Alpha-klotho and peritoneal membrane status: A hypothesis generating study.

BACKGROUND: Long-term success of peritoneal dialysis relies on the integrity of the peritoneal membrane. This proof-of-concept study addressed the hypothesis that fibrosis is already present in the membrane at pre-dialysis and that the membrane status is related to the individual's uraemic fingerprint. METHODS: A clinical-mechanistic, transversal, single-centre study was conducted. Pre-dialysis peritoneal biopsies were scored considering the submesothelial compact zone thickness (STM), vasculopathy and inflammation. We investigated if the membrane status could be inferred from a panel of proteins (α-Klotho, Galectin-3, FGF21, FGF23, Tweak, TNFα and hsPCR) in blood. RESULTS: A total 58 incident patients aged 56 ± 15 years old were included, 31% female, 55% hypertension, 29% diabetic and 24% obese. Person-to-person STM was found to be highly variable and 38% of patients were fibrosis positive. Both α-Klotho (Spearman r = -.7491, p < 0.001) and FGF21 (Spearman r = -.5102, p < 0.001) were negatively associated with STM. α-Klotho, but not FGF21, was able to discriminate fibrosis from nonfibrosis with/without inflammation and vasculopathy. PLS models identified α-Klotho as the protein most relevant for fibrosis. α-Klotho was independently associated with fibrosis of the peritoneal membrane (OR = .991 (.896-.997), p = 0.002). CONCLUSION: Before the start of dialysis in incident patients, some patients already present fibrosis of the peritoneal membrane and other patients do not. Our findings suggest that α-Klotho may be implicated in fibrosis of the peritoneal membrane.

Incremental peritoneal dialysis: Is it better for preservation of residual kidney function and clinical outcomes?

INTRODUCTION: Incremental peritoneal dialysis (IPD) is based on the prescription of a dose lower than the standard (SPD). The combination of residual kidney function (RKF) and peritoneal clearance achieves clearance goals. The aim of this study is to compare the outcomes of IPD with SPD. MATERIALS AND METHODS: This was a single-center, retrospective study that included a cohort of prevalent peritoneal dialysis (PD) adults. Patients were assigned according to their first PD protocol in two groups - group A: IPD protocol (continuous ambulatory PD: less than 4 dwells daily, less than 2 L dwell volume, and/or treatment less than 7 days/week; automated PD: without a long dwell, less than 10 L daily delivered, and/or treatment for less than 7 days/week); group B: SPD protocol. RESULTS: 87 PD patients were included, 65.5% underwent IPD. The median follow-up time was 23 months (IQR 15 - 35). IPD had a higher glomerular filtration ratio (7 vs. 3.7, mL/min/1.73m2, p < 0.001) in the first 6 months, and after 24 months (4.8 vs. 1.9, mL/min/1.73m2, p = 0.002). IPD protocol was independently associated with GFR ≥ 5 mL/min/1.73m2 at 24 months (OR 13 per point, 95% CI 1.48 - 114.36, p = 0.021). IPD was also associated with a longer technique survival (log-rank test = 4.928, p = 0.026), lower hospital admissions per year (0.23 vs. 0.5, p = 0.001), and lower mortality (1.8% vs. 13.3%, p = 0.027). Cox regression demonstrated that IPD (HR 0.30; 95% CI 0.098 - 0.93); p = 0.036) was associated with a decrease in the risk of technique failure. CONCLUSION: The prescription of IPD seems to be beneficial, in terms of outcomes, for patients with substantial RKF.

'If I hadn't seen this picture, I'd be smoking'-perceptions about innovations in health warnings for cigarette packages in Brazil: a focus group study.

