Elevated Potassium Concentration Research Articles

Evaluating Groundwater Quality for Drinking and Irrigation Purposes and Health Risk Assessment in West Midnapore District of West Bengal, India

Groundwater quality in the West Midnapore district of West Bengal, India is affected by anthropogenic activities as well as by water quality of Subarnarekha and Kangsabati rivers. This study aims to assess quality of groundwater and river water for drinking and irrigation usage, and assess the health risks of the people consuming the water across the rivers. The study also explores the groundwater-river water interaction. The river water and groundwater samples were collected three times during monsoon season from 14 sites across the rivers. The samples were analyzed for 11 water quality parameters, i.e., pH, total dissolved solids (TDS), total hardness (TH), major anions and cations, and iron (Fe). The groundwater was found slightly acidic (mean pH ~ 6.71) and correlated with nitrate concentrations. Most of the water quality parameters were found within their permissible limits of drinking water. However, elevated concentrations of potassium (K), ammonium (NH4), magnesium (Mg), phosphate (PO4), sodium (Na), and Fe were detected at some places, which were likely due to use of fertilizers. Water quality index (WQI), sodium absorption ratio (SAR), and percentage Na values were computed to evaluate the groundwater quality. The mean WQI value of 37.07 showed that the majority of groundwater samples met drinking water standards. Groundwater was also found suitable for irrigation (SAR ~ 0.26 to 1.62 meq L-1 and percentage Na ~ 13.10% to 78.12%). Health risk assessments suggested minimal immediate risks, though high Na levels in certain areas raised concerns. Piper plot showed that increased calcium concentrations in groundwater were mainly due to interactions between river water and groundwater. Overall, groundwater quality did not present any harmful health hazards to the community. The findings of this study can be instrumental for groundwater managers in identifying potential areas for treating groundwater quality.

Physicochemical characterization of agricultural soils under a traditional system in the Mezquital Valley, Hidalgo

The study examines alkaline and sodic soils, characterized by a pH exceeding 7.5 and elevated exchangeable sodium, indicative of deficiencies in nitrogen, manganese, iron, zinc, and copper in crops. Its objective is to characterize agricultural soils under traditional and conventional systems using physical and chemical parameters to advocate for regenerative agriculture. Sampling and analysis adhere to Nom-021-RECNAT-2000 standards. Predominantly, the soils exhibit clay loam and sandy loam textures across Tula de Allende, Tezontepec de Aldama, Francisco I. Madero, and San Salvador municipalities. Organic matter percentages vary, classified as very high (Tula de Allende and San Salvador), high (Tezontepec de Aldama, Mixquiahuala de Juárez, and Francisco I. Madero), and low (Santiago de Anaya). The pH ranges from moderately alcaline to highly alkaline. Cation exchange capacity in irrigation zones varies from very high to high, and medium for Tezontepec and Santiago de Anaya, which rely on rainfed irrigation. Elevated nitrate (NO3-), phosphorus (H2PO4-), and potassium (K+) concentrations are noted across different municipalities. These findings prompt reconsideration of traditional tillage practices that exacerbate sodicity in agricultural soil.

Characterization of the decomposition behaviors of catalytic pyrolysis of alkaline lignin with the addition of different concentrations of potassium

Investigating the influence of potassium concentration on alkali lignin pyrolysis is beneficial for advancing the technology of biomass catalytic pyrolysis. This study examined the catalytic effects of different concentrations of various potassium compounds on alkali lignin pyrolysis. The impregnation method was employed to load potassium compounds (KCl, K2CO3, and CH3COOK) onto alkali lignin at varying concentrations. The results showed a significant influence of potassium concentration on the catalytic pyrolysis of lignin. Increasing the potassium concentration resulted in higher pyrolysis char yield and lower pyrolysis gas yield. Furthermore, the pyrolytic char with a high concentration of potassium exhibited a distinct surface pore structure that was noticeably eroded by potassium. Furthermore, with an increase in potassium concentration, the removal of side chains, including methoxy, acetyl, and hydroxyethyl groups, became increasingly pronounced, resulting in higher yields of CO2 and phenol. The elevated potassium concentration facilitated the depolymerization of lignin through Cβ-O bond cleavage, promoted the decomposition of intermediate products, and enhanced the formation of small molecule products. Ultimately, a hypothetical mechanism explaining the influence of potassium concentration on alkali lignin pyrolysis was proposed. This study establishes a scientific foundation for the high-value utilization and resource development of alkaline lignin.

