding to the vasopressin V2 receptor promotes AQP2 targeting to the apical membrane and thus enables water reabsorption. Tolvaptan, a vasopressin V2 receptor antagonist, is effective and widely used for water retention with hyponatremia. However, there are no studies showing improvement in hard outcomes or long-term prognosis. A possible reason is that vasopressin receptors have many downstream effects other than AQP2 function. It is expected that the development of drugs that directly target AQP2 may result in increased treatment specificity and effectiveness for water balance disorders. This review summarizes recent progress in studies of AQP2 and drug development challenges for water balance disorders.

Sodium/glucose cotransporter 2 (SGLT2) is a renal low-affinity high-capacity sodium/glucose cotransporter expressed in the apical membrane of the early segment of proximal tubules. SGLT2 reabsorbs filtered glucose in the kidney, and its inhibitors represent a new class of oral medications used for type 2 diabetes mellitus, which act by increasing glucose and sodium excretion in urine, thereby reducing blood glucose levels. However, clinical trials showed marked improvement of renal outcomes, even in nondiabetic kidney diseases, although the underlying mechanism of this renoprotective effect is unclear. We showed that long-term excretion of salt by the kidneys, which predisposes to osmotic diuresis and water loss, induces a systemic body response for water conservation. The energy-intensive nature of water conservation leads to a reprioritization of systemic body energy metabolism. According to current data, use of SGLT2 inhibitors may result in similar reprioritization of energy metabolism to prevent dehydration. In this review article, we discuss the beneficial effects of SGLT2 inhibition from the perspective of energy metabolism and water conservation., Competing Interests: Conflicts of interest A.N. received research support and speaker honoraria from Boehringer Ingelheim, Taisho Pharmaceutical, and AstraZeneca. D.N. received research support from Mitsubishi Tanabe Pharma., (Copyright © 2021 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Although previous studies have made significant contributions to establishing animal traumatic brain injury (TBI) models for simulation of human TBI, the accuracy, controllability, and modeling efficiency of animal TBI models need to be further improved. This study established a novel high-efficiency graded mouse TBI model induced by shock wave., Methods: A total of 125 mice were randomly divided into sham, 0.7 mm, 0.6 mm, and 0.5 mm groups according to the depth of the cross groove of the aluminum sheets. The stability and repeatability of apparatus were evaluated, and the integrity of the blood-brain barrier, cerebral edema, neuropathologic immunohistochemistry, apoptosis-related protein, and behavioral tests of neurologic function were used to validate this new model., Results: The results showed that 4 mice were injured simultaneously in 1 experiment. They received the same intensity of shock waves. Moreover, the mortality rates caused by 3 different aluminum sheets were consistent with the mortality rates of mild TBI, moderate TBI, and severe TBI. Compared with the sham group, mice in different injured groups significantly increased brain water content, blood-brain barrier permeability, and neuronal apoptosis. And the mice in all injured groups showed poor motor ability, balancing, spatial learning, and memory abilities., Conclusions: The novel TBI apparatus has advantages in its small size, simple operation, high repeatability, high efficiency, and graded severity. Our TBI apparatus provides a novel tool to investigate the neuropathologic changes and underlying mechanisms of TBI with various levels of severities., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) is a major clinical and public health problem with few therapeutic interventions successfully translated to the clinic. Identifying imaging-based biomarkers characterizing injury severity and predicting long-term functional and cognitive outcomes in TBI patients is crucial for treatment. TBI results in white matter (WM) injuries, which can be detected using diffusion tensor imaging (DTI). Trauma-induced pathologies lead to accumulation of free water (FW) in brain tissue, and standard DTI is susceptible to the confounding effects of FW. In this study, we applied FW DTI to estimate free water volume fraction (FW-VF) in patients with moderate-to-severe TBI and demonstrated its association with injury severity and long-term outcomes. DTI scans and neuropsychological assessments were obtained longitudinally at 3, 6, and 12 months post-injury for 34 patients and once in 35 matched healthy controls. We observed significantly elevated FW-VF in 85 of 90 WM regions in patients compared to healthy controls ( p  < 0.05). We then presented a patient-specific summary score of WM regions derived using Mahalanobis distance. We observed that M VF at 3 months significantly predicted functional outcome ( p  = 0.008), executive function ( p  = 0.005), and processing speed ( p  = 0.01) measured at 12 months and was significantly correlated with injury severity ( p  < 0.001). Our findings are an important step toward implementing M VF as a biomarker for personalized therapy and rehabilitation planning for TBI patients.