OBJECTIVE: To investigate the perceptions of young people and adults, smokers and non-smokers about the current set of innovations introduced in 2018 into the Brazilian tobacco products' health warnings. METHODS: Twenty focus groups were conducted in five state capitals in Brazil. The participants (n=163) were segmented by smoking status, age (15-17 years, 18-55 years) and social grade (C, D-E classes) to examine cigarette packaging and explore the participants' perceptions of health warnings. RESULTS: Health warnings capture attention, eliciting apprehension, fear, disgust and concern about the negative consequences of cigarette consumption. The 2018 Brazil health warnings are spontaneously recalled by participants, even without the presence of cigarette packages. However, the analysis also reveals the challenges of overcoming communication barriers and distorted interpretations, especially among smokers. The inclusion of direct and provocative stimuli, such as the use of the word 'you', attracts attention and creates more proximity to the recipient of the message. The results also highlight the interest and fear elicited by warnings on toxic constituents and the importance of using contrasting colours in warnings, which differentiate them from the colours of cigarette packs. CONCLUSION: Introducing innovative components in health warnings can catch consumers' attention but considering that the interviewees encountered difficulties interpreting textual warnings about toxic constituents in cigarettes, the study reinforces the importance of adopting direct language and pictures, instead of text, which can visually transmit the warning messages and the use of specific wording that generates proximity between the emitter and receiver.

Peritoneal Dialysis Exit-Site Care Protocols in Portugal and Its Association with Catheter-Related Infections.

INTRODUCTION: Exit-site infection (ESi) prevention is a key factor in lowering the risk of peritonitis. This study aimed to evaluate the associations between exit-site (ES) care protocols and the annual incidence rates of ESi and peritonitis in Portugal. METHODS: We performed a national survey using two questionnaires: one about the incidence of catheter-related infections and the other characterizing patients' education and ES care protocols. RESULTS: In 2017 and 2018, 14 Portuguese units followed 764 and 689 patients. ESi incidence rate was 0.41 episodes/year, and the peritonitis incidence rate was 0.37. All units monitor catheter-related infections on a yearly basis, use antibiotic prophylaxis at the time of catheter placement, and treat nasal carriage of S. aureus, although with different approaches. Screening for nasal carriage of S. aureus is performed by 12 units, and daily topical antibiotic cream is recommended by 6 out of 14 of the units. We did not find statistical differences in ESi/peritonitis, comparing these practices. The rate of ESis was lower with nonocclusive dressing immediately after catheter insertion, bathing without ES dressing, with the use of colostomy bags in beach baths and was higher with the use of bath sponge. The peritonitis rate was lower with bathing without ES dressing and if shaving of the external cuff was performed in the presence of chronic ESi. CONCLUSIONS: We found potential proceedings associated with ESi and peritonitis. A regular national audit of peritoneal dialysis units is an important tool for clarifying the best procedures for reduction of catheter-related infections.

Effect of overexpression of partial TDH1 and TDH2/3 gene sequences in a starter strain of industrial bioethanol fermentation on the Brettanomyces bruxellensis contaminant growth.

Selected Saccharomyces cerevisiae strains, such as the commercial Ethanol-Red (ER) strain, are used as starters in the bioethanol industry. Yet, bioethanol fermentations are prone to microbial contaminations, mainly by Brettanomyces bruxellensis and lactic acid bacteria. Chemicals, such as sulphuric acid and antibiotics, are commonly used to combat those contaminations, but they have negative environmental impacts. Recently, ER strain was found to secrete antimicrobial peptides (AMPs) active against B. bruxellensis. Therefore, the partial TDH1 and TDH2/3 genes sequences that codify those AMPs were inserted into the pSR41k plasmid and cloned in ER strains. The relative expression levels (plasmidic/genomic) of those sequences in the respective modified ER strains were quantified by real-time quantitative polimerase chain reaction (RT-qPCR), confirming their overexpression. The effect of the modified strains on B. bruxellensis (Bb) growth was then evaluated during synthetic must (SM) and carob syrup (CS) fermentations, co-inoculated with 105 cells ml-1 of ER and Bb in SM and with 106 of ER and 5 × 103 cells ml-1 of Bb in CS. Results showed that modified ER strains exerted a much higher inhibitory effect against B. bruxellensis (72-fold in SM and 10-fold in CS) than the non-modified ER strain. In those fermentations, 90-100 g l-1 of ethanol was produced in 3-6 days.