Diagenesis and lateral sealing types of fault zones in the Lishu Depression, Songliao Basin, NE China

The Lishu Depression in the Songliao Basin is characterized by well-developed faults, and the accumulation of oil and gas is closely related to fault sealing. However, there remains a dearth of comprehensive investigation into the diagenesis of fault zones and their influence on lateral sealing. This study employed electron probe analysis, cathodoluminescence, and carbon and oxygen isotope techniques to investigate the diagenetic processes in fault zones. This research also reconstructed the evolution of porosity and displacement pressure of fault rocks, and identified the lateral sealing characteristics of fault zones and their impact on oil and gas accumulation. The majority of faults in the study region formed earlier, and the fault zones experienced intricate diagenesis, characterized by compaction, cementation, replacement, and dissolution. The displacement pressure of fault rocks is higher during fault intermittent and static periods compared to active periods, and it is influenced by diagenesis. Late-stage calcite and pore-filling chlorite were deposited subsequent to the period of fault activity, filling dissolution pores. This led to relatively higher displacement pressure and improved lateral sealing of fault zone. The kaolinite cement exhibits a relatively elevated potassium concentration, due to its connection with the dissolution of feldspar, resulting in lower displacement pressure and poor sealing of fault zone. Based on the evolutionary characteristics of displacement pressure in fault rock and reservoir during various transportation stages, this study identified six types of lateral sealing of fault zones. Notably, the sealing types characterized by "fault core and damage zone sealing during static periods" and "fault core and damage zone sealing during intermittent and static periods" exhibit superior lateral sealing properties, effectively controlling the accumulation of oil and gas in the sand bodies on either side of the fault zone.

Calcitized evaporites in the Mesoproterozoic Atar and El Meriti Groups, Mauritania, Africa

One of the most profound byproducts of the Great Oxidation Event (GOE) was the onset of oxidative weathering on land and the riverine delivery of sulfate to marine systems. Although the exact nature of marine oxygenation in the aftermath of the GOE remains uncertain, marine sulfate likely remained below 2 mM until the late Mesoproterozoic and may have remained <10 mM through the Neoproterozoic. Prior to the late Mesoproterozoic, precipitation of sulfate minerals were inhibited by low marine sulfate and possibly by elevated carbonate saturation. By ∼1.1 Ga marine sulfate concentrations were sufficient to sustain the earliest widespread evaporite deposition. Low sulfate concentrations, however, influenced both the deposition and diagenesis of evaporite deposits. Here we investigate unusual limestone deposits in the 1.1 Ga Atar Group, Mauritania, that contain both macroscopic and microscopic features that suggest a primary origin as gypsum. Elevated concentrations of carbonate-associated sulfate (CAS), sodium, and potassium are consistent with primary deposition as a sulfate evaporite and subsequent calcification under low water-rock ratios. Isotope and elemental compositions further indicate diagenetic recrystallization under marine to hypersaline marine conditions. Combined, these observations show the potential for recognizing key evaporite facies in the rock record and support a growing recognition of late Mesoproterozoic evaporite deposits.

Heparin-induced hyperkalemia, can LMWH cause hyperkalemia? A systematic review.

Hyperkalemia, an elevated blood potassium concentration exceeding 5.0mEq/L, is associated with adverse outcomes and is frequently observed in hospitalized patients. Drug-induced hyperkalemia accounts for a significant proportion of cases, with heparin, commonly used for venous thrombosis prevention, suspected to contribute, though less recognized than other heparin-related side effects. Both unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been implicated in inducing hyperkalemia, primarily through the suppression of aldosterone levels and modulation of angiotensin II receptors. This systematic review examines the relationship between heparin, particularly LMWH, and hyperkalemia. Thirteen studies involving 1407 patients were analyzed. Findings indicated a lack of highquality evidence, with no significant increase in potassium levels associated with LMWH use. LMWH did not exhibit a dose-response relationship with hyperkalemia incidence. Additionally, mechanisms underlying the hypothetical LMWHinduced hyperkalemia remained inconclusive. While this suggests that LMWH is unlikely to be a primary cause of hyperkalemia, caution is warranted, especially in patients with elevated baseline potassium levels.

