Selective Lattice Doping Enables a Low-Cost, High-Capacity and Long-Lasting Potassium Layered Oxide Cathode for Potassium and Sodium Storage.

Layered transition metal oxides are highly promising host materials for K ions, owing to their high theoretical capacities and appropriate operational potentials. To address the intrinsic issues of KxMnO2 cathodes and optimize their electrochemical properties, a novel P3-type oxide doped with carefully chosen cost-effective, electrochemically active and multi-functional elements is proposed, namely K0.57Cu0.1Fe0.1Mn0.8O2. Compared to the pristine K0.56MnO2, its reversible specific is increased from 104 to 135 mAh g-1. In addition, the Cu and Fe co-doping triples the capacity under high current densities, and contributes to long-term stability over 500 cycles with a capacity retention of 68 %. Such endeavor holds the potential to make potassium-ion batteries particularly competitive for application in sustainable, low-cost, and large-scale energy storage devices. In addition, the cathode is also extended for sodium storage. Facilitated by the interlayer K ions that protect the layered structure from collapsing and expand the diffusion pathway for sodium ions, the cathode shows a high reversible capacity of 144 mAh g-1, fast kinetics and a long lifespan over 1000 cycles. The findings offer a novel pathway for the development of high-performance and cost-effective sodium-ion batteries.

Global guidelines recommendations for dietary sodium and potassium intake.

Non-communicable diseases (NCDs) cause a significant global health challenge, with unhealthy diets identified as a major risk factor. Sodium and potassium, which are essential minerals for human health, play important roles in various bodily functions, and an imbalance in their intake can have significant health implications, particularly concerning hypertension and cardiovascular diseases. This review compiles dietary sodium and potassium intake recommendations from prominent global health organizations and compares global guidelines to Japan's Dietary Reference Intake (DRI) guidelines. Sodium and potassium intake guidelines from organizations such as the World Health Organization (WHO), American College of Cardiology (ACC) and American Heart Association (AHA), Dietary Guidelines for Americans (DGA), European Food Safety Authority (EFSA), and DRI for Japanese exhibit variations. Compared to other Asian countries, Japan's historically higher sodium goal aligns with Southeast Asia where traditional preserved foods contribute to high sodium intake. Contrarily, Japan's lower potassium goal contrasts with other countries in Asia promoting a diet rich in fruits and vegetables. The ongoing effort by Japan to align with global recommendations reflects a gradation approach considering social habits. While harmonizing international efforts is essential, appreciating regional diversities is paramount through tailoring guidelines to cultural and dietary habit practices. Implementing context-specific guidelines informed by scientific research can contribute to global efforts in promoting healthy diets and reducing the burden of NCDs. Global guidelines that recommended the daily dietary intake goal for sodium and potassium exhibit variations. These disparities are influenced by diverse factors, including cultural dietary habits, socioeconomic status, health priorities, and available scientific research. Each population should follow the recommendations of their region.

Development of Losartan Orally Disintegrating Tablets by Direct Compression: a Cost-Effective Approach to Improve Paediatric Patient's Compliance.

The development of suitable dosage forms is essential for an effective pharmacological treatment in children. Orally disintegrating tablets (ODTs) are attractive dosage forms that avoid swallowing problems, ensure dosage accuracy and are easy to administer as they disintegrate in the oral cavity. This study aimed to develop ODTs containing losartan potassium (LP) for the treatment of arterial hypertension in children. The ODTs, produced by the cost-effective manufacturing process of direct compression, consisted of a mixture of diluent, superdisintegrant, glidant and lubricant. Five superdisintegrants (croscarmellose sodium, two grades of crospovidone, sodium starch glycolate and pregelatinized starch) were tested (at two concentrations), and combined with three diluents (mannitol, lactose and sorbitol). Thus, thirty formulations were evaluated based on disintegration time, hardness and friability. Two formulations, exhibiting the best results concerning disintegration time (< 30 s), hardness and friability (≤ 1.0%), were selected as the most promising ones for further evaluation. These ODTs presented favourable drug-excipient compatibility, tabletability and flow properties. The in vitro dissolution studies demonstrated 'very rapid' drug release. Preliminary stability studies highlighted the requirement of a protective packaging. All quality properties retained appropriate results after 12 months of storage in airtight containers. In conclusion, the ODTs were successfully developed and characterised, suggesting a potential means to accomplish a final prototype that enables an improvement in childhood arterial hypertension treatment.

Early switch from intravenous to oral antibiotic therapy in patients with cancer who have low-risk neutropenic sepsis: the EASI-SWITCH RCT.

