BACKGROUND: Hyponatremia is a well-documented adverse effect of oxcarbazepine treatment, but no clinical trial has yet been conducted to explore any intervention for reducing the incidence of hyponatremia.
METHODS: This open-label trial evaluated the efficacy of add-on daily oral sodium chloride supplementation of 1-2 g/day for 12 weeks in reducing the incidence of hyponatremia in children receiving oxcarbazepine monotherapy aged 1-18 years. Apart from comparing the incidence of symptomatic and severe hyponatremia, serum and urine sodium levels, serum and urine osmolality, changes in behavior and cognition, and the number of participants with recurrence of seizures and requiring additional antiseizure medication (ASM) were also compared.
RESULTS: A total of 120 children (60 in each group) were enrolled. The serum sodium level at 12 weeks in the intervention group was higher than that of the control group (136.5 ± 2.6 vs 135.4 ± 2.5 mEq/L, p = 0.01). The number of patients with hyponatremia was significantly lower in the intervention group (4/60vs14/60, p = 0.01). However, the incidence of symptomatic and severe hyponatremia (0/60vs1/60, p = 0.67 for both), changes in social quotient and child behavior checklist total score (0.6 ± 0.8 vs 0.7 ± 0.5, p = 0.41 and 0.9 ± 1.2 vs 1.1 ± 0.9, p = 0.30 respectively), the number of patients with breakthrough seizures (9/60vs10/60, p = 0.89), and the number of patients requiring additional ASMs (8/60vs10/60, p = 0.79) were comparable in both groups.
CONCLUSIONS: Daily oral sodium chloride supplementation is safe and efficacious in reducing the incidence of hyponatremia in children with epilepsy receiving oxcarbazepine monotherapy. However, sodium chloride supplementation does not significantly reduce more clinically meaningful outcome measures like symptomatic and severe hyponatremia. Trial registry No. CTRI/2021/12/038388.

Bromide is the first effective antiseizure medication used in human medicine since the XIX century. Initially met with skepticism, bromide quickly gained enthusiasm within the medical field until being largely replaced by newer antiseizure medications with significantly fewer adverse effects in people. In veterinary medicine, bromide continues to be used in the management of epileptic patients for over 30 years, yet adverse effects can impact owners and patients alike. We sought to provide the general practitioner and veterinary neurologist with insightful information on both the positive and negative attributes of bromide, explore factors that may influence its desirability as an antiseizure medication in specific veterinary cases and elucidate its current role in modern epilepsy treatment for veterinary patients. It\'s also our endeavor to discuss the current use as an alternative or add-on with other known antiseizure medications and potential future studies that might enhance our understanding and use of this medication.

Auxin response factors (ARFs), as the main components of auxin signaling, play a crucial role in various processes of plant growth and development, as well as in stress response. So far, there have been no reports on the genome-wide identification of the ARF transcription factor family in Cyclocarya paliurus, a deciduous tree plant in the family Juglaceae. In this study, a total of 34 CpARF genes were identified based on whole genome sequence, and they were unevenly distributed on 16 chromosomes, with the highest distribution on chromosome 6. Domain analysis of CpARF proteins displayed that 31 out of 34 CpARF proteins contain a typical B3 domain (DBD domain), except CpARF12/ CpARF14/CpARF31, which all belong to Class VI. And 20 CpARFs (58.8%) contain an auxin_IAA binding domain, and are mainly distributed in classes I, and VI. Phylogenetic analysis showed that CpARF was divided into six classes (I-VI), each containing 4, 4, 1, 8, 4, and 13 members, respectively. Gene duplication analysis showed that there are 14 segmental duplications and zero tandem repeats were identified in the CpARF gene family of the C. paliurus genome. The Ka/Ks ratio of duplicate gene pairs indicates that CpARF genes are subjected to strong purification selection pressure. Synteny analysis showed that C. paliurus shared the highest homology in 74 ARF gene pairs with Juglans regia, followed by 73, 51, 25, and 11 homologous gene pairs with Populus trichocarpa, Juglans cathayensis, Arabidopsis, and rice, respectively. Promoter analysis revealed that 34 CpARF genes had cis-elements related to hormones, stress, light, and growth and development except for CpARF12. The expression profile analysis showed that almost all CpARF genes were differentially expressed in at least one tissue, and several CpARF genes displayed tissue-specific expression. Furthermore, 24 out of the 34 CpARF genes have significantly response to drought stress (P < 0.05), and most of them (16) being significantly down-regulated under moderate drought treatment. Meanwhile, the majority of CpARF genes (28) have significantly response to drought stress (P < 0.05), and most of them (26) are significantly down-regulated under severe drought treatment. Furthermore, 32 out of the 34 CpARF genes have significantly response to high, middle, and low salt stress under salt treatment (P < 0.05). Additionally, subcellular localization analysis confirmed that CpARF16 and CpARF32 were all localized to nucleus. Thus, our findings expand the understanding of the function of CpARF genes and provide a basis for further functional studies on CpARF genes in C. paliurus.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s12298-024-01474-1.

