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The epithelial NaWe explored the association of low frequency and rare variants in the genes encoding ENaC subunits, with systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure. Using whole-genome sequencing data from 14 studies participating in the Trans-Omics in Precision Medicine Whole-Genome Sequencing Program, and sequence kernel association tests.We found that variants inOur results suggest that variants in extrarenal ENaCs, in addition to ENaCs expressed in kidneys, influence blood pressure and kidney function.

Blood pressure (BP) is influenced by genetic variation and sodium intake with sex-specific differences; however, studies to identify renal molecular mechanisms underlying the influence of sodium intake on BP in nonhuman primates (NHP) have focused on males. To address the gap in our understanding of molecular mechanisms regulating BP in female primates, we studied sodium-naïve female baboons ( n = 7) fed a high-sodium (HS) diet for 6 wk. We hypothesized that in female baboons variation in renal transcriptional networks correlates with variation in BP response to a high-sodium diet. BP was continuously measured for 64-h periods throughout the study by implantable telemetry devices. Sodium intake, blood samples for clinical chemistries, and ultrasound-guided kidney biopsies were collected before and after the HS diet for RNA-Seq and bioinformatic analyses. We found that on the LS diet but not the HS diet, sodium intake and serum 17 β-estradiol concentration correlated with BP. Furthermore, kidney transcriptomes differed by diet-unbiased weighted gene coexpression network analysis revealed modules of genes correlated with BP on the HS diet but not the LS diet. Our results showed variation in BP on the HS diet correlated with variation in novel kidney gene networks regulated by ESR1 and MYC; i.e., these regulators have not been associated with BP regulation in male humans or rodents. Validation of the mechanisms underlying regulation of BP-associated gene networks in female NHP will inform better therapies toward greater precision medicine for women.

Background: Circadian rhythms play an essential role in physiological function. The molecular clock that underlies circadian physiological function consists of a core group of transcription factors, including the protein PER1 (Period1). Studies in mice show that PER1 plays a role in the regulation of blood pressure and renal sodium handling; however, the results are dependent on the strain being studied. Using male Dahl salt-sensitive (SS) rats with global knockout of PER1 (SS Per1−/− ), we aim to test the hypothesis that PER1 plays a key role in the regulation of salt-sensitive blood pressure. Methods: The model was generated using CRISPR/Cas9 and was characterized using radiotelemetry and measures of renal function and circadian rhythm. Results: SS Per1−/− rats had similar mean arterial pressure when fed a normal 0.4% NaCl diet but developed augmented hypertension after three weeks on a high-salt (4% NaCl) diet. Despite being maintained on a normal 12:12 light:dark cycle, SS Per1−/− rats exhibited desynchrony mean arterial pressure rhythms on a high-salt diet, as evidenced by increased variability in the time of peak mean arterial pressure. SS Per1−/− rats excrete less sodium after three weeks on the high-salt diet. Furthermore, SS Per1−/− rats exhibited decreased creatinine clearance, a measurement of renal function, as well as increased signs of kidney tissue damage. SS Per1−/− rats also exhibited higher plasma aldosterone levels. Conclusions: Altogether, our findings demonstrate that loss of PER1 in Dahl SS rats causes an array of deleterious effects, including exacerbation of the development of salt-sensitive hypertension and renal damage.

Cell-cell signaling peptides (e.g., peptide hormones, neuropeptides) are among the largest class of cellular transmitters and regulate a variety of physiological processes. To identify and quantify the relative abundances of cell-cell signaling peptides in different physiological states, liquid chromatography-mass spectrometry-based peptidomics workflows are commonly utilized on freshly dissected tissues. In such animal experiments, the administration of general anesthetics is an important step for many research projects. However, acute anesthetic administration may rapidly change the measured abundance of transmitter molecules and metabolites, especially in the brain and endocrine system, which would confound experimental results. The aim of this study was to evaluate the effect of short-term (5 min) anesthetic administration on the measured abundance of cell-cell signaling peptides, as evaluated by a typical peptidomics workflow. To accomplish this goal, we compared endogenous peptide abundances in the rat pituitary following administration of 5% isoflurane, 200 mg/kg sodium pentobarbital, or no anesthetic administration. Label-free peptidomics analysis demonstrated that acute use of isoflurane changed the levels of a small number of peptides, primarily degradation products of the hormone somatotropin, but did not influence the levels of most other peptide hormones. Acute use of sodium pentobarbital had negligible impact on the relative abundance of all measured peptides. Overall, our results suggest that anesthetics used in pituitary peptidomics studies do not dramatically confound observed results.

The renin-angiotensin-aldosterone and arginine vasopressin-V2 receptor-aquaporin-2 (AQP2) systems converge on the epithelial Na

Objective: Household air pollution (HAP) is a widespread environmental exposure worldwide. While several cleaner fuel interventions have been implemented to reduce personal exposures to HAP, it is unclear if cooking with cleaner fuels also affects the choice of meals and dietary intake. Design: Individually randomised, open-label controlled trial of a HAP intervention. We aimed to determine the effect of a HAP intervention on dietary and Na intake. Intervention participants received a liquefied petroleum gas (LPG) stove, continuous fuel delivery and behavioural messaging during 1 year whereas control participants continued with usual cooking practices that involved the use of biomass-burning stoves. Dietary outcomes included energy, energy-adjusted macronutrients and Na intake at baseline, 6 months and 12 months post-randomisation using 24-h dietary recalls and 24-h urine. We used t-tests to estimate differences between arms in the post-randomisation period. Setting: Rural settings in Puno, Peru. Participants: One hundred women aged 25–64 years. Results: At baseline, control and intervention participants were similar in age (47·4 v. 49·5 years) and had similar daily energy (8894·3 kJ v. 8295·5 kJ), carbohydrate (370·8 g v. 373·3 g) and Na intake (4·9 g v. 4·8 g). One year after randomisation, we did not find differences in average energy intake (9292·4 kJ v. 8788·3 kJ; P = 0·22) or Na intake (4·5 g v. 4·6 g; P = 0·79) between control and intervention participants. Conclusions: Our HAP intervention consisting of an LPG stove, continuous fuel distribution and behavioural messaging did not affect dietary and Na intake in rural Peru.

