Endoscopic findings and outcomes of gastric mucosal changes relating to potassium-competitive acid blocker and proton pump inhibitor therapy.

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

Magnesium alleviates growth inhibition under low potassium by enhancing photosynthesis and carbon-nitrogen metabolism in apple plants.

Potassium (K) and magnesium (Mg) play analogous roles in regulating plant photosynthesis and carbon and nitrogen (C-N) metabolism. Based on this consensus, we hypothesize that appropriate Mg supplementation may alleviate growth inhibition under low K stress. We monitored morphological, physiological, and molecular changes in G935 apple plants under different K (0.1 and 6 mmol L-1) and Mg supply (3 and 6 mmol L-1) conditions. Low K stress caused changes in root and leaf structure, inhibited photosynthesis, and limited the root growth of the apple rootstock. Further study on Mg supplementation showed that it could promote the uptake of K+ and NO3- by upregulating the expression of K+ transporter proteins such as Arabidopsis K+ transporter 1 (MdAKT1), high-affinity K+ transporter 1 (MdHKT1), and potassium transporter 5 (MdPT5) and nitrate transporters such as nitrate transporter 1.1/1.2/2.1/2.4 (MdNRT 1.1/1.2/2.1/2.4). Mg promoted the translocation of 15N from roots to leaves and enhanced photosynthetic N utilization efficiency (PNUE) by increasing the proportion of photosynthetic N and alleviating photosynthetic restrictions. Furthermore, Mg supplementation improved the synthesis of photosynthates by enhancing the activities of sugar-metabolizing enzymes (Rubisco, SS, SPS, S6PDH). Mg also facilitated the transport of sucrose and sorbitol from leaves to roots by upregulating the expression of sucrose transporter 1.1/1.2/4.1/4.2 (MdSUT 1.1/1.2/4.1/4.2) and sorbitol transporter 1.1/1.2 (MdSOT 1.1/1.2). Overall, Mg effectively alleviated growth inhibition in apple rootstock plants under low K stress by facilitating the uptake of N and K uptake, optimizing nitrogen partitioning, enhancing nitrogen use efficiency (NUE) and PNUE, and promoting the photosynthate synthesis and translocation.

Electrical excitability of cancer cells-CELEX model updated.

The normal functioning of every cell in the body depends on its bioelectric properties and many diseases are caused by genetic and/or epigenetic dysregulation of the underlying ion channels. Metastasis, the main cause of death from cancer, is a complex multi-stage process in which cells break away from a primary tumour, invade the surrounding tissues, enter the circulation by encountering a blood vessel and spread around the body, ultimately lodging in distant organs and reproliferating to form secondary tumours leading to devastating organ failure. Such cellular behaviours are well known to involve ion channels. The CELEX model offers a novel insight to metastasis where it is the electrical excitation of the cancer cells that is responsible for their aggressive and invasive behaviour. In turn, the hyperexcitability is underpinned by concomitant upregulation of functional voltage-gated sodium channels and downregulation of voltage-gated potassium channels. Here, we update the in vitro and in vivo evidence in favour of the CELEX model for carcinomas. The results are unequivocal for the sodium channel. The potassium channel arm is also broadly supported by existing evidence although these data are complicated by the impact of the channels on the membrane potential and consequent secondary effects. Finally, consistent with the CELEX model, we show (i) that carcinomas are indeed electrically excitable and capable of generating action potentials and (ii) that combination of a sodium channel inhibitor and a potassium channel opener can produce a strong, additive anti-invasive effect. We discuss the possible clinical implications of the CELEX model in managing cancer.

Potentiation of BKCa channels by cystic fibrosis transmembrane conductance regulator (CFTR) correctors VX-445 and VX-121.

Cystic fibrosis (CF) results from mutations in the CFTR anion channel, ultimately leading to diminished transepithelial anion secretion and mucociliary clearance. CFTR correctors are therapeutics that restore the folding/trafficking of mutated CFTR to the plasma membrane. The BKCa potassium channel is also critical for maintaining lung ASL volume. Here, we show the CFTR corrector, VX-445 (Elexacaftor), a component of Trikafta, induces K+ secretion across WT and F508del CFTR primary human bronchial epithelial cells (HBEs), which was entirely inhibited by the BKCa antagonist paxilline. Similar results were observed with VX-121 - a corrector under clinical evaluation. Whole-cell patch-clamp recordings confirmed potentiated channel activity from CFTR correctors on the BKCa α-subunit, and excised patch-clamp recordings demonstrated a significant increase in open probability. In mesenteric artery, VX-445 induced a paxilline-sensitive vasorelaxation of preconstricted arteries. VX-445 also reduced action potential firing frequency in primary hippocampal and cortical neurons. VX-445 effects were observed at low micomolar concentrations (1-10 µM) - within the range reported in plasma and tissues from CF patients. We raise the possibilities that CFTR correctors gain additional clinical benefit by activation of BKCa in the lung, yet may lead to adverse events through BKCa activation, elsewhere.