Background: Neutropenic sepsis is a common complication of systemic anticancer treatment. There is variation in practice in timing of switch to oral antibiotics after commencement of empirical intravenous antibiotic therapy. Objectives: To establish the clinical and cost effectiveness of early switch to oral antibiotics in patients with neutropenic sepsis at low risk of infective complications. Design: A randomised, multicentre, open-label, allocation concealed, non-inferiority trial to establish the clinical and cost effectiveness of early oral switch in comparison to standard care. Setting: Nineteen UK oncology centres. Participants: Patients aged 16 years and over receiving systemic anticancer therapy with fever (≥ 38°C), or symptoms and signs of sepsis, and neutropenia (≤ 1.0 × 109/l) within 24 hours of randomisation, with a Multinational Association for Supportive Care in Cancer score of ≥ 21 and receiving intravenous piperacillin/tazobactam or meropenem for < 24 hours were eligible. Patients with acute leukaemia or stem cell transplant were excluded. Intervention: Early switch to oral ciprofloxacin (750 mg twice daily) and co-amoxiclav (625 mg three times daily) within 12-24 hours of starting intravenous antibiotics to complete 5 days treatment in total. Control was standard care, that is, continuation of intravenous antibiotics for at least 48 hours with ongoing treatment at physician discretion. Main outcome measures: Treatment failure, a composite measure assessed at day 14 based on the following criteria: fever persistence or recurrence within 72 hours of starting intravenous antibiotics; escalation from protocolised antibiotics; critical care support or death. Results: The study was closed early due to under-recruitment with 129 patients recruited; hence, a definitive conclusion regarding non-inferiority cannot be made. Sixty-five patients were randomised to the early switch arm and 64 to the standard care arm with subsequent intention-to-treat and per-protocol analyses including 125 (intervention n = 61 and control n = 64) and 113 (intervention n = 53 and control n = 60) patients, respectively. In the intention-to-treat population the treatment failure rates were 14.1% in the control group and 24.6% in the intervention group, difference = 10.5% (95% confidence interval 0.11 to 0.22). In the per-protocol population the treatment failure rates were 13.3% and 17.7% in control and intervention groups, respectively; difference = 3.7% (95% confidence interval 0.04 to 0.148). Treatment failure predominantly consisted of persistence or recurrence of fever and/or physician-directed escalation from protocolised antibiotics with no critical care admissions or deaths. The median length of stay was shorter in the intervention group and adverse events reported were similar in both groups. Patients, particularly those with care-giving responsibilities, expressed a preference for early switch. However, differences in health-related quality of life and health resource use were small and not statistically significant. Conclusions: Non-inferiority for early oral switch could not be proven due to trial under-recruitment. The findings suggest this may be an acceptable treatment strategy for some patients who can adhere to such a treatment regimen and would prefer a potentially reduced duration of hospitalisation while accepting increased risk of treatment failure resulting in re-admission. Further research should explore tools for patient stratification for low-risk de-escalation or ambulatory pathways including use of biomarkers and/or point-of-care rapid microbiological testing as an adjunct to clinical decision-making tools. This could include application to shorter-duration antimicrobial therapy in line with other antimicrobial stewardship studies. Trial registration: This trial is registered as ISRCTN84288963. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/140/05) and is published in full in Health Technology Assessment; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.

Neutropenic sepsis, or infection with a low white blood cell count, can occur following cancer treatment. Usually patients receive treatment with intravenous antibiotics (antibiotics delivered into a vein) for two or more days. Patients at low risk of complications from their infection may be able to have a shorter period of intravenous antibiotics benefitting both patients and the NHS. The trial compared whether changing from intravenous to oral antibiotics (antibiotics taken by mouth as tablets or liquid) 12­24 hours after starting antibiotic treatment ('early switch') is as effective as usual care. Patients could take part if they had started intravenous antibiotics for low-risk neutropenic sepsis. Patients were randomly allocated to 'early switch' or to usual care. The main outcome measured was treatment failure. Treatment failure happened if fever persisted or recurred despite antibiotics, if patients needed to change antibiotics, if they needed to be re-admitted to hospital or needed to be admitted to intensive care within 14 days or died. We had originally intended that 628 patients would take part, but after review of the design of the study the number needed to take part was revised to 230. We were not able to complete the trial as planned as unfortunately only 129 patients took part. As the trial was smaller than expected we were not able to draw conclusions as to whether 'early switch' is no less effective than usual care. Our findings suggest that 'early switch' might result in a shorter time in hospital initially; however, treatment failure was more likely to occur, meaning some patients had to return to hospital for further antibiotics. There were no differences in side effects and no serious complications from treatment or treatment failure (such as intensive care admission or death) among the 65 patients in the 'early switch' group. Patients were satisfied with 'early switch'. Early switch may be a treatment option for some patients with low-risk neutropenic sepsis who would prefer a shorter duration of hospital admission but accept a risk of needing hospital re-admission.