BACKGROUND: Environmental stresses, including high salinity and drought, severely diminish wheat yield and quality globally. The xyloglucan endotransglucosylase/hydrolase (XTH) family represents a class of cell wall-modifying enzymes and plays important roles in plants growth, development and stress adaptation. However, systematic analyses of XTH family genes and their functions under salt and drought stresses have not been undertaken in wheat.
RESULTS: In this study, we identified a total of 135 XTH genes in wheat, which were clustered into three evolutionary groups. These TaXTHs were unevenly distributed on 21 chromosomes of wheat with a majority of TaXTHs located on homelogous groups 2, 3 and 7. Gene duplication analysis revealed that segmental and tandem duplication were the main reasons for the expansion of XTH family in wheat. Interaction network predictions indicated that TaXTHs could interact with multiple proteins, including three kinases, one methyltransferase and one gibberellin-regulated protein. The promoters of the TaXTH genes harbored various cis-acting elements related to stress and hormone responses. RNA-seq data analyses showed that some TaXTH genes were induced by salt and drought stresses. Furthermore, we verified that TaXTH17 was induced by abiotic stresses and phytohormone treatments, and demonstrated that TaXTH17 was localized in the secretory pathway and cell wall. Functional analyses conducted in heterologous expression systems and in wheat established that TaXTH17 plays a negative role in plant resistance to salt and drought.
CONCLUSIONS: We identified 135 XTH genes in wheat and conducted comprehensive analyses of their phylogenetic relationships, gene structures, conserved motifs, gene duplication events, chromosome locations, interaction networks, cis-acting elements and gene expression patterns. Furthermore, we provided solid evidence supporting the notion that TaXTH17 plays a negative role in plant resistance to salt and drought stresses. Collectively, our results provide valuable insights into understanding wheat XTHs, particularly their involvement in plant stress responses, and establish a foundation for further functional and mechanistic studies of TaXTHs.

The structures of three multicomponent crystals formed with imidazole-based drugs, namely metronidazole, ketoconazole and miconazole, in conjunction with trithiocyanuric acid are characterized. Each of the obtained adducts represents a different category of crystalline molecular forms: a cocrystal, a salt and a cocrystal of salt. The structural analysis revealed that in all cases, the N-H...N hydrogen bond is responsible for the formation of acid-base pairs, regardless of whether proton transfer occurs or not, and these molecular pairs are combined to form unique supramolecular motifs by centrosymmetric N-H...S interactions between acid molecules. The complex intermolecular forces acting in characteristic patterns are discussed from the geometric and energetic perspectives, involving Hirshfeld surface analysis, pairwise energy estimation, and natural bond orbital calculations.

The E-proteinoid 3 receptor (PTGER3), a member of the prostaglandin E2 (PGE2) subtype receptor, belongs to the G-protein-coupled superfamily of receptors. Animal studies have demonstrated its involvement in salt sensitivity by regulating sodium reabsorption. This study aimed to investigate the association between genetic variants of PTGER3 and salt sensitivity, longitudinal blood pressure (BP) changes, and the incidence of hypertension in Chinese adults. A chronic salt intake intervention was conducted involving 514 adults from 124 families in the 2004 Baoji Salt-Sensitivity Study Cohort in northern China. These participants followed a 3-day regular baseline diet, followed by a 7-day low-salt diet (3.0 g/d) and a 7-day high-salt diet (18 g/d), and were subsequently followed for 14 years. The findings revealed a significant relationship between the single nucleotide polymorphism (SNP) rs17482751 of PTGER3 and diastolic blood pressure (DBP) response to high salt intervention. Additionally, SNPs rs11209733, rs3765894, and rs2268062 were significantly associated with longitudinal changes in systolic blood pressure (SBP), DBP, and mean arterial pressure (MAP) during the 14-year follow-up period. SNP rs6424414 was significantly associated with longitudinal changes in DBP over 14 years. Finally, SNP rs17482751 showed a significant correlation with the incidence of hypertension over 14 years. These results emphasize the significant role of PTGER3 gene polymorphism in salt sensitivity, longitudinal BP changes, and the development of hypertension in the Chinese population.

