Symport and antiport mechanisms of human glutamate transporters.

Excitatory amino acid transporters (EAATs) uptake glutamate into glial cells and neurons. EAATs achieve million-fold transmitter gradients by symporting it with three sodium ions and a proton, and countertransporting a potassium ion via an elevator mechanism. Despite the availability of structures, the symport and antiport mechanisms still need to be clarified. We report high-resolution cryo-EM structures of human EAAT3 bound to the neurotransmitter glutamate with symported ions, potassium ions, sodium ions alone, or without ligands. We show that an evolutionarily conserved occluded translocation intermediate has a dramatically higher affinity for the neurotransmitter and the countertransported potassium ion than outward- or inward-facing transporters and plays a crucial role in ion coupling. We propose a comprehensive ion coupling mechanism involving a choreographed interplay between bound solutes, conformations of conserved amino acid motifs, and movements of the gating hairpin and the substrate-binding domain.

JP-1366: A novel and potent potassium-competitive acid blocker that is effective in the treatment of acid-related diseases.

The global prevalence of GERD is substantially increasing each year, and GERD is a chronic disease that reduces the quality of life of patients. The efficacy of conventional drugs is diverse, and most require long-term or lifetime administration; thus, the development of more effective therapeutic agents is needed. Herein, a more effective treatment for GERD was tested. We investigated whether JP-1366 affected gastric H+/K+-ATPase activity and used the Na+/K+-ATPase assay to confirm the selectivity of H+/K+-ATPase inhibition. To clarify the mechanism of enzyme inhibition, JP-1366 and TAK-438 were analyzed by Lineweaver-Burk. Also, we investigated the effects of JP-1366 in various models involving reflux esophagitis. We found that JP-1366 mediates strong, selective, and dose-dependent inhibition of H+/K+-ATPase. We found that JP-1366 significantly suppressed gastric acid secretion in histamine-treated pylorus-ligated rats in a dose-dependent manner. Additionally, we confirmed that JP-1366 inhibited histamine-stimulated gastric acid secretion in the HPD model. JP-1366 exhibited a more than 2-fold higher inhibitory effect on esophageal injury than TAK-438 in GERD lesions and had a more potent inhibitory effect in indomethacin- or aspirin-induced gastric ulcer rat models than TAK-438. Additionally, JP-1366 inhibited gastric ulcers. These results support the possibility that JP-1366 is a good candidate drug for treating acid-related diseases.

Seed priming with NaCl helps to improve tissue tolerance, potassium retention ability of plants, and protects the photosynthetic ability in two different legumes, chickpea and lentil, under salt stress.

MAIN CONCLUSION: Seed priming with NaCl mimicked the conditions of natural priming to improve the tissue tolerance nature of sensitive legumes, which helps to maintain survivability and yield in mildly saline areas. Seed priming with NaCl is a seed invigoration technique that helps to improve plant growth by altering Na+ and K+ content under salt stress. Legumes are overall sensitive to salt and salinity hampers their growth and yield. Therefore, a priming (50 mM NaCl) experiment was performed with two different legume members [Cicer arietinum cv. Anuradha and Lens culinaris cv. Ranjan] and different morpho-physiological, biochemical responses at 50 mM, 100 mM, and 150 mM NaCl and molecular responses at 150 mM NaCl were studied in hydroponically grown nonprimed and primed members. Similarly, a pot experiment was performed at 80 mM Na+, to check the yield. Tissue Na+ and K+ content suggested NaCl-priming did not significantly alter the accumulation of Na+ among nonprimed and primed members but retained more K+ in cells, thus maintaining a lower cellular Na+/K+ ratio. Low osmolyte content (e.g., proline) in primed members suggested priming could minimize their overall osmolytic requirement. Altogether, these implied tissue tolerance (TT) nature might have improved in case of NaCl-priming as was also reflected by a better TT score (LC50 value). An improved TT nature enabled the primed plants to maintain a significantly higher photosynthetic rate through better stomatal conductance. Along with this, a higher level of chlorophyll content and competent functioning of the photosynthetic subunits improved photosynthetic performance that ensured yield under stress. Overall, this study explores the potential of NaCl-priming and creates possibilities for considerably sensitive members; those in their nonprimed forms have no prospect in mildly saline agriculture.