Unusual dimeric flavonoids (brachydins) induce ultrastructural membrane alterations associated with antitumor activity in cancer cell lines.

Notwithstanding the advances in molecular target-based drugs, chemotherapy remains the most common cancer treatment, despite its high toxicity. Consequently, effective anticancer therapies with fewer adverse effects are needed. Therefore, this study aimed to determine the anticancer activity of the dichloromethane fraction (DCMF) isolated from Arrabidae brachypoda roots, whose components are three unusual dimeric flavonoids. The toxicity of DCMF was investigated in breast (MCF-7), prostate (DU145), and cervical (HeLa) tumor cells, as well as non-tumor cells (PNT2), using sulforhodamine B (cell viability), Comet (genotoxicity), clonogenicity (reproductive capacity) and wound healing (cell migration) assays, and atomic force microscopy (AFM) for ultrastructural cell membrane alterations. Molecular docking revealed affinity between albumin and each rare flavonoid, supporting the impact of fetal bovine serum in DCMF antitumor activity. The IC50 values for MCF7, HeLa, and DU145 were 2.77, 2.46, and 2.51 µg/mL, respectively, and 4.08 µg/mL for PNT2. DCFM was not genotoxic to tumor or normal cells when exposed to twice the IC50 for up to 24 h, but it inhibited tumor cell migration and reproduction compared to normal cells. Additionally, AFM revealed alterations in the ultrastructure of tumor nuclear membrane surfaces, with a positive correlation between DCMF concentration and tumor cell roughness. Finally, we found a negative correlation between roughness and the ability of DCMF-treated tumor cells to migrate and form colonies with more than 50 cells. These findings suggest that DCFM acts by causing ultrastructural changes in tumor cell membranes while having fewer toxicological effects on normal cells.

Fibrosis of Peritoneal Membrane, Molecular Indicators of Aging and Frailty Unveil Vulnerable Patients in Long-Term Peritoneal Dialysis.

Peritoneal membrane status, clinical data and aging-related molecules were investigated as predictors of long-term peritoneal dialysis (PD) outcomes. A 5-year prospective study was conducted with the following endpoints: (a) PD failure and time until PD failure, (b) major cardiovascular event (MACE) and time until MACE. A total of 58 incident patients with peritoneal biopsy at study baseline were included. Peritoneal membrane histomorphology and aging-related indicators were assessed before the start of PD and investigated as predictors of study endpoints. Fibrosis of the peritoneal membrane was associated with MACE occurrence and earlier MACE, but not with the patient or membrane survival. Serum α-Klotho bellow 742 pg/mL was related to the submesothelial thickness of the peritoneal membrane. This cutoff stratified the patients according to the risk of MACE and time until MACE. Uremic levels of galectin-3 were associated with PD failure and time until PD failure. This work unveils peritoneal membrane fibrosis as a window to the vulnerability of the cardiovascular system, whose mechanisms and links to biological aging need to be better investigated. Galectin-3 and α-Klotho are putative tools to tailor patient management in this home-based renal replacement therapy.

Cysteine as a Multifaceted Player in Kidney, the Cysteine-Related Thiolome and Its Implications for Precision Medicine.

In this review encouraged by original data, we first provided in vivo evidence that the kidney, comparative to the liver or brain, is an organ particularly rich in cysteine. In the kidney, the total availability of cysteine was higher in cortex tissue than in the medulla and distributed in free reduced, free oxidized and protein-bound fractions (in descending order). Next, we provided a comprehensive integrated review on the evidence that supports the reliance on cysteine of the kidney beyond cysteine antioxidant properties, highlighting the relevance of cysteine and its renal metabolism in the control of cysteine excess in the body as a pivotal source of metabolites to kidney biomass and bioenergetics and a promoter of adaptive responses to stressors. This view might translate into novel perspectives on the mechanisms of kidney function and blood pressure regulation and on clinical implications of the cysteine-related thiolome as a tool in precision medicine.

