Association of sodium-glucose cotransporter-2 inhibitors and the risk of retinal vascular occlusion: A real-world retrospective cohort study in Taiwan.

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are proposed to alleviate the development of inflammatory eye diseases. However, the association between SGLT2i and retinal vascular occlusion remains unclear. Therefore, this study aims to explore the effects of SGLT2i on the incidence of retinal vascular occlusion. MATERIALS AND METHODS: This retrospective cohort study analysed electronic medical records data from the largest multi-institutional database in Taiwan. Individuals who initiated SGLT2is and dipeptidyl peptidase 4 inhibitors (DPP4is) between 2016 and 2019 were included in our analysis. To conduct a homogenous comparison, inverse probability of treatment weighting with propensity scoring was employed. The primary outcome was retinal vascular occlusion, and the secondary outcomes were retinal vascular occlusion-related complications (macular oedema, vitreous haemorrhage, and tractional retinal detachment) and conditions requiring vitreoretinal intervention (intravitreal injection, retinal laser therapy, and vitrectomy). RESULTS: In total, 12,074 SGLT2i users and 39,318 DPP4i users were included. The incidence rate of retinal vascular occlusion in the SGLT2i and DPP4i groups was 1.2 (95% confidence interval [CI], 0.9-1.4) and 1.6 (95% CI, 1.3-1.8) events per 1000 person-years, respectively, which yielded a subdistribution hazard ratio (SHR) of 0.74 (95% CI, 0.55-0.99). Similar risk reductions were observed in the retinal vascular occlusion-related complications (SHR, 0.76; 95% CI, 0.69-0.84) and conditions requiring vitreoretinal intervention (SHR, 0.84; 95% CI, 0.77-0.94). CONCLUSIONS: In this multi-institutional study in Taiwan, SGLT2i use was associated with a reduced risk of retinal vascular occlusion. Further prospective studies are required to ascertain this association.

Changes in serum sodium concentration during hemodialysis is a predictor of mortality and cardio-cerebrovascular event.

BACKGROUND: Previous study consistently showed that lower serum sodium (SNa) was associated with a greater risk of mortality in hemodialysis (HD) patients. However, few studies have focused on the change in SNa (ΔSNa = post-HD SNa - pre-HD SNa) during an HD session. METHODS: In a retrospective cohort of maintenance HD adults, all-cause mortality and cardio-cerebrovascular event (CCVE) were followed up for a medium of 82 months. Baseline pre-HD SNa and ΔSNa were collected; time-averaged pre-HD SNa and ΔSNa were computed as the mean values within 1-year, 2-year and 3-year intervals after enrollment. Cox proportional hazards models were used to evaluate the relationships of pre-HD and ΔSNa with outcomes. RESULTS: Time-averaged pre-HD SNa were associated with all-cause mortality (2-year pre-HD SNa: HR [95% CI] 0.86 [0.74-0.99], p = 0.042) and CCVE (3-year pre-HD SNa: HR [95% CI] 0.83 [0.72-0.96], p = 0.012) with full adjustment. Time-averaged ΔSNa also demonstrated an association with all-cause mortality (3-year ΔSNa: HR [95% CI] 1.26 [1.03-1.55], p = 0.026) as well as with CCVE (3-year ΔSNa: HR [95% CI] 1.51 [1.21-1.88], p = <0.001) when fully adjusted. Baseline pre-HD SNa and ΔSNa didn't exhibit association with both outcomes. CONCLUSIONS: Lower time-averaged pre-HD SNa and higher time-averaged ΔSNa were associated with a greater risk of all-cause mortality and CCVE in HD patients.

A cross-sectional analysis of the PURE study on minerals intake among Malaysian adult population with hypertension.