Increased microglial NADPH oxidase (NOX 2 ) production may make an important contribution to the increased incidence and severity of ischemic stroke associated with diabetes. Imidazoline receptors are closely associated with neuroprotection, but the neuroprotective effects of the selective I 2 -imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline (2BFI) in diabetes has not been established. The effect of 2BFI on microglial NOX 2 production was investigated using a co-culture of neurons and microglia, and the effect on cerebral ischemia-reperfusion (IR) injury was determined in diabetic rats. Garcia neurological scores, brain infarct volumes, brain water content, TUNEL staining, blood-brain barrier, and immunofluorescent labeling for microglia were evaluated. Western blots were used to determine gp91 phox and Tyr1472 expression. Anti-inflammatory cytokine (IL-10) and inflammatory cytokine secretion was determined using ELISA kits. The brain infarct volumes, TUNEL-positive neurons, expression of microglia, brain water content, blood-brain barrier structure damage, and gp91 phox and Tyr1472 expression were increased, the Garcia neurological scores were significantly decreased in the IR group, and 2BFI relieved these alterations. The IL-10 concentration was increased in the IR group; 2BFI significantly improved this increase. The neuron apoptosis and necrosis rates, and production of reactive oxygen species (ROS) and inflammatory cytokines, including IL-6, IL-8, TNF-α, and 8-iso-PGF2α, were significantly increased by high glucose stimulation combined with oxygen-glucose deprivation treatment, which were inhibited by 2BFI. The 2BFI ameliorated cerebral ischemia-reperfusion injury in diabetes and decreased neuron death in an in vitro model. The mechanism underlying these findings may be related to the decreased production of inflammatory factors and reactive oxygen species from microglia., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Context: Pro-opiomelanocortin (POMC) and the melanocortin-4 receptor (MC4R) play a pivotal role in the leptin-melanocortin pathway. Mutations in these genes lead to monogenic types of obesity due to severe hyperphagia. In addition to dietary-induced obesity, a cardiac phenotype without hypertrophy has been identified in MC4R knockout mice., Objective: We aimed to characterize cardiac morphology and function as well as tissue Na+ content in humans with mutations in POMC and MC4R genes., Methods: A cohort of 42 patients (5 patients with bi-allelic POMC mutations, 6 heterozygous MC4R mutation carriers, 19 obese controls without known monogenic cause, and 12 normal weight controls) underwent cardiac magnetic resonance (CMR) imaging and 23Na-MRI., Results: Monogenic obese patients with POMC or MC4R mutation respectively had a significantly lower left ventricular mass/body surface area (BSA) than nonmonogenic obese patients. Left ventricular end-diastolic volume/BSA was significantly lower in POMC- and MC4R-deficient patients than in nonmonogenic obese patients. Subcutaneous fat and skin Na+ content was significantly higher in POMC- and MC4R-deficient patients than in nonmonogenic obese patients. In these compartments, the water content was significantly higher in patients with POMC and MC4R mutation than in control groups., Conclusion: Patients with POMC or MC4R mutations carriers had a lack of transition to hypertrophy, significantly lower cardiac muscle mass/BSA, and stored more Na+ within the subcutaneous fat tissue than nonmonogenic obese patients. The results point towards the role of the melanocortin pathway for cardiac function and tissue Na+ storage and the importance of including cardiologic assessments into the diagnostic work-up of these patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We aimed to validate bioelectrical impedance spectroscopy (BIS), compared with tracer dilution measurements, for assessing total body water (TBW), intracellular water (ICW), and extracellular water (ECW) in athletes differing in hydration status. A total of 201 athletes participated. Reference TBW and ECW were determined by deuterium and bromide dilution methods, respectively; ICW was calculated as TBW-ECW. Water compartments were estimated by BIS. Urine specific gravity (USG) classified athletes into well-hydrated (WH) (USG < 1.023), euhydrated (EH) (USG:1.024-1.026), and dehydrated (DH) (USG>1.027). No significant differences were found between BIS and the reference methods for WH, EH, and DH athletes for TBW, ICW nor ECW (p>0.05). Concordance of TBW and its compartments by method was significant (p < 0.001) with coefficients of determination ranging by hydration classification [EH:52-96%;DH:56-98%;WH:71-96%]. Bland-Altman analyses showed