Management of RAASi-associated hyperkalemia in patients with cardiovascular disease.

Renin-angiotensin-aldosterone system inhibitors (RAASi) reduce morbidity and mortality in heart failure (HF) with reduced ejection fraction in a dose-dependent manner. They also have a positive impact in other cardiovascular diseases (CVDs). However, RAASi may induce hyperkalemia, a potentially life-threatening disorder. This risk is further increased in those with concomitant chronic kidney disease, diabetes mellitus, and/or in patients with hypertension. Current treatment guidelines recommend maximal RAASi dosing to improve clinical outcomes; however, this is often limited by the development of hyperkalemia. When this occurs, current guidelines recommend RAASi down-titration/interruption, which, while improving short-term prognosis, is associated with a negative long-term prognostic impact. At present, the European Society of Cardiology suggests the consideration of novel potassium binders (patiromer and sodium zirconium cyclosilicate) for the management of RAASi-associated hyperkalemia. Both drugs can reduce serum potassium levels and prevent recurrent hyperkalemia. Additionally, patiromer showed enabling of RAASi optimization in high-risk patients. Nevertheless, precise recommendations on the use of these drugs are lacking. Building upon current HF guideline recommendations, a multidisciplinary expert panel convened to design an algorithm providing practical guidance on the use of novel potassium binders/patiromer in patients with HF and/or other CVD. As a result of that effort, we present an evidence-based treatment algorithm for the management of hyperkalemia with novel potassium binders/patiromer in patients with HF and/or other CVD receiving RAASi, including the necessary monitoring to avoid induction of hypokalemia. This algorithm aims to maintain or up-titrate RAASi to optimized doses, while maintaining normokalemia, improved clinical outcomes, and long-term prognosis.

Biocontrol of Brettanomyces/Dekkera bruxellensis in alcoholic fermentations using saccharomycin-overproducing Saccharomyces cerevisiae strains.

Microbial contamination of alcoholic fermentation processes (e.g. winemaking and fuel-ethanol production) is a serious problem for the industry since it may render the product unacceptable and/or reduce its productivity, leading to large economic losses. Brettanomyces/Dekkera bruxellensis is one of the most dangerous microbial contaminant of ethanol industrial fermentations. In the case of wine, this yeast species can produce phenolic compounds that confer off-flavours to the final product. In fuel-ethanol fermentations, D. bruxellensis is a persistent contaminant that affects ethanol yields and productivities. We recently found that Saccharomyces cerevisiae secretes a biocide, which we named saccharomycin, composed of antimicrobial peptides (AMPs) derived from the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Saccharomycin is active against several wine-related yeast species, namely D. bruxellensis. However, the levels of saccharomycin naturally secreted by S. cerevisiae during alcoholic fermentation are not sufficient to ensure the complete death of D. bruxellensis. Therefore, the aim of the present work was to construct genetically modified S. cerevisiae strains to overproduce these GAPDH-derived AMPs. The expression levels of the nucleotides sequences encoding the AMPs were evaluated in the modified S. cerevisiae strains by RT-qPCR, confirming the success of the recombinant approach. Furthermore, we confirmed by immunological tests that the modified S. cerevisiae strains secreted higher amounts of the AMPs by comparison with the non-modified strain, inducing total death of D. bruxellensis during alcoholic fermentations.

Cardiac Surgery in Patients with Dialysis-dependent End Stage Renal Failure: Single Centre Experience.