Hypertension (HPT) is the leading modifiable risk factor for cardiovascular diseases and premature death worldwide. Currently, attention is given to various dietary approaches with a special focus on the role of micronutrient intake in the regulation of blood pressure. This study aims to measure the dietary intake of selected minerals among Malaysian adults and its association with HPT. This cross-sectional study involved 10,031 participants from the Prospective Urban and Rural Epidemiological study conducted in Malaysia. Participants were grouped into HPT if they reported having been diagnosed with high blood pressure [average systolic blood pressure (SBP)/average diastolic blood pressure (DBP) ≥ 140/90 mm Hg]. A validated food frequency questionnaire (FFQ) was used to measure participants' habitual dietary intake. The dietary mineral intake of calcium, copper, iron, magnesium, manganese, phosphorus, potassium, sodium, and zinc was measured. The chi-square test was used to assess differences in socio-demographic factors between HPT and non-HPT groups, while the Mann-Whitney U test was used to assess differences in dietary mineral intake between the groups. The participants' average dietary intake of calcium, copper, iron, magnesium, manganese, phosphorus, potassium, selenium, sodium, and zinc was 591.0 mg/day, 3.8 mg/day, 27.1 mg/day, 32.4 mg/day, 0.4 mg/day, 1431.1 mg/day, 2.3 g/day, 27.1 µg/day, 4526.7 mg/day and 1.5 mg/day, respectively. The intake was significantly lower among those with HPT than those without HPT except for calcium and manganese. Continuous education and intervention should be focused on decreasing sodium intake and increasing potassium, magnesium, manganese, zinc, and calcium intake for the general Malaysian population, particularly for the HPT patients.

Long-term safety of desmopressin orally disintegrating tablets in men with nocturia due to nocturnal polyuria: Interim results of a specified drug use-results survey in Japan.

OBJECTIVES: This interim report presents the 12-week results of a post-marketing surveillance evaluating the safety of desmopressin orally disintegrating tablets 25 and 50 µg in Japanese men with nocturia due to nocturnal polyuria. METHODS: Of the planned study population of 1000 Japanese men receiving desmopressin for the first time for nocturia due to nocturnal polyuria, 971 cases were enrolled. In this interim analysis, 9 cases, including 6 registry violations and 3 cases of unconfirmed desmopressin dosing, were excluded from the 354 case report forms collected and fixed by the end of December 2021, and data up to 12 weeks after administration in 345 cases were defined as the safety analysis set. RESULTS: The mean age was 74.5 ± 9.9 years and 88.7% of the survey participants were aged ≥65 years. Desmopressin was started at a dose of 25 µg in 153 cases (44.3%). There were 102 adverse drug reactions (ADRs) reported in 71 cases, including 6 serious ADRs in 3 cases (0.9%). The most common ADR was hyponatremia occurring in 29 cases (8.4%). Eight of the hyponatremic cases were asymptomatic. Symptoms were resolved or slightly improved within 4 weeks of onset in 13 of 29 cases of hyponatremia. In addition, hyponatremia occurred in 11 of 217 cases (5.1%), with a serum sodium level before the administration of desmopressin of ≥140 mmol/L, and in 13 of 87 cases (14.9%), with a level of 135-139 mmol/L, and was not measured in 5 hyponatremia cases. Patient characteristics that showed significant differences in the occurrence of hyponatremia included body weight, body mass index, renal function, and pretreatment serum sodium level. Regular monitoring of serum sodium is necessary for early detection of hyponatremia. CONCLUSIONS: Hyponatremia was the most common ADR when desmopressin orally disintegrating tablets were used to treat nocturia due to nocturnal polyuria over a 12-week period.

A subgroup of light-driven sodium pumps with an additional Schiff base counterion.

Light-driven sodium pumps (NaRs) are unique ion-transporting microbial rhodopsins. The major group of NaRs is characterized by an NDQ motif and has two aspartic acid residues in the central region essential for sodium transport. Here we identify a subgroup of the NDQ rhodopsins bearing an additional glutamic acid residue in the close vicinity to the retinal Schiff base. We thoroughly characterize a member of this subgroup, namely the protein ErNaR from Erythrobacter sp. HL-111 and show that the additional glutamic acid results in almost complete loss of pH sensitivity for sodium-pumping activity, which is in contrast to previously studied NaRs. ErNaR is capable of transporting sodium efficiently even at acidic pH levels. X-ray crystallography and single particle cryo-electron microscopy reveal that the additional glutamic acid residue mediates the connection between the other two Schiff base counterions and strongly interacts with the aspartic acid of the characteristic NDQ motif. Hence, it reduces its pKa. Our findings shed light on a subgroup of NaRs and might serve as a basis for their rational optimization for optogenetics.