BACKGROUND: Salt intake in CKD patients can affect cardiovascular risk and kidney disease progression. Twenty-four hour (24h) urine collections are often used to investigate salt metabolism but are cumbersome to perform. We assessed urinary sodium (U-Na) concentration in spot urine samples and investigated the correlation with 24h U-Na excretion and concentration in CKD patients under nephrological care. Further, we studied the role of CKD stage and diuretics and evaluated the performance of commonly used formulas for the prediction of 24h U-Na excretion from spot urine samples.
METHODS: One hundred eight patients of the German Chronic Kidney Disease (GCKD) study were included. Each participant collected a 24h urine and two spot urine samples within the same period. The first spot urine sample (AM) was part of the second morning urine. The second urine sample was collected before dinner (PM). Patients were advised to take their medication as usual without changing dietary habits. U-Na concentrations in the two spot urine samples and their average ((AM + PM)/2) were correlated with U-Na concentration and total Na excretion in the 24h urine collections. Correlations were subsequently studied after stratification by CKD stage and diuretic intake. The usefulness of three commonly applied equations to estimate 24h U-Na excretion from spot urine samples (Kawasaki, Tanaka and Intersalt) was determined using Bland-Altman plots, analyses of sensitivity, specificity, as well as positive (PPV) and negative predictive values (NPV).
RESULTS: Participants (42 women, 66 men) were on average (± SD) 62.2 (± 11.9) years old, with a mean serum creatinine of 1.6 (± 0.5) mg/dl. 95% had arterial hypertension, 37% diabetes mellitus and 55% were on diuretics. The best correlation with 24h U-Na total excretion was found for the PM spot U-Na sample. We also found strong correlations when comparing spot and 24h urine U-Na concentration. Correction of spot U-Na for U-creatinine did not improve strength of correlations. Neither CKD stage, nor intake of diuretics had significant impact on these correlations. All examined formulas revealed a significant mean bias. The lowest mean bias and the strongest correlation between estimated and measured U-Na excretion in 24h were obtained using the Tanaka-formula. Also, application of the Tanaka-formula with PM U-Na provided best sensitivity, specificity, PPV and NPV to estimate U-Na excretion > 4g/d corresponding to a salt consumption > 10g/d.
CONCLUSIONS: U-Na concentration of spot urine samples correlated with 24h U-Na excretion especially when PM spot U-Na was used. However, correlation coefficients were relatively low. Neither CKD stage nor intake of diuretics appeared to have an influence on these correlations. There was a significant bias for all tested formulas with the Tanaka-formula providing the strongest correlation with measured 24h U-Na excretion. In summary, using spot urine samples together with the Tanaka-formula in epidemiological studies appears feasible to determine associations between approximate salt intake and outcomes in CKD patients. However, the usefulness of spot-urine samples to guide and monitor salt consumption in individual patients remains limited.