BACKGROUND: Patients under dialysis have a high cardiovascular risk and they are at increased risk when submitted to cardiac surgery. AIM OF THE STUDY: to evaluate morbidity, early and late mortality, and predictive factors of mortality in patients under dialysis who underwent cardiac surgery. METHODS: A retrospective observational study was performed including all dialysis dependent patients who underwent cardiac surgery (coronary, valvular or combined procedures) in our institution between 2007 and 2014. A population of 95 consecutive patients was obtained (no exclusions). Perioperative variables and predictors of mortality were analysed and the endpoints were early and late mortality. Propensity score matching, with a control group of patients with creatinine clearance >90mL/min, was performed by logistic regression, with a 1:1 matching. Kaplan Meier curves were performed for late mortality. RESULTS: Early mortality was 9.4% (EuroSCORE II 4.1%). In univariate analysis, mean time of cardiopulmonary bypass (CPB) (p=0.016) and EuroSCORE II (p=0.02) were related with early mortality. In a multivariate analysis model, combined procedures (OR 138.09; CI95% 1.82-10498.4; p=0.03) and CCS (Canadian Cardiovascular Society) 3-4 (OR 70.951; CI 95% 1.32-3810.11; p=0.037) were predictors of mortality. In multivariable analysis, CPB time >152 min was a predictor of early mortality (p=0.001). After propensity score matching, 30 day, one year and late mortality were higher in the dialysis group. CONCLUSIONS: Early and late mortality were significantly higher in dialysis dependent patients. Predictive factors of mortality were CPB time and EuroSCORE II in univariable analysis, and CCS 3-4 and combined procedures in multivariable analysis.

Genistein and Ascorbic Acid Reduce Oxidative Stress-Derived DNA Damage Induced by the Antileishmanial Meglumine Antimoniate.

Meglumine antimoniate (Glucantime) is a pentavalent antimonial used to treat leishmaniasis, despite its acknowledged toxic effects, such as its ability to cause oxidative damage to lipids and proteins. Recently, our group demonstrated that meglumine antimoniate causes oxidative stress-derived DNA damage. Knowing that antioxidants modulate reactive oxygen species, we evaluated the capacity of genistein and ascorbic acid for preventing genotoxicity caused by meglumine antimoniate. For that, mice (n = 5/group) received genistein (via gavage) in doses of 5, 10, and 20 mg/kg for three consecutive days. After this period, they were treated with 810 mg/kg meglumine antimoniate via intraperitoneal (i.p.) route. Furthermore, mice (n = 5/group) simultaneously received ascorbic acid (i.p.) in doses of 30, 60, and 120 mg/kg and 810 mg/kg meglumine antimoniate. We also conducted post- and pretreatment assays, in which animals received ascorbic acid (60 mg/kg) 24 h prior to or after receiving meglumine antimoniate. Genomic instability and mutagenicity were analyzed through conventional comet assay and enzymatic assay using formamide pyrimidine DNA glycosylase (Fpg) enzyme, as well as the micronucleus test, respectively. Meglumine antimoniate induced an increase in the DNA damage after digestion with Fpg, reinforcing its mutagenic potential by oxidizing DNA bases, which was prevented by genistein. Similarly, ascorbic acid was capable of reducing mutagenic effects in simultaneous treatment as well as in posttreatment. Therefore, our results demonstrate that both compounds are efficient in preventing mutations in mammalian cells treated with meglumine antimoniate.

Effect of GAPDH-derived antimicrobial peptides on sensitive yeasts cells: membrane permeability, intracellular pH and H+-influx/-efflux rates.

Saccharomyces cerevisiae secretes antimicrobial peptides (AMPs) derived from glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which induce the death of several non-Saccharomyces yeasts. Previously, we demonstrated that the naturally secreted GAPDH-derived AMPs (i.e. saccharomycin) caused a loss of culturability and decreased the intracellular pH (pHi) of Hanseniaspora guilliermondii cells. In this study, we show that chemically synthesised analogues of saccharomycin also induce a pHi drop and loss of culturability in H. guilliermondii, although to a lesser extent than saccharomycin. To assess the underlying causes of the pHi drop, we evaluated the membrane permeability to H+ cations of H. guilliermondii cells, after being exposed to saccharomycin or its synthetic analogues. Results showed that the H+-efflux decreased by 75.6% and the H+-influx increased by 66.5% in cells exposed to saccharomycin at pH 3.5. Since H+-efflux via H+-ATPase is energy dependent, reduced glucose consumption would decrease ATP production and consequently H+-ATPase activity. However, glucose uptake rates were not affected, suggesting that the AMPs rather than affecting glucose transporters may affect directly the plasma membrane H+-ATPase or increase ATP leakage due to cell membrane disturbance. Thus, our study revealed that both saccharomycin and its synthetic analogues induced cell death of H. guilliermondii by increasing the proton influx and inhibiting the proton efflux.