Effects of a low-sodium diet in patients with idiopathic hyperaldosteronism: a randomized controlled trial.

Background: Idiopathic hyperaldosteronism (IHA) is one of the most common types of primary aldosteronism (PA), an important cause of hypertension. Although high dietary sodium is a major risk factor for hypertension, there is no consensus on the recommended dietary sodium intake for IHA. Objective: This study investigated the effect of a low-sodium diet on hemodynamic variables and relevant disease biomarkers in IHA patients, with the aim of providing a useful reference for clinical treatment. Methods: Fifty IHA patients were evenly randomized into two groups and provided, after a 7-day run-in period (100 mmol/d sodium), either a low-sodium diet (50 mmol/d sodium) or a normal sodium diet (100 mmol/d sodium) for an additional 7 days. After the 14-day intervention (conducted without potassium supplementation), changes in blood pressure (BP) and serum potassium were evaluated in both groups. Results: After the dietary intervention, the low sodium group exhibited, compared to the normal sodium group, decreased BP (SBP: 121.8 ± 12.8 vs. 129.9 ± 12.1 mmHg, p < 0.05; DBP: 82.6 ± 7.6 vs. 86.4 ± 8.2 mmHg, p < 0.05; MAP: 95.7 ± 8.8 vs. 100.9 ± 8.4 mmHg, p < 0.05) and increased serum potassium levels (3.38 ± 0.33 vs. 3.07 ± 0.27 mmol/L, p < 0.001). The low sodium group showed also better control of both BP and serum potassium: BP <140/90 mmHg in 70.0% of total patients (76.0% vs. 64.0%, in the low and normal sodium groups, respectively; p > 0.05), BP <130/85 mmHg in 38.0% of total patients (56.0% vs. 20.0%, p < 0.05), BP <120/80 mmHg in 28.0% of total patients (44.0% vs. 12.0%, p < 0.05); serum potassium ≥3.5 mmol/L in 22.0% of total patients (32.0% vs. 12.0% in the low and normal sodium groups, respectively; p = 0.088). There were differences between the controlled BP group (<120/80 mmHg) and the non-controlled BP group (≥120/80 mmHg) in gender, BP at baseline, and type of diet (low vs. normal sodium). Female gender and low-sodium diet were protective factors for BP control. Conclusions: A low-sodium diet is effective in lowering BP and elevating serum potassium in IHA patients. Female patients on a low-sodium diet are more likely to achieve BP control (<120/80 mmHg). We advocate a dietary sodium intake of 50 mmol/d for IHA patients. Clinical trial registration: https://clinicaltrials.gov, Identifier NCT05649631.

Different LED light spectra's and nano-chelated potassium affect the quality traits of Dolce Vita cut roses in soilless culture condition.

Roses are classified as neutral day plants, but high light and cool temperatures produce high quality flowers in roses. As light quantity, the light quality and its special spectra can affect the flower yield and quality. This research aimed to study of the effect of LED light (control (sunlight), blue and red spectra's) and nano-chelated potassium at three levels (0, 1.5 and 3 g/l) on some morphophysiological and biochemical traits of Rosa hybrida cv. Dolce Vita. Light and nano-chelated potassium treatments have a significant effect on most traits measured in the present study. According to the results, the use of red light and nano-chelated potassium in rose cultivation improved the quality characteristics and increased vase life. The highest fresh and dry weight of flowering branch and plant height was observed in red light treatment and the concentration of 3 g/l nano-chelated potassium. Biochemical parameters such as phenolic compounds, leaf and petal flavonoids, petal anthocyanin content, antioxidant capacity and vase life were also significantly increased under red light and with the concentration of 3 g/l nano-chelated potassium compared to the control. In general, it can be said that the use of red light and a concentration of 3 g/l nano-chelated potassium, can be effective in improving the quality of rose flowers, especially in low light condition.