Ion channel profiles of extraocular motoneurons and internuclear neurons in human abducens and trochlear nuclei.

Introduction: Extraocular muscles are innervated by two anatomically and histochemically distinct motoneuron populations: motoneurons of multiply-innervated fibers (MIF), and of singly-innervated fibers (SIF). Recently, it has been established by our research group that these motoneuron types of monkey abducens and trochlear nuclei express distinct ion channel profiles: SIF motoneurons, as well as abducens internuclear neurons (INT), express strong Kv1.1 and Kv3.1b immunoreactivity, indicating their fast-firing capacity, whereas MIF motoneurons do not. Moreover, low voltage activated cation channels, such as Cav3.1 and HCN1 showed differences between MIF and SIF motoneurons, indicating distinct post-inhibitory rebound characteristics. However, the ion channel profiles of MIF and SIF motoneurons have not been established in human brainstem tissue. Methods: Therefore, we used immunohistochemical methods with antibodies against Kv, Cav3 and HCN channels to (1) examine the human trochlear nucleus in terms of anatomical organization of MIF and SIF motoneurons, (2) examine immunolabeling patterns of ion channel proteins in the distinct motoneurons populations in the trochlear and abducens nuclei. Results: In the examination of the trochlear nucleus, a third motoneuron subgroup was consistently encountered with weak perineuronal nets (PN). The neurons of this subgroup had -on average- larger diameters than MIF motoneurons, and smaller diameters than SIF motoneurons, and PN expression strength correlated with neuronal size. Immunolabeling of various ion channels revealed that, in general, human MIF and SIF motoneurons did not differ consistently, as opposed to the findings in monkey trochlear and abducens nuclei. Kv1.1, Kv3.1b and HCN channels were found on both MIF and SIF motoneurons and the immunolabeling density varied for multiple ion channels. On the other hand, significant differences between SIF motoneurons and INTs were found in terms of HCN1 immunoreactivity. Discussion: These results indicated that motoneurons may be more variable in human in terms of histochemical and biophysiological characteristics, than previously thought. This study therefore establishes grounds for any histochemical examination of motor nuclei controlling extraocular muscles in eye movement related pathologies in the human brainstem.

Homogeneous Adsorption of Multiple Potassiation Products of Red Phosphorus Anode toward Stable Potassium Storage.

Potassium ion batteries (PIBs) are a viable alternative to lithium-ion batteries for energy storage. Red phosphorus (RP) has attracted a great deal of interest as an anode for PIBs owing to its cheapness, ideal electrode potential, and high theoretical specific capacity. However, the direct preparation of phosphorus-carbon composites usually results in exposure of the RP to the exterior of the carbon layer, which can lead to the deactivation of the active material and the production of "dead phosphorus". Here, the advantage of the π-π bond conjugated structure and high catalytic activity of metal phthalocyanine (MPc) is used to prepare MPc@RP/C composites as a highly stable anode for PIBs. It is shown that the introduction of MPc greatly improves the uneven distribution of the carbon layer on RP, and thus improves the initial Coulombic efficiency (ICE) of PIBs (the ICE of FePc@RP/C is 75.5% relative to 62.9% of RP/C). The addition of MPc promotes the growth of solid electrolyte interphase with high mechanical strength, improving the cycle stability of PIBs (the discharge-specific capacity of FePc@RP/C is 411.9 mAh g-1 after 100 cycles at 0.05 A g-1). Besides, density functional theory theoretical calculations show that MPc exhibits homogeneous adsorption energies for multiple potassiation products, thereby improving the electrochemical reactivity of RP. The use of organic molecules with high electrocatalytic activity provides a universal approach for designing superior high-capacity, large-volume expansion anodes for PIBs.

Deletion of KS-WNK1 promotes NCC activation by increasing WNK1/4 abundance.

