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Kidney response to acute and mechanically induced variation in ventilation associated with different levels of PEEP has not been investigated. We aimed to quantify the effect of ventilatory settings on renal acid-base compensation. Forty-one pigs undergoing hypo- (<0.2 Lkg-1 min-1, PEEP 25 cmH2O), intermediate (0.2-0.4 Lkg-1 min-1 with either PEEP 5 or 25 cmH2O), or hyper-ventilation (>0.4 Lkg-1 min-1, PEEP 5 cmH2O) for 48 h were retrospectively included. The decrease in pH paralleled the decrease in plasma strong ion difference (SID) in hyper- and intermediately ventilated groups with lower PEEP. In contrast, the plasma SID remained nearly constant in hypo- and intermediately ventilated groups with higher PEEP. Changes in plasma chloride concentration accounted for the changes in plasma SID (conditional R2 = 0.86). The plasma SID changes were paralleled by mirror changes in urinary SID. Higher PEEP (25 cmH2O), compared to lower PEEP (5 cmH2O) dampened or abolished the renal compensation through its effect on hemodynamics (higher central venous and mean pulmonary pressures), irrespective of minute ventilation. During mechanical ventilation, the compensatory renal response to respiratory derangement is immediate and progressive but can be dampened by high PEEP levels.

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An adolescent girl presented with recurrent lower limb fractures and was managed as osteogenesis imperfecta. Low phosphate levels noted on routine investigation were the clue for the phosphaturia and subsequent diagnosis of proximal renal tubular acidosis (RTA). Further, with a history of jaundice, she was diagnosed with Wilson's disease, which was the underlying cause of proximal RTA with isolated phosphaturia and consequent fractures. Standard treatment for Wilson's disease along with supplementation of oral phosphate and bicarbonate led to complete recovery of fragile bones.

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Glycosuria can be isolated or it can be associated with other tubulopathies like proximal renal tubular acidosis, Fanconi syndrome and endocrine conditions like diabetes mellitus. The SLC5A2 gene codes for the SGLT2 transporter, which is responsible for glucose reabsorption in the proximal tubule. Previously reported cases show that mutation in this gene is associated with intellectual disability, seizure disorder and renin and angiotensin system dysfunction. In his early childhood, a male child displayed persistently high urine glucose levels. We ruled out diabetes mellitus and other tubulopathies before diagnosing the child with familial renal glycosuria, with a novel mutation in the SLC5A2 gene, and screened family members for the same condition. Child's father was found to have isolated renal glycosuria and tested positive for mutation in the SLC5A2 gene.

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Renal chloride metabolism is currently poorly understood but may serve as both a diagnostic and a treatment approach for acute kidney injury. We investigated whether plasma chloride, ammonia and glutamine as well as urinary chloride, ammonium and glutamine concentrations may serve as markers for acute kidney injury in paediatric patients. We conducted a prospective observational trial in a tertiary care paediatric intensive care unit. Ninety-one patients after cardiopulmonary bypass surgery were enrolled. Plasma glutamine, creatinine, (serum) albumin, urinary electrolytes and glutamine were collected pre-cardiopulmonary bypass surgery, at paediatric intensive care unit admission, and at 6, 12, 24, 48 and 72 h after paediatric intensive care unit admission. The urinary strong ion difference was calculated. The median urinary chloride excretion decreased from 51 mmol/L pre-cardiopulmonary bypass to 25 mmol/L at paediatric intensive care unit admission, and increased from 24 h onwards. Patients with acute kidney injury had lower urinary chloride excretion than those without. The median urinary strong ion difference was 59 mmol/L pre-cardiopulmonary bypass, rose to 131 mmol/L at 24 h and fell to 20 mmol/L at 72 h. The plasma chloride rose from 105 mmol/L pre-cardiopulmonary bypass to a maximum of 109 mmol/L at 24 h. At 24 h the plasma chloride concentration was associated with the presence of acute kidney injury. There was no association between plasma or urinary amino acids and chloride excretion or kidney injury. In conclusion, renal chloride excretion decreased in all patients, although this decrease was more pronounced in patients with acute kidney injury. Our findings may reflect a response of the kidneys to critical illness, and acute kidney injury may make these changes more pronounced. Targeting chloride metabolism may offer treatment approaches to acute kidney injury.