no trend for TBW and its compartments with the exception of ICW in the WH athletes. The 95% confidence BIS intervals for the WH group ranged from -3.08 to 2.68 kg for TBW, -4.28 to 4.14 kg for ICW, and -3.29 to 3.02 kg for ECW. For the EH athletes, the 95% confidence intervals ranged from -2.78 to 2.24 kg for TBW, -4.10 to 3.94 kg for ICW, and -3.44 to 3.06 kg for ECW. In DH group, TBW ranged between -1.99 and 2.01 kg, ICW between -3.78 and 6.34 kg, and ECW between -6.22 and 3.74 kg. These findings show that BIS is useful at a group level in assessing water compartments in athletes differing in hydration status. However, the usefulness of BIS is limited at an individual level, especially in dehydrated athletes., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Microcirculatory alterations are key mechanisms in sepsis pathophysiology leading to tissue hypoxia, edema formation, and organ dysfunction. Hyperspectral imaging (HSI) is an emerging imaging technology that uses tissue-light interactions to evaluate biochemical tissue characteristics including tissue oxygenation, hemoglobin content and water content. Currently, clinical data for HSI technologies in critical ill patients are still limited., Methods and Analysis: TIVITA® Tissue System was used to measure Tissue oxygenation (StO2), Tissue Hemoglobin Index (THI), Near Infrared Perfusion Index (NPI) and Tissue Water Index (TWI) in 25 healthy volunteers and 25 septic patients. HSI measurement sites were the palm, the fingertip, and a suprapatellar knee area. Septic patients were evaluated on admission to the ICU (E), 6 h afterwards (E+6) and three times a day (t3-t9) within a total observation period of 72 h. Primary outcome was the correlation of HSI results with daily SOFA-scores., Results: Serial HSI at the three measurement sites in healthy volunteers showed a low mean variance expressing high retest reliability. HSI at E demonstrated significantly lower StO2 and NPI as well as higher TWI at the palm and fingertip in septic patients compared to healthy volunteers. StO2 and TWI showed corresponding results at the suprapatellar knee area. In septic patients, palm and fingertip THI identified survivors (E-t4) and revealed predictivity for 28-day mortality (E). Fingertip StO2 and THI correlated to SOFA-score on day 2. TWI was consistently increased in relation to the TWI range of healthy controls during the observation time. Palm TWI correlated positively with SOFA scores on day 3., Discussion: HSI results in septic patients point to a distinctive microcirculatory pattern indicative of reduced skin oxygenation and perfusion quality combined with increased blood pooling and tissue water content. THI might possess risk-stratification properties and TWI could allow tissue edema evaluation in critically ill patients., Conclusion: HSI technologies could open new perspectives in microcirculatory monitoring by visualizing oxygenation and perfusion quality combined with tissue water content in critically ill patients - a prerequisite for future tissue perfusion guided therapy concepts in intensive care medicine., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To use magnetic resonance imaging (MRI) to measure age-dependent changes in total and free water in human lenses in vivo., Methods: Sixty-four healthy adults aged 18 to 86 years were recruited, fitted with a 32-channel head receiver coil, and placed in a 3 Tesla clinical MR scanner. Scans of the crystalline lens were obtained using a volumetric interpolated breath-hold examination sequence with dual flip angles, which were corrected for field inhomogeneity post-acquisition using a B1-map obtained using a turbo-FLASH sequence. The spatial distribution and content of corrected total (ρlens) and free (T1) water along the lens optical axis were extracted using custom-written code., Results: Lens total water distribution and content did not change with age (all P > 0.05). In contrast to total water, a gradient in free water content that was highest in the periphery relative to the center was present in lenses across all ages. However, this initially parabolic free water gradient gradually developed an enhanced central plateau, as indicated by increasing profile shape parameter values (anterior: 0.067/y, P = 0.004; posterior: 0.050/y, P = 0.020) and central free water content (1.932 ms/y, P = 0.022) with age., Conclusions: MRI can obtain repeatable total and free water measurements of in vivo human lenses. The observation that the lens steady-state free, but not total, water gradient is abolished with age raises the possibility that alterations in protein-water interactions are an underlying cause of the degradation in lens optics and overall vision observed with aging.

