Sodium-glucose cotranspor ter 2 (SGLT2) inhibitors in nephrolithiasis: should we "gliflozin" patients with kidney stone disease? / Inibidores de cotransportadores sódio-glicose-2 (SGLT2) na nefrolitíase - devemos "gliflozinar" os litiásicos?

ABSTRACT The prevalence of nephrolithiasis is increasing worldwide. Despite advances in understanding the pathogenesis of lithiasis, few studies have demonstrated that specific clinical interventions reduce the recurrence of nephrolithiasis. The aim of this review is to analyze the current data and potential effects of iSGLT2 in lithogenesis and try to answer the question: Should we also "gliflozin" our patients with kidney stone disease?

RESUMO A prevalência da nefrolitíase está aumentando em todo o mundo. Apesar dos avanços na compreensão da patogênese da doença litiásica, poucos estudos demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. O objetivo desta revisão é analisar os dados atuais e efeitos potenciais dos iSGLT2 na doença litiásica e tentar responder à pergunta: devemos também "gliflozinar" os litiásicos?

Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia.

BACKGROUND: Patients with chronic heart failure (CHF) frequently develop hyperuricemia, an elevated serum uric acid level, associated with adverse outcomes. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction (HFrEF), irrespective of diabetes. However, dapagliflozin's effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear. AIM: To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 200 patients with CHF and hyperuricemia, with HFrEF and serum uric acid levels ≥ 7 mg/dL (≥ 416 µmol/L). The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months. The primary endpoint was the change in serum uric acid level from baseline to 24 months. Secondary endpoints included changes in left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and quality of life (QoL) scores, as well as the incidence of cardiovascular death and hospitalization for heart failure. RESULTS: At 24 months, dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL (71 µmol/L) compared with placebo (95%CI: -1.5 to -0.9; P < 0.001). Dapagliflozin also significantly improved LVEF by 3.5% (95%CI: 2.1-4.9; P < 0.001), NT-proBNP by 25% (95%CI: 18-32; P < 0.001), and QoL scores by 10 points (95%CI: 7-13; P < 0.001) and reduced the risk of cardiovascular death and hospitalization for heart failure by 35% (95%CI: 15-50; P = 0.002) compared with the placebo. Adverse events were similar between the two groups, except for a higher rate of genital infections in the dapagliflozin group (10% vs 2%, P = 0.01). CONCLUSION: Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia. Therefore, dapagliflozin may be a useful therapeutic option for this high-risk population.

Therapeutic efficacy of methylprednisolone sodium succinate via diverse administration routes for mid- to high-frequency sudden sensorineural hearing loss.

BACKGROUND: Sudden sensorineural hearing loss (SSNHL), characterized by a rapid and unexplained loss of hearing, particularly at moderate to high frequencies, presents a significant clinical challenge. The therapeutic use of methylprednisolone sodium succinate (MPSS) via different administration routes, in combination with conventional medications, remains a topic of interest. AIM: To compare the therapeutic efficacy of MPSS administered via different routes in combination with conventional drugs for the treatment of mid- to high-frequency SSNHL. METHODS: The medical records of 109 patients with mid- to high-frequency SSNHL were analyzed. The patients were divided into three groups based on the route of administration: Group A [intratympanic (IT) injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection], Group B (intravenous injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection), and Group C (single IT injection of MPSS). The intervention effects were compared and analyzed. RESULTS: The posttreatment auditory thresholds in Group A (21.23 ± 3 .34) were significantly lower than those in Groups B (28.52 ± 3.36) and C (30.23 ± 4.21; P < 0.05). Group A also exhibited a significantly greater speech recognition rate (92.23 ± 5.34) than Groups B and C. The disappearance time of tinnitus, time to hearing recovery, and disappearance time of vertigo in Group A were significantly shorter than those in Groups B and C (P < 0.05). The total effective rate in Group A (97.56%) was significantly greater than that in Groups B and C (77.14% and 78.79%, χ 2 = 7.898, P = 0.019). Moreover, the incidence of adverse reactions in Groups A and C was significantly lower than that in Group B (4.88%, 3.03% vs 2.57%, χ 2 = 11.443, P = 0.003), and the recurrence rate in Group A was significantly lower than that in Groups B and C (2.44% vs 20.00% vs 21.21%, χ 2 = 7.120, P = 0.028). CONCLUSION: IT injection of MPSS combined with conventional treatment demonstrates superior efficacy and safety compared to systemic administration via intravenous infusion and a single IT injection of MPSS. This approach effectively improves patients' hearing and reduces the risk of disease recurrence.