Impact of Arbuscular mycorrhizal Fungal Strains Isolated from Soil on the Growth, Yield, and Fruit Quality of Tomato Plants under Different Fertilization Regimens

Arbuscular mycorrhizal fungi (AMF) have emerged as a promising and environmentally friendly solution for sustainable agriculture, offering a reduction in dependence on chemical inputs. The objective of this greenhouse experiment was to assess the efficacy of a natural endomycorrhizal inoculum obtained from leek root fragments, which acted as a trap plant to capture indigenous fungal spores present in the soil of the Guercif region in Morocco. The investigation aimed to comprehensively evaluate the influence of this inoculum on various parameters related to tomato plant growth, yield, and sensory quality. Additionally, different levels of chemical fertilizers, equivalent to 50%, 75%, and 100% of the recommended dosage, were administered in combination with or without the inoculum. The findings elucidated significant advantages associated with mycorrhizal inoculation. The plants subjected to inoculation exhibited increased plant height, augmented leaf and root dry weights, and improved nutrient uptake compared to the control group. Notably, tomato plants treated with 75% of the recommended chemical fertilizer dosage yielded the highest crop production, with no statistically significant difference observed when compared to those receiving the full dosage (100%). Intriguingly, tomato plants grown in substrates receiving 50% chemical fertilizers demonstrated the highest levels of mycorrhization, exhibiting a frequency (F) of 100% and an intensity (M) of 63%. Importantly, the combination of inoculation with a reduced dose of NPK fertilizer (50% of the recommended amount) resulted in significantly elevated concentrations of calcium (Ca), potassium (K), iron (Fe), zinc (Zn), and phosphorus (P) in the plants, attributable to the heightened mycorrhizal colonization of the roots. In terms of fruit characteristics, no significant variations were detected in pH and electrical conductivity (EC) among the treatment groups. However, the inoculated plants exhibited a notable increase in the Brix index, an indicator of sweetness, compared to the control group across all fertilizer doses. Furthermore, inoculation positively influenced the levels of total carotenoids in the fruits. Remarkably, the values of these compounds in the inoculated plants subjected to 50% of the recommended fertilizer dosage surpassed those recorded in the non-inoculated plants receiving the full dosage.

Methodology-related pseudohyperkalemia associated with marked muscle enzyme leakage in a dog.

As hyperkalemia may be life-threatening, it is critical to recognize artifactually increased potassium concentrations. Pseudohyperkalemia may occur in myopathies when using the VetScan2 analyzer (VS2), but the degree of pseudohyperkalemia and relationships relative to creatine kinase activity (CK) are unknown. We aimed to determine what degree of muscle enzyme leakage, as reflected by increased serum CK activity, results in cases with falsely elevated potassium concentrations when measured by the VS2. We also sought to establish if a linear relationship exists between potassium concentrations measured by the VS2 and CK activity. Serum samples from dogs with increased CK activity and with CK activity within the reference interval and without clinically relevant biochemical alterations were used to create diluted samples having various CK activities. Potassium concentrations and CK activities were determined on VS2 and Cobas c501 (Cobas) analyzers. Wilcoxon signed rank, Bland-Altman, and Passing-Bablok analyses were used to compare potassium concentrations generated by the VS2 and Cobas analyzers. Least squares regression analysis was performed to evaluate if a linear relationship exists between VS2 potassium concentrations and Cobas CK activities. Potassium concentrations from the VS2 were higher (median and standard deviation (SD) = 5.2 +/- 0.46 mmol/L) than those from the Cobas analyzer (4.4 +/- 0.35 mmol/L; P < 0.000), and a positive mean bias was found (mean difference = 0.774 mmol/L; 95% Confidence Interval (CI) = 0.706-0.842; limits of agreement = 0.21-1.34). Passing-Bablok regression showed a positive proportional bias for potassium concentrations on the VS2 compared with paired Cobas results (Slope = 1.328; 95% CI = 1.100-1.500) but did not reveal systematic bias (Intercept = -0.714; 95% CI = -1.46-0.265). Least squares regression analysis showed a poor non-significant relationship (R2 = 0.19) between potassium measured by the VS2 and CK measured by the Cobas analyzer. A defined threshold value of CK activity at which potassium concentration begins to falsely increase when measured on the VS2 was not established as data widely varied. A poor non-significant relationship between potassium concentrations and CK activities did not allow prediction of the threshold at which falsely increased potassium concentrations would be expected on the VS2.