Nanoscale zero-valent iron (Fe) modified by sodium (Na) bentonite (B-nZVI) was prepared to remove copper (II) (Cu2+) and lead (II) (Pb2+) from an aqueous solution. B-nZVI and sodium bentonite were characterised by X-ray diffraction, Lorentz transmission electron microscopy and X-ray photoelectron spectroscopy (XPS). From the XPS spectra, lead (II) was detected on the surface of B-nZVI, indicating that lead (II) was removed by adsorption to B-nZVI. The copper (II) in the solution obtained electrons from B-nZVI and was reduced to copper (0). Sodium bentonite (B-nZVI) showed higher removal efficiencies for lead (II) than copper (II) under various conditions. As the concentration of copper (II) increased from 75 to 200 mg/l at a constant lead (II) concentration of 100 mg/l, the removal efficiency of lead (II) decreased considerably, from 81 to 49%. The removal efficiencies of copper (II) and lead (II) by B-nZVI were close to 100% at pH = 6. The temperature of best removal efficiency for copper (II) and lead (II) was 50°C when the adsorbent dose was 1 g/l, the pH was 5, the concentration of lead (II) was 200 mg/l, the concentration of copper (II) was 100 mg/l and the adsorption time was 4 h. In general, the synthesised B-nZVI exhibits great potential as an excellent material for use in the treatment of waste water that simultaneously contains copper (II) and lead (II).

n application of mechanical energy was explored as a new non-thermal method to drive H2 emission from undoped sodium alanate at room temperature. It was found that mild rubbing of NaAlH4 pellets under vacuum led to intensive and almost instantaneous gas emission. The dominating species in the emitted gases was H2 (>99%). Traces of mono- and polyalanes, NaAlH4 vapours, CO2 and other non-identified gases were registered. H2 emission involved several first-order processes, whose characteristic time constants ranged widely from 0.6 to 465 s. None of the dehydrogenation reactions could be connected to either the thermal effect of friction or the direct coupling of mechanical forces to the energy landscape of chemical reactions. In turn, it was suggested that the tribochemical reactions can be triggered by plastic deformation and shearing. A linked diffusion-wear model of NaAlH4 triboinduced dehydrogenation, which consistently explains all empirical findings, was put forward., This work was financially supported by the Ministry of Science and Innovation of Spain (grants PID2019-111063RB-I00, PID2020-112770RB-C22 and RTI2018-099794-B-I00) and the Basque Government via the EMAITEK Plus 2020 programme.

Despite large, randomized controlled trials and guideline recommendations, patients with heart failure with reduced ejection fraction (HFrEF) continue to receive suboptimal guideline-directed medical treatment (GDMT). This study aimed to evaluate the potential effect of inpatient initiation of sodium-glucose cotransport-2 (SGLT2) inhibitors on postdischarge prescribing rates and the downstream impact on clinical outcomes. The INitiation of SGlt2i in Hospital for HFrEF (INSIGHT-HF) study was a retrospective analysis of hospitalized patients older than 18 years with a left ventricular ejection fraction (LVEF) ≤40% conducted from July 2020 and July 2021. Our primary outcome was SGLT2i prescription rates at 30 days. Among 2,663 eligible patients with documented HFrEF, 177 (6.6%) had SGLT2i initiated during their index hospitalization. The rate of SGLT2i prescriptions at 30 days was significantly higher in those with inpatient initiation of SGLT2i compared with those who did not start while inpatient (96% vs 14.7%, p0.0001). The heart failure readmission rate in the first 30 days was significantly lower in those with inpatient initiation of SGLT2i compared with those who did not start during hospitalization. (9.3% vs 22.7%, p = 0.04). Cardiovascular mortality was numerically, but not significantly, different between groups (4% vs 10.7%, p = 0.21). Inpatient initiation of an SGLT2i was associated with a significantly higher postdischarge rate of SGLT2i prescriptions and significantly lower heart failure readmission rates at 30 days. In conclusion, these findings highlight the importance of initiating SGLT2i during inpatient hospitalization to improve the quality of care in patients with HFrEF.

Hydrogels are widely used as sensors in the field of wearable devices. However, the hydrogels were rarely designed to endure the harsh outdoor environment in winter, including extremely low temperature, ultraviolet (UV) radiation and variable humidity. In addition, physical damage is also a challenge for hydrogels. In this study, a self-healing hydrogel with adhesion was prepared as a sensor for winter sports using a one-pot method. Polyvinyl alcohol was used as the hydrogel matrix, providing the hydrogel preferable self-healing properties and adhesion to various surfaces such as porcine skin, metal, glass, and plastic. Lithium chloride was used for the chain entanglement of polyvinyl alcohol, forming a hydrogel with excellent ionic conductivity (24.29 S m

Combined usage of Layer-by-Layer (LbL) coating and alkaline phosphatase (ALP) - responsive charge reversal strategies can improve the cellular internalisation of the colloidal drug delivery systems by also decreasing their cytotoxic effects.Anionic core NLCs were formed by combining the melt emulsification method and ultrasonication. The resulting core NLCs were coated sequentially first with protamine (Prot NLCs) and then with sodium tripolyphosphate (TPP) or sodium polyphosphate (Graham's salt, PP) generating TPP or PP NLCs, respectively. The developed NLCs were characterised regarding their size and zeta potential. Enzyme-induced charge reversal of the TPP and PP NLCs was evaluated by zeta potential measurements upon their incubation with alkaline phosphatase (ALP). In parallel, time-dependent phosphate release was monitored in the presence of isolated as well as cell-associated ALP. Morphological evaluations were performed by scanning electron microscopy (SEM) studies. Moreover, cell viability and cellular uptake studies were carried out in vitro on Caco-2 cells.The core NLCs were obtained with a mean size of 272.27 ± 5.23 nm and a zeta potential of -25.70 ± 0.26 mV. Upon coating with protamine, the zeta potential raised to positive values with a total change up to Δ29.3 mV also displaying an increase in particle size. The second layer coating with TPP and PP provided a negative surface charge. Subsequent to ALP treatment, the zeta potential of the TPP and PP NLCs reversed from negative to positive values with total changes of Δ8.56 and Δ7.47 mV, respectively. Conformably, significant amounts of phosphate were released from both formulations. Compared with core NLCs, improved cellular viability as well as increased cellular uptake were observed in case of Prot, TPP and PP NLCs.