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Congenital proximal renal tubular acidosis (pRTA) is a rare systemic disease caused by mutations in the SLC4A4 gene that encodes the electrogenic sodium bicarbonate cotransporter, NBCe1. The major NBCe1 protein variants are designated NBCe1-A, NBCe1-B, and NBCe1-C. NBCe1-A expression is kidney-specific, NBCe1-B is broadly expressed and is the only NBCe1 variant expressed in the heart, and NBCe1-C is a splice variant of NBCe1-B that is expressed in the brain. No cardiac manifestations have been reported from patients with pRTA, but studies in adult rats with virally induced reduction in cardiac NBCe1-B expression indicate that NBCe1-B loss leads to cardiac hypertrophy and prolonged QT intervals in rodents. NBCe1-null mice die shortly after weaning, so the consequence of congenital, global NBCe1 loss on the heart is unknown. To circumvent this issue, we characterized the cardiac function of NBCe1-B/C-null (KOb/c) mice that survive up to 2 months of age and which, due to the uninterrupted expression of NBCe1-A, do not exhibit the confounding acidemia of the globally null mice. In contrast to the viral knockdown model, cardiac hypertrophy was not present in KOb/c mice as assessed by heart-weight-to-body-weight ratios and cardiomyocyte cross-sectional area. However, echocardiographic analysis revealed reduced left ventricular ejection fraction, and intraventricular pressure-volume measurements demonstrated reduced load-independent contractility. We also observed increased QT length variation in KOb/c mice. Finally, using the calcium indicator Fura-2 AM, we observed a significant reduction in the amplitude of Ca2+ transients in paced KOb/c cardiomyocytes. These data indicate that congenital, global absence of NBCe1-B/C leads to impaired cardiac contractility and increased QT length variation in juvenile mice. It remains to be determined whether the cardiac phenotype in KOb/c mice is influenced by the absence of NBCe1-B/C from neuronal and endocrine tissues.

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This study investigated the effect of oral and topical sodium bicarbonate (SB) on soccer-specific performance during simulated soccer exercise. In a block randomized, double-blind, crossover design, 10 collegiate male soccer players (stature: 181.7 ± 3.2 cm, body mass: 81.7 ± 10.5 kg) performed soccer-specific performance tests (countermovement jumps, Illinois agility, 8 × 25 m repeated sprints) throughout a 90-min soccer-specific aerobic field test (SAFT90) following 0.3 g/kg body mass SB in capsules (SB-ORAL), 0.9036 g/kg body mass PR Lotion (SB-LOTION), or placebo capsules and lotion (PLA). Soccer-specific performance tests were conducted pre-SAFT90, during half-time and post-SAFT90. Blood samples were analyzed for acid-base balance (pH; bicarbonate, HCO3-) and strong ions (sodium, Na+; potassium, K+). Average sprint times were quicker for SB-ORAL than PLA during half-time (3.7%; p = .049; g = .57) and post-SAFT90 (4.9%; p = .041; g = .66). SB-ORAL increased pH and HCO3- prewarm-up and during half-time (p < .05), and lowered K+ during half-time (p = .035) compared with PLA. SB-LOTION increased pH (p = .019) and lowered K+ (p = .012) during half-time compared with PLA. SB-LOTION increased Na+ postexercise compared with PLA (p = .008). Repeated sprint times during simulated soccer exercise improved for SB-ORAL, which might have been mechanistically underpinned by elevated blood buffering capacity and greater regulation of strong ion concentration. Consuming SB in capsules is a more effective strategy than topical SB application for improving blood buffering capacity and repeated sprint performance throughout competitive soccer matches.

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SLC4A11 is the most abundant membrane transport protein in corneal endothelial cells. Its functional presence is necessary to support the endothelial fluid pump that draws fluid from the corneal stroma, preventing corneal edema. Several molecular actions have been proposed for SLC4A11 including H2O transport and cell adhesion. One of the most reproduced actions that SLC4A11 mediates is a H+ (or OH-) conductance that is enhanced in the presence of NH4Cl. The mechanism by which this occurs is controversial with some providing evidence in favor of NH3-H+ cotransport and others providing evidence for uncoupled H+ transport that is indirectly stimulated by the effects of NH4Cl upon intracellular pH and membrane potential. In the present study we provide new evidence and revisit previous studies, to support a model in which NH4Cl causes direct allosteric activation of SLC4A11 by means of an acidic shift in the intracellular pK (pKi) that governs the relationship between intracellular pH (pHi) and SLC4A11 H+-conductance. These findings have important implications for the assignment of a physiological role for SLC4A11.