KCNQ2 channels regulate the population activity of neonatal GABAergic neurons ex vivo.

Over the last decade KCNQ2 channels have arisen as fundamental and indispensable regulators of neonatal brain excitability, with KCNQ2 loss-of-function pathogenic variants being increasingly identified in patients with developmental and epileptic encephalopathy. However, the mechanisms by which KCNQ2 loss-of-function variants lead to network dysfunction are not fully known. An important remaining knowledge gap is whether loss of KCNQ2 function alters GABAergic interneuron activity early in development. To address this question, we applied mesoscale calcium imaging ex vivo in postnatal day 4-7 mice lacking KCNQ2 channels in interneurons (Vgat-ires-cre;Kcnq2f/f;GCamp5). In the presence of elevated extracellular potassium concentrations, ablation of KCNQ2 channels from GABAergic cells increased the interneuron population activity in the hippocampal formation and regions of the neocortex. We found that this increased population activity depends on fast synaptic transmission, with excitatory transmission promoting the activity and GABAergic transmission curtailing it. Together, our data show that loss of function of KCNQ2 channels from interneurons increases the network excitability of the immature GABAergic circuits, revealing a new function of KCNQ2 channels in interneuron physiology in the developing brain.

Influence of Water Hardness on Chronic Toxicity of Potassium Chloride to a Unionid Mussel (Lampsilis siliquoidea).

Elevated concentrations of potassium (K) often occur in effluents from wastewater treatment plants, oil and gas production operations, mineral extraction processes, and other anthropogenic sources. Previous studies have demonstrated that freshwater mussels are highly sensitive to K in acute and chronic exposures, and that acute toxicity of K decreases with increasing water hardness. However, little is known about the influence of hardness on the chronic toxicity of K. The objective of our study was to evaluate the chronic toxicity of K (tested as KCl) to a commonly tested unionid mussel (fatmucket, Lampsilis siliquoidea) at five hardness levels (25, 50, 100, 200, and 300 mg/L as CaCO3 ) representing most surface waters in the United States. Chronic 28-day K toxicity tests were conducted with 3-week-old juvenile fatmucket in the five hardness waters using an ASTM International standard method. The maximum acceptable toxicant concentrations (geometric mean of the no-observed-effect concentration and the lowest-observed-effect concentration) increased from 15.1 to 69.3 mg K/L for survival and from 15.1 to 35.8 mg K/L for growth (length and dry wt) and biomass when water hardness was increased from 25 mg/L (soft) to 300 mg/L (very hard). These results provide evidence to support water hardness influence on chronic K toxicity to juvenile fatmucket. However, the chronic effect concentrations based on the more sensitive endpoint (growth or biomass) increased only 2.4-fold from the soft water to the very hard water, indicating that water hardness had a limited influence on the chronic toxicity of K to the mussels. These results can be used to establish chronic toxicity thresholds for K across a broad range of water hardness and to derive environmental guideline values for K to protect freshwater mussels and other organisms. Environ Toxicol Chem 2023;42:1085-1093. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

Depolarization-induced bursts of miniature synaptic currents in individual synapses of developing cerebellum.

In central synapses, spontaneous transmitter release observed in the absence of action potential firing is often considered as a random process lacking time or space specificity. However, when studying miniature glutamatergic currents at cerebellar synapses between parallel fibers and molecular layer interneurons, we found that these currents were sometimes organized in bursts of events occurring at high frequency (about 30 Hz). Bursts displayed homogeneous quantal size amplitudes. Furthermore, in the presence of the desensitization inhibitor cyclothiazide, successive events within a burst displayed quantal amplitude occlusion. Based on these findings, we conclude that bursts originate in individual synapses. Bursts were enhanced by increasing either the external potassium concentration or the external calcium concentration, and they were strongly inhibited when blocking voltage-gated calcium channels by cadmium. Bursts were prevalent in elevated potassium concentration during the formation of the molecular layer but were infrequent later in development. Since postsynaptic AMPA receptors are largely calcium permeant in developing parallel fiber-interneuron synapses, we propose that bursts involve presynaptic calcium transients implicating presynaptic voltage-gated calcium channels, together with postsynaptic calcium transients implicating postsynaptic AMPA receptors. These simultaneous pre- and postsynaptic calcium transients may contribute to the formation and/or stabilization of synaptic connections.