This paper presents an experimental investigation on the durability properties of metakaolin (MK) and bottom ash (BA) blended geopolymer under different environmental exposure. The blended geopolymer concrete (GPC) was prepared with sodium based alkaline activators under ambient curing temperature. The concentration of sodium hydroxide used was 8 M. The ratio of sodium silicate to sodium hydroxide was kept as 2.0. The performance of blended geopolymer concrete was compared with conventional concrete (CC). The test results reveal that blended geopolymer concrete develops a better performance against sulphate and acid resistance. Also, MK-BA GPC shows enhanced performance over the conventional concrete in terms of sorptivity, rapid chloride and water absorption.

Anaerobic digestion of organic waste results in production of biogas and a nutrient-rich digestate that has an established use as fertilizer in plant production. This study evaluated use of anaerobic digestate based on a high concentration of organic household waste as a fertilizer in sawdust-based production of oyster mushrooms (Pleurotus ostreatus). Inclusion of 0.5 L of anaerobic digestate (AD) per kg sawdust gave similar productivity in terms of biological efficiency (79.5 +/- 5.4 %), and protein concentration (24.7 +/- 2.4 % of dry weight (dw)) as standard mushroom substrate (78.1 +/- 5.3 %, and 21.9 +/- 3.0 % of dw, respectively). However, mushroom growth was impaired at the highest concentration of anaerobic digestate tested, 1 L digestate per kg dw sawdust. Comparison of the AD-fertilized substrate with a mushroom substrate with standard components (sawdust, wheat bran, calcium sulfate) and with similar C/N-ratio revealed some differences in elemental composition of the fruiting bodies, with an major increase in sodium concentration for the AD-fertilized substrate compared with the standard substrate (413.3 +/- 28.9 and 226.7 +/- 30.6 mg kg(-1) dw, respectively). This difference can be explained by high sodium concentration in the anaerobic digestate, most likely due to inclusion of food scraps from households and restaurants in the biodigester feedstock. Screening of both substrates for a total of 133 micro -pollutants revealed that total sum of micropollutants was significantly higher in the AD-fertilized substrate (258 +/- 12 ng/g dw substrate) than in the standard substrate (191 +/- 35 ng/g dw substrate). Nitrogen losses during preparation of the AD-fertilized substrate were negligible.

Background: Sodium-glucose cotransporter-2 inhibitors are foundational therapy in patients with heart failure with reduced ejection fraction (HFrEF), but underlying mechanisms of benefit are not well defined. We sought to investigate the relationships between sodium-glucose cotransporter-2 inhibitor treatment, changes in metabolic pathways, and outcomes using targeted metabolomics. Methods: DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients With HF With Reduced Ejection Fraction) was a placebo-controlled trial of dapagliflozin in HFrEF. We performed targeted mass spectrometry profiling of 63 metabolites (45 acylcarnitines [markers of fatty acid oxidation], 15 amino acids, and 3 conventional metabolites) in plasma samples at randomization and 12 weeks. Using mixed models, we identified principal components analysis–defined metabolite clusters that changed differentially with treatment and examined the relationship between change in metabolite clusters and change in Kansas City Cardiomyopathy Questionnaire scores and NT-proBNP (N-terminal probrain natriuretic peptide). Models were adjusted for relevant clinical covariates and nominal P P Results: Among the 234 DEFINE-HF participants with targeted metabolomic data, the mean age was 62.0±11.1 years, 25% were women, 38% were Black, and mean ejection fraction was 27±8%. Dapagliflozin increased ketone-related and short-chain acylcarnitine as well as medium-chain acylcarnitine principal components analysis–defined metabolite clusters compared with placebo (nominal P =0.01, false discovery rate–adjusted P =0.08 for both clusters). However, ketosis (β-hydroxybutyrate levels >500 μmol/L) was achieved infrequently (3 [2.5%] in dapagliflozin arm versus 1 [0.9%] in placebo arm) and supraphysiologic levels were not observed. Increases in long-chain acylcarnitine, long-chain dicarboxylacylcarnitine, and aromatic amino acid metabolite clusters were associated with decreases in Kansas City Cardiomyopathy Questionnaire scores (ie, worse quality of life) and increases in NT-proBNP levels, without interaction by treatment group. Conclusions: In this study of targeted metabolomics in a placebo-controlled trial of sodium-glucose cotransporter-2 inhibitors in HFrEF, we observed effects of dapagliflozin on key metabolic pathways, supporting a role for altered ketone and fatty acid biology with sodium-glucose cotransporter-2 inhibitors in patients with HFrEF. Only physiologic levels of ketosis were observed. In addition, we identified several metabolic biomarkers associated with adverse HFrEF outcomes. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02653482.

In nondiabetic rats, the Na+-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin increased vasopressin-related stimulation of fluid intake and free water reabsorption and maintained fluid balance and serum creatinine, whereas the loop diuretic furosemide reduced vasopressin and induced a negative fluid balance followed by a subsequent increase in serum creatinine. This study suggests that differences in vasopressin secretion in response to a SGLT2 inhibitor or loop diuretic may contribute to differences in body fluid status and subsequent renal function.

Pre-eclampsia is a common pregnancy complication with many associated maternal and fetal risks, yet its pathophysiology remains poorly understood. Hyponatraemia is a rarely described finding in pre-eclampsia that has been associated with both maternal and fetal complications and medically indicated delivery. We present a case of hyponatraemia in a patient admitted for induction of labour for gestational hypertension, which developed into pre-eclampsia with severe features requiring magnesium sulfate therapy for seizure prophylaxis. The patient’s hyponatraemia resolved with delivery, fluid restriction and serial sodium monitoring. Adjustment to the components of the patient’s magnesium sulfate infusion was made to reduce free water intake and avoid further exacerbation of her hyponatraemia. While there is currently no recommendation to routinely monitor sodium levels in hypertensive disorders of pregnancy, careful consideration of this potential finding in cases of pre-eclampsia should be given due to the overlap between symptoms of hyponatraemia and cerebral symptoms of pre-eclampsia.