New perspectives in the management of diabetic nephropathy.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease and is also associated with increased risk for cardiovascular events. Until recently, strict glycemic control and blockade of the renin-angiotensin system (RAS) constituted the mainstay of treatment of DN. However, randomized controlled trials showed that sodium-glucose cotransporter 2 inhibitors further reduce the progression of DN. Therefore, these agents are recommended in all patients with DN regardless of DN stage and HbA1c levels. Moreover, additional blockade of the RAS with finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, was also shown to prevent both the decline of renal function and cardiovascular events in this population. Finally, promising preliminary findings suggest that glucagon-like peptide 1 receptor agonists might also exert reno- and cardioprotective effects in patients with DN. Hopefully, this knowledge will improve the outcomes of this high-risk group of patients.

Efficacy of recombinant human epidermal growth factor plus sodium hyaluronate eye drops in diabetic dry eye post-cataract surgery.

BACKGROUND: Dry eye syndrome (DES) after diabetic cataract surgery can seriously affect the patient's quality of life. Therefore, effective alleviation of symptoms in patients with this disease has important clinical significance. AIM: To explore the clinical effect of recombinant human epidermal growth factor (rhEGF) plus sodium hyaluronate (SH) eye drops on DES after cataract surgery in patients with diabetes. METHODS: We retrospectively evaluated 82 patients with diabetes who experienced DES after cataract surgery at Tianjin Beichen Hospital, Affiliated Hospital of Nankai University between April 2021 and April 2023. They were classified into an observation group (42 cases, rhEGF + SH eye drops) and a control group (40 cases, SH eye drops alone), depending on the different treatment schemes. The thera-peutic efficacy, dry eye symptom score, tear film breakup time (TFBUT), basic tear secretion score [assessed using Schirmer I test (SIt)], corneal fluorescein staining (FL) score, tear inflammatory markers, adverse reactions during treatment, and treatment satisfaction were compared between the two groups. RESULTS: Therapeutic efficacy was higher in the observation group compared with the control group. Both groups showed improved TFBUT and dry eye, as well as improved SIt and FL scores after treatment, with a more pronounced improvement in the observation group. Although no marked differences in adverse reactions were observed between the two groups, treatment satisfaction was higher in the observation group. CONCLUSION: rhEGF + SH eye drops rendered clinical benefits to patients by effectively ameliorating dry eye and visual impairment with favorable efficacy, fewer adverse reactions, and high safety levels. Thus, this treatment should be promoted in clinical practice.

Influence of sodium/glucose cotransporter-2 inhibitors on the incidence of acute kidney injury: a meta-analysis.