The Arabian camel (Camelus dromedarius) is the most important livestock animal in arid and semi-arid regions and provides basic necessities to millions of people. In the current context of climate change, there is renewed interest in the mechanisms that enable camelids to survive in arid conditions. Recent investigations described genomic signatures revealing evolutionary adaptations to desert environments. We now present a comprehensive catalogue of the transcriptomes and proteomes of the dromedary kidney and describe how gene expression is modulated as a consequence of chronic dehydration and acute rehydration. Our analyses suggested an enrichment of the cholesterol biosynthetic process and an overrepresentation of categories related to ion transport. Thus, we further validated differentially expressed genes with known roles in water conservation which are affected by changes in cholesterol levels. Our datasets suggest that suppression of cholesterol biosynthesis may facilitate water retention in the kidney by indirectly facilitating the AQP2-mediated water reabsorption.

Body water turnover is a marker of hydration status for measuring total fluid gains and losses over a 24-h period. It can be particularly useful in predicting (and hence, managing) fluid loss in individuals to prevent potential physical, physiological and cognitive declines associated with hypohydration. There is currently limited research investigating the interrelationship of fluid balance, dietary intake and activity level when considering body water turnover. Therefore, this study investigates whether dietary composition and energy expenditure influences body water turnover. In our methodology, thirty-eight males (19 sedentary and 19 physically active) had their total body water and water turnover measured via the isotopic tracer deuterium oxide. Simultaneous tracking of dietary intake (food and fluid) is carried out via dietary recall, and energy expenditure is estimated via accelerometery. Our results show that active participants display a higher energy expenditure, water intake, carbohydrate intake and fibre intake; however, there is no difference in sodium or alcohol intake between the two groups. Relative water turnover in the active group is significantly greater than the sedentary group (Mean Difference (MD) [95% CI] = 17.55 g·kg -1 ·day -1 [10.90, 24.19]; p = < 0.001; g [95% CI] = 1.70 [0.98, 2.48]). A penalised linear regression provides evidence that the fibre intake ( p = 0.033), water intake ( p = 0.008), and activity level ( p = 0.063) predict participants' relative body water turnover ( R 2 = 0.585). In conclusion, water turnover is faster in individuals undertaking regular exercise than in their sedentary counterparts, and is, in part, explained by the intake of water from fluid and high-moisture content foods. The nutrient analysis of the participant diets indicates that increased dietary fibre intake is also positively associated with water turnover rates. The water loss between groups also contributes to the differences observed in water turnover; this is partly related to differences in sweat output during increased energy expenditure from physical activity.

Background: Acute capsaicinoid and capsinoid supplementation has endurance and resistance exercise benefits; however, if these short-term performance benefits translate into chronic benefits when combined with resistance training is currently unknown. This study investigated changes of chronic Capsiate supplementation on muscular adaptations, inflammatory response and performance in untrained men., Methods: Twenty untrained men were randomized to ingest 12 mg Capsiate (CAP) or placebo in a parallel, double-blind design. Body composition and performance were measured at pre-training and after 6 weeks of resistance training. An acute resistance exercise session test was performed pre and post-intervention. Blood samples were collected at rest and post-resistance exercise to analyze Tumor necrosis factor- (TNF-), Soluble TNF- receptor (sTNF-r), Interleukin-6 (IL-6) and Interleukin-10 (IL-10)., Results: Exercise and CAP supplementation increased fat-free mass in comparison to baseline by 1.5 kg (P < 0.001), however, the majority of the increase (1.0 kg) resulted from an increase in total body water. The CAP change scores for fat-free mass were significantly greater in comparison to the placebo (CAP ∆%= 2.1 ± 1.8 %, PLA ∆%= 0.7 ± 1.3 %, P = 0.043) and there was a significant difference between groups in the bench press exercise (P = 0.034) with greater upper body strength change score for CAP (∆%= 13.4 ± 9.1 %) compared to placebo (∆%= 5.8 ± 5.2 %), P = 0.041. CAP had no effect on lower body strength and no supplementation interactions were observed for all cytokines in response to acute resistance exercise (P > 0.05)., Conclusion: Chronic Capsiate supplementation combined with resistance training during short period (6 weeks) increased fat-free mass and upper body strength but not inflammatory response and performance in young untrained men.