Following non-elective orthopaedic surgery, a 61-year-old man with poorly controlled type 2 diabetes mellitus on empagliflozin developed high anion gap metabolic acidosis in the high-dependency unit. Metabolic acidosis persisted despite intravenous sodium bicarbonate, contributing to tachycardia and a run of non-sustained ventricular tachycardia. He was euglycaemic throughout hospital admission. Investigations revealed elevated urine and capillary ketones, and a diagnosis of sodium–glucose cotransporter-2 inhibitor-associated euglycaemic diabetic ketoacidosis was made. He was treated with an intravenous sliding scale insulin infusion and concurrent dextrose 5% with potassium chloride. Within 24 hours of treatment, his arterial pH, anion gap and serum bicarbonate levels normalised. After a further 12 hours, the intravenous insulin infusion was converted to a basal/bolus regimen of subcutaneous insulin, and he was transferred to the general ward. He was discharged well on subcutaneous insulin 6 days postoperatively.

Determining the non-specific and specific electrostatic contributions of magnesium binding to RNA is a challenging problem. We introduce a single-molecule method based on measuring the folding energy of a native RNA in magnesium and at its equivalent sodium concentration. The latter is defined so that the folding energy in sodium equals the non-specific electrostatic contribution in magnesium. The sodium equivalent can be estimated according to the empirical 100/1 rule (1 M NaCl is equivalent to 10 mM MgCl

Hyponatraemia is the most common electrolyte disturbance observed in hospital inpatients. We report a 90-year-old woman admitted generally unwell following a fall with marked confusion. Examination revealed a tender suprapubic region, and investigations observed elevated inflammatory markers and bacteriuria. Admission investigations demonstrated a serum sodium of 110 mmol/L with associated serum osmolality 236 mmol/kg and urine osmolality 346 mmol/kg. She was treated for hyponatraemia secondary to syndrome of inappropriate antidiuretic hormone (SIADH) and urosepsis. However, her serum sodium failed to normalise despite fluid restriction, necessitating treatment with demeclocycline and hypertonic saline. Despite slow reversal of hyponatraemia over 1 month, the patient developed generalised seizures with pontine and thalamic changes on MRI consistent with osmotic demyelination syndrome (ODS). This case highlights the risk of ODS, a rare but devastating consequence of hyponatraemia treatment, despite cautious sodium correction.

Ionizing radiation-induced paramagnetic defects in calcified tissues like tooth enamel are indicators of irradiation dose. Hydroxyapatite (HA), the principal constituent in these materials, incorporates a variety of anions (CO

Background: Salt sensitivity of blood pressure is an independent predictor of cardiovascular morbidity and mortality. The exact mechanism by which salt intake increases blood pressure and cardiovascular risk is unknown. We previously found that sodium entry into antigen-presenting cells (APCs) via the amiloride-sensitive epithelial sodium channel EnaC (epithelial sodium channel) leads to the formation of IsoLGs (isolevuglandins) and release of proinflammatory cytokines to activate T cells and modulate salt-sensitive hypertension. In the current study, we hypothesized that ENaC-dependent entry of sodium into APCs activates the NLRP3 (NOD [nucleotide-binding and oligomerization domain]-like receptor family pyrin domain containing 3) inflammasome via IsoLG formation leading to salt-sensitive hypertension. Methods: We performed RNA sequencing on human monocytes treated with elevated sodium in vitro and Cellular Indexing of Transcriptomes and Epitopes by Sequencing analysis of peripheral blood mononuclear cells from participants rigorously phenotyped for salt sensitivity of blood pressure using an established inpatient protocol. To determine mechanisms, we analyzed inflammasome activation in mouse models of deoxycorticosterone acetate salt–induced hypertension as well as salt-sensitive mice with ENaC inhibition or expression, IsoLG scavenging, and adoptive transfer of wild-type dendritic cells into NLRP3 deficient mice. Results: We found that high levels of salt exposure upregulates the NLRP3 inflammasome, pyroptotic and apoptotic caspases, and IL (interleukin)-1β transcription in human monocytes. Cellular Indexing of Transcriptomes and Epitopes by Sequencing revealed that components of the NLRP3 inflammasome and activation marker IL-1β dynamically vary with changes in salt loading/depletion. Mechanistically, we found that sodium-induced activation of the NLRP3 inflammasome is ENaC and IsoLG dependent. NLRP3 deficient mice develop a blunted hypertensive response to elevated sodium, and this is restored by the adoptive transfer of NLRP3 replete APCs. Conclusions: These findings reveal a mechanistic link between ENaC, inflammation, and salt-sensitive hypertension involving NLRP3 inflammasome activation in APCs. APC activation via the NLRP3 inflammasome can serve as a potential diagnostic biomarker for salt sensitivity of blood pressure.

The inwardly rectifying potassium channel (Kir) 4.1 (encoded by

Background:Emerging evidence over the past several years suggests that diurnal control of sodium excretion is sex dependent and involves the renal endothelin system. Given recent awareness of disruptions of circadian function in obesity, we determined whether diet-induced obesity impairs renal handling of an acute salt load at different times of day and whether this varies by sex and is associated with renal endothelin dysfunction.Methods:Male and female Sprague-Dawley rats were placed on a high-fat diet for 8 weeks before assessing renal sodium handling and blood pressure.Results:Male, but not female, rats on high fat had a significantly reduced natriuretic response to acute NaCl injection at the beginning of their active period that was associated with lower endothelin 1 (ET-1) excretion, lower ET-1 mRNA expression in the cortex and outer medulla as well as lower ETBreceptor expression in the outer medulla of the high-fat rats. Obese males also had significantly higher blood pressure (telemetry) that was exacerbated by adding high salt to the diet during the last 2 weeks. While female rats developed hypertension with a high-fat diet, they were not salt sensitive and ET-1 excretion was unchanged.Conclusions:These data identify diet-induced obesity as a sex-specific disruptive factor for maintaining proper sodium handling. Although high-fat diets induce hypertension in both sexes, these data reveal that males are at greater risk of salt-dependent hypertension and further suggest that females have more redundant systems that can be productive against salt-sensitive hypertension in at least some circumstances.