Background: Sodium/glucose cotransporter-2 inhibitors (SGLT2i) are associated with cardiovascular benefits. The aim of this systematic review and meta-analysis is to summarize the influence of SGLT2i on the incidence of acute kidney injury (AKI), and to ascertain whether it is affected by confounding variables such as age, baseline renal function and concurrent use of renin-angiotensin-aldosterone system inhibitors (RAASi) or mineralocorticoid receptor antagonists (MRA). Methods: PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials comparing the influence of SGLT2i versus placebo/blank treatment on AKI in the adult population. A fixed-effect model was used if the heterogeneity was not significant; otherwise, a randomized-effect model was used. Results: Eighteen studies comprising 98,989 patients were included. Compared with placebo/blank treatment, treatment with SGLT2i significantly reduced the risk of AKI (risk ratio [RR]: 0.78, 95% confidence interval [CI]: 0.71 to 0.84, p < 0.001; I 2 = 0%). Subgroup analysis suggested consistent results in patients with diabetes, chronic kidney disease, and heart failure (for subgroup difference, p = 0.32). Finally, univariate meta-regression suggested that the influence of SGLT2i on the risk of AKI was not significantly modified by variables such as age (coefficient: 0.011, p = 0.39), baseline estimated glomerular filtration rate (coefficient: -0.0042, p = 0.13) or concomitant use of RAASi (coefficient: 0.0041, p = 0.49) or MRA (coefficient: -0.0020, p = 0.34). Conclusion: SGLT2i may be effective in reducing the risk of AKI, and the effect might not be modified by age, baseline renal function and concurrent use of RAASi or MRA.

Induced genetic diversity through mutagenesis in wheat gene pool and significant use of SCoT markers to underpin key agronomic traits.

BACKGROUND: This research explores the efficacy of mutagenesis, specifically using sodium azide (SA) and hydrazine hydrate (HZ) treatments, to introduce genetic diversity and enhance traits in three wheat (Triticum aestivum L.) genotypes. The experiment entails subjecting the seeds to different doses of SA and HZ and cultivating them in the field for two consecutive generations: M1 (first generation) and M2 (second generation). We then employed selective breeding techniques with Start Codon Targeted (SCoT) markers to select traits within the wheat gene pool. Also, the correlation between SCoT markers and specific agronomic traits provides insights into the genetic mechanisms underlying mutagenesis-induced changes in wheat. RESULTS: In the study, eleven genotypes were derived from parent varieties Sids1, Sids12, and Giza 168, and eight mutant genotypes were selected from the M1 generation and further cultivated to establish the M2 generation. The results revealed that various morphological and agronomical characteristics, such as plant height, spikes per plant, spike length, spikelet per spike, grains per spikelet, and 100-grain weight, showed increases in different genotypes from M1 to M2. SCoT markers were employed to assess genetic diversity among the eleven genotypes. The bioinformatics analysis identified a correlation between SCoT markers and the transcription factors ABSCISIC ACID INSENSITIVE3 (ABI3) and VIVIPAROUS1 (VP1), crucial for plant development, growth, and stress adaptation. A comprehensive examination of genetic distance and the function identification of gene-associated SCoT markers may provide valuable insights into the mechanisms by which SA and HZ act as mutagens, enhancing wheat agronomic qualities. CONCLUSIONS: This study demonstrates the effective use of SA and HZ treatments to induce gene diversity through mutagenesis in the wheat gene pool, resulting in the enhancement of agronomic traits, as revealed by SCoT markers. The significant improvements in morphological and agronomical characteristics highlight the potential of mutagenesis techniques for crop improvement. These findings offer valuable information for breeders to develop effective breeding programs to enhance wheat quality and resilience through increased genetic diversity.

Prediction of the minimum amount of anti-adhesive agent required for entire intra-abdominal cavity using fluorescent dye.

PURPOSE: Studies on the appropriate amount of anti-adhesive agents for preventing postoperative adhesion are lacking. This animal study aimed to investigate the distribution of an anti-adhesive agent in the abdominal cavity and estimate the necessary amount to cover the entire cavity. METHODS: Fluorescent dye Flamma-552 was conjugated to Guardix-sol to create Guardix-Flamma, which was laparoscopically applied to the abdominal cavity of two 10-kg pigs in different amounts: 15 mL for G1 and 35 mL for G2. After 24 hours, the distribution of Guardix-Flamma was examined under the near-infrared mode of the laparoscope, and the thickness was measured in tissues from the omentum, small, and large intestine by immunohistochemistry. RESULTS: The average area of the abdominal cavity in 10 kg pigs was 2,755 cm2. Guardix-Flamma fluorescence was detected in the greater omentum, ascites in the pelvis, and right quadrant area in G1, whereas in G2, it was detected everywhere. On average, the total thickness of G1 and G2 were 12.68 ± 9.80 µm and 18.16 ± 15.57 µm, respectively. Guardix-Flamma thickness applied to the omentum, small, and large intestines of G2 were 1.31-, 1.45-, and 1.49-times thicker than those of G1, respectively, and were all statistically significant (P < 0.05). CONCLUSION: The entire abdominal cavity of the 10 kg pig was not evenly covered with 15 mL of Guardix. Although 35 mL of Guardix is sufficient to cover the same area with an average thickness of 18 µm, further studies should evaluate the minimum thickness required for an effective anti-adhesive function.