Relationship between electrolytes and glycated hemoglobin among diabetic patients with poor adherence to antidiabetic medications: a cross-sectional study.

Introduction: type 2 Diabetes mellitus is a chronic metabolic disease with devastating effects on patients and results in numerous healthcare challenges in terms of its management and the cost burden among the affected. Successful management involves maintaining optimal glycemic control to prevent complications, with adherence to antidiabetic medications playing a crucial role in achieving this objective. Additionally, maintaining a healthy electrolyte balance is key for overall well-being and physiological function. However, the correlation between glycated hemoglobin and electrolyte balance remains under investigated, particularly in patients with suboptimal adherence. The aim of this research was to study the relationship between glycated hemoglobin and electrolytes among diabetic patients with poor adherence to antidiabetic medications. Methods: this study was conducted at Samburu County Referral Hospital in Samburu County, Kenya. We employed a descriptive cross-sectional design focusing on adult diabetic patients aged 18 years and above who had visited the diabetic clinic over a three-month period. To evaluate their adherence levels, we employed a Morisky Medication Adherence Scale-8. Seventy-two diabetic patients who got adherence level scores of < 6 were categorized as having low adherence and their blood samples were collected for measuring glycated hemoglobin levels and electrolytes levels particularly potassium, sodium, calcium, magnesium, phosphorus and chloride. Relationship between electrolytes and glycated hemoglobin among diabetic patients with poor adherence to antidiabetics was determined using Karl Pearson correlation. Results: among the study participants, the lowest hemoglobin A1C (HbA1c) level recorded was 5.1% while the highest was 15.0% and the majority (41.7%) fell within the HbA1c range of 5-7%. A high proportion of individuals (58.3%) with poor adherence to antidiabetics had elevated HbA1c levels, indicating poor glycemic control. The correlations observed between glycated hemoglobin and electrolytes which included magnesium, sodium, chloride, calcium and phosphorus was r= -0.07, -0.32, -0.05 -0.24 and -0.04 respectively. Conclusion: this study concluded that there is a relationship between electrolytes and glycated hemoglobin among diabetic patients with poor adherence to antidiabetics. A statistically significant negative correlation was observed between glycated hemoglobin and calcium level (r=-0.2398 P ≤0.05) and also sodium (r=-0.31369 P≤0.05). A negative correlation (P≥0.05) was observed between phosphorus, magnesium, chloride and potassium with HbA1c levels though not statistically significant.

Cardiovascular Disease Management With Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes: A Cardiology Primer.

Patients with type 2 diabetes face an elevated risk of cardiovascular disease. This review centers on sodium-glucose cotransporter-2 (SGLT2) inhibitors, a class of drugs that, according to a growing body of evidence, may have major potential for managing cardiovascular disease in patients with type 2 diabetes. This review presents findings from multiple clinical trials suggesting that SGLT2 inhibitors can not only serve as preventive therapeutic agents but also play a role in the active management of heart failure. The discussion includes the mechanism of action of SGLT2 inhibitors, emphasizing that they enhance urinary glucose excretion, which could lead to improved glycemic control and contribute to metabolic shifts beneficial to cardiac function. Alongside these cardiometabolic effects, safety concerns and practical considerations for prescribing these agents are addressed, taking into account potential adverse effects such as genitourinary infections and diabetic ketoacidosis as well as the financial implications for patients. Despite these drawbacks, therapeutic indications for SGLT2 inhibitors continue to expand, including for kidney protection, although further research is necessary to fully understand the mechanisms driving the cardioprotective and kidney-protective effects of SGLT2 inhibitors. By synthesizing current knowledge, this review intends to inform and guide clinical decision-making, thereby enhancing cardiovascular disease outcomes in patients with type 2 diabetes.