Elevated effluent potassium concentrations predict the development of postreperfusion hyperkalemia in deceased liver transplantation: a retrospective cohort study

BackgroundPostreperfusion hyperkalemia (PRHK) has garnered increasing attention in regard to deceased liver transplantation (LT), especially for LT using the expanded criteria donor grafts. However, the impact of the effluent potassium (eK+) concentration on PRHK has been largely overlooked. We evaluated whether elevated eK+ concentrations are associated with PRHK in deceased LT.MethodsIn this single-institution, retrospective cohort study, we included all adults who underwent deceased LT with intraoperative eK+ concentration monitoring between November 2016 and December 2018. The eK+ concentrations were obtained from the effluent samples collected following a standard portal vein flush. PRHK was defined as any serum potassium (sK+) level of > 5.5 mmol/L following reperfusion. Logistic regression was performed to identify predictors for PRHK, and linear regression was used to examine predictors of the maximum percentage increase in the sK+ level following reperfusion.ResultsOf the 86 patients who met the inclusion criteria, 54 (62.8%) developed PRHK. Independent predictors for PRHK included greater graft weight (OR 1.283 [95% CI 1.029–1.599] per 100 g, P = 0.027), an elevated eK+ concentration (OR 1.291 [95% CI 1.068–1.561] per mol/L, P = 0.008), and a higher sK+ level before reperfusion (OR 4.459 [95% CI 1.543–12.884] per mol/L, P = 0.006). An eK+ concentration of more than 6.9 mmol/L had a sensitivity of 59.26% and a specificity of 78.12% for predicting PRHK (area under the receiver operating characteristic curve, 0.694). Multiple linear regression analyses indicated that the eK+ and sK+ levels before reperfusion were significant predictors of the maximum percentage increase in the sK+ level following reperfusion. In addition, PRHK was associated with an increased risk of postreperfusion significant arrhythmias, severe postreperfusion syndrome, and postoperative early allograft dysfunction.ConclusionsThis study shows that the eK+ concentration could predict the risk of PRHK in deceased LT. Further prospective studies are warranted to clarify these associations.

POCT errors can lead to false potassium results.

Point-of-care-testing (POCT) facilitates rapid availability of results that allows prompt clinical decision making. These results must be reliable and the whole process must not compromise its quality. Blood gas analyzers are one of the most used methods for POCT tests in Emergency Departments (ED) and in critical patients. Whole blood is the preferred sample, and we must be aware that hemolysis can occur. These devices cannot detect the presence of hemolysis in the sample, and because of the characteristics of the sample, we cannot visually detect it either. Hemolysis can alter the result of different parameters, including potassium with abnormal high results or masking low levels (hypokalemia) when reporting normal concentrations. Severe hyperkalemia is associated with the risk of potentially fatal cardiac arrhythmia and demands emergency clinical intervention. Hemolysis can be considered the most frequent cause of pseudohyperkalemia (spurious hyperkalemia) or pseudonormokalemia and can be accompanied by a wrong diagnosis and an ensuing inappropriate clinical decision making. A complete review of the potential causes of falsely elevated potassium concentrations in blood is presented in this article. POCT programs properly led and organized by the clinical laboratory can help to prevent errors and their impact on patient care.

The Secret of the Main Campus Water-Wells, Arba Minch University, Ethiopia.