This study examined the association between salt-related knowledge, attitudes, and behaviors (KAB) and salt excretion using the 24-hour (24 h) urinary collection method. Data were utilized from the Community-Based Management of Non-Communicable Diseases in Nepal (COBIN) Salt Survey, a community-based cross-sectional study conducted among a sub-sample of COBIN cohort in Pokhara Metropolitan City, Western Nepal, from July to December 2018, among adults aged 25-70 years. A total of 451 adults participated in the study, and a single 24 h urine sample was collected from each participant. The mean [(standard deviation (SD)] age of the participants was 49.6 (9.82) years, and the majority were female (65%). The mean urinary salt excretion was 13.28 (SD: 4.72) g/day, with 98% of participants consuming ≥5 g of salt/day. Although 83% of participants knew the risks of high salt intake and 87% believed it was important to reduce their intake, only 10% reported doing so. Salt-related attitude i.e., self-perceived salt intake was significantly associated with urinary salt excretion, adding extra salt to food, consuming processed foods, and taking actions to salt control. Participants who perceived themselves as consuming high salt had higher urinary salt excretion [(14.42 g/day; 95% confidence interval (95% CI): 13.45, 15.39, p = 0.03)], were more likely to add extra [(Odds ratio (OR) = 3.59; 95% CI: 2.03, 6.33, p < 0.001)], and consume processed foods more often (OR = 1.90; 95% CI: 1.06, 3.40, p < 0.05) compared to those who self-perceived consuming a normal amount of salt. Conversely, participants who perceived themselves as consuming low salt were more likely to take actions to control salt intake (OR = 4.22; 95% CI: 1.90, 9.37, p < 0.001) compared to their counterparts who perceived consuming a normal amount of salt. There existed a gap between salt-related knowledge, attitudes, and actual behaviors, resulting in a high salt intake among the Nepalese population. Nepal urgently requires tailored national salt reduction programs that comprise both policy and community-level interventions to achieve a 30% reduction in mean population salt intake by 2025. Further validation studies are needed to assess the effectiveness of community-based intervention in Nepal.

BACKGROUND: For decades standard teaching recommended salt intake (sodium) reduction in patients suffering from heart failure. Neurohumoral activation with subsequent fluid retention provided a solid rationale for this long-standing recommendation. Until recently no large randomized clinical trial of sodium restriction was available, while some observational studies and metanalyses even suggested a worse outcome with strict sodium restriction in patients with heart failure.
METHODS: In this narrative review we aimed to extricate from the literature whether strict sodium restriction is beneficial in patients with heart failure. We searched PubMed indexed articles between 2000 and 2023 for these terms: heart failure, salt, sodium, fluid intake.
RESULTS: Most randomized trials were small and showed a wide heterogeneity of interventions. A single large, randomized clinical trial was stopped early due to futility. Overall, there is no evidence that severe sodium restriction reduces the incidence of mortality and hospitalization in patients with heart failure. Quality of life and functional class may improve slightly with sodium restriction.
CONCLUSIONS: Morbidity and mortality are not reduced with sodium restriction in patients with heart failure, although some symptomatic improvement may be expected.

Drought and salinity are two abiotic stresses that affect plant productivity. We exposed 2-year-old Platycladus orientalis saplings to single and combined stress of drought and salinity. Subsequently, the responses of physiological traits and soil properties were investigated. Biochemical traits such as leaf and root phytohormone content significantly increased under most stress conditions. Single drought stress resulted in significantly decreased nonstructural carbohydrate (NSC) content in stems and roots, while single salt stress and combined stress resulted in diverse response of NSC content. Xylem water potential of P. orientalis decreased significantly under both single drought and single salt stress, as well as the combined stress. Under the combined stress of drought and severe salt, xylem hydraulic conductivity significantly decreased while NSC content was unaffected, demonstrating that the risk of xylem hydraulic failure may be greater than carbon starvation. The tracheid lumen diameter and the tracheid double wall thickness of root and stem xylem was hardly affected by any stress, except for the stem tracheid lumen diameter, which was significantly increased under the combined stress. Soil ammonium nitrogen, nitrate nitrogen and available potassium content was only significantly affected by single salt stress, while soil available phosphorus content was not affected by any stress. Single drought stress had a stronger effect on the alpha diversity of rhizobacteria communities, and single salt stress had a stronger effect on soil nutrient availability, while combined stress showed relatively limited effect on these soil properties. Regarding physiological traits, responses of P. orientalis saplings under single and combined stress of drought and salt were diverse, and effects of combined stress could not be directly extrapolated from any single stress. Compared to single stress, the effect of combined stress on phytohormone content and hydraulic traits was negative to P. orientalis saplings, while the combined stress offset the negative effects of single drought stress on NSC content. Our study provided more comprehensive information on the response of the physiological traits and soil properties of P. orientalis saplings under single and combined stress of drought and salt, which would be helpful to understand the adapting mechanism of woody plants to abiotic stress.