Spatiotemporal variations, health risk assessment, and sources of potentially toxic elements in potamic water of the Anday Stream Basin (Türkiye), Black Sea Region.

Monitoring and protecting freshwater habitats are paramount for a sustainable water management perspective. This study investigated potentially toxic elements (PTEs) in the potamic water of the Anday Stream Basin (Türkiye), Black Sea Region, for a hydrological year (from May 2020 to April 2021). Among PTEs, the highest average values were recorded for sodium (Na) at 41.3 mg/L and the lowest for mercury (Hg) at 0.009 µg/L and noted under quality guidelines. The stream was found to be at the level of "Low Heavy Metal Pollution" and "Low Contamination" based on the ecotoxicological risk indices. The highest calculated hazard quotient (HQ) value of 1.21E-02 for Cd was noted in the children via the dermal pathway and the lowest of 6.91E-06 for Fe in adults via the ingestion pathway. Results revealed a higher hazard index (HI) value of 1.50E-02 for Cd to children and the lowest of 1.98E-05 for Fe to adults. As a result of applying agricultural risk indices, the stream showed sodium adsorption ratio values less than 6 and was found to be "Excellent" for agriculture. However, the sodium percentage values were less than 20 and found "Permissible" and the magnesium hazard > 50 and noted as "Unsuitable" for agriculture. Statistical analysis revealed that natural factors mainly attributed to PTE contamination of the Anday Stream Basin.

Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly recognized for their role in reducing the risk and improving the prognosis of heart failure (HF). However, the precise mechanisms involved remain to be fully delineated. Evidence points to their potential anti-inflammatory pathway in mitigating the risk of HF. METHODS: A two-sample, two-step Mendelian Randomization (MR) approach was employed to assess the correlation between SGLT-2 inhibition and HF, along with the mediating effects of inflammatory biomarkers in this relationship. MR is an analytical methodology that leverages single nucleotide polymorphisms as instrumental variables to infer potential causal inferences between exposures and outcomes within observational data frameworks. Genetic variants correlated with the expression of the SLC5A2 gene and glycated hemoglobin levels (HbA1c) were selected using datasets from the Genotype-Tissue Expression project and the eQTLGen consortium. The Genome-wide association study (GWAS) data for 92 inflammatory biomarkers were obtained from two datasets, which included 14,824 and 575,531 individuals of European ancestry, respectively. GWAS data for HF was derived from a meta-analysis that combined 26 cohorts, including 47,309 HF cases and 930,014 controls. Odds ratios (ORs) and 95% confidence interval (CI) for HF were calculated per 1 unit change of HbA1c. RESULTS: Genetically predicted SGLT-2 inhibition was associated with a reduced risk of HF (OR 0.42 [95% CI 0.30-0.59], P < 0.0001). Of the 92 inflammatory biomarkers studied, two inflammatory biomarkers (C-X-C motif chemokine ligand 10 [CXCL10] and leukemia inhibitory factor) were associated with both SGLT-2 inhibition and HF. Multivariable MR analysis revealed that CXCL10 was the primary inflammatory cytokine related to HF (MIP = 0.861, MACE = 0.224, FDR-adjusted P = 0.0844). The effect of SGLT-2 inhibition on HF was mediated by CXCL10 by 17.85% of the total effect (95% CI [3.03%-32.68%], P = 0.0183). CONCLUSIONS: This study provides genetic evidence supporting the anti-inflammatory effects of SGLT-2 inhibitors and their beneficial impact in reducing the risk of HF. CXCL10 emerged as a potential mediator, offering a novel intervention pathway for HF treatment.

Study of Serum Electrolytes (Sodium and Potassium) Abnormalities in Acute Stroke.