PIMT Controls Insulin Synthesis and Secretion through PDX1.

Pancreatic beta cell function is an important component of glucose homeostasis. Here, we investigated the function of PIMT (PRIP-interacting protein with methyl transferase domain), a transcriptional co-activator binding protein, in the pancreatic beta cells. We observed that the protein levels of PIMT, along with key beta cell markers such as PDX1 (pancreatic and duodenal homeobox 1) and MafA (MAF bZIP transcription factor A), were reduced in the beta cells exposed to hyperglycemic and hyperlipidemic conditions. Consistently, PIMT levels were reduced in the pancreatic islets isolated from high fat diet (HFD)-fed mice. The RNA sequencing analysis of PIMT knockdown beta cells identified that the expression of key genes involved in insulin secretory pathway, Ins1 (insulin 1), Ins2 (insulin 2), Kcnj11 (potassium inwardly-rectifying channel, subfamily J, member 11), Kcnn1 (potassium calcium-activated channel subfamily N member 1), Rab3a (member RAS oncogene family), Gnas (GNAS complex locus), Syt13 (synaptotagmin 13), Pax6 (paired box 6), Klf11 (Kruppel-Like Factor 11), and Nr4a1 (nuclear receptor subfamily 4, group A, member 1) was attenuated due to PIMT depletion. PIMT ablation in the pancreatic beta cells and in the rat pancreatic islets led to decreased protein levels of PDX1 and MafA, resulting in the reduction in glucose-stimulated insulin secretion (GSIS). The results from the immunoprecipitation and ChIP experiments revealed the interaction of PIMT with PDX1 and MafA, and its recruitment to the insulin promoter, respectively. Importantly, PIMT ablation in beta cells resulted in the nuclear translocation of insulin. Surprisingly, forced expression of PIMT in beta cells abrogated GSIS, while Ins1 and Ins2 transcript levels were subtly enhanced. On the other hand, the expression of genes, PRIP/Asc2/Ncoa6 (nuclear receptor coactivator 6), Pax6, Kcnj11, Syt13, Stxbp1 (syntaxin binding protein 1), and Snap25 (synaptosome associated protein 25) associated with insulin secretion, was significantly reduced, providing an explanation for the decreased GSIS upon PIMT overexpression. Our findings highlight the importance of PIMT in the regulation of insulin synthesis and secretion in beta cells.

A novel solution to tartrate instability in white wines.

Tartrate stabilization remains a necessary step in commercial wine production to avoid the precipitation of crystals in bottled wine. The conventional refrigeration method to prevent crystallization of potassium bitartrate is time-consuming, energy-intensive, and involves a filtration step to remove the sediment. Nevertheless, it is still the most used stabilization method by winemakers. This work exploits for the first time an alternative to traditional cold stabilization that explores the potential of carefully tailored surface coatings obtained by plasma polymerization. Coatings containing amine functional groups were most potent in binding and removing potassium in heat-unstable wines. In contrast, carboxyl acid groups rich surfaces had the most significant impact on heat-stabilized wines. The results of this study demonstrate that surfaces with carefully designed chemical functionalities can remove tartaric acid from wine and induce cold stabilization. This process can operate at higher temperatures, reducing the need for cooling facilities, saving energy, and improving cost-effectiveness.

Balanced crystalloid solutions versus 0.9% saline for treating acute diarrhoea and severe dehydration in children.

