Assessing the role of Chemokine (C-C motif) ligand 14 in AKI: a European consensus meeting.

BACKGROUND: Urinary Chemokine (C-C motif) ligand 14 (CCL14) is a biomarker associated with persistent severe acute kidney injury (AKI). There is limited data to support the implementation of this AKI biomarker to guide therapeutic actions. METHODS: Sixteen AKI experts with clinical CCL14 experience participated in a Delphi-based method to reach consensus on when and how to potentially use CCL14. Consensus was defined as ≥ 80% agreement (participants answered with 'Yes', or three to four points on a five-point Likert Scale). RESULTS: Key consensus areas for CCL14 test implementation were: identifying challenges and mitigations, developing a comprehensive protocol and pairing it with a treatment plan, and defining the target population. The majority agreed that CCL14 results can help to prioritize AKI management decisions. CCL14 levels above the high cutoff (> 13 ng/mL) significantly changed the level of concern for modifying the AKI treatment plan (p < 0.001). The highest level of concern to modify the treatment plan was for discussions on renal replacement therapy (RRT) initiation for CCL14 levels > 13 ng/mL. The level of concern for discussion on RRT initiation between High and Low, and between Medium and Low CCL14 levels, showed significant differences. CONCLUSION: Real world urinary CCL14 use appears to provide improved care options to patients at risk for persistent severe AKI. Experts believe there is a role for CCL14 in AKI management and it may potentially reduce AKI-disease burden. There is, however, an urgent need for evidence on treatment decisions and adjustments based on CCL14 results.

A Brief Review on the Electrohydrodynamic Techniques Used to Build Antioxidant Delivery Systems from Natural Sources.

Extracts from plants have been one of the main sources of antioxidants, namely polyphenols. The associated drawbacks, such as instability against environmental factors, low bioavailability, and loss of activity, must be considered during microencapsulation for a better application. Electrohydrodynamic processes have been investigated as promising tools to fabricate crucial vectors to minimize these limitations. The developed microstructures present high potential to encapsulate active compounds and for controlling their release. The fabricated electrospun/electrosprayed structures present different benefits when compared with structures developed by other techniques; they present a high surface-area-to-volume ratio as well as porosity, great materials handling, and scalable production-among other advantages-which make them able to be widely applied in different fields, namely in the food industry. This review presents a summary of the electrohydrodynamic processes, main studies, and their application.

Climate-Change Adaptation Framework for Multiple Urban Areas in Northern Portugal.

Climate change is increasingly exerting pressure with intensified impacts in the short-, medium-, and long-term. Cities are highly vulnerable to the impacts of climate change, and it is recognized that they play a significant role in the European Strategy on adaptation to climate change. This study intends to develop a climate adaptation framework to identify effective measures that will be evaluated using a multi-urban area located in the north of Portugal, as a case study. The climate adaptation framework was developed following the Urban Adaptation Support Tool (AST), adapted to the Portuguese reality. The Weather Research and Forecasting (WRF) model was used to provide future projections with a high level of spatial resolution over the study area, increasing the accuracy of the identification of future climatic vulnerabilities. The results show a tendency for an increase of extreme weather events associated with the increase of both temperature and annual accumulated precipitation variables. A set of both urban and rural measures to promote a sustainable development path to climate adaptability and increase cities resilience to climate change are presented and discussed.

Is the management of diabetes different in dialysis patients?

Diabetes is highly and increasingly prevalent in the dialysis population and negatively impacts both quality and quantity of life. Nevertheless, the best approach to these patients is still debatable. The question of whether the management of diabetes should be different in dialysis patients does not have a clear yes or no answer but is divided into too many sub-issues that should be carefully considered. In this review, lifestyle, cardiovascular risk, and hyperglycemia management are explored, emphasizing the possible pros and cons of a similar approach to diabetes in dialysis patients compared to the general population.

Renal regeneration after acute kidney injury.

Acute kidney injury is common and associated with negative renal and patient outcomes. The human kidney has a real but limited regeneration capacity. Understanding renal regeneration may allow us to manipulate this process and thus develop therapeutic weapons to improve patients' outcome. In the first part of this paper we discuss the clinical factors associated with renal recovery: baseline patient particularities, acute kidney injury characteristics and the medical approach taken in the short and long-term. In the second part, the cellular and molecular mechanisms underlying renal regeneration are explored. The immune system seems to have an important role, first promoting inflammation and then tissue healing. Other players, such as cellular senescence, mitochondrial dysfunction, renal haemodynamics and metabolic reprogramming also have a role in renal regeneration. We aim to develop a short review of renal regeneration, offering a holistic view of this process.