A design of experiment based RP-HPLC method for the simultaneous estimation of antihypertensive drugs with greenness assessment.

The correlation between blood pressure (BP) and cardiovascular risk has a continuous, positive, and linear pattern. Lowering high BP decreases the risk associated with cardiovascular disease. Chlorthalidone (CHD) and Losartan potassium (LOS) combination is used to treat hypertension. The analytical community was concerned with minimizing or reducing the use of toxic chemicals and solvents. Therefore, the current study aimed to develop a rapid, sensitive, and cost-effective green RP-HPLC method to determine CHD and LOS simultaneously in a short analysis of time. Method optimization was performed by Central composite design (CCD), the flow rate and the change of time were chosen as factors. Effective separation was conducted on Zorbax SB-C18 (4.6 mm × 150 mm, 5 µm) column by gradient mobile phase comprising phosphate buffer and ethanol flowing at 0.859 ml/min, and the wavelength detected at 230 nm. As per ICH criteria, the technique was proven to be precise, accurate, and linear over the concentration range of 4.3-8.1 µg/ml for CHD and 35-65 µg/ml for LOS. Furthermore, the method's greenness was examined by three different metrics, confirming that less toxic effect on the environment. Hence, the optimized approach proves to be eco-friendly, simple, and robust for the concurrent evaluation of CHD and LOS in pharmaceutical formulations.

Large-Scale Wearable Textile-Based Sweat Sensor with High Sensitivity, Rapid Response, and Stable Electrochemical Performance.

Textile-based sweat sensors display great potential to enhance wearable comfort and health monitoring; however, their widespread application is severely hindered by the intricate manufacturing process and electrochemical characteristics. To address this challenge, we combined both impregnation coating technology and conjugated electrospinning technology to develop an electro-assisted impregnation core-spinning technology (EAICST), which enables us to simply construct a sheath-core electrochemical sensing yarn (TPFV/CPP yarn) via coating PEDOT:PSS-coated carbon fibers (CPP) with polyurethane (TPU)/polyacrylonitrile (PAN)/poloxamer (F127)/valinomycin as shell. The TPFV/CPP yarn was sewn into the fabric and integrated with a sensor to achieve a detachable feature and efficiently monitor K+ levels in sweat. By introducing EAICST, a speed of 10 m/h can be realized in the continuous preparation of the TPFV/CPP yarn, while the interconnected pores in the yarn sheath enable it to quickly capture and diffuse sweat. Besides, the sensor exhibited excellent sensitivity (54.26 mV/decade), fast response (1.7 s), anti-interference, and long-term stability (5000 s or more). Especially, it also possesses favorable washability and wear resistance properties. Taken together, this study provides a crucial technical foundation for the development of advanced wearable devices designed for sweat analysis.

Assessment of the Electrolyte Heterogeneity of Tissues in Mandibular Bone-Infiltrating Head and Neck Cancer Using Laser-Induced Breakdown Spectroscopy.

Laser-induced breakdown spectroscopy (LIBS) was recently introduced as a rapid bone analysis technique in bone-infiltrating head and neck cancers. Research efforts on laser surgery systems with controlled tissue feedback are currently limited to animal specimens and the use of nontumorous tissues. Accordingly, this study aimed to characterize the electrolyte composition of tissues in human mandibular bone-infiltrating head and neck cancer. Mandible cross-sections from 12 patients with bone-invasive head and neck cancers were natively investigated with LIBS. Representative LIBS spectra (n = 3049) of the inferior alveolar nerve, fibrosis, tumor stroma, and cell-rich tumor areas were acquired and histologically validated. Tissue-specific differences in the LIBS spectra were determined by receiver operating characteristics analysis and visualized by principal component analysis. The electrolyte emission values of calcium (Ca) and potassium (K) significantly (p < 0.0001) differed in fibrosis, nerve tissue, tumor stroma, and cell-rich tumor areas. Based on the intracellular detection of Ca and K, LIBS ensures the discrimination between the inferior alveolar nerve and cell-rich tumor tissue with a sensitivity of ≥95.2% and a specificity of ≥87.2%. The heterogeneity of electrolyte emission values within tumorous and nontumorous tissue areas enables LIBS-based tissue recognition in mandibular bone-infiltrating head and neck cancer.