BACKGROUND: Although acute diarrhoea is a self-limiting disease, dehydration may occur in some children. Dehydration is the consequence of an increased loss of water and electrolytes (sodium, chloride, potassium, and bicarbonate) in liquid stools. When these losses are high and not replaced adequately, severe dehydration appears. Severe dehydration is corrected with intravenous solutions. The most frequently used solution for this purpose is 0.9% saline. Balanced solutions (e.g. Ringer's lactate) are alternatives to 0.9% saline and have been associated with fewer days of hospitalization and better biochemical outcomes. Available guidelines provide conflicting recommendations. It is unclear whether 0.9% saline or balanced intravenous fluids are most effective for rehydrating children with severe dehydration due to diarrhoea. OBJECTIVES: To evaluate the benefits and harms of balanced solutions for the rapid rehydration of children with severe dehydration due to acute diarrhoea, in terms of time in hospital and mortality compared to 0.9% saline. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 4 May 2022. SELECTION CRITERIA: We included randomized controlled trials in children with severe dehydration due to acute diarrhoea comparing balanced solutions, such as Ringer's lactate or Plasma-Lyte with 0.9% saline solution, for rapid rehydration. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. time in hospital and 2. MORTALITY: Our secondary outcomes were 3. need for additional fluids, 4. total amount of fluids received, 5. time to resolution of metabolic acidosis, 6. change in and the final values of biochemical measures (pH, bicarbonate, sodium, chloride, potassium, and creatinine), 7. incidence of acute kidney injury, and 8. ADVERSE EVENTS: We used GRADE to assess the certainty of the evidence. MAIN RESULTS: Characteristics of the included studies We included five studies with 465 children. Data for meta-analysis were available from 441 children. Four studies were conducted in low- and middle-income countries and one study in two high-income countries. Four studies evaluated Ringer's lactate, and one study evaluated Plasma-Lyte. Two studies reported the time in hospital, and only one study reported mortality as an outcome. Four studies reported final pH and five studies reported bicarbonate levels. Adverse events reported were hyponatremia and hypokalaemia in two studies each. Risk of bias All studies had at least one domain at high or unclear risk of bias. The risk of bias assessment informed the GRADE assessments. Primary outcomes Compared to 0.9% saline, the balanced solutions likely result in a slight reduction of the time in hospital (mean difference (MD) -0.35 days, 95% confidence interval (CI) -0.60 to -0.10; 2 studies; moderate-certainty evidence). However, the evidence is very uncertain about the effect of the balanced solutions on mortality during hospitalization in severely dehydrated children (risk ratio (RR) 0.33, 95% CI 0.02 to 7.39; 1 study, 22 children; very low-certainty evidence). Secondary outcomes Balanced solutions probably produce a higher increase in blood pH (MD 0.06, 95% CI 0.03 to 0.09; 4 studies, 366 children; low-certainty evidence) and bicarbonate levels (MD 2.44 mEq/L, 95% CI 0.92 to 3.97; 443 children, four studies; low-certainty evidence). Furthermore, balanced solutions likely reduces the risk of hypokalaemia after the intravenous correction (RR 0.54, 95% CI 0.31 to 0.96; 2 studies, 147 children; moderate-certainty evidence). Nonetheless, the evidence suggests that balanced solutions may result in no difference in the need for additional intravenous fluids after the initial correction; in the amount of fluids administered; or in the mean change of sodium, chloride, potassium, and creatinine levels. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effect of balanced solutions on mortality during hospitalization in severely dehydrated children. However, balanced solutions likely result in a slight reduction of the time in the hospital compared to 0.9% saline. Also, balanced solutions likely reduce the risk of hypokalaemia after intravenous correction. Furthermore, the evidence suggests that balanced solutions compared to 0.9% saline probably produce no changes in the need for additional intravenous fluids or in other biochemical measures such as sodium, chloride, potassium, and creatinine levels. Last, there may be no difference between balanced solutions and 0.9% saline in the incidence of hyponatraemia.

Unidirectional fluxes of monovalent ions in human erythrocytes compared with lymphoid U937 cells: Transient processes after stopping the sodium pump and in response to osmotic challenge.