Optical perturbation of Agtr1a-containing neurons and afferents within the caudal nucleus of the solitary tract modulates sodium intake.

Angiotensin-II (Ang-II) production is driven by deviations in blood volume and osmolality, and serves the role of regulating blood pressure and fluid intake to maintain cardiovascular and hydromineral homeostasis. These actions are mediated by Ang-II acting on its type 1a receptor (AT1aR) within the central nervous system and periphery. Of relevance, AT1aR are expressed on sensory afferents responsible for conveying cardiovascular information to the nucleus of the solitary tract (NTS). We have previously determined that optical excitation of neurons and vagal afferents within the NTS that express AT1aR (referred to as NTSAT1aR) mimics the perception of increased vascular stretch and induces compensatory responses to restore blood pressure. Here, we test whether NTSAT1aR are also involved in the modulation of water and sodium intake. We directed the light-sensitive excitatory channelrhodopsin-2 (ChR2) or inhibitory halorhodopsin (Halo) to Agtr1a-containing neurons and measured water and sodium chloride (NaCl) intake in the presence and absence of optical stimulation within the NTS during various challenges to fluid homeostasis. Optical perturbation of NTSAT1aR modulates NaCl intake, such that excitation attenuates, whereas inhibition increases intake. This effect is only observed in the water-deprived condition, suggesting that NTSAT1aR are involved in the regulation of sodium intake during an imbalance in both the intracellular and extracellular fluid compartments. Furthermore, optical excitation of NTSAT1aR increases c-Fos expression within oxytocinergic neurons of the paraventricular nucleus of the hypothalamus (PVN), indicating that the regulation of sodium intake by NTSAT1aR may be mediated by oxytocin. Collectively, these results reveal that NTSAT1aR are sufficient and necessary to modulate sodium intake relative to perceived changes in vascular stretch.

Short Caco-2 model for evaluation of drug permeability: A sodium valerate-assisted approach.

The human colorectal adenocarcinoma cell line Caco-2, widely used for studying intestinal drug permeability, is typically grown on permeable filter supports and matures in 21 days with frequent media changes. The process is labor-intensive, prone to contamination, and has low throughput, contributing to the overall high utilization cost. Efforts to establish a low-cost, high-throughput, short-duration model have encountered obstacles, such as weaker tight junctions causing monolayer leaks, incomplete differentiation resulting in low transporter expression, intricate and challenging protocols, and cytotoxicity, limiting the usability. Hence, this study aimed to develop a low-cost, efficient, and short-duration model by addressing the aforementioned concerns by customizing the media and finding a safe differentiation inducer. We generated a new rapid model using sodium valerate, which demonstrated sufficient transporter activity, improved monolayer integrity, and higher levels of differentiation markers than the 21-day model. Furthermore, this model exhibited consistent and reliable results when used to evaluate drug permeability over multiple days of repeated use. This study demonstrates the potential of a sodium valerate-assisted abbreviated model for drug permeability assessment with economic and practical advantages.

Neuropilin-1 is a novel host factor modulating the entry of hepatitis B virus.