Groundwater is one of the precious water sources for domestic, irrigation, and industrial demands in arid and semiarid regions of the world. The same is true in Ethiopia context. In this study, seven groundwater samples were collected and analyzed for various chemical constituents (pH, TDS, Na+, K+, Ca2+, Mg2+, SO42−, Cl−, HCO3−, and NO3−) to assess the hydrogeochemical characteristics and water types of the groundwater wells. Among the seven sampled groundwater wells, five wells are found and used for domestic water supply in Arba Minch University (AMU) main campus. The remaining two are used for industrial and irrigation demands located at the compound of Textile Factory and Haile Resort, respectively. Results showed that the main campus groundwater wells are saline and harder than the two wells from Textile Factory and Haile Resort. Moreover, elevated concentration of nitrate and potassium (greater than the maximum permissible level allowed in Ethiopia) were obtained in the groundwater sources used mainly in the AMU main campus wells. These elevated concentrations of potassium and nitrate beyond the enriched salt contents in the AMU main campus wells could pose kidney, cardiovascular, and other related health problems. This study, therefore, recommends the AMU to find other groundwater sources for drinking purpose other than the studied water-well field.

The Motor Neuron-Like Cell Line NSC-34 and Its Parent Cell Line N18TG2 Have Glycogen that is Degraded Under Cellular Stress

Brain glycogen has a long and versatile history: Primarily regarded as an evolutionary remnant, it was then thought of as an unspecific emergency fuel store. A dynamic role for glycogen in normal brain function has been proposed later but exclusively attributed to astrocytes, its main storage site. Neuronal glycogen had long been neglected, but came into focus when sensitive technical methods allowed quantification of glycogen at low concentration range and the detection of glycogen metabolizing enzymes in cells and cell lysates. Recently, an active role of neuronal glycogen and even its contribution to neuronal survival could be demonstrated. We used the neuronal cell lines NSC-34 and N18TG2 and could demonstrate that they express the key-enzymes of glycogen metabolism, glycogen phosphorylase and glycogen synthase and contain glycogen which is mobilized on glucose deprivation and elevated potassium concentrations, but not by hormones stimulating cAMP formation. Conditions of metabolic stress, namely hypoxia, oxidative stress and pH lowering, induce glycogen degradation. Our studies revealed that glycogen can contribute to the energy supply of neuronal cell lines in situations of metabolic stress. These findings shed new light on the so far neglected role of neuronal glycogen. The key-enzyme in glycogen degradation is glycogen phosphorylase. Neurons express only the brain isoform of the enzyme that is supposed to be activated primarily by the allosteric activator AMP and less by covalent phosphorylation via the cAMP cascade. Our results indicate that neuronal glycogen is not degraded upon hormone action but by factors lowering the energy charge of the cells directly.

Membrane Depolarization Inhibits BIMEL Upregulation but Prevents Neuronal Apoptosis Primarily by Increasing Cellular GSH Levels.

Sympathetic neurons deprived of nerve growth factor (NGF) die by apoptosis. Chronic depolarization with elevated concentrations of extracellular potassium ([K+]E) supports long-term survival of these and other types of neurons in culture. While depolarization has long been used to support neuronal cultures, little is known about the mechanism. We explored how chronic depolarization of NGF-deprived mouse sympathetic neurons in culture blocks apoptotic death. First, we determined the effects of elevated [K+]E on proapoptotic BH3-only proteins reported to be upregulated in sympathetic neurons after NGF withdrawal. Upregulation of BIMEL was blocked by depolarization while upregulation of PUMA was not. BMF levels did not increase after NGF withdrawal, and elevated [K+]E had no effect on its expression. dp5/HRK was not detectable. A large increase in production of mitochondria-derived reactive species (RS), including reactive oxygen species (ROS), occurs in NGF-deprived sympathetic neurons. Suppressing these RS prevents cytochrome c release from mitochondria and apoptosis. The addition of high [K+]E to cultures rapidly blocked increased RS and cytochrome c release. Elevated [K+]E caused an increase of the cellular antioxidant glutathione (GSH). Preventing this increase prevented the elevated [K+]E from blocking cytochrome c release and death. While suppression of BIMEL upregulation by elevated [K+]E may contribute to high [K+]E pro-survival effects, we conclude that elevated [K+]E prevents apoptotic death of NGF-deprived sympathetic neurons primarily via an antioxidant mechanism.

PDB59 THE IMPACT OF HYPERKALAEMIA AND ITS CONCURRENCE WITH CARDIORENAL COMORBIDITIES ON HEALTHCARE RESOURCE USE IN THE UK

Hyperkalaemia (HK) is a potentially life-threatening electrolyte abnormality characterized by elevated serum potassium concentrations above 5.0mmol/L. The clinical and economic burden of HK is of concern for patients with cardiovascular and renal comorbidities. However, there is limited data on the impact of HK and its concurrence with comorbidities on healthcare resource use (HRU) in the UK. In this study we aimed to characterise HRU associated with HK hospitalisations in patients with different cardiovascular and renal comorbidities in the UK.