Recently, we have developed software that allows, using a minimum of required experimental data, to find the characteristics of ion homeostasis and a list of all unidirectional fluxes of monovalent ions through the main pathways in the cell membrane both in a balanced state and during the transient processes. Our approach has been successfully validated in human proliferating lymphoid U937 cells during transient processes after stopping the Na/K pump by ouabain and for staurosporine-induced apoptosis. In present study, we used this approach to find the characteristics of ion homeostasis and the monovalent ion fluxes through the cell membrane of human erythrocytes in a resting state and during the transient processes after stopping the Na/K pump with ouabain and in response to osmotic challenge. Due to their physiological significance, erythrocytes remain the object of numerous studies, both experimental and computational methods. Calculations showed that, under physiological conditions, the K+ fluxes through electrodiffusion channels in the entire erythrocyte ion balance is small compared to the fluxes through the Na/K pump and cation-chloride cotransporters. The proposed computer program well predicts the dynamics of the erythrocyte ion balance disorders after stopping the Na/K pump with ouabain. In full accordance with predictions, transient processes in human erythrocytes are much slower than in proliferating cells such as lymphoid U937 cells. Comparison of real changes in the distribution of monovalent ions under osmotic challenge with the calculated ones indicates a change in the parameters of the ion transport pathways through the plasma membrane of erythrocytes in this case. The proposed approach may be useful in studying the mechanisms of various erythrocyte dysfunctions.

Prediction of hyperkalemia in ESRD patients by identification of multiple leads and multiple features on ECG.

BACKGROUND: Patients with end-stage renal disease (ESRD) especially those undergoing dialysis have a high prevalence of hyperkalemia, which must be detected and treated immediately. But the initial symptoms of hyperkalemia are insidious, and traditional laboratory serum potassium concentration testing takes time. Therefore, rapid and real-time measurement of serum potassium is urgently needed. In this study, different machine learning methods were used to make rapid predictions of different degrees of hyperkalemia by analyzing the ECG. METHODS: A total of 1024 datasets of ECG and serum potassium concentrations were analyzed from December 2020 to December 2021. The data were scaled into training and test sets. Different machine learning models (LR, SVM, CNN, XGB, Adaboost) were built for dichotomous prediction of hyperkalemia by analyzing 48 features of chest leads V2-V5. The performance of the models was also evaluated and compared using sensitivity, specificity, accuracy, accuracy, F1 score and AUC. RESULTS: We constructed different machine models to predict hyperkalemia using LR and four other common machine-learning methods. The AUCs of the different models ranged from 0.740 (0.661, 0.810) to 0.931 (0.912,0.953) when different serum potassium concentrations were used as the diagnostic threshold for hyperkalemia, respectively. As the diagnostic threshold of hyperkalemia was raised, the sensitivity, specificity, accuracy and precision of the model decreased to various degrees. And AUC also performed less well than when predicting mild hyperkalemia. CONCLUSION: Noninvasive and rapid prediction of hyperkalemia can be achieved by analyzing specific waveforms on the ECG by machine learning methods. But overall, XGB had a higher AUC in mild hyperkalemia, but SVM performed better in predicting more severe hyperkalemia.

The miR166d/TaCPK7-D Signaling Module Is a Critical Mediator of Wheat (Triticum aestivum L.) Tolerance to K+ Deficiency.

It is well established that potassium (K+) is an essential nutrient for wheat (Triticum aestivum L.) growth and development. Several microRNAs (miRNAs), including miR166, are reportedly vital roles related to plant growth and stress responses. In this study, a K+ starvation-responsive miRNA (miR166d) was identified, which showed increased expression in the roots of wheat seedlings exposed to low-K+ stress. The overexpression of miR166d considerably increased the tolerance of transgenic Arabidopsis plants to K+ deprivation treatment. Furthermore, disrupting miR166d expression via virus-induced gene silencing (VIGS) adversely affected wheat adaptation to low-K+ stress. Additionally, miR166d directly targeted the calcium-dependent protein kinase 7-D gene (TaCPK7-D) in wheat. The TaCPK7-D gene expression was decreased in wheat seedling roots following K+ starvation treatment. Silencing TaCPK7-D in wheat increased K+ uptake under K+ starvation. Moreover, we observed that the miR166d/TaCPK7-D module could affect wheat tolerance to K+ starvation stress by regulating TaAKT1 and TaHAK1 expression. Taken together, our results indicate that miR166d is vital for K+ uptake and K+ starvation tolerance of wheat via regulation of TaCPK7-D.

High sodium intake does not worsen low potassium-induced kidney damage.