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Numerous studies report on the influence of temperature on blood gases in ectothermic vertebrates, but there is merely a cursory understanding of these effects in developing animals. Animals that develop in eggs are at the mercy of environmental temperature and are expected to lack the capacity to regulate gas exchange and may regulate blood gases by means of altered conductance for gas exchange. We, therefore, devised a series of studies to characterize the developmental changes in blood gases when embryonic alligators were exposed to 25, 30 and 35 °C. To determine how blood parameters were impacted by changes in embryonic temperature, blood was sampled from the chorioallantoic membrane artery. The blood in the chorioallantoic membrane artery is a mixture of oxygen-poor and oxygen-rich blood, which based on the embryonic vascular anatomy may reflect blood that perfuses the chemoreceptors of the developing animal. Our findings indicate that following a 48 h exposure to 25 °C or 35 °C, there was a positive relationship between CAM artery blood PO2, PCO2 and glucose. However, blood pH suggests embryonic alligators lack an acute regulatory mechanism for adjusting blood pH.

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The environmental transport and fate of nanoscale zero-valent iron particles (nZVI) in soil and groundwater can be altered by their hetero-aggregation with clay mineral particles (CMP). This study examines the interactions between bare or carboxymethyl cellulose (CMC)-coated nZVI with typical CMP, specifically kaolinite and montmorillonite. Methods include co-settling experiments, aggregation kinetic studies, electron microscopy, Derjaguin-Landau-Verwey-Overbeek (DLVO) and extended DLVO (EDLVO) energy analysis, and density functional theory calculations, focusing on the pH dependency of these interactions. The EDLVO theory effectively described the interactions between nZVI and CMP in aquatic environments. Under acidic conditions (pH 3.5), the interfacial interaction between bare nZVI and kaolinite is regulated by van der Waals forces, while complexation, van der Waals forces, and electrostatic attraction govern the interaction of bare nZVI with montmorillonite, primarily depositing on the SiO face. In contrast, the positively charged AlO face and edge of CMP are the main deposition sites for CMC-coated nZVI through hydrogen bonding, van der Waals forces, and electrostatic attraction. At neutral (pH 6.5) and alkaline (pH 9.5) conditions, both bare and CMC-coated nZVI predominantly attach to the AlO face and edge, facilitated by complexation or hydrogen bonding, alongside van der Waals forces. The attachment of CMC-coated nZVI to CMP surfaces shows reversible aggregation or deposition due to the steric repulsion from the CMC coating. These findings hold significant implications for the environmental applications and risk of nZVI.

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The electrochemical conversion of CO2 into valuable chemicals using renewable electricity shows significant promise for achieving carbon neutrality and providing alternative energy storage solutions. However, its practical application still faces significant challenges, including high energy consumption, poor selectivity, and limited stability. Here, we propose a hybrid acid/alkali electrolyzer that couples the acidic CO2 reduction reaction (CO2RR) at the cathode with alkaline methanol oxidation reaction (MOR) at the anode. This dual electro-synthesis cell is implemented by developing Bi nanosheets as cathode catalysts and oxide-decorated Cu2Se nanoflowers as anode catalysts, enabling high-efficiency electron utilization for formate production with over 180% coulombic efficiency and more than 90% selectivity for both CO2RR and MOR conversion. The hybrid acid/alkali CO2RR-MOR cell also demonstrates long-term stability exceeding 100 hours of continuous operation, delivers a formate partial current density of 130 mA cm-2 at a voltage of only 2.1 V, and significantly reduces electricity consumption compared to the traditional CO2 electrolysis system. This study illuminates an innovative electron-efficiency and energy-saving techniques for CO2 electrolysis, as well as the development of highly efficient electrocatalysts.

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BACKGROUND: Arterial blood gas evaluation is crucial for critically ill patients, as it provides essential information about acid-base metabolism and respiratory balance, but evaluation can be complex and time-consuming. Artificial intelligence can perform tasks that require human intelligence, and it is revolutionizing healthcare through technological advancements. AIM: This study aims to assess arterial blood gas evaluation using artificial intelligence algorithms. METHODS: The study included 21.541 retrospective arterial blood gas samples, categorized into 15 different classes by experts for evaluating acid-base metabolism status. Six machine learning algorithms were utilized; accuracy, balanced accuracy, sensitivity, specificity, precision, and F1 values of the models were determined; and ROC curves were drawn to assess areas under the curve for each class. Evaluation of which sample was estimated in which class was conducted using the confusion matrices of the models. RESULTS: The bagging classifier (BC) model achieved the highest balanced accuracy with 99.24%, whereas the XGBoost model reached the highest accuracy with 99.66%. The BC model shows 100% sensitivity for nine classes and 100% specificity for 10 classes, and the model correctly predicted 6438 of 6463 test samples and achieved an accuracy of 99.61%, with an area under the curve > 0.9 in all classes on a class basis. CONCLUSION: The machine learning models developed exhibited remarkable accuracy, sensitivity, and specificity in predicting the status of acid-base metabolism. However, implementing these models can aid clinicians, freeing up their time for more intricate tasks.