Stroke is the common cause of death and disability worldwide, as well as in Bangladesh. Serum electrolytes abnormalities or dyselectrolytaemia is one of the major acute complications of stroke. Dyselectrolytaemia or serum electrolytes (sodium and potassium) abnormalities are more common in patients with acute stroke that can be easily measured. The study was planned to find out the serum electrolytes (sodium and potassium) abnormalities in acute stroke patients. This cross-sectional study was conducted in the Department of Neurology and Medicine, Mymensingh Medical College and Hospital from January 2019 to June 2020. Total 84 purposively selected patients with acute strokes were evaluated following informed written consent. Diagnosis was confirmed by neuroimaging of brain. Moreover, serum electrolytes level was measured for each patient. Data were collected by interviews, clinical examinations & laboratory investigations of the patients using a case record form and analysis was carried out by the help of SPSS 25.0. Mean age of the patients with acute strokes were 57.65±15.79 years. About two thirds (60.7%) of the patients were male and the remaining (39.3%) were female. Sodium imbalances were observed in 32.2% and potassium imbalances in 25.0% cases. About 66.7% haemorrhagic strokes patients and 42.2% ischaemic strokes patients had dyselectrolytaemia (p<0.05). More than twenty eight percent (28.6%) of all stroke patients had hyponatraemia, which was more common (35.9%) among haemorrhagic strokes patients (p<0.05). Of all stroke patients 21.4% had hypokalaemia, which was more common (28.2%) in haemorrhagic strokes patients (p<0.05). This study reveals that, serum electrolytes (sodium and potassium) abnormalities are more common in haemorrhagic than ischaemic strokes, which is mainly hyponatraemia and hypokalaemia.

Exploring Bariatric Surgery's Impact on Weight Loss and Diabetes: Sodium and Glucose Receptor Modulation.

Sodium-glucose cotransporters (SGLT) and glucose transporters (GLUT) have been shown to influence diabetes management by modulating glucose uptake by the intestine. Therefore, alterations in gastrointestinal anatomy during bariatric surgery can change SGLT and GLUT receptor activity. These changes offer an additional mechanism for weight loss and may explain the differential impact of the various bariatric surgical procedures. This review examines the current literature on SGLT and GLUT receptors and their effects on weight loss through genetic studies, pharmacologic inhibition, and how SGLT/GLUT receptors impact surgical physiologic modulation. A better understanding of Type I sodium-glucose cotransport receptors (SGLT-1), GLUT-2, and GLUT-5 could provide insight for improved procedures and allow us to determine the best method to tailor operations to a patient's individual needs.

Sociodemographic disparities in sodium-glucose cotransporter-2 inhibitor use among US kidney transplant recipients: An observational study of real-world pharmacy records.

BACKGROUND: Recent clinical trials demonstrate benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with chronic kidney disease, but data on use in kidney transplant (KTx) recipients are limited. METHODS: We examined a novel database linking SRTR registry data for KTx recipients (2000-2021) with outpatient fill records from a large pharmaceutical claims warehouse (2015-2021). Adult (≥18 years) KTx recipients treated with SGLT2i were compared to those who received other noninsulin diabetes medications without SGLT2i. Characteristics associated with SGLT2i use were quantified by multivariable logistic regression (adjusted odds ratio, 95%LCLaOR95%UCL). RESULTS: Among 18 988 KTx recipients treated with noninsulin diabetes agents in the study period, 2224 filled an SGLT2i. Mean time from KTx to prescription was 6.7 years for SGLT2i versus 4.7 years for non-SGLT2i medications. SGLT2i use was more common in Asian adults (aOR, 1.091.311.58) and those aged > 30-59 years (compared with 18-30 years) or with BMI > 35 kg/m2 (aOR, 1.191.411.67), and trended higher with self-pay status. SGLT2i use was lower among KTx recipients who were women (aOR, .79.87.96), Black (aOR, .77.881.00) and other (aOR, .52.751.07) race, publicly insured (aOR, .82.921.03), or with less than college education (aOR, .78.87.96), and trended lower in those age 75 years and older. SGLT2i use in KTx patients increased dramatically in 2019-2021 (aOR, 5.015.636.33 vs. prior years). CONCLUSION: SGLT2i use is increasing in KTx recipients but varies with factors including race, education, and insurance. While ongoing study is needed to define risks and benefits of SGLT2i use in KTx patients, attention should also focus on reducing treatment disparities related to sociodemographic traits.