Background and Aim: The aim of this study was to identify the factors that contribute to the maintenance of relative dose intensity (RDI) of lenvatinib in hepatocellular carcinoma (HCC) patients., Methods: Thirty-two patients with advanced HCC treated with lenvatinib were enrolled. We evaluated the relationship between maintenance of RDI and various clinical data, parameters obtained by body composition measurements with bioelectrical impedance analysis (BIA) and grip strength at the start of lenvatinib treatment., Results: Multivariate analysis showed that only the extracellular water to total body water ratio (ECW/TBW) ≤ 0.400 at initiation of treatment was associated with RDI ≥ 50% (odds ratio, 6.94; 95% confidence interval [CI], 1.00-48.00; P = 0.049). When the RDI was compared between ECW/TBW ≤ 0.400 group and ECW/TBW > 0.400 group, the RDI was significantly higher in the ECW/TBW ≤ 0.400 group at each of 0-4W, 4-6W, and 6-8W points. The P value at each point was 0.003, 0.003, and 0.005, respectively. On the other hand, multivariate analysis showed that only the ECW/TBW ≤ 0.400 at initiation of treatment was associated with the extension of duration until reduction or withdrawal of lenvatinib (hazard ratio, 4.86; 95% CI, 1.52-15.50; P = 0.007)., Conclusion: The extracellular water to total body water ratio, a parameter of body composition measurement by BIA, was significantly associated with the maintenance of RDI and the duration until reduction or withdrawal of lenvatinib in HCC patients. In addition to standard predictors such as Child-Pugh score and modified albumin-bilirubin grade that have been used to date, ECW/TBW might be a new predictor of RDI in HCC patients treated with lenvatinib., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Our brains consist of 80% water, which is continuously shifted between different compartments and cell types during physiological and pathophysiological processes. Disturbances in brain water homeostasis occur with pathologies such as brain oedema and hydrocephalus, in which fluid accumulation leads to elevated intracranial pressure. Targeted pharmacological treatments do not exist for these conditions owing to our incomplete understanding of the molecular mechanisms governing brain water transport. Historically, the transmembrane movement of brain water was assumed to occur as passive movement of water along the osmotic gradient, greatly accelerated by water channels termed aquaporins. Although aquaporins govern the majority of fluid handling in the kidney, they do not suffice to explain the overall brain water movement: either they are not present in the membranes across which water flows or they appear not to be required for the observed flow of water. Notably, brain fluid can be secreted against an osmotic gradient, suggesting that conventional osmotic water flow may not describe all transmembrane fluid transport in the brain. The cotransport of water is an unconventional molecular mechanism that is introduced in this Review as a missing link to bridge the gap in our understanding of cellular and barrier brain water transport.

Purpose: Bioelectrical impedance analysis (BIA) has been used recently to measure the body water of patients with acute heart failure. We used BIA in this study to better understand, and possibly identify a predictive marker for, perioperative water behavior in cardiac surgery patients., Methods: We measured body water and studied its behavior in 44 patients undergoing surgery for cardiac valvular disease at our hospital. Measurements included the levels of extracellular water (ECW), intracellular water (ICW), and total body water, the edema index (EI), and the ratio of ECW to total body water. The first measured EI was defined as the "preoperative EI" and the maximum as the "peak EI"., Results: A negative correlation was found between the preoperative EI and the preoperative estimated glomerular filtration rate (eGFR) (R = 0.644, p < 0.001). Positive correlations were found between the peak EI and the ICU stay (R = 0.625, p < 0.001), the peak EI and the ventilation time (R = 0.366, p < 0.01), and the preoperative EI and the ICU stay (R = 0.464, p = 0.026)., Conclusion: The EI is possibly a predictive marker for perioperative water management in cardiac surgery.