Dietary potassium deficiency causes stimulation of sodium reabsorption leading to increased risk in blood pressure elevation. The distal convoluted tubule is the main rheostat linking plasma K+ levels to the activity of the Na-Cl cotransporter (NCC). This occurs through basolateral membrane potential sensing by Kir4.1/5.1; decrease in intracellular Cl-; activation of WNK4, interaction and phosphorylation of Ste20/SPS1-related Proline/Alanine-rich Kinase (SPAK); binding of the calcium-binding protein 39 (cab39) adaptor protein to SPAK leading to its trafficking to the apical membrane; and SPAK binding, phosphorylating, and activating NCC. As Kidney-Specific With-No-Lysine (K) Kinase 1 (WNK1) isoform (KS-WNK1) is another participant in this pathway, we examined its function in NCC regulation. We eliminated KS-WNK1 specifically in the DCT and demonstrated increased expression of WNK4 and L-WNK1 and increased phosphorylation of NCC. As in other KS-WNK1 models, the mice are not hyperkalemic. While wild-type mice under low dietary K+ conditions demonstrated increased NCC phosphorylation, the phosphorylation levels of the transporter, already high in the KS-WNK1, did not change under the low K+ diet. Thus, in the absence of KS-WNK1 the transporter has lost its sensitivity to low plasma K+. We also show that under low K+ conditions, in the absence of KS-WNK1, there is no formation of WNK bodies. These bodies are observed in adjacent segments, not affected by the targeting of KS-WNK1. As our data are overall consistent with those of the global KS-WNK1 knockout, they indicate that the DCT is the predominant segment affecting the salt transport regulated by KS-WNK1.

Control of cyanobacterial growth with potassium; implications for bloom control in nuclear storage ponds.

Microbial blooms have been reported in the First Generation Magnox Storage Pond at the Sellafield Nuclear Facility. The pond is kept alkaline with NaOH to minimise fuel rod corrosion, however alkali-tolerant microbial blooms dominated by the cyanobacterium Pseudanabaena catenata are able to thrive in this hostile environment. This study assessed the impact of alternative alkali-dosing regimens (KOH versus NaOH treatment) on biomass accumulation, using a P. catenata dominated mixed culture, which is representative of the pond environment. Optical density was reduced by 40-67 % with KOH treatment over the 3-month chemostat experiment. Microbial community analysis and proteomics demonstrated that the KOH-dependent inhibition of cell growth was mostly specific to P. catenata. The addition of KOH to nuclear storage ponds may therefore help control growth of this pioneer photosynthetic organism due to its sensitivity to potassium, while maintaining the high pH needed to inhibit the corrosion of stored nuclear fuel.

Atrial fibroblast-derived exosomal miR-21 upregulate myocardial KCa3.1 via the PI3K-Akt pathway during rapid pacing.

Background: Fibroblast-derived exosomes can regulate the electrical remodeling of cardiomyocytes, and the intermediate-conductance calcium-activated potassium channel (KCa3.1) is important in atrial electrical remodeling. However, the underlying molecular mechanisms remain unclear. This study aimed to investigate the regulation of cardiac electrophysiology by exosomes linked to KCa3.1. Methods: Atrial myocytes (AMs) and atrial fibroblasts were isolated from Sprague-Dawley suckling rats and cultured individually. The cellular atrial fibrillation (AF) model was established via electrical stimulation (1.0 v/cm, 10 Hz), and fibroblast-derived exosomes were isolated via ultracentrifugation. Exosomes were co-cultured with AMs to investigate their influences on KCa3.1 and the underlying mechanisms. Nanoparticle tracking analysis and transmission electron microscopy were used to measure exosome particle sizes and concentrations. Whole-cell patch clamp was applied to record the current density of KCa3.1 and action potential duration (APD). The expression of miR-21-5p was detected by reverse-transcription polymerase chain reaction (RT-PCR). Western blotting or immunofluorescence was used to measure the expression of exosomal markers, Akt phosphorylation, and KCa3.1. Results: Rapid pacing promoted the secretion of exosomes from atrial fibroblasts and miR-21-5p expression in atrial fibroblasts and exosomes. KCa3.1 protein expression and current density significantly increased, and APD50 and APD90 were sharply shortened after rapid pacing in AMs. TRAM-34 (KCa3.1 blocker) extended APD and reduced susceptibility to AF. KCa3.1 and P-AKT expressions were amplified after co-culturing AMs with exosomes secreted by atrial fibroblasts. In contrast, the increase in KCa3.1 expression was reversed after the cells were co-cultured with exosomes secreted by atrial fibroblasts that were transfected with miR-21-5p inhibitors or after the use of LY294002, a PI3K/Akt pathway inhibitor. Conclusions: Rapid pacing promoted the secretion of exosomes from fibroblasts, and miR-21-5p was upregulated in exosomes. Moreover, the miR-21-5p-enriched exosomes upregulated KCa3.1 expression in AMs via the PI3K/Akt pathway.

