IL-6 and IL-17 as potential links between pre-existing hypertension and long-term COVID sequelae in patients undergoing hemodialysis: a multicenter cross-sectional study.

Long COVID, characterized by persistent symptoms following acute infection, poses a significant health challenge, particularly for patients with pre-existing chronic conditions such as hypertension. We hypothesized that an increase in the production of interleukins (IL)-6 and IL-17 could serve as a potential mechanism linking pre-existing uncontrolled blood pressure (BP) to the occurrence of long-term COVID sequelae in patients undergoing hemodialysis (HD). This cross-sectional study examined serum IL-6 and IL-17 levels in 80 patients undergoing HD, considering preinfection BP, the presence of long-term COVID sequelae, and the time interval after acute COVID-19 infection, which was either 5 or 10 months. Controlled BP was defined as a 3-month average pre-dialysis BP < 140/90 mmHg and post-dialysis < 130/80 mmHg. The findings suggest that the prevalence of long-term COVID sequelae was significantly higher in patients with uncontrolled BP than in the BP-controlled group. Both IL-6 and IL-17 concentrations were also significantly higher in patients with uncontrolled BP compared with the BP-controlled group. The patients with long-term COVID sequelae had higher IL-6 and IL-17 values than the fully recovered patients at both time points, but their concentrations decreased significantly over time. Further research and prospective studies are warranted to validate these findings.

Gut Microbiota's Oxalate-Degrading Activity and Its Implications on Cardiovascular Health in Patients with Kidney Failure: A Pilot Prospective Study.

Background and Objectives: The present study aims to investigate the association between gut microbiota's oxalate-degrading activity (ODA) and the risk of developing cardiovascular disease (CVD) over a three-year follow-up period in a cohort of patients undergoing kidney replacement therapy (KRT). Additionally, various factors were examined to gain insight into the potential mechanisms underlying the ODA-CVD link. Materials and Methods: A cohort of 32 KRT patients and 18 healthy volunteers was enrolled in this prospective observational pilot study. Total fecal ODA, routine clinical data, plasma oxalic acid (POx), serum indoxyl sulfate, lipid profile, oxidative stress, and proinflammatory markers were measured, and the patients were followed up for three years to assess CVD events. Results: The results revealed that patients with kidney failure exhibited significantly lower total fecal ODA levels compared to the healthy control group (p = 0.017), with a higher proportion showing negative ODA status (≤-1% per 0.01 g) (p = 0.01). Negative total fecal ODA status was associated with a significantly higher risk of CVD events during the three-year follow-up period (HR = 4.1, 95% CI 1.4-16.3, p = 0.003), even after adjusting for potential confounders. Negative total fecal ODA status was significantly associated with elevated POx and indoxyl sulfate levels and linked to dyslipidemia, increased oxidative stress, and inflammation, which are critical contributors to CVD. Conclusions: The findings contribute novel insights into the relationship between gut microbiota's ODA and cardiovascular health in patients undergoing KRT, emphasizing the need for further research to elucidate underlying mechanisms and explore potential therapeutic implications of targeting gut microbiota's ODA in this vulnerable population.

Optimal Scheduling in General Multi-Queue System by Combining Simulation and Neural Network Techniques.

The problem of optimal scheduling in a system with parallel queues and a single server has been extensively studied in queueing theory. However, such systems have mostly been analysed by assuming homogeneous attributes of arrival and service processes, or Markov queueing models were usually assumed in heterogeneous cases. The calculation of the optimal scheduling policy in such a queueing system with switching costs and arbitrary inter-arrival and service time distributions is not a trivial task. In this paper, we propose to combine simulation and neural network techniques to solve this problem. The scheduling in this system is performed by means of a neural network informing the controller at a service completion epoch on a queue index which has to be serviced next. We adapt the simulated annealing algorithm to optimize the weights and the biases of the multi-layer neural network initially trained on some arbitrary heuristic control policy with the aim to minimize the average cost function which in turn can be calculated only via simulation. To verify the quality of the obtained optimal solutions, the optimal scheduling policy was calculated by solving a Markov decision problem formulated for the corresponding Markovian counterpart. The results of numerical analysis show the effectiveness of this approach to find the optimal deterministic control policy for the routing, scheduling or resource allocation in general queueing systems. Moreover, a comparison of the results obtained for different distributions illustrates statistical insensitivity of the optimal scheduling policy to the shape of inter-arrival and service time distributions for the same first moments.

Oxalate Homeostasis in Non-Stone-Forming Chronic Kidney Disease: A Review of Key Findings and Perspectives.