5-Methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY) is considered to be the most crystalline polymorphic organic molecule discovered to date with 12 fully characterized crystal structures present in the Cambridge Structural Database (CSD). However, metal complexes of ROY have not previously been described. Here, we explore the synthetic chemistry of ROY (denoted as

The sodium/iodide symporter (NIS) is the essential plasma membrane protein that mediates active iodide (I

The scientific community has shown a great deal of interest in sodium lauroyl glycine (SLG) and sodium lauroyl lactylate (SLL), two sustainable and eco-friendly substances that are considered as potential bio-friendly alternatives for petrochemical-based amphiphiles. In the present work, the formation of mixed micelle for SLG and SLL surfactant in water was investigated. Meanwhile, the surface interaction and thermodynamic parameters were calculated according to the surface tension curves. The results indicated that at certain ratios, SLG/SLL surfactant mixtures had synergistic effects that could yield higher surface activity and improve application performance. When the mole fraction of SLL (α

High-intensity focused ultrasound transducers operating at 4 MHz based on lead-free piezoceramics from the sodium bismuth titanate (NBT) family are described. First, the piezoelectric material (Pz12X) is evaluated from the standpoint of transducer design and its important characteristics, including temperature dependance of several parameters such as dielectric and mechanical coefficients. Then, the performance of six transducers of the same design is evaluated in terms of electro-acoustic efficiency and its dependency on the operating acoustic power level up to 30 W. Overall, the initial electro-acoustic efficiency of three independent transducers is approximately 50% at low acoustic power levels and slightly drops down to 42% as the input electric power reaches 10 W. This process is stable and fully reversible. Moreover, the stability of electro-acoustic efficiency over extended power burst cycling is studied using another two transducers up to 95 × 10

In this work, a novel bamboo-like carbon nanotubes@Sn4P3@carbon (BLCNTs@Sn4P3@C) coaxial nanotubes are designed and prepared using a newly developed hydrothermal method followed by a phophidation process. The prepared Sn4P3 nanoparticles are uniformly coated and wrapped on the one-dimensional (1D) bamboo-like CNTs, which is covered by a uniform carbon layer to form a sandwich-like structure with Sn4P3 in between. The inner CNT and outer carbon can effectively maintain the structural stability and serve as the good electron conductors. Additionally, the outer carbon coating layer can effectively keep BLCNTs@Sn4P3@C nanotubes separate each other, preventing aggregation of Sn4P3 during charge/discharge when this material is used as anode for sodium ion batteries. The anode of BLCNTs@Sn4P3@C shows excellent reversible capacity and a long cycling of over 2000 cycles. The unique design of coaxial nanotubes is greatly beneficial to the electrochemical performance of Sn4P3 for sodium ion storage.

Ultrafiltration (UF) has been increasingly implemented in drinking water treatment plants; however, algae and their secretions can cause severe membrane fouling and pose great challenges to UF in practice. In this study, a simple and practical chemically enhanced backwashing (CEB) process was developed to address such issues using various cleaning reagents, including sodium hypochlorite (NaClO), sodium chloride (NaCl), sodium hydroxide (NaOH), sodium citrate, and their combinations. The results indicate that the type of chemical played a fundamental role in alleviating the hydraulically irreversible membrane fouling (HIMF), with NaClO as the best-performing reagent, followed by NaCl. Furthermore, a CEB process using a combination of NaClO with NaCl, NaOH, or sodium citrate delivered little improvement in the alleviation of membrane fouling compared with NaClO alone. The optimized dosage and dosing frequency of NaClO were 10 mg·L−1 two times per day. Long-term pilot-scale and full-scale experiments further verified the feasibility of the CEB process in relieving algae-derived membrane fouling. Compared with the conventional hydraulic backwashing without chemical involvement, the CEB process can effectively remove the organic foulants including biopolymers, humic substances, and protein-like substances by means of oxidization, thereby weakening the cohesive forces between the organic foulants and the membrane surface. Therefore, the CEB process can efficiently alleviate the algae-related membrane fouling with lower chemical consumption, and is proposed as an alternative to control membrane fouling in treating the algae-containing surface water.

The mammalian distal nephron is a target of highly effective antihypertensive drugs. Genetic variants that alter its transport activity are also inherited causes of high or low blood pressure, clearly establishing its central role in human blood pressure regulation. Much has been learned during the past 25 years about salt transport along this nephron segment, spurred by the cloning of major transport proteins and the discovery of disease-causing genetic variants. Recognition is increasing that substantial cellular and segmental heterogeneity is present along this segment, with electroneutral sodium transport dominating more proximal segments and electrogenic sodium transport dominating more distal segments. Coupled with recent insights into factors that modulate transport along these segments, we now understand one important mechanism by which dietary potassium intake influences sodium excretion and blood pressure. This finding has solved the aldosterone paradox, by demonstrating how aldosterone can be both kaliuretic, when plasma potassium is elevated, and anti-natriuretic, when extracellular fluid volume is low. However, what also has become clear is that aldosterone itself only stimulates a portion of the mineralocorticoid receptors along this segment, with the others being activated by glucocorticoid hormones instead. These recent insights provide an increasingly clear picture of how this short nephron segment contributes to blood pressure homeostasis and have important implications for hypertension prevention and treatment.