What is the Role of HbA1c in Diabetic Hemodialysis Patients?

The definition of a good glycemic control in patients with diabetes mellitus on hemodialysis is far from settled. In the general population, hemoglobin A1c is highly correlated with the average glycemia of the last 8-12 weeks. However, in hemodialysis patients, the correlation of hbA1c with glycemia is weaker as it also reflects changes in hemoglobin characteristics and red blood cells half-life. As expected, studies show that the association between HbA1c and outcomes in these patients differ from the general population. Therefore, the value of HbA1c in the treatment of hemodialysis patients has been questioned. Guidelines are generally cautious in their recommendations about possible targets of HbA1c in this population. Indeed, the risk of not treating hyperglycemia should be weighed against the particularly high risk of precipitating hypoglycemia in dialysis patients. In this review, a critical analysis of the current role of HbA1c in the care of hemodialysis patients is presented.

Structural characterization of functionalized gold nanoparticles for drug delivery in cancer therapy: a NMR based approach.

In the present paper, we report results from a study of the structure and physicochemical properties of gold nanoparticles modified with poly(ethylene glycol) (PEG) designed for the drug delivery of the proteasome inhibitor Bortezomib (BTZ) in cancer therapy. A number of advanced analytical techniques were used to define important physicochemical characteristics such as composition, structure, surface properties, particle size and morphology. A new approach based on detailed NMR studies was employed to define specific intermolecular interactions and mechanisms of drug immobilization and location into surface modified gold nanoparticles (AuNPs). Particularly important information was gained from analysis of NMR spectroscopic parameters such as the spectral line shape, translation diffusion, the nuclear Overhauser effect (NOE) and spin-lattice relaxation (T1). The results confirmed the coexistence of two different types of BTZ inclusion into polyethylene glycol coated gold nanoparticles: (i) association with the polymer chains by weak H-bonds and/or dipole-charge interactions and (ii) adsorption on the surface of the gold nanoparticles. The results allowed for determination of the overall structure of Bortezomib loaded PEG coated AuNPs, which is related to the therapeutic drug efficacy and activity in the treatment of cancer.

Effects of the organic matter from swine wastewater on the adsorption and desorption of alachlor in soil.

The application of swine wastewater to the soil for agricultural purposes results in the addition of total and dissolved organic matter to the soil, which may interfere with the dynamics of pesticides in the soil. The objective of this study was to evaluate the effects of the application of total and dissolved organic matter from a biodigester and a treatment lagoon of swine wastewater in the adsorption and desorption of alachlor [2-chloro-2,6-diethyl-N(methoxymethyl acetamide)]. The assay was performed by the batch equilibrium method, and the results were fitted to the Freundlich model. The curve comparison test revealed a greater adsorption of alachlor in the soil treated with swine wastewater from the biodigester. The adsorption and desorption of alachlor increased in the soils where swine wastewater was added, and hysteresis was observed in all of the treatments.

Recent Advances in Water-Soluble Vitamins Delivery Systems Prepared by Mechanical Processes (Electrospinning and Spray-Drying Techniques) for Food and Nutraceuticals Applications-A Review.

Water-soluble vitamins are essential micronutrients in diets and crucial to biochemical functions in human body physiology. These vitamins are essential for healthy diets and have a preventive role against diseases. However, their limitations associated with high sensitivity against external conditions (temperature, light, pH, moisture, oxygen) can lead to degradation during processing and storage. In this context, microencapsulation may overcome these conditions, protecting a biomolecule's bioavailability, stability, and effectiveness of delivery. This technique has been used to produce delivery systems based on polymeric agents that surround the active compounds. The present review focuses on the most relevant topics of water-soluble vitamin encapsulation using promising methods to produce delivery vehicles-electrohydrodynamic (electrospinning and electrospraying) and spray-drying techniques. An overview of the suitable structures produced by these processes is provided. The review introduces the general principles of the methods, advantages, disadvantages, and involved parameters. A brief list of the used physicochemical techniques for the systems' characterization is discussed in this review. Electrospinning and spray-drying techniques are the focus of this investigation in order to guarantee vitamins' bioaccessibility and bioavailability. Recent studies and the main encapsulating agents used for these micronutrients in both processes applied to functional food and nutraceutical areas are highlighted in this review.