High sodium and low potassium intake have both been linked to poor cardiovascular health outcomes and increased mortality rates. A combination of the two is thought to be particularly detrimental. While mechanisms are multiple, the kidney is an important target of harmful effects and low potassium influences on both proximal and distal nephron segments are especially potent. We recently reported that a combined high sodium/low potassium diet causes kidney injury and that low potassium in isolation can have similar effects. However, how sodium intake alters this process is not well-understood. Here we tested the hypothesis that a high sodium intake amplifies effects of low dietary potassium on kidney injury. We observed adding high sodium to low potassium caused an expected increase in blood pressure, but did not worsen markers of kidney injury, inflammation, and fibrosis. It also did not increase abundance or phosphorylation of the sodium chloride cotransporter or its regulatory kinases, SPAK and OxSR1, known renal targets of low potassium. Findings support the claim that dietary potassium deficiency, and not high sodium, is a dominant factor affecting kidney injury in animal models of high sodium/low potassium intake. This suggests further investigation is required to identify optimal ranges of sodium and potassium intake in both healthy populations and in those with kidney disease.

[Activation of renal outer medullary potassium channel in the renal distal convoluted tubule by high potassium diet].

Renal outer medullary potassium (ROMK) channel is an important K+ excretion channel in the body, and K+ secreted by the ROMK channels is most or all source of urinary potassium. Previous studies focused on the ROMK channels of thick ascending limb (TAL) and collecting duct (CD), while there were few studies on the involvement of ROMK channels of the late distal convoluted tubule (DCT2) in K+ excretion. The purpose of the present study was mainly to record the ROMK channels current in renal DCT2 and observe the effect of high potassium diet on the ROMK channels by using single channel and whole-cell patch-clamp techniques. The results showed that a small conductance channel current with a conductance of 39 pS could be recorded in the apical membrane of renal DCT2, and it could be blocked by Tertiapin-Q (TPNQ), a ROMK channel inhibitor. The high potassium diet significantly increased the probability of ROMK channel current occurrence in the apical membrane of renal DCT2, and enhanced the activity of ROMK channel, compared to normal potassium diet (P < 0.01). Western blot results also demonstrated that the high potassium diet significantly up-regulated the protein expression levels of ROMK channels and epithelial sodium channel (ENaC), and down-regulated the protein expression level of Na+-Cl- cotransporter (NCC). Moreover, the high potassium diet significantly increased urinary potassium excretion. These results suggest that the high potassium diet may activate the ROMK channels in the apical membrane of renal DCT2 and increase the urinary potassium excretion by up-regulating the expression of renal ROMK channels.

[Treatment of acute diabetic metabolic crises in adults (Update 2023) : Hyperglycemic hyperosmolar state and ketoacidotic metabolic disorder]. / Therapie der akuten diabetischen Stoffwechselentgleisungen bei Erwachsenen (Update 2023) : Hyperglykämisch-hyperosmolare und ketoazidotische Stoffwechselentgleisung.

Diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS) represent potentially life-threatening situations in adults. Therefore, rapid comprehensive diagnostic and therapeutic measures with close monitoring of vital and laboratory parameters are required. The treatment of DKA and HHS is essentially the same and replacement of the mostly substantial fluid deficit with several liters of a physiological crystalloid solution is the first and most important step. Serum potassium concentrations need to be carefully monitored to guide its substitution. Regular insulin or rapid acting insulin analogues can be initially administered as an i.v. bolus followed by continuous infusion. Insulin should be switched to subcutaneous injections only after correction of the acidosis and stable glucose concentrations within an acceptable range.

Changes in K+ Concentration as a Signaling Mechanism in the Apicomplexa Parasites Plasmodium and Toxoplasma.

During their life cycle, apicomplexan parasites pass through different microenvironments and encounter a range of ion concentrations. The discovery that the GPCR-like SR25 in Plasmodium falciparum is activated by a shift in potassium concentration indicates that the parasite can take advantage of its development by sensing different ionic concentrations in the external milieu. This pathway involves the activation of phospholipase C and an increase in cytosolic calcium. In the present report, we summarize the information available in the literature regarding the role of potassium ions during parasite development. A deeper understanding of the mechanisms that allow the parasite to cope with ionic potassium changes contributes to our knowledge about the cell cycle of Plasmodium spp.