Biopolymer electrolytes based on iota-carrageenan (I-carrageenan) with sodium trifluoromethanesulfonate (NaTf) were prepared by way of the conventional solution-casting technique. The biopolymer I-carrageenan was fixed as 1 g, and the concentration of NaTf was varied from 0.1 to 0.5 wt% in steps of 0.1 wt%. Distilled water was used as a solvent. Alternating current (AC) impedance measurements were carried out in the frequency window of 42 Hz–1 MHz. The same measurements were also carried out at different temperatures for all the prepared biopolymer samples. A maximum ionic conductivity of 2.6771 × 10−5 S/cm was obtained for the 0.3 wt% NaTf-added I-carrageenan system at room temperature. The temperature-dependent conductivity plot of the polymer electrolyte seemed to obey the Arrhenius relation. A low activation energy of 0.021 eV was observed for the sample with the highest ionic conductivity. From AC impedance data, dielectric parameters were obtained. The magnitude of the dielectric constant was found to increase with the increase in temperature. A low relaxation time was observed for the sample that possesses the maximum ionic conductivity.

The present study describes a model-based approach for correcting off-resonance in the context of double half-echo k-space acquisitions. This technique employs center-out readouts in forward and reverse directions to reduce echo-times but is sensitive to off-resonance, which manifests as pixel shifts in both directions. Demodulating the k-space signal with a constant off-resonance term per slice removes pixel shifts and results in a marked reduction in blurring. Phantom and in vivo datasets are demonstrated from low bandwidth sodium imaging.

Serum sodium is an established prognostic marker in heart failure (HF) patients and is associated with an increased risk of morbidity and mortality. We sought to study the prognostic value of serum sodium in left ventricular assist device (LVAD) patients and whether hyponatremia reflects worsening HF or an alternative mechanism. We identified HF patients that underwent LVAD implantation between 2008 and 2019. Hyponatremia was defined as Na ≤134 mEq/L at 3 months after implantation. We assessed for differences in hyponatremia before and after LVAD implantation. We also evaluated the association of hyponatremia with all-cause mortality and recurrent HF hospitalizations. There were 342 eligible LVAD patients with a sodium value at 3 months. Among them, there was a significant improvement in serum sodium after LVAD implantation compared to preoperatively (137.2 vs. 134.7 mEq/L, P0.0001). Patients with and without hyponatremia had no significant differences in echocardiographic and hemodynamic measurements. In a multivariate analysis, hyponatremia was associated with a markedly increased risk of all-cause mortality (HR 3.69, 95% CI, 1.93-7.05, P0.001) when accounting for age, gender, co-morbidities, use of loop diuretics, and B-type natriuretic peptide levels. Hyponatremia was also significantly associated with recurrent HF hospitalizations (HR 2.11, 95% CI, 1.02-4.37, P = 0.04). Hyponatremia in LVAD patients is associated with significantly higher risk of all-cause mortality and recurrent HF hospitalizations. Hyponatremia may be a marker of ongoing neurohormonal activation that is more sensitive than other lab values, echocardiography parameters, and hemodynamic measurements.

To assess the hospitalized sick children admitted to the pediatric emergency department (ED) and to find new patterns of clinical and laboratory attributes using association rule mining (ARM).In this observational study, 158 children with median (IQR) age 11 months and a PRISM III score of 5 (2-9) were enrolled. Hotspot data mining method was applied to assess clinical attributes, lab investigations and pre-defined outcome parameters of children and their association in sick hospitalized children aged 1 month to 12 years.We obtained 30 rules with value for outcome as discharge is given attributes as follows: duration of hospitalization4 days, lactate1.2 mmol/L, platelet = 3.67/μL, dur_ventil = 0 h, serumARM is an effective data analysis technique to find meaningful patterns using clinical features with actual numbers in pediatric critical illness. It can prove to be important while analysing the association of clinical attributes with disease pattern, its features, and therapeutic or intervention success patterns.

In the present review, we synthesize information on the mechanisms of chronic copper (Cu) toxicity using an adverse outcome pathway framework and identify three primary pathways for chronic Cu toxicity: disruption of sodium homeostasis, effects on bioenergetics, and oxidative stress. Unlike acute Cu toxicity, disruption of sodium homeostasis is not a driving mechanism of chronic toxicity, but compensatory responses in this pathway contribute to effects on organism bioenergetics. Effects on bioenergetics clearly contribute to chronic Cu toxicity with impacts at multiple lower levels of biological organization. However, quantitatively translating these impacts into effects on apical endpoints such as growth, amphibian metamorphosis, and reproduction remains elusive and requires further study. Copper-induced oxidative stress occurs in most tissues of aquatic vertebrates and is clearly a significant driver of chronic Cu toxicity. Although antioxidant responses and capacities differ among tissues, there is no clear indication that specific tissues are more sensitive than others to oxidative stress. Oxidative stress leads to increased apoptosis and cellular damage in multiple tissues, including some that contribute to bioenergetic effects. This also includes oxidative damage to tissues involved in neuroendocrine axes and this damage likely alters the normal function of these tissues. Importantly, Cu-induced changes in hormone concentrations and gene expression in endocrine-mediated pathways such as reproductive steroidogenesis and amphibian metamorphosis are likely the result of oxidative stress-induced tissue damage and not endocrine disruption. Overall, we conclude that oxidative stress is likely the primary driver of chronic Cu toxicity in aquatic vertebrates, with bioenergetic effects and compensatory response to disruption of sodium homeostasis contributing to some degree to observed effects on apical endpoints. Environ Toxicol Chem 2022;00:1-18. (c) 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

We aim to make desmopressin a safe treatment option for (older) patients at risk for hyponatremia, by introducing a new way of sodium monitoring. The goal is to reduce the risk of hyponatremia, enhance patient safety and ultimately introduce self-monitoring of sodium levels. The first step in the aforementioned is to validate capillary sodium.100 randomly selected patients admitted to the urology department received a single finger prick to collect capillary blood (250 µl) in a lithium-heparin tube. Each patient acted as its own control for the capillary and venous blood sample. Venous and capillary plasma sodium were analyzed by indirect ion-selective electrode measurement. The primary outcome was the agreement between capillary and venous sodium measurements, measured by the intra-class correlation coefficient (ICC).One hundred paired blood samples were obtained of which four were excluded. There was no significant statistical difference observed between venous and capillary sodium (-0.23 mmol/L, p = 0.374). The ICC for single measures between capillary and venous sodium was 0.82 (95% confidence interval 0.75-0.88). Inter-method differences analyzed by a Bland-Altman plot and a Passing-Bablock regression did not reveal a statistically significant difference between both groups.We demonstrated that venous and capillary sodium levels are interchangeable, taken into account the inter- and intravariability between analyses. We provided the first step towards a simple and safe solution for frequent sodium monitoring through a minimal invasive capillary blood collection. The results are of direct clinical relevance to safely use desmopressin in (older) patients at risk.