Peritoneal dialysis is a reasonable option in patients with cardiovascular disease
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INTRODUCTION: Peritoneal dialysis (PD) has been proposed as a therapeutic option for patients with end-stage renal disease (ESRD) and cardiovascular (CV) disease. The study presented here aimed to compare incident PD patients with and without CV disease at baseline, in order to determine the impact of CV disease in the outcomes of long-term PD patients. METHODS: This is a prospective cohort study performed at a single PD unit where 112 consecutive incident patients admitted to the PD program during 5 years were studied. The background of CV disease at PD initiation was defined as: presence of coronary artery disease, cerebrovascular disease, heart failure, or peripheral arterial disease. Laboratory measurements as well as PD adequacy were obtained at the beginning of PD and at the last evaluation. The outcomes examined were patient and technique survival, hospitalization and peritonitis rate. RESULTS: Prevalence of diabetes was higher in patients with CV disease (53.3% vs. 31.7%, p = 0.036). Patients who suffered from CV disease were, on average, older (62.8 ± 13.1 vs. 49.7 ± 15.7 years, p < 0.05). There were no significant differences in other demographic or clinical variables, including hospital admissions (0.99 vs. 0.72 episodes/patient-year, p = 0.057) or peritonitis rates (0.69 vs. 0.61 episodes/patient-year, p = 0.652). The overall rates of PD technique failure were similar between both groups (CV disease patients: 12.7 transfers to hemodialysis (HD)/100 patient-years vs. CONTROL: 13.7 transfers to HD/100 patient-year; p = 0.54). Diabetes and age were independently associated with the presence of CV disease (p = 0.011), in a model adjusted for time on PD. The mortality rate was higher in CV disease patients (14.9 vs. 0.8 deaths/100 patient-years, p = 0.000) and 75% of all-cause mortality occurred in diabetic patients. In a multivariate analysis, diabetes (hazard ratio (HR): 5.5, confidence interval (CI): 0.84 - 36.29, p = 0.049) and age (HR: 1.07, CI: 1.0 - 1.13, p = 0.047) were independent predictors of death in a model adjusted for residual diuresis, body mass index, and time on PD. CONCLUSIONS: This study compared incident PD patients with and without CV disease. CV disease patients were older but clinical and laboratorial targets, peritonitis rates, hospitalizations, and technique survival were similar between both groups, suggesting PD as an effective therapy for patients with CV comorbidities.
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Antimicrobial properties and death-inducing mechanisms of saccharomycin, a biocide secreted by Saccharomyces cerevisiae.

We recently found that Saccharomyces cerevisiae (strain CCMI 885) secretes antimicrobial peptides (AMPs) derived from the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) that are active against various wine-related yeast and bacteria. Here, we show that several other S. cerevisiae strains also secrete natural biocide fractions during alcoholic fermentation, although at different levels, which correlates with the antagonistic effect exerted against non-Saccharomyces yeasts. We, therefore, term this biocide saccharomycin. The native AMPs were purified by gel-filtration chromatography and its antimicrobial activity was compared to that exhibited by chemically synthesized analogues (AMP1 and AMP2/3). Results show that the antimicrobial activity of the native AMPs is significantly higher than that of the synthetic analogues (AMP1 and AMP2/3), but a conjugated action of the two synthetic peptides is observed. Moreover, while the natural AMPs are active at pH 3.5, the synthetic peptides are not, since they are anionic and cannot dissolve at this acidic pH. These findings suggest that the molecular structure of the native biocide probably involves the formation of aggregates of several peptides that render them soluble under acidic conditions. The death mechanisms induced by the AMPs were also evaluated by means of epifluorescence microscopy-based methods. Sensitive yeast cells treated with the synthetic AMPs show cell membrane disruption, apoptotic molecular markers, and internalization of the AMPs. In conclusion, our work shows that saccharomycin is a natural biocide secreted by S. cerevisiae whose activity depends on the conjugated action of GAPDH-derived peptides. This study also reveals that S. cerevisiae secretes GAPDH-derived peptides as a strategy to combat other microbial species during alcoholic fermentations.