To induce diet-induced obesity (DIO) in rodents, diets high in saturated fat and/or carbohydrates are commonly used. In the laboratory, standardised diets evolved over time without paying particular attention to the effect of fat composition on metabolic alterations. In the present study, customised high-fat diets (HFD) enriched with a combination of lard and different concentrations of New Zealand green-lipped mussel (Perna canaliculus) oil or MSC Hoki (Macruronus novaezelandiae, blue grenadier) liver oil, important sources of n-3 PUFA, in comparison with a solely lard-based diet, were fed to lean and DIO male C57BL/6 mice and their effects on metabolic parameters were monitored. Intriguingly, an isoenergetic HFD containing 63 % of total fat in the form of mussel oil and only 28 % in the form of lard attenuated HFD-induced body weight gain after 1 and 4 weeks, respectively. Consistently, changing a lard-enriched HFD to the mussel oil diet reduced body weight markedly even after mice had been exposed to the former diet for 10 months. The weight-reducing effect of the diet was not caused by altered energy intake or expenditure, but was associated with reduced visceral fat mass. Collectively, these data suggest a novel weight-reducing potential of green-lipped mussel oil.

In vertebrates, skin upholds homeostasis by preventing body water loss. The skin's permeability barrier is located intercellularly in the stratum corneum and consists of stacked lipid lamellae composed of ceramides, cholesterol, and free fatty acids. We have combined cryo-electron microscopy with molecular dynamics modeling and electron microscopy simulation in our analysis of the lamellae's formation, a maturation process beginning in stratum granulosum and ending in stratum corneum. Previously, we have revealed the lipid lamellae's initial- and end-stage molecular organizations. In this study, we reveal two cryo-electron microscopy patterns representing intermediate stages in the lamellae's maturation process: a single-band pattern with 2.0‒2.5 nm periodicity and a two-band pattern with 5.5‒6.0 nm periodicity, which may be derived from lamellar lipid structures with 4.0‒5.0 nm and 5.5‒6.0 nm periodicity, respectively. On the basis of the analysis of the data now available on the four maturation stages identified, we can present a tentative molecular model for the complete skin barrier formation process., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Knowledge of the proper dry weight plays a critical role in the efficiency of dialysis and the survival of hemodialysis patients. Recently, bioimpedance spectroscopy(BIS) has been widely used for set dry weight in hemodialysis patients. However, BIS is often misrepresented in clinical healthy weight. In this study, we tried to predict the clinically proper dry weight (DWCP) using machine learning for patient's clinical information including BIS. We then analyze the factors that influence the prediction of the clinical dry weight., Methods: As a retrospective, single center study, data of 1672 hemodialysis patients were reviewed. DWCP data were collected when the dry weight was measured using the BIS (DWBIS). The gap between the two (GapDW) was calculated and then grouped and analyzed based on gaps of 1 kg and 2 kg., Results: Based on the gap between DWBIS and DWCP, 972, 303, and 384 patients were placed in groups with gaps of <1 kg, ≧1kg and <2 kg, and ≧2 kg, respectively. For less than 1 kg and 2 kg of GapDW, It can be seen that the average accuracies for the two groups are 83% and 72%, respectively, in usign XGBoost machine learning. As GapDW increases, it is more difficult to predict the target property. As GapDW increase, the mean values of hemoglobin, total protein, serum albumin, creatinine, phosphorus, potassium, and the fat tissue index tended to decrease. However, the height, total body water, extracellular water (ECW), and ECW to intracellular water ratio tended to increase., Conclusions: Machine learning made it slightly easier to predict DWCP based on DWBIS under limited conditions and gave better insights into predicting DWCP. Malnutrition-related factors and ECW were important in reflecting the differences between DWBIS and DWCP., Competing Interests: The authors have declared that no competing interests exist.