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INTRODUCTION: The hydrogen ion (H+) mobilization model has been previously shown to provide a quantitative description of intradialytic changes in blood bicarbonate (HCO3) concentration during hemodialysis (HD). The current study evaluated the accuracy of different methods for estimating the H+ mobilization parameter (Hm) from this model. METHODS: The study compared estimates of the H+ mobilization parameter using predialysis, hourly during the HD treatment, and postdialysis blood HCO3 concentrations (Hm-full2) with those determined using only predialysis and postdialysis blood HCO3 concentrations assuming steady state conditions (Hm-SS2) during the midweek treatment in 24 chronic HD patients treated thrice weekly. RESULTS: Estimated Hm-full2 values (0.163 ± 0.079 L/min [mean ± standard deviation]) were higher than, but not statistically different (p = 0.067) from, those of Hm-SS2 (0.152 ± 0.065 L/min); the values of Hm-full2 and Hm-SS2 were highly correlated with a correlation coefficient of 0.948 and a mean difference that was small (0.011 L/min). Further, the H+ mobilization parameter values calculated using only predialysis and postdialysis blood HCO3 concentrations during the first and third HD treatments of the week were not different from those calculated during the midweek treatment. CONCLUSIONS: The H+ mobilization model can be used to provide estimates of the H+ mobilization parameter without the need to measure hourly intradialytic blood HCO3 concentrations.

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In order to achieve the high adsorption and catalytic performance of CO2, the direct self-assembly of robust defect-engineered MOFs is a scarcely reported and challenging proposition. Herein, a highly robust nanoporous indium(III)-organic framework of {[In2(CPPDA)(H2O)3](NO3)·2DMF·3H2O}n (NUC-107) consisting of two kinds of inorganic units of chain-shaped [In(COO)2(H2O)]n and watery binuclear [In2(COO)4(H2O)8] was generated by regulating the growth environment. It is worth mentioning that [In2(COO)4(H2O)8] is very rare in terms of its richer associated water molecules, implying that defect-enriched metal ions in the activated host framework can serve as strong Lewis acid. Compared to reported skeleton of [In4(CPPDA)2(µ3-OH)2(DMF)(H2O)2]n (NUC-66) with tetranuclear clusters of [In4(µ3-OH)2(COO)10(DMF)(H2O)2] as nodes, the void volume of NUC-107 (50.7%) is slightly lower than the one of NUC-66 (52.8%). However, each In3+ ion in NUC-107 has an average of 1.5 coordinated small molecules (H2O), which far exceeds the average of 0.75 in NUC-66 (H2O and DMF). After thermal activation, NUC-107a characterizes the merits of unsaturated In3+ sites, free pyridine moieties, solvent-free nanochannels (10.2 × 15.7 Å2). Adsorption tests prove that the host framework of NUC-107a has a higher CO2 adsorption (113.2 cm3/g at 273 K and 64.8 cm3/g at 298 K) than NUC-66 (91.2 cm3/g at 273 K and 53.0 cm3/g at 298 K). Catalytic experiments confirmed that activated NUC-107a with the aid of n-Bu4NBr was capable of efficiently catalyzing the cycloaddition of CO2 with epoxides into corresponding cyclic carbonates under the mild conditions. Under the similar conditions of 0.10 mol% MOFs, 0.5 mol% n-Bu4NBr, 0.5 MP CO2, 60 °C and 3 h, compared with NUC-66a, the conversion of SO to SC catalyzed by NUC-107a increased by 21%. Hence, this work offers a valuable perspective that the in situ creation of robust defect-engineered MOFs can be realized by regulating the growth environment.