Isolation and Characterization of Potassium-Solubilizing Rhizobacteria (KSR) Promoting Cotton Growth in Saline-Sodic Regions.

Cotton is highly sensitive to potassium, and Xinjiang, China's leading cotton-producing region, faces a severe challenge due to reduced soil potassium availability. Biofertilizers, particularly potassium-solubilizing rhizobacteria (KSR), convert insoluble potassium into plant-usable forms, offering a sustainable solution for evergreen agriculture. This study isolated and characterized KSR from cotton, elucidated their potassium solubilization mechanisms, and evaluated the effects of inoculating KSR strains on cotton seedlings. Twenty-three KSR strains were isolated from cotton rhizosphere soil using modified Aleksandrov medium. Their solubilizing capacities were assessed in a liquid medium. Strain A10 exhibited the highest potassium solubilization capacity (21.8 ppm) by secreting organic acids such as lactic, citric, acetic, and succinic acid, lowering the pH and facilitating potassium release. A growth curve analysis and potassium solubilization tests of A10 under alkali stress showed its vigorous growth and maintained solubilization ability at pH 8-9, with significant inhibition at pH 10. Furthermore, 16S rRNA sequencing identified strain A10 as Pseudomonas aeruginosa. Greenhouse pot experiments showed that inoculating cotton plants with strain A10 significantly increased plant height and promoted root growth. This inoculation also enhanced dry biomass accumulation in both the aerial parts and root systems of the plants, while reducing the root-shoot ratio. These results suggest that Pseudomonas aeruginosa A10 has potential as a biofertilizer, offering a new strategy for sustainable agriculture.

Low-Potassium Fruits and Vegetables: Research Progress and Prospects.

With the increasing number of patients with chronic kidney disease (CKD) and the improved recognition of nutritional therapy, research on low-potassium (LK) fruits and vegetables for CKD patients has gained global attention. Despite its already commercial availability primarily in Japan, public awareness remains limited, and cultivation methods lack a comprehensive strategy. This review offers an extensive examination of the developmental significance, current cultivation techniques, and existing limitations of functional LK fruits and vegetables with the objective of providing guidance and inspiration for their exploitation. Additionally, this review investigates various factors influencing K content, including varieties, temperature, light, exogenous substances, harvest time, and harvest parts, with a focus on optimizing production methods to enhance potassium utilization efficiency (KUE) and decrease the K content in plants. Finally, the review outlines the shortcomings and prospects of research on LK fruits and vegetables, emphasizing the importance of interdisciplinary research (in agriculture technology, medicine, and business) for patients with CKD and the future development of this field.

Exploring the Organic Acid Secretion Pathway and Potassium Solubilization Ability of Pantoea vagans ZHS-1 for Enhanced Rice Growth.

Soil potassium deficiency is a common issue limiting agricultural productivity. Potassium-solubilizing bacteria (KSB) show significant potential in mitigating soil potassium deficiency, improving soil quality, and enhancing plant growth. However, different KSB strains exhibit diverse solubilization mechanisms, environmental adaptability, and growth-promoting abilities. In this study, we isolated a multifunctional KSB strain ZHS-1, which also has phosphate-solubilizing and IAA-producing capabilities. 16S rDNA sequencing identified it as Pantoea vagans. Scanning electron microscopy (SEM) showed that strain ZHS-1 severely corroded the smooth, compact surface of potassium feldspar into a rough and loose state. The potassium solubilization reached 20.3 mg/L under conditions where maltose was the carbon source, sodium nitrate was the nitrogen source, and the pH was 7. Organic acid metabolism profiling revealed that strain ZHS-1 primarily utilized the EMP-TCA cycle, supplemented by pathways involving pantothenic acid, glyoxylic acid, and dicarboxylic acids, to produce large amounts of organic acids and energy. This solubilization was achieved through direct solubilization mechanisms. The strain also secreted IAA through a tryptophan-dependent metabolic pathway. When strain ZHS-1 was inoculated into the rhizosphere of rice, it demonstrated significant growth-promoting effects. The rice plants exhibited improved growth and root development, with increased accumulation of potassium and phosphorus. The levels of available phosphorus and potassium in the rhizosphere soil also increased significantly. Additionally, we observed a decrease in the relative abundance of Actinobacteria and Proteobacteria in the rice rhizosphere soil, while the relative abundance of genera associated with acid production and potassium solubilization, such as Gemmatimonadota, Acidobacteria, and Chloroflexi, as well as Cyanobacteria, which are beneficial to plant growth, increased. These findings contribute to a deeper understanding of the potassium solubilization mechanisms of strain ZHS-1 and highlight its potential as a plant growth-promoting rhizobacteria.