Trends in Diet Quality and Increasing Inadequacies of Micronutrients Vitamin C, Vitamin B12, Iron and Potassium in US Type 2 Diabetic Adults.

BACKGROUND: Prevalence of diabetes was high and rose significantly in the US between 1999 and 2018. A healthy dietary pattern that provides micronutrient adequacy is one of the most important lifestyle choices for battling the progress of diabetes. Yet, the patterns and trends of diet quality of the US type 2 diabetes are understudied. OBJECTIVES: We aim to examine the patterns and trends of diet quality and major food sources of macronutrients of US type 2 diabetic adults. METHODS: The 24 h dietary recalls of 7789 type 2 diabetic adults, comprising 94.3% of total adults with diabetes from the US National Health and Nutrition Examination Survey cycles (1999-2018), were analyzed. Diet quality was measured by the total Healthy Eating Index (HEI)-2015 scores and 13 individual components. Trends of usual intakes of vitamin C (VC), vitamin B12 (VB12), iron, and potassium and supplements from two 24 h recalls were also examined for type 2 diabetic population. RESULTS: Diet quality of type 2 diabetic adults worsened between 1999 and 2018 while that of US adults of general population improved based on the total HEI 2015 scores. For people with type 2 diabetes, consumption of saturated fat and added sugar increased while consumption of vegetables and fruits declined significantly, although consumption of refined grain declined and consumption of seafood and plant protein increased significantly. In addition, usual intakes of micronutrients VC, VB12, iron, and potassium from food sources declined significantly during this period. CONCLUSIONS: Diet quality generally worsened for US type 2 diabetic adults between 1999 and 2018. Declining consumptions of fruits, vegetables, and non-poultry meat may have contributed to the increasing inadequacies of VC, VB12, iron, and potassium in the US type 2 diabetic adults.

Functional interactions between potassium-chloride cotransporter (KCC) and inward rectifier potassium (Kir) channels in the insect central nervous system.

The K+/Cl- cotransporter (KCC) is the primary mechanism by which mature neurons maintain low intracellular chloride (Cl-) concentration and has been shown to be functionally coupled to the GABA-gated chloride channels (GGCC) in Drosophila central neurons. Further, pharmacological inhibition of KCC has been shown to lead to acute toxicity of mosquitoes that highlights the toxicological relevance of insect KCC. Yet, gaps in knowledge remain regarding physiological drivers of KCC function and interactions of ion flux mechanisms upstream of GGCC in insects. Considering this, we employed electrophysiological and fluorescent microscopy techniques to further characterize KCC in the insect nervous system. Fluorescent microscopy indicated insect KCC2 is expressed in rdl neurons, which is the neuron type responsible for GABA-mediated neurotransmission, and are coexpressed with inward rectifier potassium (Kir) 2 channels. Coexpression of Kir2 and KCC2 suggested the possibility of functional coupling between these two K+ flux pathways. Indeed, extracellular recordings of Drosophila CNS showed pre-block of Kir channels prior to block of KCC led to a significant (P < 0.001) increase in CNS firing rates over baseline that when taken together, supports functional coupling of Kir to KCC function. Additionally, we documented a synergistic increase to toxicity of VU0463271, an established KCC inhibitor, above the expected additive toxicity after co-treatment with the Kir inhibitor, VU041. These data expand current knowledge regarding the physiological roles of KCC and Kir channels in the insect nervous system by defining additional pathways that facilitate inhibitory neurotransmission through GGCC.

Mid-Point of the Active Phase Is Better to Achieve the Natriuretic Effect of Acute Salt Load in Mice.