Electrospinning of Microstructures Incorporated with Vitamin B9 for Food Application: Characteristics and Bioactivities.

The food industry has been expanding, and new vectors to entrap vitamins have been constantly investigated, aiming at versatile systems with good physico-chemical characteristics, low-cost production, high stability and the efficient release of active ingredients. The vitamin B9 (folic acid or folate) is essential for the healthy functioning of a variety of physiological processes in humans and is beneficial in preventing a range of disorders. In this study, two approaches were developed to encapsulate vitamin B9. Zein and the combination of modified starch with two plasticizers were the selected encapsulating agents to produce microstructures via the electrospinning technique. The objective was to improve the stability and the B9 antioxidant capacity in the final formulations. The work strategy was to avoid limitations such as low bioavailability, stability and thermosensitivity. The microstructures were fabricated and the morphology and shape were assessed by scanning electron microscopy. The B9 release profiles of modified starch and zein microstructures were analyzed in simulated gastric fluid at 37 °C, and in deionized water and ethanol at room temperature. The B9 encapsulation efficiency and the stability of the systems were also studied. The ABTS assay was assessed and the antioxidant activity of the produced microstructures was evaluated. The physico-chemical characterization of loaded B9 in the microstructures was achieved. High encapsulation efficiency values were achieved for the 1% B9 loaded in 12% w/w modified starch film; 5% B9 vitamin encapsulated by the 15% w/w modified starch with 4% w/w tween 80; and 4% w/w glycerol film with heterogeneous microstructures, 5% w/w zein compact film and 10% w/w zein film. In conclusion, the combinations of 7 wt.% of modified starch with 4 wt.% tween 80 and 4 wt.% glycerol; 15 wt.% of modified starch with 4 wt.% tween 80 and 4 wt.% glycerol; and 12 wt.% modified starch and 5 wt.% zein can be used as delivery structures in order to enhance the vitamin B9 antioxidant activity in the food and nutraceutical fields.

Nanocarriers Based on Gold Nanoparticles for Epigallocatechin Gallate Delivery in Cancer Cells.

Gold nanoparticles (AuNPs) are inorganic and biocompatible nanovehicles capable of conjugating biomolecules to enhance their efficacy in cancer treatment. The high and reactive surface area provides good advantages for conjugating active compounds. Two approaches were developed in this work to improve the Epigallocatechin-3-gallate (EGCG) antioxidant efficacy. AuNPs were synthesized by reducing gold salt with chitosan. One other nanosystem was developed by functionalizing AuNPs with cysteamine using the Turkevitch method. The physico-chemical characterization of EGCG conjugated in the two nanosystems-based gold nanoparticles was achieved. The in vitro toxic effect induced by the nanoconjugates was evaluated in pancreatic cancer cells, showing that encapsulated EGCG keeps its antioxidant activity and decreasing the BxPC3 cell growth. A significant cell growth inhibition was observed in 50% with EGCG concentrations in the range of 2.2 and 3.7 µM in EGCG-ChAuNPs and EGCG-Cyst-AuNPs nanoconjugates, respectively. The EGCG alone had to be present at 23 µM to induce the same cytotoxicity response. Caspase-3 activity assay demonstrated that the conjugation of EGCG induces an enhancement of BxPC3 apoptosis compared with EGCG alone. In conclusion, AuNPs complexes can be used as delivery carriers to increase EGCG antioxidant activity in cancer tissues.

Optimization of electrospinning parameters for the production of zein microstructures for food and biomedical applications.

Electrohydrodynamic techniques have been focus for the development of structures for encapsulation purposes. Their physico-chemical characteristics confer them significant benefits for food and nutraceutical applications. The study reports the optimization of zein microstructures (electrosprayed beads/electrospun fibers/films). The effect of zein polymer properties (viscosity and conductivity), flow rate, applied voltage and distance tip-collector were investigated. Results by scanning electron microscopy revealed the morphology observed with zein. The importance of chain entanglement for fibers/beads/films formation in the optimum conditions system was evaluated. Compact electrosprayed microbeads with diameters ranging from 0.9 µm to 2.0 µm were obtained for 5 wt.% zein solution. For 30 wt.% zein, uniform smooth electrospun fibers with diameters of approximately 0.60 to 0.75 µm were produced. Films with different characteristics (with more or less homogeneous matrix and more or less bubbles) were also obtained. The developed zein microstructures are potential vectors that might encapsulate bioactive ingredients for functional food, nutraceutical and medical applications.