A Study of Synaptic Plasticity in the Rat Hippocampal Field CA1 in Conditions of Deficiency of Acetylcholine and Other Neurotransmitters

Experiments showed that high-amplitude, long-lasting tetanic potentiation could be induced in synaptic terminals formed by Schaffer collaterals on field CA1 pyramidal cells in rat hippocampal slices in which acetylcholine deficiency was modeled by application of the choline reuptake inhibitor hemicholine and the vesicular acetylcholine uptake inhibitor vesamicol. Deficiencies of different neurotransmitters were modeled by 5-min incubation of slices in solution containing an elevated potassium concentration, which led, as demonstrated previously, to depletion of the release of these neurotransmitters from nerve endings. The result of this procedure was that synapses formed by Schaffer collaterals developed long-term potentiation. Long-term post-tetanic potentiation was also induced in slices on this background in the model of neurotransmitter deficiency. Its amplitude was not significantly different from the amplitude of long-term potentiation in controls but was less than that obtained using vesamicol or hemicholine. As deficiency of serotonin, noradrenaline, and dopamine is known to be able to decrease the extent of long-term potentiation of synaptic transmission between fields CA3 and CA1, these result points to the possibility that acetylcholine deficiency partially compensates for this decrease. Considering known data on the locations of different types of nicotinic and muscarinic cholinoreceptors both on pyramidal cells and on inhibitory interneurons, the possible effects of acetylcholine on the efficiency of the inputs formed by Schaffer collaterals were studied. This analysis and consideration of the data obtained here led to the hypothesis that in conditions of acetylcholine deficiency, the main influence on the efficiency of excitation of pyramidal cells in field CA1 by field CA3 is exerted by disinhibition via a network of interacting interneurons.

Bioinorganic markers of lens capsule barrier properties loss in age-related cataracts development

The study demonstrates the significance of development mechanism of age-related cataract consequent to the loss of barrier properties of the lens capsule based on analysis of the accumulation of sodium, calcium, phosphorus and potassium. Spatial cluster analysis and correlation analysis were used to reveal for the first time the relation between the diffusion of light in the body of the crystalline lens and changes in its elemental composition. Distribution fields of elevated concentrations of sodium, calcium, phosphorus, potassium and chlorine are consistent with geometry of the lens capsule and clusterize together with areas of opacification in its body. The accumulation geometry of the elements in the lens body is also commonly seen in the aqueous humor of the anterior chamber, which can be considered evidence for excessive transitioning of their compounds through the lens capsule shell, while spatial connection with transparency changes - proof of its participation in cataractogenesis.

Resolving the reversed rate effect of calcium channel blockers on human induced pluripotent stem cell-derived cardiomyocytes and the impact on in vitro cardiac safety evaluation

Calcium channel blockers (CCBs), such as diltiazem, nifedipine, and verapamil, cause tachycardia effects on several commercially available human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), when tested in culture media provided by suppliers, rather than bradycardia effects, as seen in vivo. We found that in test conditions where Na+ current of hiPSC-CMs was reduced to certain threshold by either specific Na+ channel blocker tetrodotoxin (TTX), or by voltage-dependent inactivation using elevated extracellular potassium concentrations, CCBs produced bradycardia effects on hiPSC-CMs. However, elevated extracellular potassium concentrations or the presence of TTX did not change other pharmacological responses of hiPSC-CMs, including CCBs' effects on contraction intensity and duration; beating rate change by calcium channel opener FPL64176, HCN blocker ivabradine, and β-adrenergic agonist isoproterenol; and action potential duration prolongation by hERG channel blocker dofetilide. We concluded that action potentials of hiPSC-CMs, with regards to the CCB phenotype, were Na+ current driven. When Na+ channel availability was reduced to a critical level, their action potentials became Ca2+ current driven, and their responses to CCBs correlated well to those seen in vivo. Importantly, the corrected bradycardia effect of calcium channel block with our defined conditions will provide more reliable results in cardiac safety readouts of test compounds that integrate multiple effects including calcium channel inhibition.