Reactive oxygen species impair Na+ transport and renal components of the renin-angiotensin-aldosterone system after paraquat poisoning.

Paraquat (1,1'-dimethyl-4,4'-bipyridyl dichloride) is an herbicide widely used worldwide and officially banned in Brazil in 2020. Kidney lesions frequently occur, leading to acute kidney injury (AKI) due to exacerbated reactive O2 species (ROS) production. However, the consequences of ROS exposure on ionic transport and the regulator local renin-angiotensin-aldosterone system (RAAS) still need to be elucidated at a molecular level. This study evaluated how ROS acutely influences Na+-transporting ATPases and the renal RAAS. Adult male Wistar rats received paraquat (20 mg/kg; ip). After 24 h, we observed body weight loss and elevation of urinary flow and serum creatinine. In the renal cortex, paraquat increased ROS levels, NADPH oxidase and (Na++K+)ATPase activities, angiotensin II-type 1 receptors, tumor necrosis factor-α (TNF-α), and interleukin-6. In the medulla, paraquat increased ROS levels and NADPH oxidase activity but inhibited (Na++K+)ATPase. Paraquat induced opposite effects on the ouabain-resistant Na+-ATPase in the cortex (decrease) and medulla (increase). These alterations, except for increased serum creatinine and renal levels of TNF-α and interleukin-6, were prevented by 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (tempol; 1 mmol/L in drinking water), a stable antioxidant. In summary, after paraquat poisoning, ROS production culminated with impaired medullary function, urinary fluid loss, and disruption of Na+-transporting ATPases and angiotensin II signaling.

Water Conservation Overrides Osmotic Diuresis During SGLT2 Inhibition in Patients With Heart Failure.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential. OBJECTIVES: The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment. METHODS: DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance. RESULTS: Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor-naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51-4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d [95% CI: 1.98-3.51]; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L [95% CI: 0.45-10.5]; P < 0.05) and late (7.8 pmol/L [95% CI: 2.77-12.81]; P < 0.01), leading to proportional reductions in free water clearance (early: -9.1 mL/kg/d [95% CI: -14 to -4.12; P < 0.001]; late: -11.0 mL/kg/d [95% CI: -15.94 to -6.07; P < 0.0001]) and elevated urine concentrations (late: 134 mmol/L [95% CI: 39.28-229.12]; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d [95% CI: -1.97 to 7.48; P = 0.25]; mean difference late: 0.9 mL/kg/d [95% CI: -3.83 to 5.62]; P = 0.70). CONCLUSIONS: Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment [DAPA-Shuttle1]; NCT04080518).

The effect of ascending- descending ultrafiltration and sodium profiles on blood pressure in hemodialysis patients: a randomized cross-over study.

BACKGROUND: Considering no previous research into the utilization of ascending/descending ultrafiltration and linear sodium profiles in improving blood pressure among hemodialysis patients, the present study aimed to explore the effect of the A/D-UF along with linear sodium profiles on HD patients with hypotension. METHODS: Applying a crossover design, this clinical trial was fulfilled between December 2022 and June 2023 on 20 patients undergoing HD, randomized into two groups, each one receiving two intervention protocols, viz., (a) an intervention protocol in which the liquid sodium in the dialysis solution was linear and the UF profiling was A/D, and (b) a routine protocol or HD, wherein both liquid sodium and UF in the dialysis solution remained constant. The HD patients' BP was then checked and recorded at six intervals, namely, before HD, one, two, three, and four hours after it, and following its completion, within each session. The data were further statistically analyzed using the IBM SPSS Statistics 20 and the related tests. RESULTS: In total, 20 patients, including 12 men (60%) and 8 women (40%), with the mean age of 58.00 ± 14.54 on HD for an average of 54 months, were recruited in this study. No statistically significant difference was observed in the mean systolic and diastolic BP levels in the group receiving the A/D-UF profile all through the desired hours (p > 0.05), indicating that the patients did not face many changes in these two numbers during HD. Our cross-over clinical trial demonstrated a statistically significant reduction in symptomatic IDH episodes from 55 to 15% with the application of the A/D-UF profile (p < 0.05). CONCLUSION: The study demonstrated that the A/D-UF profile could contribute to the stability of blood pressure levels among HD patients, with no significant fluctuations observed during treatment sessions. TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials (no. IRCT20180429039463N5) on 07/01/2023.