BACKGROUND & AIMS: Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for hepatitis B virus (HBV). However, hepatocytes expressing NTCP exhibit varying susceptibilities to HBV infection. This study aimed to investigate whether other host factors modulate the process of HBV infection. METHODS: Liver biopsy samples obtained from children with hepatitis B were used for single-cell sequencing and susceptibility analysis. Primary human hepatocytes, HepG2-NTCP cells, and human liver chimeric mice were used to analyze the effect of candidate host factors on HBV infection. RESULTS: Single-cell sequencing and susceptibility analysis revealed a positive correlation between neuropilin-1 (NRP1) expression and HBV infection. In the HBV-infected cell model, NRP1 overexpression before HBV inoculation significantly enhanced viral attachment and internalization, and promoted viral infection in the presence of NTCP. Mechanistic studies indicated that NRP1 formed a complex with LHBs and NTCP. The NRP1 b domain mediated its interaction with conserved arginine residues at positions 88 and 92 in the preS1 domain of the HBV envelope protein LHBs. This NRP1-preS1 interaction subsequently promoted the binding of preS1 to NTCP, facilitating viral infection. Moreover, disruption of the NRP1-preS1 interaction by the NRP1 antagonist EG00229 significantly attenuated the binding affinity between NTCP and preS1, thereby inhibiting HBV infection both in vitro and in vivo. CONCLUSIONS: Our findings indicate that NRP1 is a novel host factor for HBV infection, which interacts with preS1 and NTCP to modulate HBV entry into hepatocytes. IMPACT AND IMPLICATIONS: HBV infection is a global public health problem, but the understanding of the early infection process of HBV remains limited. Through single-cell sequencing, we identified a novel host factor, NRP1, which modulates HBV entry by interacting with HBV preS1 and NTCP. Moreover, antagonists targeting NRP1 can inhibit HBV infection both in vitro and in vivo. This study could further advance our comprehension of the early infection process of HBV.

Hypernatremia in hospitalised adult patients: A protocol for a scoping review.

BACKGROUND: Hypernatremia is a common electrolyte disturbance in hospitalised patients associated with adverse outcomes. The aetiology is diverse but often related to fluid therapy and sodium-containing medicaments. We aim to outline the evidence base on hypernatremia in adult hospitalised patients. METHODS: We will conduct a scoping review and adhere to the preferred reporting items for systematic and meta-analysis extension for scoping reviews (PRISMA-ScR). We will systematically search the Cochrane Library, Medline, Pubmed, and Embase from inception with no limitations to language, and include all study designs. We will use the population, exposure, comparator, and outcome-based approach to define eligibility criteria. The population: adult hospitalised patients; exposure: hypernatremia; comparator: no hypernatremia or all types of treatments of hypernatremia; and outcomes: all reported outcomes. Two authors will independently screen and select studies followed by full-text assessment and data extraction in duplicate. All outcome measures will be reported, and descriptive analyses will be performed. The certainty of evidence will be assessed according to an adapted grading of recommendations assessment, development, and evaluation (GRADE) approach. DISCUSSION: This scoping review will provide an overview of the current evidence regarding the incidence of hypernatremia, treatment modalities, and outcomes reported for hospitalised adult patients with hypernatremia.

The role of exercise training and dietary sodium restriction in heart failure rehabilitation: A systematic review.

Heart failure (HF) rehabilitation seeks to enhance the entire well-being and quality of life of those with HF by focusing on both physical and mental health. Non-pharmacological measures, particularly exercise training, and dietary salt reduction, are essential components of heart failure rehabilitation. This study examines the impact of these components on the recovery of patients with heart failure. By conducting a comprehensive analysis of research articles published from 2010 to 2024, we examined seven relevant studies collected from sources that include PubMed and Cochrane reviews. Our findings indicate that engaging in physical activity leads to favorable modifications in the heart, including improved heart contractility, vasodilation, and cardiac output. These alterations enhance the delivery of oxygen to the peripheral tissues and reduce symptoms of heart failure, such as fatigue and difficulty breathing. Nevertheless, decreasing the consumption of salt in one's diet to less than 1500 mg per day did not have a substantial impact on the frequency of hospitalizations, visits to the emergency room, or overall mortality when compared to conventional treatment. The combination of sodium restriction and exercise training can have synergistic effects due to their complementary modes of action. Exercise improves cardiovascular health and skeletal muscle metabolism, while sodium restriction increases fluid balance and activates neurohormonal pathways. Therefore, the simultaneous usage of both applications may result in more significant enhancements in HF symptoms and clinical outcomes compared to using each program alone.