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Introduction: Hypervirulent Klebsiella pneumoniae (hvKp) and carbapenem-resistant K. pneumoniae (CR-Kp) are rapidly emerging as opportunistic pathogens that have a global impact leading to a significant increase in mortality rates among clinical patients. Anti-virulence strategies that target bacterial behavior, such as adhesion and biofilm formation, have been proposed as alternatives to biocidal antibiotic treatments to reduce the rapid emergence of bacterial resistance. The main objective of this study was to examine the efficacy of fatty acid-enriched extract (AWME3) derived from the fat of Black Soldier Fly larvae (Hermetia illucens) in fighting against biofilms of multi-drug resistant (MDR) and highly virulent Klebsiella pneumoniae (hvKp) pathogens. Additionally, the study also aimed to investigate the potential mechanisms underlying this effect. Methods: Crystal violet (CV) and ethidium bromide (EtBr) assays show how AWME3 affects the formation of mixed and mature biofilms by the KP ATCC BAA-2473, KPi1627, and KPM9 strains. AWME3 has shown exceptional efficacy in combating the hypermucoviscosity (HMV) virulent factors of KPi1627 and KPM9 strains when tested using the string assay. The rudimentary motility of MDR KPM9 and KP ATCC BAA-2473 strains was detected through swimming, swarming, and twitching assays. The cell wall membrane disturbances induced by AWME3 were detected by light and scanning electron microscopy and further validated by an increase in the bacterial cell wall permeability and Lewis acid-base/van der Waals characteristics of K. pneumoniae strains tested by MATS (microbial adhesion to solvents) method. Results: After being exposed to 0.5 MIC (0.125 mg/ml) of AWME3, a significant reduction in the rudimentary motility of MDR KPM9 and KP ATCC BAA-2473 strains, whereas the treated bacterial strains exhibited motility between 4.23 ± 0.25 and 4.47 ± 0.25 mm, while the non-treated control groups showed significantly higher motility ranging from 8.5 ± 0.5 to 10.5 ± 0.5 mm. Conclusion: In conclusion, this study demonstrates the exceptional capability of the natural AWME3 extract enriched with a unique combination of fatty acids to effectively eliminate the biofilms formed by the highly drug-resistant and highly virulent K. pneumoniae (hvKp) pathogens. Our results highlight the opportunity to control and minimize the rapid emergence of bacterial resistance through the treatment using AWME3 of biofilm-associated infections caused by hvKp and CRKp pathogens.

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Electrochemical sensing (ES) is crucial for improving data acquisition in wastewater treatment, but obtaining the signal for a low electroactive analyte is challenging. Here, we propose an electrochemical acid-base transport limitation (eABTL) principle for inertness-based sensing, offering a new insight into generating ES signals from an interfacial transport process rather than electron transfer. This principle enables potential ES application for various weak acids and bases (WABs) without reactions themselves. We established an eABTLP method for detecting orthophosphate in solutions as a proof of concept, demonstrating commendable accuracy and precision, and a wide detection range from 10 µM to over 300 mM. Endogenous interferences were identified using 23 weak acids, indicating no significant endogenous interfering factors in typical wastewaters. Of them, volatile fatty acids are the main interference, but their effect can be eliminated by adjusting pH above 6.0. Exogenous factors like anions, cations, ion strength, temperature, organic load, and dissolved oxygen were examined, and most of their effects can be ignored by maintaining consistent analytical procedures between calibration curve and sample. Furthermore, measurement of wastewater samples confirmed the applicability toward domestic wastewater and demonstrated its wide applicability when combined with digestion pretreatment. Given the merits of inertness-based sensing, the eABTL-based methods have the potential to be a crucial part of ES techniques for environmental and industrial monitoring.

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Sodium bicarbonate (SB) supplementation is an ergogenic strategy for athletes competing in high-intensity exercise, but the efficacy of SB for accelerating recovery from exercise and thus improving performance during repeated bouts of exercise is not fully understood. In a similar fashion to using SB as a pre-exercise buffer, it is possible accelerated restoration of blood pH and bicarbonate following an exercise bout mechanistically underpins the use of SB as a recovery aid. Physiological mechanisms contributing to beneficial effects for SB during repeated bout exercise could be more far-reaching however, as alterations in strong ion difference (SID) and attenuated cellular stress response might also contribute to accelerated recovery from exercise. From inspection of existing literature, ingestion of 0.3 g kg-1 body mass SB ~60-90 min pre-exercise seems to be the most common dosage strategy, but there is evidence emerging for the potential application of post-exercise supplementation timing, gradual SB doses throughout a competition day, or even ingestion during exercise. Based on this review of literature, an SB ingestion recovery framework is proposed to guide athletes and practitioners on the use of SB to enhance performance for multiple bouts of exercise.