Functional properties and skin care effects of sodium trehalose sulfate.

BACKGROUND: It is known that heparinoid, a mucopolysaccharide polysulfate, is effective in improving rough skin and promoting blood circulation as medicines for diseased areas. However, heparinoid has a molecular weight of more than 5000 and cannot penetrate healthy stratum corneum. OBJECTIVE: We tested the efficacy of sulfated oligosaccharides with a molecular weight of less than 2000 on the human skin barrier function and moisturizing function. METHODS: We measured the transepidermal water loss (TEWL) of a three-dimensional human epidermis model cultured for 3 days after topical application of sulfated oligosaccharides, then observed the effects on TEWL suppression. The mRNA levels of proteins involved in intercellular lipid transport and storage in the stratum corneum, and moisture retention were measured using RT-qPCR. RESULTS: An increase in the mRNA levels of the ATP-binding cassette subfamily A member 12 (ABCA12), which transports lipids into stratum granulosum, was confirmed. Increases were also observed in the mRNA levels of filaggrin (FLG), which is involved in the generation of natural moisturizing factors, and of caspase-14, calpain-1 and bleomycin hydrolase, which are involved in the degradation of FLG. Antibody staining confirmed that the application of sodium trehalose sulfate to 3D model skin resulted in more ABCA12, ceramide, transglutaminase1, and FLG than those in controls. In a randomized, placebo-controlled, double-blind study, participants with low stratum corneum water content applied a lotion and emulsion containing sodium trehalose sulfate to their faces for 4 weeks. Sodium trehalose sulfate decreased the TEWL and increased the stratum corneum water content. CONCLUSION: These results suggest that cosmetics containing sodium trehalose sulfate act on the epidermis by increasing barrier factors and moisturizing factors, thereby ameliorating dry skin.

Catalase activity as a diagnostic indicator of the health of oil-contaminated soils after remediation.

The work objective was to assess the ecological state of soils by changing the residual oil content and restoring catalase activity after remediation. The soils were selected in various ecosystems: a steppe of the Rostov Region (Haplic Chernozem), beech-hornbeam forests in the Republic of Adygea (Haplic Cambisols), and semi-desert of the Caspian province of the Republic of Kalmykia (Eutric Cambisols). Soil samples were polluted with oil at a concentration of 5% of the soil mass. After that, ameliorants (biochar, nitroammophoska, sodium humate, and Baikal EM-1) were introduced into the oil-contaminated soil. The catalase activity of Haplic Cambisols was stimulated only with the introduction of D2 biochar by 11% relative to the control, and in Haplic Chernozem, catalase was most stimulated with the addition of nitroammophoska D0.5 and D1 by 65% and 57% of the control, respectively. Nitroammophoska in all doses significantly stimulated the enzymatic activity, in Eutric Cambisols by four to six times compared to the control. The range of soil stability determined by catalase activity: Eutric Cambisols > Haplic Chernozem > Haplic Cambisols. Thus, it is most effective to apply biochar in doses of D and D2 and D0.5 and D nitroammophoska during the remediation of oil-contaminated Haplic Chernozem. For the remediation of Haplic Cambisols, it is effective to introduce biochar in dose of D2, and Eutric Cambisols-biochar and sodium humate in dose of D0.5 and nitroammophoska (all doses). The results of the study allow using catalase activity as a very informative and statistically significant diagnostical indicator of the health of oil-contaminated soils after remediation.

Combining different species in restoration is not always the right decision: Monocultures can provide higher ecological functions than intercropping in a desert ecosystem.