Peritoneal dialysis as a successful treatment in patients with refractory congestive heart failure: a one-center experience.

INTRODUCTION: Ultrafiltration (UF) technique is a valuable alternative to pharmacological therapy in the treatment of patients with refractory congestive heart failure (HF). The aim of this study was to describe a single-center experience in the treatment of refractory HF patients with peritoneal dialysis (PD). METHODS: Retrospective study of 5 patients included in a single PD Unit, showing symptoms and signs of severe refractory congestive HF to optimal pharmacological therapy (NYHA class IV). Clinical and laboratory parameters, survival, hospitalization, and peritonitis rates were recorded. RESULTS: Patients were followed for 9.36 (± 6.36) months; population mean age was 62 (± 16) years and Charlson's comorbidity index was 7.2 (± 2.1). After PD therapy, functional class of NYHA significantly improved (class IV to class II in 4 patients). Doppler-echocardiography improved in terms of ejection fraction (EF) or systolic pressure of the pulmonary artery (SPPA) in 3 patients. No patient was readmitted due to HF. Hospitalization days substantially decreased in 4 patients. One patient presented with peritonitis episodes. Three patients died but the mean survival was higher than expected according to their comorbidity index. CONCLUSION: PD, applied to refractory HF in addition to optimal pharmacological therapy, improves quality of life and functional class and reduces hospitalization days due to HF.

Soy isoflavones have antimutagenic activity on DNA damage induced by the antileishmanial Glucantime (meglumine antimoniate).

Isoflavones are phytoestrogens reported to be potent antioxidant agents. In contrast, the antileishmanial meglumine antimoniate has mutagenic activities. This study evaluated the ability of soy isoflavones to reduce DNA damage induced by meglumine antimoniate. Antimutagenic effects (by micronucleus test) were tested using Swiss mice divided into seven groups treated with meglumine antimoniate (425 mg/kg bw pentavalent antimony); cyclophosphamide (50 mg/kg bw); water (negative control); single isoflavones dose (1.6 mg/kg bw), and three groups received one dose of isoflavones via gavage (0.4 mg/kg bw, 0.8 mg/kg bw or 1.6 mg/kg bw) plus meglumine antimoniate via intraperitoneal, simultaneously. To evaluate antigenotoxicity (by Comet assay), each group with 10 animals received the above-mentioned control doses; single dose of isoflavones 0.8 mg/kg bw, and three groups received isoflavones (0.8 mg/kg bw) by gavage along with intraperitoneal meglumine antimoniate, which were treated with isoflavones 24 h before or after receiving meglumine antimoniate (pre-treatment and post-treatment, respectively) or simultaneously. Cells were harvested 24 h after the treatment, and the data were evaluated by ANOVA followed by Tukey's test (p < 0.05). The data from the simultaneous treatment by micronucleus test revealed that isoflavones (0.4 and 0.8 mg/kg) were able to reverse the mutagenic effect of Glucantime. Moreover, all regimes of the treatment with 0.8 mg/kg bw dose were able to reduce the genotoxicity caused by meglumine antimoniate. It is suggested that the protective effect of isoflavones against DNA damage is related to their ability to reduce oxidative stress caused by the trivalent Sb(III) metabolite of meglumine antimoniate.

Identification of novel GAPDH-derived antimicrobial peptides secreted by Saccharomyces cerevisiae and involved in wine microbial interactions.