Urinary immune cell phenotype of severe AKI in critically ill patients.

PURPOSE: Cellular mechanisms involved in human renal recovery after an episode of acute kidney injury (AKI) are understudied. We aim to characterize the urinary immune cell phenotype of patients with AKI and evaluate its ability to predict renal recovery. METHODS: A prospective study of critically ill patients with stage ≥ 2 AKI by KDIGO and sterile leukocyturia at admission was performed. Urine samples were collected fresh at day 0 and 2 and samples were analyzed by flow cytometry for different leukocytes. Patients were categorized in renal recovery or no-recovery groups. RESULTS: 28 patients were included, all with sepsis, 60.7% of which recovered renal function. The main urinary leukocytes present were neutrophils, followed by mononuclear phagocytic cells and B cells. Patients who recovered renal function had more M2 macrophages at day 2 (p = 0.043) and less B cells at admission (p = 0.006). M2 macrophages had an AUC-ROC of 0.796 (0.601-0.990) for recovery prediction and B cells an AUC-ROC of 0.743 (0.560-0.926) for no recovery. B regulatory cells were found in the urine of AKI patients. CONCLUSIONS: The urinary immune cell phenotype of severe AKI patients was composed essentially of neutrophils, mononuclear phagocytic cells and B cells. Our data suggest that M2 macrophages may promote and B cells preclude renal recovery. More studies are needed to validate our results and further explore the role of immune cells in renal recovery.

Encapsulation in food industry with emerging electrohydrodynamic techniques: Electrospinning and electrospraying - A review.

Nowadays the world population has been more conscious about healthy food products based on bioactive ingredients in order to protect against diseases and to develop healthy diets. Emerging electrohydrodynamic techniques have been object of interest in the scientific community as well as in the industry. In fact, electrospinning and electrospraying methods are promising techniques to fabricate delivery vehicles. These vehicles present structural and functional benefits for encapsulation of bioactive ingredients. They can be used in several food and nutraceutical matrices, protecting the ingredients from environmental conditions. They can also enhance biomolecules bioavailability and controlled release, at the same time that improve the product's shelf life. This review provides the recent state of art for electrospinning/electrospraying techniques. It highlights the crucial parameters that influence these techniques. Further, the recent studies of vitamins encapsulation for applications in functional foods and nutraceuticals fields are summarized. Electrosprayed particles/electrospun fibres are easily produced and present suitable physico-chemical characteristics to encapsulate bioactives to improve the functional foods.

Leptospirosis, a Re-emerging Threat.

Leptospirosis is a zoonosis transmitted by an animal vector and caused by the spirochete bacteria Leptospira. Human infection is rare and acquired by exposure to environmental sources (animal urine, contaminated water, soil, or infected animal tissue). It can have an extremely broad presentation, ranging from asymptomatic to serious illness. We report the case of a 59-year-old man admitted to the hospital with myalgia, fever, and abdominal discomfort. Routine laboratory tests revealed raised inflammatory markers, thrombocytopenia, kidney dysfunction, and hepatic cytolysis and cholestasis. The hypothesis of zoonosis was raised based on symptoms and analytical changes despite the weak epidemiological history to support it. Although leptospira serology tests were negative on admission, a polymerase chain reaction test was requested due to a high degree of suspicion which came back positive. The patient completed eight days of doxycycline with favorable clinical and analytical progression. This case highlights the changing epidemiology of leptospirosis and the importance of having a high degree of suspicion even outside endemic zones. It also highlights the importance of a wise choice of diagnostic tests according to the disease stage.

Impact of sterile leukocyturia on outcome of critically ill patients with severe acute kidney injury.