Initiation of combination antiretroviral therapy (cART) reduces inflammation in HIV-infected (HIV+) individuals. Recent studies demonstrated that diffusion MRI based extracellular free water (FW) modeling can be sensitive to neuroinflammation. Here, we investigate the FW in HIV-infection, its temporal evolution, and its association with blood markers, and cognitive scores. Using 96 age-matched participants, we found that FW was significantly elevated in grey and white matter in cART-naïve HIV+ compared to HIV-uninfected (HIV-) individuals at baseline. These increased FW values positively correlated with neurofilament light chain (NfL) and negatively correlated with CD4 counts. FW in grey and white matter, as well as NfL decreased in the HIV+ after 12 weeks of cART treatment. No significant FW differences were noted between the HIV+ and HIV- cohorts at 1 and 2-year follow-up. Results suggest that FW elevation in cART-naïve HIV+ participants is likely due to neuroinflammation. The correlation between FW and NfL, and the improvement in both FW and NfL after 12 weeks of cART treatment further reinforces this conclusion. The longer follow-up at 1 and 2 years suggests that cART helped control neuroinflammation as inferred by FW. Therefore, FW could be used as a biomarker to monitor HIV-associated neuroinflammation.

Situational or persistent body fluid deficit (i.e., de- or hypo-hydration) is considered a significant health risk factor. Bioimpedance analysis (BIA) has been suggested as an alternative to less reliable subjective and biochemical indicators of hydration status. The present study aimed to compare various BIA models in the prediction of direct measures of body compartments associated with hydration/osmolality. Fish (n = 20) was selected as a biological model for physicochemically measuring proximate body compartments associated with hydration such as water, dissolved proteins, and non-osseous minerals as the references or criterion points. Whole-body and segmental/local impedance measures were used to investigate a pool of BIA models, which were compared by Akaike Information Criterion in their ability to accurately predict the body components. Statistical models showed that 'volumetric-based' BIA measures obtained in parallel, such as distance 2 /R p , could be the best approach in predicting percent of body moisture, proteins, and minerals in the whole-body schema. However, serially-obtained BIA measures, such as the ratio of the reactance to resistance and the resistance adjusted for distance between electrodes, were the best fitting in predicting the compartments in the segmental schema. Validity of these results should be confirmed on humans before implementation in practice.

In patients with anorexia nervosa (AN), decreased intracellular (ICW), extracellular (ECW), and total body water (TBW) as well as changes in serum cytokine concentrations have been reported. In this exploratory study, we measured body composition and serum cytokine levels in patients with AN ( n = 27) and healthy controls (HCs; n = 13). Eating disorder symptom severity was assessed using the Eating Disorder Examination-Questionnaire (EDE-Q). Body composition was determined by bioimpedance analysis (BIA) which provided information on ICW, ECW, and TBW. Following blood collection, 27 cytokines and chemokines were quantified using multiplex ELISA-based technology: Eotaxin, Eotaxin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon- (IFN-) γ , interleukin- (IL-) 1 α , IL-1 β , IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, interferon γ -induced protein- (IP-) 10, macrophage inflammatory protein- (MIP-) 1 α , MIP-1 β , monocyte chemoattractant protein- (MCP-) 1, MCP-4, thymus and activation-regulated chemokine (TARC), TNF- α , and TNF- β . ICW, ECW, and TBW volumes were significantly lower in patients with AN than in HCs. In the whole sample, GM-CSF, MCP-4, and IL-4 were positively, whereas IFN- γ , IL-6, and IL-10 were negatively associated with all three parameters of body water. In AN participants, we found a statistically significant negative correlation of IL-10 with ICW, ECW, and TBW. Our results suggest an interaction between body water and the cytokine system. Underlying mechanisms are unclear but may involve a loss of water from the gut, kidneys, or skin due to AN-associated inflammatory processes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Hubertus Himmerich et al.)

The kidney plays a major role to maintain the constancy of the "milieu intérieur" by adjusting the urinary excretion of water and solutes to the requirement of the body balance. This function is coordinated with elimination of waste products generated among others by the catabolism of proteins and nucleic acids. To cope with these two major functions, the human kidneys generate each day about 180 L of ultrafiltrate from plasma and reabsorbs the vast majority of filtered water and solutes to excrete daily about one-two liter(s) of urine containing concentrations of sodium, potassium and chloride ranging from 20 to 200 mM. The final adjustment of urine composition is finely tuned along the aldosterone-sensitive distal nephron (ASDN) which includes the distal convoluted tubule and the collecting system (connecting tubule and collecting duct). Sodium reabsorption is predominant along the distal tubule if potassium must be spared, or along the collecting system when large amounts of potassium must be secreted. Nephrotic syndrome is characterized by heavy proteinuria consecutive to a glomerular injury, associated with renal sodium and water retention taking initially place along ASDN and leading to edema., (© 2021 médecine/sciences – Inserm.)