Effect of Type-2 Diabetes Mellitus on the Expression and Function of Smooth Muscle ATP-Sensitive Potassium Channels in Human Internal Mammary Artery Grafts.

Here we have shown for the first time altered expression of the vascular smooth muscle (VSM) KATP channel subunits in segments of the human internal mammary artery (HIMA) in patients with type-2 diabetes mellitus (T2DM). Functional properties of vascular KATP channels in the presence of T2DM, and the interaction between its subunits and endogenous ligands known to relax this vessel, were tested using the potassium (K) channels opener, pinacidil. HIMA is the most commonly used vascular graft in cardiac surgery. Previously it was shown that pinacidil relaxes HIMA segments through interaction with KATP (SUR2B/Kir6.1) vascular channels, but it is unknown whether pinacidil sensitivity is changed in the presence of T2DM, considering diabetes-induced vascular complications commonly seen in patients undergoing coronary artery bypass graft surgery (CABG). KATP subunits were detected in HIMA segments using Western blot and immunohistochemistry analyses. An organ bath system was used to interrogate endothelium-independent vasorelaxation caused by pinacidil. In pharmacological experiments, pinacidil was able to relax HIMA from patients with T2DM, with sensitivity comparable to our previous results. All three KATP subunits (SUR2B, Kir6.1 and Kir6.2) were observed in HIMA from patients with and without T2DM. There were no differences in the expression of the SUR2B subunit. The expression of the Kir6.1 subunit was lower in HIMA from T2DM patients. In the same group, the expression of the Kir6.2 subunit was higher. Therefore, KATP channels might not be the only method of pinacidil-induced dilatation of T2DM HIMA. T2DM may decrease the level of Kir6.1, a dominant subunit in VSM of HIMA, altering the interaction between pinacidil and those channels.

Role of the Stress Index in Predicting Mortality among Patients with Traumatic Femoral Fractures.

BACKGROUND: Traumatic femoral fractures, often resulting from high-energy impacts such as traffic accidents, necessitate immediate management to avoid severe complications. The Stress Index (SI), defined as the glucose-to-potassium ratio, serves as a predictor of mortality and adverse outcomes in various trauma contexts. This study aims to evaluate the prognostic value of the SI in patients with traumatic femoral fractures. METHODS: This retrospective cohort study included adult trauma patients aged 20 or above with traumatic femoral fractures from the Trauma Registry System at a level 1 trauma center in southern Taiwan between 1 January 2009 and 31 December 2022. At the emergency room, serum electrolyte levels were assessed using baseline laboratory testing. By dividing blood glucose (mg/dL) by potassium (mEq/L), the SI was calculated. The best cut-off value of the SI for predicting mortality was determined using the Area Under the Curve (AUC) of Receiver Operating Characteristic (ROC). RESULTS: A total of 3717 patients made up the final group, of which 3653 survived and 64 died. In comparison to survivors, deceased patients had substantially higher blood glucose levels (199.3 vs. 159.0 mg/dL, p < 0.001) and SIs (53.1 vs. 41.6, p < 0.001). The optimal SI cut-off value for predicting mortality was 49.7, with a sensitivity of 53.1% and a specificity of 78.7% (AUC = 0.609). High SI was associated with increased mortality (4.2% vs. 1.0%, p < 0.001) and longer hospital stays (12.8 vs. 9.5 days, p < 0.001). The adjusted odds ratios of mortality, controlled by comorbidities, the Glasgow Coma Scale, and the Injury Severity Score, were significantly higher in patients with a higher SI (AOR 2.05, p = 0.016) than those with a lower SI. CONCLUSIONS: Elevated SI upon admission correlates with higher mortality and extended hospital stay in patients with traumatic femoral fractures. Although the SI has a moderate predictive value, it remains a useful early risk assessment tool, necessitating further prospective, multi-center studies for validation and standardization.