Vegetation restoration in deserts is challenging due to these ecosystems' inherent fragility and harsh environmental conditions. One approach for active restoration involves planting native species, which can accelerate the recovery of ecosystem functions. To ensure the effectiveness of this process, carefully selecting species for planting is crucial. Generally, it is expected that a more diverse mix of species in the plantation will lead to the recovery of a greater number of ecosystem functions, especially when the selected species have complementary niche traits that facilitate maximum cooperation and minimize competition among them. In this study, we evaluated the planting of two native species from the hyper-desert of Taklamakan, China, which exhibit marked morpho-physiological differences: a phreatophytic legume (Alhagi sparsifolia) and a halophytic non-legume (Karelinia caspia). These species were grown in both monoculture and intercrop communities. Monoculture of the legume resulted in the highest biomass accumulation. Intercropping improved several ecosystem functions in the 50 cm-upper soil, particularly those related to phosphorus (P), carbon (C), and sulfur (S) concentrations, as well as soil enzyme activities. However, it also increased soil sodium (Na+) concentration and pH. Halophyte monocultures enhanced ecological functions associated with nitrogen concentrations in the upper soil and with P, S, C, and cation concentrations (K+, Ca2+, Mg2+, Cu2+, Fe2+, Zn2+, Co2+, Ni2+), along with enzyme activities in the deep soil. It also maximized Na+ accumulation in plant biomass. In summary, we recommend legume monoculture when the primary goal is to optimize biomass accumulation. Conversely, halophyte monoculture is advisable when the objective is to extract sodium from the soil or enhance ecosystem functions in the deep soil. Intercropping the two species is recommended to maximize the ecosystem functions of the upper soil, provided there is no salinization risk. When planning restoration efforts in desert regions, it is essential to understand the impact of each species on ecosystem function and how complementary species behave when intercropped. However, these interactions are likely species- and system-specific, highlighting the need for more work to optimize solutions for different arid ecosystems.

Nascent shifts in renal cellular metabolism, structure, and function due to chronic empagliflozin in prediabetic mice.

Sodium-glucose cotransporter, type 2 inhibitors (SGLT2i) are emerging as the gold standard for treatment of type 2 diabetes (T2D) with renal protective benefits independent of glucose lowering. We took a high-level approach to evaluate the effects of the SGLT2i, empagliflozin (EMPA) on renal metabolism and function in a prediabetic model of metabolic syndrome. Male and female 12-wk-old TallyHo (TH) mice, and their closest genetic lean strain (Swiss-Webster, SW) were treated with a high-milk-fat diet (HMFD) plus/minus EMPA (@0.01%) for 12-wk. Kidney weights and glomerular filtration rate were slightly increased by EMPA in the TH mice. Glomerular feature analysis by unsupervised clustering revealed sexually dimorphic clustering, and one unique cluster relating to EMPA. Periodic acid Schiff (PAS) positive areas, reflecting basement membranes and mesangium were slightly reduced by EMPA. Phasor-fluorescent life-time imaging (FLIM) of free-to-protein bound NADH in cortex showed a marginally greater reliance on oxidative phosphorylation with EMPA. Overall, net urine sodium, glucose, and albumin were slightly increased by EMPA. In TH, EMPA reduced the sodium phosphate cotransporter, type 2 (NaPi-2), but increased sodium hydrogen exchanger, type 3 (NHE3). These changes were absent or blunted in SW. EMPA led to changes in urine exosomal microRNA profile including, in females, enhanced levels of miRs 27a-3p, 190a-5p, and 196b-5p. Network analysis revealed "cancer pathways" and "FOXO signaling" as the major regulated pathways. Overall, EMPA treatment to prediabetic mice with limited renal disease resulted in modifications in renal metabolism, structure, and transport, which may preclude and underlie protection against kidney disease with developing T2D.NEW & NOTEWORTHY Renal protection afforded by sodium glucose transporter, type 2 inhibitors (SGLT2i), e.g., empagliflozin (EMPA) involves complex intertwined mechanisms. Using a novel mouse model of obesity with insulin resistance, the TallyHo/Jng (TH) mouse on a high-milk-fat diet (HMFD), we found subtle changes in metabolism including altered regulation of sodium transporters that line the renal tubule. New potential epigenetic determinants of metabolic changes relating to FOXO and cancer signaling pathways were elucidated from an altered urine exosomal microRNA signature.