Purpose: Although there is no lymphatic system in the central nervous system (CNS), there seems to be a mechanism to remove macro molecules from the brain. Cerebrospinal fluid (CSF) and interstitial fluid (ISF) are thought to be parts of this pathway, but the details are not known. In this study, MR signal of the extracellular water was decomposed into components with distinct T 2 's, to obtain some information about distribution of waste material in the brain., Methods: Images were acquired using a Curr, Purcell, Meiboom, Gill (CPMG) imaging sequence. In order to reduce T 1 contamination and the signal oscillation, hard pulses were used as refocusing pulses. The signal was then decomposed into many T 2 components using non-negative least squares (NNLS) in pixel-by-pixel basis. Finally, a color map was generated by assigning different color for each T 2 component, then adding them together., Results: From the multi-echo images, it was possible to decompose the decaying signal into separate T 2 components. By adjusting the color table to create the color map, it is possible to visualize the extracellular water distribution, as well as their T 2 values. Several observation points include: (1) CSF inside ventricles has very long T 2 (~2 s), and seems to be relatively homogeneous, (2) subarachnoid CSF also have long T 2 , but there are short T 2 component at the brain surface, at the surface of dura, at the blood vessels in the subarachnoid space, etc., (3) in the brain parenchyma, short T 2 components (longer than intracellular component but shorter than CSF) exists along the white matter, in the choroid plexus, etc. These can be considered as distribution of macromolecules (waste materials) in the brain., Conclusion: From T 2 component analysis it is possible to obtain some insight into pathways for the transport of large molecules in the CNS, where no lymphatic system is present.

This study aims to investigate whether escin ameliorates the impairments of neurological function by ameliorating systemic inflammation instead of targeting the brain directly in intracerebral hemorrhage (ICH) mice. It showed that escin did not cross the blood brain barrier (BBB). Compared with the ICH group, the Garcia test scores in the escin groups were significantly increased. Brain water contents and Evans blue extravasation of the right basal ganglia in the ICH group were augmented, and significantly reduced by escin. Escin abated the increases of monocyte counts and serum IL-1β levels induced by ICH. IL-1β administration reversed the effect of escin on Garcia test scores, the brain water contents, and the Evans blue extravasation. Escin ameliorated the increasing levels of RhoA, ROCK1, nuclear NF-κB and the decreasing expression of IκBα, cytosolic NF-κB, occludin, claudin-5 in the ICH group. IL-1β administration blocked not only escin-mediated increases of IκBα, cytosolic NF-κB, occludin, and claudin-5, but also escin-caused decreases of RhoA, ROCK1, and nuclear NF-κB. The results indicate that escin improves neurological outcomes and the BBB function in ICH mice, which is associated with attenuating ICH-induced peripheral system inflammation, and therefore, inhibiting IL-1β/RhoA/NF-κB signaling pathway in BBB, at least in part. These findings suggest that it may be useful to ameliorate brain injury by inhibiting systemic inflammation instead of aiming to target the brain directly after ICH., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aprocitentan is a novel, oral, dual endothelin receptor antagonist (ERA) in development in difficult-to-control hypertension. As fluid retention and edema are concerns with ERAs, we investigated whether aprocitentan causes weight gain in healthy subjects on a high sodium diet and explored potential mechanisms if occurring. This double-blind, randomized, placebo-controlled, crossover study enrolled 28 subjects. Three doses of aprocitentan (10, 25, or 50 mg/day for 9 days) were compared with placebo. Increases in body weight were observed with aprocitentan (placebo-corrected mean weight gains [90% confidence interval]) of 0.43 [0.05-0.80], 0.77 [0.03-1.51], and 0.83 [0.33-1.32] kg at 10 mg, 25 mg, and 50 mg, respectively. Decreases in hemoglobin and uric acid were observed. Plasma volume increased at most by 5.5% without dose-response relationship. Urinary sodium excretion decreased at 10 mg and 25 mg but not at 50 mg. Therefore, aprocitentan produced moderate weight increases in healthy subjects on high sodium diet, without obvious sodium retention., (© 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)