Association between sodium and potassium excretion estimated from spot urine and socioeconomic status among primary school children and their mothers in Okinawa, Japan.

Hypertension is the greatest and the most preventable risk factor for cardiovascular disease. Excessive sodium (Na) intake and insufficient potassium (K) intake have been identified as risk factors for hypertension. Socioeconomic status (SES) may be related to diet quality. In Japan, few studies have examined the relationship between urinary Na and K excretion and SES in adults, and there are no studies in children. In 2014, 1944 children (1382 households) in all public elementary schools in Yaese town, Okinawa, Japan were recruited to participate in a study. Casual urine specimens were collected to estimate 24-h urinary Na and K excretion and urinary Na/K ratio. Mother's educational background and household incomes were assessed and used as indicators of SES. A total of 236 pairs of children and their mothers were analyzed in this study. Urinary Na and K excretion were not significantly related to educational levels of mothers and household incomes in children. On the other hand, in mothers, lower household income group had higher 24-h estimated urinary Na excretion and urinary Na/K ratio than other groups. There was no significant difference between urinary excretion and educational levels in mothers. Household income disparities in urinary levels seen in mothers were not seen in children. There may be some factors that moderate the dietary inequalities in children.

Phenotypic and functional assessment of two novel KCNQ2 gain-of-function variants Y141N and G239S and effects of amitriptyline treatment.

While loss-of-function (LoF) variants in KCNQ2 are associated with a spectrum of neonatal-onset epilepsies, gain-of-function (GoF) variants cause a more complex phenotype that precludes neonatal-onset epilepsy. In the present work, the clinical features of three patients carrying a de novo KCNQ2 Y141N (n â€‹= â€‹1) or G239S variant (n â€‹= â€‹2) respectively, are described. All three patients had a mild global developmental delay, with prominent language deficits, and strong activation of interictal epileptic activity during sleep. Epileptic seizures were not reported. The absence of neonatal seizures suggested a GoF effect and prompted functional testing of the variants. In vitro whole-cell patch-clamp electrophysiological experiments in Chinese Hamster Ovary cells transiently-transfected with the cDNAs encoding Kv7.2 subunits carrying the Y141N or G239S variants in homomeric or heteromeric configurations with Kv7.2 subunits, revealed that currents from channels incorporating mutant subunits displayed increased current densities and hyperpolarizing shifts of about 10 â€‹mV in activation gating; both these functional features are consistent with an in vitro GoF phenotype. The antidepressant drug amitriptyline induced a reversible and concentration-dependent inhibition of current carried by Kv7.2 Y141N and G239S mutant channels. Based on in vitro results, amitriptyline was prescribed in one patient (G239S), prompting a significant improvement in motor, verbal, social, sensory and adaptive behavior skillsduring the two-year-treatment period. Thus, our results suggest that KCNQ2 GoF variants Y141N and G239S cause a mild DD with prominent language deficits in the absence of neonatal seizures and that treatment with the Kv7 channel blocker amitriptyline might represent a potential targeted treatment for patients with KCNQ2 GoF variants.

Differences in Intakes of Select Nutrients by Urbanization Level in the United States Population 2 Years and Older, NHANES 2013-2018.

BACKGROUND: Differences in nutrient intakes by urbanization level in the Unites States is not well understood. OBJECTIVE: Describe, by urbanization level: 1) intake of protein, fiber, percent of energy from added sugars (AS) and saturated fat (SF), calcium, iron, potassium, sodium, and vitamin D; 2) the percent of the population meeting nutrient recommendations. METHODS: Twenty-four-hour dietary recalls from 23,107 participants aged 2 y and over from the 2013-2018 National Health and Nutrition Examination Surveys were analyzed. Usual intakes were estimated, and linear regression models adjusted for age, sex, race and Hispanic origin, and whether family income met the 130% threshold examined intake differences by urbanization levels-large urban areas (LUA), small to medium metro areas (SMMA), and rural areas (RA). RESULTS: A small percentage of the population met the nutrient recommendations, except for protein (92.8%) and iron (70.5%). A higher percentage of the population met recommendations than SMMA and RA for fiber (11.8% compared with 8.1% and 5.3%, P < 0.001), AS (40.2% compared with 33.4% and 31.3%, P < 0.001), SF (26.8% compared with 18.2% and 20.1%, P < 0.001), and potassium (31.5% compared with 25.5% and 22.0%, P < 0.001). Mean protein intake were also higher in LUA than RA (80.0 g compared with 77.7 g, P = 0.003) and fiber intake higher in LUA than SMMA (16.5 g compared with 15.9 g, P = 0.01) and RA (16.5 g compared with 15.2 g, P = 0.001). In addition, contributions to energy intake were lower in LUA than SMMA for AS (11.3% compared with 12.0%, P < 0.001) and SF (11.5% compared with 11.7%, P < 0.001), and for LUA than RA for AS (11.3% compared with 12.9%, P < 0.001) and SF (11.5% compared with 11.8%, P < 0.001). CONCLUSIONS: RA had some markers of poorer diet quality-lower protein and fiber intake and higher AS intake-compared with LUA, and these differences persisted in adjusted regression models. These results may inform public health efforts to address health disparities by urbanization levels in the Unites States.