Effects of Balanced Versus Saline-based Solutions on Acute Kidney Injury in Off-pump Coronary Artery Bypass Surgery: A Randomized Controlled Trial.

OBJECTIVES: To determine whether balanced solutions can reduce the incidence of acute kidney injury after off-pump coronary artery bypass surgery compared with saline. DESIGN: Randomized controlled trial. SETTING: Single tertiary care center. PARTICIPANTS: Patients who underwent off-pump coronary artery bypass surgery between June 2014 and July 2020. INTERVENTIONS: Balanced solution-based chloride-restrictive intravenous fluid strategy. MEASUREMENTS AND MAIN RESULTS: The primary outcome was acute kidney injury within 7 postoperative days, as defined by the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline. The incidence of acute kidney injury was 4.4% (8/180) in the balanced group and 7.3% (13/178) in the saline group. The difference was not statistically significant (risk difference, -2.86%; 95% confidence interval [CI], -7.72% to 2.01%; risk ratio, 0.61, 95% CI, 0.26 to 1.43; p = 0.35). Compared with the balanced group, the saline group had higher levels of intraoperative serum chloride and lower base excess, which resulted in a lower pH. CONCLUSIONS: In patients undergoing off-pump bypass surgery with a normal estimated glomerular filtration rate, the intraoperative balanced solution-based chloride-restrictive intravenous fluid administration strategy did not decrease the rate of postoperative acute kidney injury compared with the saline-based chloride-liberal intravenous fluid administration strategy.

A validated stability­indicating reversed­phase­UPLC method for simultaneous estimation of promethazine hydrochloride, methylparaben, propylparaben and sodium benzoate assay of cough suppressant and antihistamine liquid oral dosage forms.

A quick, simple, sensitive, efficient and stability-indicating reverse-phase ultraperformance liquid chromatographic method for the estimation of propylparaben, methylparaben and sodium benzoate in a pharmaceutical liquid oral formulation was developed. A Waters Acquity UPLC BEH C18, 50 × 2.1 mm, 1.7 µm i.d. column was used to perform chromatographic separation with a 0.1% perchloric acid mobile phase used as solvent A and a mixture of 0.1 % perchloric acid and methanol in the ratio 20:80 (v/v), respectively, as solvent B. The experiments were carried out at a flow rate of 0.4 ml/min and the detection wavelength was 240 nm. The compartment temperature of the column was set at 40°C and the injection volume was set at 2 µl. The main aim of the research was to develop a single UPLC assay method for promethazine (active ingredient) and preservatives in the oral solution of promethazine HCl and dextromethorphan HBr that contains promethazine (active ingredient) and methylparaben, propylparaben and sodium benzoate (preservatives). An assay of dextromethorphan HBr was developed and validated by another HPLC method. The drug and preservatives were eluted at retention times of 19.3 min for promethazine HCl, 9.3 min for methylparaben, 18.9 min for propylparaben and 8.9 min for sodium benzoate. Validation of the developed method was carried out as stated by the International Conference on Harmonization guidelines ICH Q2B and under USP<1225>. The analytical parameters verified specificity/selectivity, linearity, accuracy, ruggedness and robustness. The linearity ranges of promethazine HCL, methylparaben, propylparaben and sodium benzoate were 10-100, 10-80, 1.0-8.0 and 10-80 µg/ml, respectively, with a correlation coefficient of active ingredients and preservatives of 1.00. Percentage recoveries of promethazine, propylparaben, methylparaben, and sodium benzoate were 100.0-100.2, 99.0-100.3, 99.5-98.0 and 99.0-100.0%. The validated analytical method proves that the method is specific, precise, linear, accurate, sensitive, rugged and stable, indicating the quantification of the active ingredient and all preservatives in liquid oral formulations.