Chronic kidney disease (CKD) is a significant global public health concern associated with high morbidity and mortality rates. The maintenance of oxalate homeostasis plays a critical role in preserving kidney health, particularly in the context of CKD. Although the relationship between oxalate and kidney stone formation has been extensively investigated, our understanding of oxalate homeostasis in non-stone-forming CKD remains limited. This review aims to present an updated analysis of the existing literature, focusing on the intricate mechanisms involved in oxalate homeostasis in patients with CKD. Furthermore, it explores the key factors that influence oxalate accumulation and discusses the potential role of oxalate in CKD progression and prognosis. The review also emphasizes the significance of the gut-kidney axis in CKD oxalate homeostasis and provides an overview of current therapeutic strategies, as well as potential future approaches. By consolidating important findings and perspectives, this review offers a comprehensive understanding of the present knowledge in this field and identifies promising avenues for further research.

The Gut-Peritoneum Axis in Peritoneal Dialysis and Peritoneal Fibrosis.

Peritoneal fibrosis is an important cause of peritoneal dialysis (PD) discontinuation worldwide and is associated with high morbidity and mortality rate. Although the era of metagenomics has provided new insights into the interactions between the gut microbiota and fibrosis in various organs and tissues, its role in peritoneal fibrosis has rarely been discussed. This review provides a scientific rationale and points out the potential role of gut microbiota in peritoneal fibrosis. In addition, the interaction between the gut, circulatory, and peritoneal microbiota is highlighted, with an emphasis on the relationship to PD outcomes. More research is needed to elucidate the mechanisms underlying the role of gut microbiota in peritoneal fibrosis and potentially unveil new target options for the management of PD technique failure.

How Advanced Is Our Understanding of the Role of Intestinal Barrier Dysfunction in the Pathogenesis of Recurrent Urinary Tract Infections.

A comprehensive understanding of urinary tract infections (UTIs), one of the most common human infections, is required as they are complex and poorly understood diseases. Periurethral and vaginal colonization by rectal flora, with the constant presence of pathogens in the urethra, is the initial step of the recurrent UTIs pathway. Current scientific data describe the genetic, etiological, biological, and behavioral risk factors for recurring UTIs, but they do not include the effect of intestinal barrier function on the disease. Although gut microbiota has been proposed as the main source for UTIs, the cross-talk between intestinal barrier dysfunction and the recurrence of UTIs has not yet been supported by scientific data. In this opinion review, based on published data and the results of our clinical studies, I aimed to outline the possible contribution of intestinal barrier dysfunction to the pathogenesis of recurrent UTIs. I believe that the unanswered questions raised by this review can guide further experimental and controlled studies to clarify the mechanisms underlying the role of intestinal barrier dysfunction in the pathogenesis of recurrent UTIs.

Oxalate Balance in Peritoneal Dialysis Patients: A Potential Role of Dialysis-related Peritonitis.

BACKGROUND: Little evidence is available on oxalate balance in peritoneal dialysis (PD) patients. PATIENTS AND METHODS: We performed a cross-sectional observational pilot study with 62 adult PD patients to document oxalate balance and explore its association with PD-related peritonitis. Plasma oxalate concentration, levels of oxalate excretion in 24-h urine, and peritoneal dialysis effluent were evaluated. The peritoneal oxalate transport status and renal and peritoneal oxalate clearances were calculated according to the PD-related peritonitis history. RESULTS: PD patients with a history of peritonitis had a statistically significantly lower peritoneal oxalate clearance, daily peritoneal oxalate excretion, and overall oxalate removal rate compared with the peritonitis-free PD patients. They had a 4-fold risk of plasma oxalic acid increase, and even a single episode of dialysis-related peritonitis resulted in plasma oxalate elevation. CONCLUSION: Peritoneal oxalate clearance plays an important role in oxalate balance in PD patients and, therefore, dialysis-related peritonitis is a significant predictor for hyperoxalemia. Further well-designed clinical trials need to be undertaken before the association between peritonitis and oxalate balance in PD patients is more clearly understood.

Synbiotic supplementation and oxalate homeostasis in rats: focus on microbiota oxalate-degrading activity.