Simultaneous Immobilization of Heavy Metals in MKPC-Based Mortar-Experimental Assessment.

Heavy metal contamination, associated with the increase in industrial production and the development of the population in general, poses a significant risk in terms of the contamination of soil, water, and, consequently, industrial plants and human health. The presence of ecotoxic heavy metals (HMs) thus significantly limits the sustainable development of society and contributes to the deterioration of the quality of the environment as a whole. For this reason, the stabilization and immobilization of heavy metals is a very topical issue. This paper deals with the possibility of the simultaneous immobilization of heavy metals (Ba2+, Pb2+, and Zn2+) in mortar based on magnesium potassium phosphate cement (MKPC). The structural, mechanical, and hygric parameters of mortars artificially contaminated with heavy metals in the form of salt solutions were investigated together with the formed hydration products. In the leachates of the prepared samples, the content of HMs was measured and the immobilization ratio of each HM was determined. The immobilization rate of all the investigated HMs was >98.7%, which gave information about the effectiveness of the MKPC-based matrix for HM stabilization. Furthermore, the content of HMs in the leachates was below the prescribed limits for non-hazardous waste that can be safely treated without any environmental risks. Although the presence of heavy metals led to a reduction in the strength of the prepared mortar (46.5% and 57.3% in compressive and flexural strength, respectively), its mechanical resistance remained high enough for many construction applications. Moreover, the low values of the parameters characterizing the water transport (water absorption coefficient Aw = 4.26 × 10-3 kg·m-2·s-1/2 and sorptivity S = 4.0 × 10-6 m·s-1/2) clearly demonstrate the limited possibility of the leaching of heavy metals from the MKPC matrix structure.

Financial Implication of Sodium Zirconium Cyclosilicate Therapy in Patients with Systolic Heart Failure and Hyperkalemia.

Sodium zirconium cyclosilicate (SZC), a newly-introduced potassium binder, can be used to manage hyperkalemia especially in patients with chronic kidney disease and in those on medical therapy which may raise serum potassium levels. The medication may incur additional costs but may in turn have a significant benefit in the effect of maintaining guideline-directed medical therapy for heart failure. We aimed to investigate the financial impact of SZC therapy in patients with systolic heart failure.Patients with systolic heart failure who received SZC for hyperkalemia between July 2020 and March 2023 were included. In-hospital medical costs were compared between the patients who discontinued SZC and those who continued SZC. For the continue group, the cost of SZC was added. All patients were followed for 2 years or until May 2023.A total of 36 patients (median age 81 years, 56% male, median left ventricular ejection fraction 43%) were included. Total medical costs were significantly lower in the continue group (n = 12) compared to the discontinue group (n = 24) (3.1 [3.1, 6.2] versus 12.1 [3.8, 48.6] × 104 JPY per month, P = 0.039). In the continue group, serum potassium levels were decreased, renin-angiotensin-aldosterone system inhibitor doses were up-titrated, and the left ventricular ejection fraction was increased, whereas these parameters remained unchanged or worsened in the discontinue group.SZC may have the potential to assist in the up-titration of potassium-sparing heart failure-specific medications, prevent readmissions, and minimize medical costs, by preventing recurrent hyperkalemia in patients with systolic heart failure.

Nutrigenomics: SNPs correlated to minerals' deficiencies.