Saccharomyces cerevisiae plays a primordial role in alcoholic fermentation and has a vast worldwide application in the production of fuel-ethanol, food and beverages. The dominance of S. cerevisiae over other microbial species during alcoholic fermentations has been traditionally ascribed to its higher ethanol tolerance. However, recent studies suggested that other phenomena, such as microbial interactions mediated by killer-like toxins, might play an important role. Here we show that S. cerevisiae secretes antimicrobial peptides (AMPs) during alcoholic fermentation that are active against a wide variety of wine-related yeasts (e.g. Dekkera bruxellensis) and bacteria (e.g. Oenococcus oeni). Mass spectrometry analyses revealed that these AMPs correspond to fragments of the S. cerevisiae glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein. The involvement of GAPDH-derived peptides in wine microbial interactions was further sustained by results obtained in mixed cultures performed with S. cerevisiae single mutants deleted in each of the GAPDH codifying genes (TDH1-3) and also with a S. cerevisiae mutant deleted in the YCA1 gene, which codifies the apoptosis-involved enzyme metacaspase. These findings are discussed in the context of wine microbial interactions, biopreservation potential and the role of GAPDH in the defence system of S. cerevisiae.

Transitioning to peritoneal dialysis: it does not matter where you come from.

INTRODUCTION: Patients with end-stage renal disease (ESRD) frequently change renal replacement (RRT) therapy modality due to medical or social reasons. We aimed to evaluate the outcomes of patients under peritoneal dialysis (PD) according to the preceding RRT modality. METHODS: We conducted a retrospective observational single-center study in prevalent PD patients from January 1, 2010, to December 31, 2017, who were followed for 60 months or until they dropped out of PD. Patients were divided into three groups according to the preceding RRT: prior hemodialysis (HD), failed kidney transplant (KT), and PD-first. RESULTS: Among 152 patients, 115 were PD-first, 22 transitioned from HD, and 15 from a failing KT. There was a tendency for ultrafiltration failure to occur more in patients transitioning from HD (27.3% vs. 9.6% vs. 6.7%, p = 0.07). Residual renal function was better preserved in the group with no prior RRT (p < 0.001). A tendency towards a higher annual rate of peritonitis was observed in the prior KT group (0.70 peritonitis/year per patient vs. 0.10 vs. 0.21, p = 0.065). Thirteen patients (8.6%) had a major cardiovascular event, 5 of those had been transferred from a failing KT (p = 0.004). There were no differences between PD-first, prior KT, and prior HD in terms of death and technique survival (p = 0.195 and p = 0.917, respectively) and PD efficacy was adequate in all groups. CONCLUSIONS: PD is a suitable option for ESRD patients regardless of the previous RRT and should be offered to patients according to their clinical and social status and preferences.

Incremental Peritoneal Dialysis-Definition, Prescription, and Clinical Outcomes.

ABSTRACT: Incremental peritoneal dialysis (IPD) is a strategy of RRT that is based on the prescription of a lower dose rather than the standard full dose of peritoneal dialysis (PD). The clearance goals are achieved through the combination of residual kidney function (RKF) and peritoneal clearance. The dialysis prescription should be increased as the RKF declines. IPD has been associated with clinical, economic, and environmental advantages. We emphasize possible better quality of life, fewer mechanical symptoms, lower costs, slight adverse metabolic effects, and less plastic waste and water consumption. The potential benefits for RKF preservation and the lower risk of peritonitis have also been discussed. There are some concerns regarding this strategy, such as inadequate clearance of uremic toxins and/or severe electrolyte disturbances due to undetected loss of RKF, lower clearance of medium-sized molecules (such as ß-2-microglobulin) which mostly depends on the total PD dwell time, and patients' reluctance to dose adjustments. Current clinical evidence is based on moderate-quality to low-quality studies and suggests that the outcomes of IPD will be at least identical to those of full dose. This review aims to define IDP, discuss strategies for prescription, and review its advantages and disadvantages according to the current evidence.