The present study aimed (i) to evaluate whether ceftriaxone treatment could affect not only intestinal oxalate-degrading bacteria number but also their total activity to degrade oxalate and influence oxalate homeostasis in rats, (ii) and to estimate the ability of commercially available inulin-contained synbiotic to restore fecal oxalate-degrading activity and ceftriaxone-induced disruption of oxalate homeostasis in rats. Twenty-eight female Wistar rats (200-300 g) were randomly divided into four groups (n = 7). Group 1 was treated with vehicle sterile water (0.1 ml, i.m., 14 days); Group 2 received synbiotic (30 mg/kg, per os, 14 days); Group 3 was treated with ceftriaxone (300 mg/kg, i.m., 7 days); Group 4 was supplemented with ceftriaxone and synbiotic. Oxalate-degrading bacteria number and their total activity, urinary and plasma oxalate concentrations were measured on days 1 and 57 after the treatment withdrawal. The redoximetric titration with KMnO4 was adopted to evaluate the total oxalate-degrading activity in highly selective Oxalate Medium. Ceftriaxone treatment reduced total fecal oxalate-degrading activity independently on oxalate-degrading bacteria number and increased urinary and plasma oxalate concentrations. The synbiotic had higher oxalate-degrading activity vs probiotics and was able to restore fecal oxalate-degrading activity and significantly decrease urinary oxalate excretion in antibiotic-treated rats. Total fecal oxalate-degrading activity but not oxalate-degrading bacteria number should be thoroughly examined in the future to develop predictive diagnostics methods, targeted prevention and personalized treatment in kidney stone disease. Synbiotic supplementation had a beneficial effect on the total oxalate-degrading activity of gut microbiota, which resulted in decreased UOx excretion in rats.

Plasma oxalic acid and cardiovascular risk in end-stage renal disease patients: a prospective, observational cohort pilot study.

BACKGROUND/AIMS: It was hypothesized that oxalate might be strongly involved in atherogenesis and the inflammatory pathway that could result in an increased risk of cardiovascular disease (CVD) in end-stage renal disease (ESRD) patients. Therefore, this study aimed to address two primary research questions: to characterize the lipid profile and the pattern of pro-inflammatory cytokines according to plasma oxalic acid (POx) concentration in ESRD patients; to evaluate the potential role of elevated POx concentration in the development of CVD risk. METHODS: A total of 73 participants were enrolled in this prospective, observational cohort pilot study. Among them, there were 50 ESRD patients and 23 healthy volunteers. The lipid profile and the pro-inflammatory cytokines were analyzed according to the distribution of POx concentration into tertiles. After the clinical examination, 29 hemodialysis patients and 21 peritoneal dialysis patients without prevalent CVD were observed for CVD events for 2 years. The Cox regression analysis and a set of different types of sensitivity analyses were used to determine whether elevated POx was associated with an increased risk of CVD. RESULTS: An increasing trend in the atherogenic lipoprotein fractions and the pro-inflammatory markers as well as a linear decrease in high-density lipoprotein was significantly associated with elevated POx. POx concentration ≥ 62.9 µmol/L was significantly associated with CVD events independently of other examined CVD risk factors. CONCLUSION: This pilot study firstly demonstrated a potential contribution of POx to atherogenesis, inflammation and CVD risk in ESRD patients.

The distribution of microplastics in the surface layer of the Atlantic Ocean from the subtropics to the equator according to visual analysis.

This study reports the levels of plastic contamination in the Atlantic Ocean between 35°N and 32°S during the 1st stage of the 79th cruise of the "Akademik Mstislav Keldysh" from December 12, 2019, to January 4, 2020. A subsurface pump system and a Manta net were used for seawater filtration. Twenty-seven samples were visually analyzed with a microscope. It was found that almost every subsurface sample contained potentially plastic particles, which were classified according to their type and size. Plastic fragments were more commonly found in the samples taken from the surface. In the subsurface layer, the majority of the detected particles were fibers. These results also indicate that minimal concentrations of plastics tend to be found near the equator and to the north of the Canary Islands. The maximum microplastic concentrations were found in tropical zones. The obtained results are in good agreement with previous models and field studies.

Dyslipidemia and Intraperitoneal Inflammation Axis in Peritoneal Dialysis Patients: A Cross-Sectional Pilot Study.

BACKGROUND: We have hypothesized that the problem of dyslipidemia in peritoneal dialysis (PD) patients lies beyond certain levels of plasma lipoprotein and involves cardiovascular risk, but can also influence the development of chronic intraperitoneal inflammation. OBJECTIVES: The aim of our work was to define whether the association of dyslipidemia with intraperitoneal inflammation really exists and if it could it be used in a prospective cohort of PD patients. PATIENTS AND METHODS: We performed a cross-sectional, single-center, pilot study involving 40 nondiabetic PD patients (27 men and 13 women with an average age of 49.3 ± 12.2 years). The median time on PD was 29 (18.5-37) months. The parameters dialysis adequacy, blood lipid profile, and the concentrations of tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-10 in peritoneal dialysate effluent (PDE) were determined. Cohen's d effect size was computed post hoc to determine the differences between groups in the concentrations of pro- and anti-inflammatory mediators. RESULTS: PD patients with atherogenic dyslipidemia had significantly high levels of MCP-1 compared with dyslipidemia-free patients (Cohen's d = 1.32). A reduced high-density lipoprotein cholesterol level was associated with a high intraperitoneal production of the proinflammatory mediator TNF-α (p < 0.0001) and anti-inflammatory IL-10 (p < 0.0001). Atherogenic index of plasma was directly correlated with MCP-1 (p < 0.0001) and TNF-α (p < 0.0001). In multiple regression analysis, MCP-1 appeared to predict PD inadequacy (R 2 = 0.58; F ratio = 9.4; p = 0.006) independently of age and blood C-reactive protein level. Effect size was 1.38 with α = 0.05, n = 40, and 3 predictors. CONCLUSIONS: Our cross-sectional pilot study first demonstrated a close interaction between the atherogenic lipid profile and a high concentration of MCP-1 in PDE; this might be a prognostic marker for PD inadequacy. The potential significance of our finding is that it provides useful preliminary information necessary for further research into this area.