Abstract: Nutrigenetics and nutrigenomics are two interrelated fields that explore the influence of genetic diversity on nutrient responses and function. While nutrigenetics investigates the effects of hereditary ge-netic variations on micronutrient metabolism, nutrigenomics examines the intricate relationship between diet and the genome, studying how genetic variants impact nutrient intake and gene expression. These disciplines offer valuable insights into predicting and managing chronic diseases through personalized nutritional approaches. Nutrigenomics employs cutting-edge genomics technologies to study nutrient-genome interactions. Key principles involve genetic variability among ethnic groups, affecting nutrient bioavailability and metabolism, and the influence of dietary choices based on cultural, geographic, and socioeconomic factors. Polymorphisms, particularly single-nucleotide polymorphisms (SNPs), significantly influence gene activity and are associated with specific phenotypes that are related to micronutrient deficiencies. Minerals are inorganic elements, vital for various physiological functions. Understanding the SNPs associated with mineral deficien-cies is crucial for assessing disease risk and developing personalized treatment plans. This knowledge can inform public health interventions, targeted screening programs, educational campaigns, and fortified food products to address deficiencies effectively. Nutrigenomics research has the potential to revolutionize clinical and nutritional practices, providing personalized recommendations, enhancing illness risk assessment, and advancing public health initiatives. Despite the need for further research, harnessing nutrigenomics' potential can lead to more focused and efficient methods for preventing and treating mineral deficiencies.

The availability, price, and characteristics of low sodium salt based on an online salt market survey in China: Implications for scaling up its use.

Low sodium salt (LSS) is an effective way to reduce the primary source of sodium from home cooking. To investigate the availability, price and characteristics of LSS, price gap between LSS and regular salt, and the potential size of subsidy needed to equalize the price of LSS and regular salt. A market survey of salts was conducted using two major online shopping sites JD and Taobao from November to December 2022. Of 360 salts, 76 (21.1%) are LSS and 284 (78.9%) are regular salt. The average proportion of potassium chloride is low (16.8%), and half of the brands contain less than 15% and only 6.6% contains ≥25%. The mean price of LSS is slightly but not significantly higher than that of regular salts (1.82 versus 1.67 yuan/100 g, p = .07). In the lowest quartile by price, the cost of LSS is significantly higher than regular salts (difference 0.13, p = .0048). Further, when comparing the lowest price LSS to the lowest price regular since within the same brand, the mean price LSS is 2.11-fold that of the regular salt (1.66 versus 0.79 yuan/100 g, p < .05). The price of iodized LSS is also significantly higher than that of iodized regular salt (1.86 verse 1.44 yuan/100 g, p = .044). An annual subsidy based on the difference in price in the first quartile would cost 4.75 yuan per capita. A variety of LSS are available in China's salt market.

Medical Costs in Patients with Hyperkalemia on Long-Term Sodium Zirconium Cyclosilicate Therapy: The RECOGNIZE II Study.

Purpose: Hyperkalemia, defined as abnormally high serum potassium levels of ≥5.1 mmol/L, is associated with increased medical costs. This real-world study evaluated the impact of long-term sodium zirconium cyclosilicate (SZC) therapy on medical costs in patients with hyperkalemia. Patients and Methods: This retrospective, comparative study used claims data from IQVIA PharMetrics® Plus. Patients aged ≥18 years with hyperkalemia who had outpatient SZC fills (>3-month supply over 6 months) between July 2019 and December 2021 and continuous insurance coverage 6 months before and 6 months after the first SZC fill were included. These patients (SZC cohort) were 1:1 exact- and propensity score-matched on baseline variables with patients with hyperkalemia who did not receive SZC (non-SZC cohort). The primary endpoint was hyperkalemia-related medical costs to payers over 6 months. Results: Each cohort included 661 matched patients. Mean per-patient hyperkalemia-related medical costs were reduced by 49.5% ($3728.47) for the SZC versus non-SZC cohort ($3798.04 vs $7526.51; P<0.001), whereas mean all-cause medical costs were reduced by 21.0% ($5492.20; $20,722.23 vs $26,214.43; P<0.01). A 39.8% ($3621.03) increase in all-cause pharmacy costs ($12,727.20 vs $9106.17; P<0.01) was offset by the medical cost savings. Conclusion: This study demonstrated that long-term (>3 months) outpatient treatment with SZC was associated with medical cost savings compared with no SZC therapy.

Impact of Sodium Zirconium Cyclosilicate Plus Renin-Angiotensin-Aldosterone System Inhibitor Therapy on Short-Term Medical Costs in Hyperkalemia: OPTIMIZE II Real-World Study.