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Objectives Neurosurgical patients often receive 0.9% normal saline (NS) during the perioperative period. Theoretically, a balanced salt solution (BSS) is better than 0.9% saline. We compared the effects of two different fluids on acid-base balance, renal function, and neurological outcome in patients who underwent clipping following subarachnoid hemorrhage from a ruptured intracranial aneurysm. Materials and Methods Patients in group NS ( n = 30) received 0.9% saline and group BSS ( N = 30) received BSS (Plasmalyte-A) in the perioperative period for 48 hours. Comparison of arterial pH, bicarbonate, and base deficit measured preoperatively, intraoperatively (first and second hour), and postoperatively (at 24 and 48 hours) was the primary outcome of the study. The secondary outcome compared serum electrolytes, renal function tests, urine neutrophil gelatinase-associated lipocalin (NGAL), serum cystatin C, and the neurological outcome using modified Rankin score (MRS) at discharge, 1, and 3 months. Results In group NS, significantly low pH at 1-hour intraoperative period was seen compared with group BSS (7.37 ± 0.06 vs. 7.40 ± 0.05, p = 0.024). The bicarbonate level in group NS was significantly lower and the base deficit was higher at second intraoperative hour (bicarbonate: 17.49 vs. 21.99 mEq/L, p = 0.001; base deficit: 6.41 mmol/L vs. 1.89 mmol/L, p = 0.003) and at 24 hours post-surgery (bicarbonate: 20.38 vs. 21.96 mEq/L, p = 0.012; base deficit: 3.56 mmol/L vs. 2.12 mmol/L, p = 0.034)). Serum creatinine was higher in group NS at 24 hours (0.66 vs. 0.52 mg/dL, p = 0.013) and 48 hours (0.62 vs. 0.53 mg/dL, p = 0.047). Serum urea, electrolytes, cystatin, urine NGAL, and MRS were comparable. Conclusion In neurosurgical patients undergoing clipping for ruptured intracranial aneurysm, using a BSS during the perioperative period is associated with a better acid-base and renal profile. However, the biomarkers of kidney injury and long-term outcomes were comparable.

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Improvement in drug solubility is a major challenge for developing pharmaceutical products. It was demonstrated earlier that aqueous solubilities of weakly basic drugs could be increased greatly by interaction with weak acids that would not form salts with the drugs, and the highly concentrated solutions thus produced converted to amorphous solids upon drying. The technique was called acid-base supersolubilization (ABS). The current investigation explored whether the ABS principle could also be applied to weakly acidic drugs. By taking flurbiprofen (pKa 4.09; free acid solubility 0.011 mg/mL) as the model weakly acidic drug and tromethamine, lysine, meglumine, and NaOH as bases, it was studied which of the bases would result in ABS. While in the presence of NaOH and tromethamine, flurbiprofen converted to salts having aqueous solubility of 11-19 mg/mL, the solubility increased to > 399 mg/mL with lysine and > 358 mg/mL with meglumine, producing supersolubilization. However, crystallization of lysine salt was observed with time, followed by some decrease in solubility after reaching maximum solubility with lysine. In contrast, the supersolubilization was maintained with meglumine, and no crystallization of meglumine salt was observed. Upon drying, flurbiprofen-meglumine solutions produced amorphous materials that dissolved rapidly and produced high drug concentrations in aqueous media. Thus, the ABS principle also applies to acidic drugs depending on the weak base used.

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We present a case of a young man with a new-onset supraventricular arrhythmia accompanied by polyuria and natriuresis with subsequent renal salt-wasting causing hypovolemic hyponatremia. Resolution of the electrolyte imbalance occurred only after successful atrial flutter ablation.

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Modern isothermal titration calorimetry instruments give great precision, but for comparable accuracy they require chemical calibration. For the heat factor, one recommended process is HCl into the weak base TRIS. In studying this reaction with a VP-ITC and two Nano-ITCs, we have encountered some problems, most importantly a titrant volume shortfall Δv ≈ 0.3 µL, which we attribute to diffusive loss of HCl in the syringe tip. This interpretation is supported by a mathematical treatment of the diffusion problem. The effect was discovered through a variable-v protocol, which thus should be used to properly allow for it in any reaction that similarly approaches completion. We also find that the effects from carbonate contamination and from OH- from weak base hydrolysis can be more significant that previously thought. To facilitate proper weighting in the least-squares fitting of data, we have estimated data variance functions from replicate data. All three instruments have low-signal precision of σ ≈ 1 µJ; titrant volume uncertainty is a factor of ∼2 larger for the Nano-ITCs than for the VP-ITC. The final heat factors remain uncertain by more than the ∼1 % precision of the instruments and are unduly sensitive to the HCl concentration.

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