Association between Dyslipidemia and Peritoneal Dialysis Technique Survival.

BACKGROUND: A large body of research has investigated the effects of pro-atherogenic lipid profile on cardiovascular diseases (CVD) in peritoneal dialysis (PD) patients. However, there is a general lack of research on the association between atherogenic dyslipidemia and PD technique survival. AIM: The study aimed to define the association between dyslipidemia and PD technique survival. METHODS: It was a prospective single-centre observational study involving 40 outpatients on continuous ambulatory PD treatment for more than 3 months between 2010 and 2016 in a single centre in Ukraine. There were 27 males and 13 females. The mean age of the participants was 49.3 ± 12.2 years. The primary outcome measures were all-cause technique failure. RESULTS: Atherogenic dyslipidemia was identified in 28/40 (70 %) patients and correlated with PD adequacy parameters. During the 36-month- follow-up period technique failure occurred in 2/12 (16.6 %) patients with atherogenic dyslipidemia compared with 12 / 28 (42.9 %) patients without atherogenic dyslipidemia (χ2 = 2.5; p = 0.12). In the univariate Cox regression model, atherogenic dyslipidemia at baseline was significantly associated with a higher risk of all-cause PD technique failure (HR 4.5; 95% CI 1.6 to 12.9; χ2 = 5.5, p = 0.019). CONCLUSION: The presence of atherogenic dyslipidemia was significantly associated with a higher risk of technique failure in PD patients. This is an important issue for future research. Further well-designed clinical trials are needed to determine the impact of dyslipidemia on PD adequacy and technique survival.

Oxidative Stress in Peritoneal Dialysis Patients: Association with the Dialysis Adequacy and Technique Survival.

INTRODUCTION: Increased oxidative stress is suggested as one of the possible mechanisms of structural and functional damage to the peritoneal membrane in peritoneal dialysis patients. But there are few available data on the association of oxidative stress with peritoneal dialysis adequacy and technique survival. The present study was undertaken to investigate the association of oxidative stress biomarkers with the peritoneal dialysis adequacy and technique survival. METHODS: This prospective single-center observational study was conducted between January 2010 and May 2015. Adequacy of dialysis, malondialdehyde levels in the serum and erythrocytes (as an indicator of lipid peroxidation), the concentration of ceruloplasmin, transferrin, and sulfhydryl groups in the blood, and total peroxidase activity in erythrocyte (as indicators of antioxidant system) were determined in 44 stable ambulatory non-diabetic peritoneal dialysis patients. RESULTS: The follow-up period was 3 years. We identified a negative correlation between the serum level of malondialdehyde in the patients and total weekly Kt/V. Peritoneal weekly CrCl was positively correlated with the levels of transferrin, total peroxidase activity, and SH- groups. Daily peritoneal ultrafiltration had a positive correlation with the total peroxidase activity and the serum transferrin levels. The results of the Kaplan-Meier analysis and the log-rank test also demonstrated a significant difference in the cumulative technique survival rate between the patients with ceruloplasmin level ≤0.19 g/l and ≥0.2 g/l. CONCLUSIONS: The results mentioned above could be considered as one of the ways to explain better technique survival in PD patients.

Microplastics in sea coastal zone: Lessons learned from the Baltic amber.

Baltic amber, adored for its beauty already in Homer's Odyssey (ca. 800 B.C.E), has its material density close to that of wide-spread plastics like polyamide, polystyrene, or acrylic. Migrations of amber stones in the sea and their massive washing ashore have been monitored by Baltic citizens for ages. Based on the collected information, we present the hypothesis on the behaviour of microplastic particles in sea coastal zone. Fresh-to-strong winds generate surface waves, currents and roll-structures, whose joint effect washes ashore from the underwater slope both amber stones and plastics - and carries them back to the sea in a few days. Analysis of underlying hydrophysical processes suggests that sea coastal zone under stormy winds plays a role of a mill for plastics, and negatively buoyant pieces seem to repeatedly migrate between beaches and underwater slopes until they are broken into small enough fragments that can be transported by currents to deeper areas and deposited out of reach of stormy waves. Direct observations on microplastics migrations are urged to prove the hypothesis.