INTRODUCTION: Patients receiving cardiorenal-protective renin-angiotensin-aldosterone system inhibitors (RAASis) are at increased risk of developing hyperkalemia, which is associated with increased medical costs. The aim of this study was to evaluate the impact of adding sodium zirconium cyclosilicate (SZC) therapy on 3-month medical costs in patients who experienced hyperkalemia while receiving RAASi therapy. METHODS: The retrospective OPTIMIZE II study used medical and pharmacy claims data from IQVIA PharMetrics® Plus. Patients aged ≥ 18 years who received SZC (≥ 60 day supply over 3 months' follow-up) and continued RAASi between July 2019 and December 2021 (Continue RAASi + SZC cohort) were 1:1 exact and propensity score matched with patients who discontinued RAASi after hyperkalemia diagnosis and did not receive SZC (Discontinue RAASi + no SZC cohort). The primary outcome was hyperkalemia-related medical costs to payers over 3 months; all-cause medical and pharmacy costs were also analyzed. RESULTS: In the Continue RAASi + SZC (n = 467) versus Discontinue RAASi + no SZC (n = 467) cohort, there were significant reductions in mean per-patient hyperkalemia-related medical costs (reduction of $2216.07; p = 0.01) and all-cause medical costs (reduction of $6102.43; p < 0.001); mean hyperkalemia-related inpatient medical costs and all-cause inpatient and emergency department medical costs were significantly reduced. The reduction in all-cause medical cost in the Continue RAASi + SZC cohort offset an increase in the mean per-patient all-cause pharmacy cost (increase of $3117.71; p < 0.001). CONCLUSION: RAASi therapy has well-established cardiorenal benefits. In OPTIMIZE II, management of RAASi-induced hyperkalemia with SZC was associated with lower hyperkalemia-related and all-cause medical costs than RAASi discontinuation without SZC, demonstrating medical cost savings with maintaining RAASi therapy with SZC.

Screen-Printed Wearable Sweat Sensor for Cost-Effective Assessment of Human Hydration Status through Potassium and Sodium Ion Detection.

Human sweat is intricately linked to human health, and unraveling its secrets necessitates a substantial volume of experimental data. However, conventional sensors fabricated via complex processes such as photolithography offer high detection precision at the expense of prohibitive costs. In this study, we presented a cost-effective and high-performance wearable flexible sweat sensor for real-time monitoring of K+ and Na+ concentrations in human sweat, fabricated using screen printing technology. Initially, we evaluated the electrical and electrochemical stability of the screen-printed substrate electrodes, which demonstrated good consistency with a variation within 10% of the relative standard deviation (RSD), meeting the requirements for reliable detection of K+ and Na+ in human sweat. Subsequently, we employed an "ion-electron" transduction layer and an ion-selective membrane to construct the sensors for detecting K+ and Na+. Comprehensive tests were conducted to assess the sensors' sensitivity, linearity, repeatability, resistance to interference, and mechanical deformation capabilities. Furthermore, we evaluated their long-term stability during continuous monitoring and storage. The test results confirmed that the sensor's performance indicators, as mentioned above, met the requirements for analyzing human sweat. In a 10-day continuous and regular monitoring experiment involving volunteers wearing the sensors, a wealth of data revealed a close relationship between K+ and Na+ concentrations in human sweat and hydration status. Notably, we observed that consistent and regular physical exercise effectively enhanced the body's resistance to dehydration. These findings provided a solid foundation for conducting extensive experiments and further exploring the intricate relationship between human sweat and overall health. Our research paved a practical and feasible path for future studies in this domain.

Theoretical Assessment of the Ligand/Metal/Quadruplex Recognition in the Non-Canonical Nucleic Acids Structures.

Quadruplexes (GQs), peculiar DNA/RNA motifs concentrated in specific genomic regions, play a vital role in biological processes including telomere stability and, hence, represent promising targets for anticancer therapy. GQs are formed by folding guanine-rich sequences into square planar G-tetrads which stack onto one another. Metal cations, most often potassium, further stabilize the architecture by coordinating the lone electron pairs of the O atoms. The presence of additional nucleic acid bases, however, has been recently observed experimentally and contributes substantially to the structural heterogeneity of quadruplexes. Therefore, it is of paramount significance to understand the factors governing the underlying complex processes in these structures. The current study employs DFT calculations to model the interactions between metal cations (K+, Na+, Sr2+) and diverse tetrads composed of a guanine layer in combination with a guanine (G)-, adenine (A)-, cytosine (C)-, thymine (T)-, or uracil (U)-based tetrad layer. Moreover, the addition of 4-(3,4-dihydroisoquinolin-2-yl)-2-(quinolin-2-yl)quinazoline to the modeled quadruplexes as a possible mechanism of its well-exerted antitumor effect is assessed. The calculations imply that the metal cation competition and ligand complexation are influenced by the balance between electronic and implicit/explicit solvation effects, the composition of the tetrad layers, as well as by the solvent exposure to the surrounding environment expressed in terms of different dielectric constant values. The provided results significantly enhance our understanding of quadruplex diversity, ligand recognition, and the underlying mechanisms of stabilization at an atomic level.