SUMMARY OBJECTIVE: This study aimed to evaluate the effects of sodium-glucose cotransporter-2 inhibitors on nutritional status in patients with heart failure with reduced ejection fraction. METHODS: The sodium-glucose cotransporter-2 inhibitor treatment was initiated in 153 patients with heart failure with reduced ejection fraction who were symptomatic despite optimal medical treatment and were followed up for 6 months. The Minnesota Living With Heart Failure Questionnaire scores, New York Heart Association functional class, NT-pro-BNP levels, and nutritional index scores of the patients were evaluated before sodium-glucose cotransporter-2 inhibitor treatment and at the 6-month follow-up. The nutritional status of the patients was evaluated with the COntrolling NUTritional Status score, Geriatric Nutritional Risk Index, and Prognostic Nutritional Index. RESULTS: After sodium-glucose cotransporter-2 inhibitor treatment, significant changes were observed in the mean scores of the three different nutritional indexes: COntrolling NUTritional Status (before: 2.76±2.43 vs. after: 1.12±1.23, p

Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure or chronic kidney disease, or with type 2 diabetes and high risk of atherosclerotic cardiovascular disease. None of the trials recruiting patients with and without diabetes were designed to assess outcomes separately in patients without diabetes.We did a systematic review and meta-analysis of SGLT2 inhibitor trials. We searched the MEDLINE and Embase databases for trials published from database inception to Sept 5, 2022. SGLT2 inhibitor trials that were double-blind, placebo-controlled, performed in adults (age ≥18 years), large (≥500 participants per group), and at least 6 months in duration were included. Summary-level data used for analysis were extracted from published reports or provided by trial investigators, and inverse-variance-weighted meta-analyses were conducted to estimate treatment effects. The main efficacy outcomes were kidney disease progression (standardised to a definition of a sustained ≥50% decrease in estimated glomerular filtration rate [eGFR] from randomisation, a sustained low eGFR, end-stage kidney disease, or death from kidney failure), acute kidney injury, and a composite of cardiovascular death or hospitalisation for heart failure. Other outcomes were death from cardiovascular and non-cardiovascular disease considered separately, and the main safety outcomes were ketoacidosis and lower limb amputation. This study is registered with PROSPERO, CRD42022351618.We identified 13 trials involving 90 413 participants. After exclusion of four participants with uncertain diabetes status, we analysed 90 409 participants (74 804 [82·7%] participants with diabetes [99% with type 2 diabetes] and 15 605 [17·3%] without diabetes; trial-level mean baseline eGFR range 37-85 mL/min per 1·73 mIn addition to the established cardiovascular benefits of SGLT2 inhibitors, the randomised data support their use for modifying risk of kidney disease progression and acute kidney injury, not only in patients with type 2 diabetes at high cardiovascular risk, but also in patients with chronic kidney disease or heart failure irrespective of diabetes status, primary kidney disease, or kidney function.UK Medical Research Council and Kidney Research UK.

Hypertension is characterized by increased sodium (Na+) reabsorption along the aldosterone-sensitive distal nephron (ASDN) as well as chronic systemic inflammation. Interleukin-6 (IL-6) is thought to be a mediator of this inflammatory process. Interestingly, increased Na+ reabsorption within the ASDN does not always correlate with increases in aldosterone (Aldo), the primary hormone that modulates Na+ reabsorption via the mineralocorticoid receptor (MR). Thus, understanding how increased ASDN Na+ reabsorption may occur independent of Aldo stimulation is critical. Here, we show that IL-6 can activate the MR by activating Rac1 and stimulating the generation of reactive oxygen species (ROS) with a consequent increase in thiazide-sensitive Na+ uptake. Using an in vitro model of the distal convoluted tubule (DCT2), mDCT15 cells, we observed nuclear translocation of eGFP-tagged MR after IL-6 treatment. To confirm the activation of downstream transcription factors, mDCT15 cells were transfected with mineralocorticoid response element (MRE)-luciferase reporter constructs; then treated with vehicle, Aldo, or IL-6. Aldosterone or IL-6 treatment increased luciferase activity that was reversed with MR antagonist cotreatment, but IL-6 treatment was reversed by Rac1 inhibition or ROS reduction. In both mDCT15 and mpkCCD cells, IL-6 increased amiloride-sensitive transepithelial Na+ current. ROS and IL-6 increased 22Na+ uptake via the thiazide-sensitive sodium chloride cotransporter (NCC). These results are the first to demonstrate that IL-6 can activate the MR resulting in MRE activation and that IL-6 increases NCC-mediated Na+ reabsorption, providing evidence for an alternative mechanism for stimulating ASDN Na+ uptake during conditions where Aldo-mediated MR stimulation may not occur.

Although left ventricular assist device (LVAD) therapy is associated with improved survival, the impact of preoperative liver function on short-term outcomes is unclear. We conducted a retrospective review of all primary HeartMate 3 LVAD implants at a single center. Composite metrics of hepatic function including the model for end-stage liver disease (MELD), the MELD with sodium, and the MELD excluding international normalized ratio (MELD-XI) were evaluated. Receiver operator characteristic curves were compared to determine which equation was most predictive of 1-year survival. Primary stratification was based on MELD-XI tertiles. Secondary stratification was based on hypoalbuminemia (3.0 mg/100 ml). A total of 94 patients underwent primary LVAD implantation from 2017 to 2022. MELD-XI and hypoalbuminemia were most associated with 1-year outcomes. When stratified by MELD tertiles, higher MELD was strongly associated with decreased 30 days (100.00% vs 100.00% vs 90.32%, p = 0.04), 1-year (93.00% vs 93.32% vs 69.79%, p = 0.01), and 2-year survival (93.00% vs 83.21% vs 69.79%, p = 0.04). In addition, while hypoalbuminemia was associated with similar 30 days (97.87% vs 95.74%, p = 0.56) survival, it was associated with a significant decrease in 1-year (92.93% vs 77.92%, p = 0.03) and 2-year survival (92.93% vs 68.89%, p0.01). These results persisted on multivariable analysis for both MELD-XI score (p = 0.04) and hypoalbuminemia (p = 0.04). In conclusion, this is the first study to demonstrate that preoperative MELD-XI score and serum albumin levels are associated with short-term HeartMate 3 outcomes.