Dietary Sodium and Potassium Intakes and Kidney Stone Prevalence: The National Health and Nutrition Examination Survey 2011-2018.

The associations between dietary sodium intake (DSI), dietary potassium intake (DPI), and kidney stone disease (KSD) are not clear. We examined The National Health and Nutrition Examination Survey 2011-2018 to determine the independent associations between daily DSI, DPI, DSI/DPI, and KSD prevalence. In total, 19,405 participants were included for analysis, of which 1,895 had KSD. Higher DSI was not associated with increased odds of KSD in regression analysis when DSI was modeled as a continuous variable (OR = 0.99, 95% CI: 0.99-1.00, p = 0.2), or when comparing highest quartile of DSI to lowest quartile (OR = 0.84, 95% CI: 0.68-1.04, p = 0.1). Unlike DSI, higher DPI was strongly associated with reduced odds of KSD in regression analysis when DPI was modeled as a continuous variable (OR = 0.99, 95% CI: 0.99-0.99, p = 0.02), or when comparing highest quartile of DPI to lowest quartile (OR = 0.75, 95% CI: 0.60-0.94, p = 0.01). Lastly, higher DSI/DPI was also strongly associated with increased odds of KSD in regression analysis when DSI/DPI was modeled as a continuous variable (OR = 1.1, 95% CI: 1.01-1.20, p = 0.03), or when comparing highest quartile of DPI to lowest quartile (OR = 1.30, 95% CI: 1.10-1.70, p = 0.008). All the observed relationships were independent of total calorie intake. In conclusion, both lower DPI and higher DSI/DPI are associated with an increased risk of KSD. Future prospective studies are needed to clarify these causal relationships.

Astrocyte regulation of extracellular space parameters across the sleep-wake cycle.

Multiple subfields of neuroscience research are beginning to incorporate astrocytes into current frameworks of understanding overall brain physiology, neuronal circuitry, and disease etiology that underlie sleep and sleep-related disorders. Astrocytes have emerged as a dynamic regulator of neuronal activity through control of extracellular space (ECS) volume and composition, both of which can vary dramatically during different levels of sleep and arousal. Astrocytes are also an attractive target of sleep research due to their prominent role in the glymphatic system, a method by which toxic metabolites generated during wakefulness are cleared away. In this review we assess the literature surrounding glial influences on fluctuations in ECS volume and composition across the sleep-wake cycle. We also examine mechanisms of astrocyte volume regulation in glymphatic solute clearance and their role in sleep and wake states. Overall, findings highlight the importance of astrocytes in sleep and sleep research.

Trans-abdominal fetal reduction in higher order multiple pregnancies: a pioneer cohort retrospective study in Nepal.

Objective: To share the initial experience of trans-abdominal multifetal pregnancy reduction (MFPR) in Nepal. Method: The procedure was performed in 108 patients in a private hospital over a period of 3 years. Under ultrasound guidance, intracardiac injection of 0.2-3.0 ml of 15% w/v (2 mEq/ml) potassium chloride (KCl) was administered via trans-abdominal route. Results: A total of 108 fetal reduction procedures were carried out at the seventh to fifteenth weeks of gestation, a maximum of 44 (40.7%) of which were done at the ninth to tenth weeks of gestation. A total of 123 fetuses were reduced. Out of total 108 multifetal pregnancies, 96 (88.8%) were due to in-vitro fertilization (IVF). Eighty-five pregnancies (78.7%) underwent reduction from triplet to twin. The second-time reduction was needed in five cases. Two attempts (in the same sitting) were required in three cases. The inadvertent demise of the second fetus was noted in three cases of dichorionic tri-amniotic triplet pregnancy. Conclusion: Ultrasound-guided trans-abdominal fetal reduction performed between the seventh and twelfth weeks of gestation is safe and effective.

Contribution of inwardly rectifying potassium channel 4.1 in orofacial neuropathic pain: Regulation of pannexin 3 via the reactive oxygen species-activated P38 MAPK signal pathway.