Safety and efficacy of a feed additive consisting of sodium ferrocyanide and potassium ferrocyanide for all animal species (Eusalt a.i.s.b.l.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of sodium ferrocyanide and potassium ferrocyanide as technological feed additives for all animal species. In its previous opinion on the safety and efficacy of the additives, the FEEDAP Panel concluded that the use of sodium ferrocyanide and potassium ferrocyanide is safe, when added to sodium chloride at a maximum content of 80 mg ferrocyanide anions (anhydrous)/kg for turkeys for fattening and laying hens and other laying/breeding birds, all porcine species and categories, all ruminant species and categories, rabbits, horses, salmonids and other minor fin fish, dogs and cats. However, the Panel could not conclude on the safety of the additives for chickens for fattening and other poultry species for fattening or reared for laying/breeding other than turkeys, and for all species/categories other than the above listed. In the current assessment, the applicant is proposing a maximum content of 60 mg ferrocyanide anions (anhydrous)/kg sodium chloride for chickens for fattening and other poultry species (except turkeys) for fattening or reared for laying/breeding and for all species/categories other than the listed above. The FEEDAP Panel concluded that sodium ferrocyanide and potassium ferrocyanide are safe at a maximum content of 80 mg ferrocyanide anions (anhydrous)/kg sodium chloride for: turkeys for fattening and reared for breeding, laying hens and other laying/breeding birds, all porcine species, all ruminant species, rabbits, equines, salmonids and minor fin fish, dogs and cats. The Panel concluded also that a maximum content of 60 mg ferrocyanide anions (anhydrous)/kg sodium chloride is safe for chickens for fattening and minor poultry species for fattening or reared for laying/breeding and all other animal species.

Design and Characterization of an Osmotic Pump System for Optimal Feeding and pH Control in E. coli Culture to Increase Biomass.

Background: Batch cultures used for various purposes, such as expression screening and recombinant protein production in laboratories, usually have some drawbacks due to the bolus addition of carbon sources, such as glucose and buffers, that lead to overflow metabolism, decreased pH, high osmolality, low biomass yield, and low protein production. Objectives: This study aimed to overcome the problems of batch culture using the controlled release concept by a controlled porosity osmotic pump (CPOP) system. Methods: The CPOP was formulated with glucose as a carbon source feeding and sodium carbonate as a pH modifier in the core of the tablet that was coated with a semipermeable membrane containing cellulose acetate and polyethylene glycol (PEG) 400. The release rate was regulated with Eudragit L100 as a retardant agent in the core and PEG 400 as a pore-former agent in the coating membrane. Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM) were used to elucidate compatibility between components and release mechanism, respectively. The in-vitro release of glucose and Na2CO3 studies were performed for 24 hours in a mineral culture medium (M9). Then, the effectiveness of CPOP in the growth of Escherichia coli (E. coli BL21) as a microorganism model was evaluated. Glucose consumption, changes in medium's pH, and acetate concentration as a by-product were also monitored during the bacterial growth. Results: Fourier-transform infrared spectroscopy confirmed the compatibility between the components in the osmotic pump, and SEM elucidated the release mechanism due to in-situ delivery pores created by dissolving soluble components (PEG 400) on the coated membrane upon contact with the dissolution medium. The in-vitro release studies indicated that the osmotic pump was able to deliver glucose and sodium carbonate in a zero-order manner. The use of CPOP in E. coli (BL21) cultivation resulted in a statistically significant improvement in biomass (over 80%), maintaining the pH of the medium (above 6.8) during the exponential phase, and reducing metabolic by-product formation (acetate), compared to bolus feeding (P < 0.05). Conclusions: The use of CPOP, which is capable of controlled release of glucose as a carbon source and sodium carbonate as a pH modifier, can overcome the drawbacks of bolus feeding, such as decreased pH, increased acetate concentration, and low productivity. It has a good potential for commercialization.