Excess sodium intake and insufficient potassium intake are a prominent global issue because of their influence on high blood pressure. Supplementation of potassium induces kaliuresis and natriuresis, which partially explains its antihypertensive effect. Balancing of minerals takes place in the kidney and is controlled by the circadian clock; in fact, various renal functions exhibit circadian rhythms. In our previous research, higher intake of potassium at lunch time was negatively associated with blood pressure, suggesting the importance of timing for sodium and potassium intake. However, the effects of intake timing on urinary excretion remain unclear. In this study, we investigated the effect of 24 h urinary sodium and potassium excretion after acute sodium and potassium load with different timings in mice. Compared to other timings, the middle of the active phase resulted in higher urinary sodium and potassium excretion. In Clock mutant mice, in which the circadian clock is genetically disrupted, urinary excretion differences from intake timings were not observed. Restricted feeding during the inactive phase reversed the excretion timing difference, suggesting that a feeding-induced signal may cause this timing difference. Our results indicate that salt intake timing is important for urinary sodium and potassium excretion and provide new perspectives regarding hypertension prevention.

The Effect of TWIK-1 Two Pore Potassium Channels on Cardiomyocytes in Low Extracellular Potassium Conditions.

BACKGROOUND: At low extracellular potassium ([K+]e) conditions, human cardiomyocytes can depolarize to -40 mV. This is closely related to hypokalemia-induced fatal cardiac arrhythmia. The underlying mechanism, however, is still not well understood. TWIK-1 channels are background K+ channels that are highly expressed in human cardiomyocytes. We previously reported that TWIK-1 channels changed ion selectivity and conducted leak Na+ currents at low [K+]e. Moreover, a specific threonine residue (Thr118) within the ion selectivity filter was responsible for this altered ion selectivity. METHODS: Patch clamp were used to investigate the effects of TWIK-1 channels on the membrane potentials of cardiomyocytes in response to low [K+]e. RESULTS: At 2.7 mM [K+]e and 1 mM [K+]e, both Chinese hamster ovary (CHO) cells and HL-1 cells ectopically expressed human TWIK-1 channels displayed inward leak Na+ currents and reconstitute depolarization of membrane potential. In contrast, cells ectopically expressed human TWIK-1-T118I mutant channels that remain high selectivity to K+ exhibited hyperpolarization of membrane potential. Furthermore, human iPSC-derived cardiomyocytes showed depolarization of membrane potential in response to 1 mM [K+]e, while the knockdown of TWIK-1 expression eliminated this phenomenon. CONCLUSIONS: These results demonstrate that leak Na+ currents conducted by TWIK-1 channels contribute to the depolarization of membrane potential induced by low [K+]e in human cardiomyocytes.

Evaluation of the Impact of Remote Monitoring Using the Sharesource Connectivity Platform on Adherence to Automated Peritoneal Dialysis in 51 Patients.

BACKGROUND This study from a single center in Taiwan aimed to evaluate the impact of remote patient monitoring (RPM) using the Sharesource connectivity platform on adherence to automated peritoneal dialysis (APD) in 51 patients. MATERIAL AND METHODS We analyzed data on 51 patients with end-stage renal disease (ESRD) under APD. They were treated with a traditional APD machine HomeChoice (phase 1), changed to new APD machine HomeChoice Claria for 12 weeks (phase 2), then connected to the Sharesource platform for another 12 weeks (phase 3), and were followed up for 1 year. The non-adherence rate was compared between the 3 phases. The secondary outcomes included peritonitis rate, hospitalization rate, and hospitalization days, 1 year before and after receiving a new APD machine. Patients were subdivided into good and poor adherence (>1 episode of non-adherence in phase 1) groups for further analysis. RESULTS The average non-adherence rates were 10.5%, 5.1%, and 4.9% in phases 1, 2, and 3, respectively, although differences were not significant. Serum potassium (P<0.0001) and C-reactive protein (CRP) (P=0.026) levels significantly decreased in phase 3. The 1-year peritonitis rate, hospitalization rate, and number of days of hospitalization showed no significant changes. Subgroup analysis revealed that the non-adherence rate in the poor adherence group decreased from 48.4% in phase 1 to 14.2% and 12.4% in phases 2 and 3, respectively (P=0.007). CONCLUSIONS Remoting monitoring using the Sharesource connectivity platform increased dialysis adherence in APD treatment, especially in patients with poor adherence. Serum potassium level and inflammation status were also improved by this system.