The effect of blocking the persistent component of the sodium channel current (late I

The management of heart failure with preserved ejection fraction (HFpEF) is rapidly evolving. The pharmacologic treatment of patients with HFpEF includes symptom management with diuretics and optimization of comorbidities, including hypertension, obesity, diabetes mellitus, and atrial fibrillation. Specific therapies, including angiotensin II receptor blockers, mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors, and sodium-glucose cotransporter-2 inhibitors, are well tolerated and can reduce the risk of HF hospitalization, particularly in those on the lower end of the HFpEF left ventricular ejection fraction spectrum. Ongoing trials should continue to inform optimal therapy in this evolving field.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently been a significant focus of attention because of their multiple pleiotropic effects. However, the impact of SGLT2i on atrial fibrillation (AF) remains unclear.The goal of this study was to examine the effects of SGLT2i on AF after catheter ablation (CA).This prospective, randomized controlled study compared the suppressive effect of SGLT2i vs dipeptidyl peptidase-4 inhibitors on AF recurrence after CA. Eighty AF patients with type 2 diabetes mellitus were randomized (by a computer-generated random sequence) to the tofogliflozin group (20 mg/d) or the anagliptin group (200 mg/d) stratified according to left atrial diameter and AF type (paroxysmal AF [PAF] or non-paroxysmal atrial fibrillation [PAF]) at screening. The primary outcome was AF recurrence at 12 months after CA.Seventy patients were analyzed (mean age 70.3 ± 8.1 years; 48 male; 30 with paroxysmal AF; 38 tofogliflozin treated). Recurrent AF was detected in 24 (34.3%) of 70 patients, and the AF recurrence ratio was higher in the anagliptin group than in the tofogliflozin group (15 of 32 patients [47%] vs 9 of 38 patients [24%]; P = 0.0417). Moreover, univariate analysis revealed that compared with the nonrecurrence group (n = 46), the recurrence group (n = 24) had a higher prevalence rate of non-PAF, elevated brain natriuretic peptide, higher urinary albumin-creatinine ratio, lower rate of SGLT2i use, larger left atrial diameter, elevated E wave, lower left ventricular ejection fraction, and lower rate of cryoballoon pulmonary vein isolation.Compared with anagliptin, tofogliflozin achieved greater suppression of AF recurrence after CA in patients with type 2 diabetes mellitus.

Background: GPCRs (G protein–coupled receptors) are implicated in blood pressure (BP) and fluid intake regulation. There is a developing concept that these effects are mediated by both canonical G protein signaling and noncanonical β-arrestin mediated signaling, but the contributions of each remain largely unexplored. Here, we hypothesized that β-arrestin contributes to fluid homeostasis and blood pressure (BP) regulation in deoxycorticosterone acetate (DOCA) salt hypertension, a prototypical model of salt-sensitive hypertension. Methods: Global β-arrestin1 ( Arrb1 ) and β-arrestin2 ( Arrb2 ) knockout mice were employed to evaluate drinking behavior, and BP was evaluated in Arrb2 -knockout mice. Age- and sex-matched C57BL/6 mice served as controls. We measured intake of water and different sodium chloride solutions and BP employing a 2-bottle choice paradigm with and without DOCA. Results: Without DOCA (baseline), Arrb2 -knockout mice exhibited a significant elevation in saline intake with no change in water intake. With DOCA treatment, Arrb2 -knockout mice exhibited a significant increase in both saline and water intake. Although Arrb2 -knockout mice exhibited hypernatremia at baseline conditions, we did not find significant changes in total body sodium stores or sodium palatability. In a separate cohort, BP was measured via telemetry in Arrb2 -knockout and C57BL/6 mice with and without DOCA. Arrb2 -knockout did not exhibit significant differences in BP before DOCA treatment when provided water alone, or when provided a choice of water and saline. However, Arrb2 -knockout exhibited an increased pressor response to DOCA-salt. Conclusions: These findings suggest that in salt-sensitive hypertension, ARRB2, but not ARRB1 (β-arrestin 1), might counterbalance the canonical signaling of GPCRs.

The aim of the study was to investigate the properties of sodium caseinate dispersions and oil-in-water emulsions obtained from cows' milk of either A1/A1, A1/A2, or A2/A2 β-casein phenotype. Protein structural characterisation was examined using Fourier Transform Infrared and Nuclear Magnetic Resonance spectroscopies, with physicochemical and interfacial properties assessed by analysing adsorbed protein content, hydrophobicity, solubility, and emulsion stability of the samples. Results showed variations in the secondary structure of all samples dependent of the presence of A1 or A2 β-caseins. The main differences included greater amounts of α-helix and β-sheet in A1/A1 and A1/A2 sodium caseinate dispersions that influenced their lower solubility, while random coils/polyproline II helixes were found only in A2/A2 sodium caseinate dispersion. In contrast, upon adsorption on the interface of A2/A2 sodium caseinate emulsion, the protein adopted ordered conformational motifs. This conformational shift supposedly arose from structural differences between the two β-casein proteoforms, which most likely enhanced the emulsion properties of A2/A2 sodium caseinate compared to either A1/A1 or A1/A2 sodium caseinates. The A2 β-casein in both, A1/A2 and A2/A2 sodium caseinates, appears to be able to more rapidly reach the oil droplet surface and was more efficient as emulsifying agent. The current results demonstrated that the conformational rearrangement of proteins upon adsorption to emulsion interfaces was dependent not only on hydrophobicity and on solubility, but also on the conformational flexibility of A1/A1, A1/A2, and A2/A2 β-casein phenotypes. These findings can assist in predicting the behaviour of sodium caseinates during relevant industrial processing.