Comparison of Blood Gas Analysis and Auto-Analyzer Results for Sodium and Potassium Levels in Elderly and Non-elderly Adult Emergency Department Patients.

Objectives This study aims to evaluate the concordance between blood gas and biochemical measurement methods for sodium and potassium levels in elderly and non-elderly patients within an emergency department (ED) setting. Methods A retrospective method comparison study was conducted at an ED from February 1, 2023, to March 1, 2023. The study included 414 patients, categorized into "elderly" (aged 65 and above; n = 138, 33.3%) and "non-elderly" (aged 18 to 64; n = 276, 66.7%) groups. Concordance was assessed using Bland-Altman, Passing-Bablok, and Lin's concordance correlation methods. Results In sodium measurements, the elderly group exhibited an average bias of -1.52 mEq/L (95% confidence interval [CI] -2.12 to -0.92), with lower and upper limits of agreement (LoA) at -8.46 and 5.42 mEq/L, respectively, indicating a broader variance than non-elderly patients, who showed an average bias of -0.82 mEq/L with limits of -4.97 to 3.32 mEq/L. For potassium, the elderly group's average bias was -0.46 mEq/L (95% CI -0.36 to -0.57), with limits of agreement from -1.68 to 0.75 mEq/L, compared to non-elderly patients with a bias of -0.29 mEq/L and limits of -0.71 to 0.13 mEq/L. Furthermore, concordance correlation coefficients revealed a reduced agreement in the elderly for both sodium (r ccc = 0.799) and potassium (r ccc = 0.529) compared to the non-elderly cohort (sodium r ccc = 0.821, potassium r ccc = 0.715). Conclusion The study identifies significant discrepancies in sodium and potassium levels between elderly and non-elderly patients, suggesting a need for diagnostic precision. It emphasizes the importance of customizing diagnostic approaches to better serve the elderly population in EDs.

Entropy-Assisted Anion-Reinforced Solvation Structure for Fast-Charging Sodium-Ion Full Batteries.

Anion-reinforced solvation structure favors the formation of inorganic-rich robust electrode-electrolyte interface, which endows fast ion transport and high strength modulus to enable improved electrochemical performance. However, such a unique solvation structure inevitably injures the ionic conductivity of electrolytes and limits the fast-charging performance. Herein, a trade-off in tuning anion-reinforced solvation structure and high ionic conductivity is realized by the entropy-assisted hybrid ester-ether electrolyte. Anion-reinforced solvation sheath with more anions occupying the inner Na+ shell is constructed by introducing the weakly coordinated ether tetrahydrofuran into the commonly used ester-based electrolyte, which merits the accelerated desolvation energy and gradient inorganic-rich electrode-electrolyte interface. The improved ionic conductivity is attributed to the weakly diverse solvation structures induced by entropy effect. These enable the enhanced rate performance and cycling stability of Prussian blue||hard carbon full cells with high electrode mass loading. More importantly, the practical application of the designed electrolyte was further demonstrated by industry-level 18650 cylindrical cells.

Structural Engineering of Prussian Blue Analogues Enabling All-Climate and Ultralong Cycling Sodium-Ion Batteries.

The development of cost-efficient, long-lifespan, and all-climate sodium-ion batteries is of great importance for advancing large-scale energy storage but is plagued by the lack of suitable cathode materials. Here, we report low-cost Na-rich Mn-based Prussian blue analogues with superior rate capability and ultralong cycling stability over 10,000 cycles via structural optimization with electrochemically inert Ni atoms. Their thermal stability, all-climate properties, and potential in full cells are investigated in detail. Multiple in situ characterizations reveal that the outstanding performances benefit from their highly reversible three-phase transformations and trimetal (Mn-Ni-Fe) synergistic effects. In addition, a high sodium diffusion coefficient and a low volume distortion of 2.3% are observed through in situ transmission electron microscopy and first-principles calculations. Our results provide insights into the structural engineering of Prussian blue analogues for advanced sodium-ion batteries in large-scale energy storage applications.