The involvement of inwardly rectifying potassium channel 4.1 (Kir4.1) in neuropathic pain has been established. However, there is limited understanding of the downstream mechanism through which Kir4.1 contributes to orofacial neuropathic pain. The objective of this study was to examine the regulation of Kir4.1 on the expression of pannexin 3 (Panx3) in the trigeminal ganglion (TG) and the underlying mechanism in the context of orofacial neuropathic pain caused by chronic constriction injury of the infraorbital nerve (CCI-ION). The study observed a significant increase in Panx3 expression in the TG of mice with CCI-ION. Inhibition of Panx3 in the TG of CCI-ION mice resulted in alleviation of orofacial mechanical allodynia. Furthermore, conditional knockdown (CKD) of Kir4.1 in the TG of both male and female mice led to mechanical allodynia and upregulation of Panx3 expression. Conversely, overexpression of Kir4.1 decreased Panx3 levels in the TG and relieved mechanical allodynia in CCI-ION mice. In addition, silencing Kir4.1 in satellite glial cells (SGCs) decreased Panx3 expression and increased the phosphorylation of P38 MAPK. Moreover, silencing Kir4.1 in SGCs increased the levels of reactive oxygen species (ROS). The elevated phosphorylation of P38 MAPK resulting from Kir4.1 silencing was inhibited by using a superoxide scavenger known as the tempol. Silencing Panx3 in the TG in vivo attenuated the mechanical allodynia caused by Kir4.1 CKD. In conclusion, these findings suggest that the reduction of Kir4.1 promotes the expression of Panx3 by activating the ROS-P38 MAPK signalling pathway, thus contributing to the development of orofacial neuropathic pain.

Repellency, toxicity, and physiological actions of low molecular weight basic amines in mosquitoes.

BACKGROUND: This study investigated the behavioral responses and toxicity of three basic amines: 1-methylpiperazine, 1-methylpyrrolidine, and triethylamine (TEA), compounds suggested previously to be anosmic in vapor exposures to caged mosquitoes. RESULTS: These compounds showed repellency of Aedes aegypti mosquitoes, followed by flightlessness, knockdown, and paralysis, all increasing with exposure time and dosage. Electrophysiological experiments showed a blocking effect on nerve discharge of the Drosophila melanogaster larval central nervous system (CNS) with little evidence of hyperexcitation. Blockage of voltage-gated (Kv2) potassium channel currents under patch clamp occurred at similar concentrations. Involvement of K+ channels in the action of basic amines was supported by behavior and CNS recordings of a Shaker Kv1 mutant exposed to TEA, where instead of blockage, a hyperexcitation of nerve firing was observed. Experiments on cockroach leg mechanoreceptors demonstrated neuronal excitation and on mosquito antennae strong electroantennogram (EAG) signals with an augmentation of blank air responses after a single puff of basic amine. CONCLUSIONS: The neurophysiological effects of basic amines are consistent with K+ channel block, whereas the antennal EAG response was not obviously associated with anosmia. The low-dose effects of basic amines appear to be repellency and bradykinesia. Overall, the findings provide key insights into the mechanisms underlying the biological activity of basic amines. © 2024 Society of Chemical Industry.

Sodium and potassium excretion and its association with cardiovascular disorders in Mexican adults.

Worldwide, as well as in Mexico, the leading cause of death is cardiovascular disease (CVD). Hypertension is the main risk factor for CVD; about 50% of the adult population suffers from this condition. High sodium (Na) intake combined with low potassium (K) intake can trigger cardiovascular disorders such as high blood pressure (BP). The aim of this study was to estimate the mean excretion of Na and K in Mexican adults using a spot urine sample, and its association with cardiovascular disorders. Information on 2,778 adults, 20-59 years of age, who participated in ENSANUT-2016 was analyzed. Na and K were estimated using Tanaka formulae. Biomarkers such as glucose, total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol, and anthropometry were measured. Mean Na was 3,354 mg/day (95%CI: 3,278, 3,429), 1,440 mg/day of K (95%CI: 1,412, 1,469), and the Na-K ratio was 2.4. The excretion of Na was greater in adults with high BP (3,542 mg/day) compared to those with normal BP (3,296 mg/day). In adults with hypertension, excretion of K was 10% greater (1,534 mg/day) than in adults with normal BP (1,357 mg/day). In adults with moderate reduction of renal function, Na excretion was 22% less (2,772 mg/day) than in adults with normal kidney function (3,382 mg/day). The results of this study show that the cardiovascular health of Mexican adults is at risk, as they showed high Na excretion and low K excretion.