Assessment of 24 h Sodium and Potassium Urinary Excretion in Normotensive and Hypertensive Dominican Adults.

Higher salt (sodium) intake has been associated with higher blood pressure (BP). The degree of association may be influenced by factors such as age, origin, and dietary components. This study aimed to evaluate the 24 h urinary sodium (Na) and potassium (K) excretion in normotensive and hypertensive Dominican adults and estimate their salt intake. 163 volunteers (18-80 years old) participated in a cross-sectional study. The 24 h Na and K urinary excretion were measured using an ion-selective electrode technique. Na and K urinary excretion (99.4 ± 46.5 and 35.0 ± 17.5 mmol/24 h) did not correlate with BP, except in the normotensive group, in which K correlated with SBP (0.249, p = 0.019). Na and K excretion were similar in normotensive and hypertensive subjects. When considering two age groups (18-45, 46-80 years), the Na-to-K molar ratio (3.1 ± 1.3) was higher in younger subjects (p = 0.040). Na-to-K ratio was associated with DBP in the total group (r = 0.153, p = 0.052), in the hypertensive group (r = 0.395, p < 0.001), and in the older group with SBP (0.350, p = 0.002) and DBP (0.373, p < 0.001). In the older group, Na-to-K ratio and DBP correlated after controlling for subjects with hypertension controlled by treatment (r = 0.236, p = 0.041). The Na-to-K ratio correlated, when salt intake was over 5 g/day (52.2%), with SBP (rho = 0.219, p = 0.044) and DBP (rho = 0.259, p = 0.017). Determinants of BP in the total sample were age (SBP, beta: 0.6 ± 0.1, p < 0.001; DBP, beta: 0.2 ± 0.1, p < 0.002), sex (SBP, beta: 11.2 ± 3.5, p = 0.001), body mass index (BMI) (SBP, beta: 1.0 ± 0.3, p < 0.001; DBP, beta: 0.4 ± 0.2, p = 0.01), and Na-to-K ratio (SBP, beta: 3.0 ± 1.1, p = 0.008; DBP, beta: -12.3 ± 4.0, p = 0.002). Sex and BMI were determinants in the younger group. Na-to-K molar ratio was determinant in the older group (SBP, beta: 6.7 ± 2.4, p = 0.005; DBP, beta: 3.8 ± 1.1, p < 0.001). The mean Na and salt intakes (2.3 and 5.8 g/day) were slightly higher and the K intake lower (1.4 g/day) than WHO recommendations.

Efficacy and safety assessment of mineralocorticoid receptor antagonists in patients with chronic kidney disease.

BACKGROUND: The objective of our study is to evaluate the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) and determine the optimal MRA treatment regimen in patients with chronic kidney disease (CKD). METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library from their inception to June 20, 2022. The composite kidney outcome, cardiovascular events, urinary albumin to creatinine ratio (UACR), estimated glomerular filtration rate (EGFR), serum potassium, systolic blood pressure (SBP), diastolic blood pressure (DBP), creatine and creatine clearance were included for analysis. We conducted pairwise meta-analyses and Bayesian network meta-analyses (NMA) and calculated the surface under the cumulative ranking curve (SUCRA). RESULTS: We included 26 studies with 15,531 participants. By pairwise meta-analyses, we found that MRA treatment could significantly reduce UACR in CKD patients with or without diabetes. Notably, compared to placebo, Finerenone was associated with a lower risk of composite kidney outcome and cardiovascular events. Data from NMA demonstrated an overt UACR reduction without increasing serum potassium by Apararenone, Esaxerenone, and Finerenone in CKD patients. Spironolactone decreased SBP and DBP but elevated CKD patients' serum potassium. CONCLUSIONS: Compared to placebo, Apararenone, Esaxerenone, and Finerenone might ameliorate albuminuria in CKD patients without causing elevated serum potassium levels. Remarkably, Finerenone conferred a cardiovascular benefit, and Spironolactone lowered blood pressure in CKD patients.