INTRODUCTION: The role of immunological mechanisms on renal regeneration and functional recovery after an episode of Acute Kidney Injury (AKI) is still understudied. We aim to evaluate the impact of sterile leukocyturia on outcomes of critically-ill AKI patients. METHODS: A retrospective analysis of critically-ill patients with stage ≥2 AKI by KDIGO was performed. Patients with urinary tract infection, previous renal replacement therapy, chronic kidney disease stage >3 and kidney, urinary tract or prostatic cancer were excluded. Sterile leukocyturia was defined as a positive leukocyte esterase value. RESULTS: 108 patients with stage ≥2 AKI were included, 39.8% of which had sterile leukocyturia. AKI patients with sterile leukocyturia were older, had more cardiovascular disease and a lower baseline renal function (p < 0.05). They had a higher serum creatinine and leukocytosis at admission, were more frequently septic (p < 0.05) and had more persistent AKI by both KDIGO criteria at multivariable analysis (OR 6.130, 95% CI 2.007-18.747). CONCLUSION: Sterile leukocyturia was associated with different patient baseline and AKI characteristics and more persistent AKI by both KDIGO criteria. Sterile leukocyturia may represent a surrogate marker of renal inflammation during AKI.

Reactivation of SARS-CoV-2 after Asymptomatic Infection while on High-Dose Corticosteroids. Case Report.

As SARS-CoV-2 and its related clinical syndrome (COVID-19) became a pandemic worldwide, questions regarding its clinical presentation, infectivity, and immune response have been the subject of investigation. We present a case of a patient previously considered recovered from nosocomially transmitted asymptomatic COVID-19 illness, who presented with new respiratory, radiological, and RT-PCR findings consistent with COVID-19, while on high-dose prednisolone due to a suspected secondary demyelinating disease. Importantly, it led to three subsequent cases within patient's household after discharge from the hospital. After reviewing this case in light of current evidence and debates surrounding SARS-CoV-2 RT-PCR results, we hypothesize that patients on corticosteroids may have particular viral shedding dynamics and should prompt a more conservative approach in regard to isolation discontinuation and monitoring.

Doxorubicin and Varlitinib Delivery by Functionalized Gold Nanoparticles Against Human Pancreatic Adenocarcinoma.

The aim of this study was to develop drug delivery nanosystems based on pegylated gold nanoparticles (PEGAuNPs) for a combination against pancreatic cancer cells. Doxorubicin and varlitinib, an anthracycline and a tyrosine kinase inhibitor respectively, were conjugated with gold nanoparticles. The systems were characterized, after synthesis, regarding their size, stability and morphology. An efficient conjugation of doxorubicin and varlitinib with PEGAuNPs was revealed. The cytotoxicity effect induced by the combination of the nanoconjugates was investigated in pancreatic cancer cell lines. Doxorubicin and varlitinib conjugated with PEGAuNPs revealed a combined effect to decrease the cell survival of the cancer line S2-013s, while reducing the drugs' toxicity for the healthy pancreatic cells hTERT-HPNE. This study highlights the promising potential of PEGAuNPs for targeted delivery of therapeutic drugs into human cells, enhancing the antitumor growth-inhibition effect on cancer cells, and decreasing the toxicity against normal cells. In cancer therapy, the present approach based on PEGAuNP functionalization can be further explored to increase drug targeting efficiency and to reduce side effects.

Transient and persistent acute kidney injury in acute liver failure.

BACKGROUND: Acute Kidney Injury (AKI) is a very frequent complication in the Acute Liver Failure (ALF) population associated with negative outcomes. We aim to evaluate the impact of AKI duration on the outcomes of an ALF population. METHODS: A 20-year retrospective analysis of ALF patients admitted to an Intensive Care Unit (ICU) was performed. Chronic liver failure, chronic kidney disease on renal replacement therapy, dialysis requirement within the week prior or an ICU stay of less than 48 h after AKI diagnosis, were exclusion criteria. AKI was defined according to the KDIGO criteria and classified into transient (< 48 h duration) or persistent (48 h duration). RESULTS: A total of 51 patients were included in the analysis and most had AKI (66.7%). Persistent AKI patients (70.6%) presented more frequently with AKI at admission and a higher SOFA score than transient AKI and no AKI, p < 0.05. More severe AKI, sepsis, vasopressor support and mechanical ventilation were also more common (p < 0.05). Nineteen (55.9%) were classified as persistent AKI exclusively by serum creatinine and 15 (44.1%) by both serum creatinine and urine output criteria. Mean survival time at 30 days was 11.3 days for persistent AKI, 25.3 days for transient AKI and 27.0 days for no AKI, p = 0.01. Adjusted multivariate cox regression analysis showed that persistent AKI predicted in-hospital mortality but it lost significance when AKI severity was introduced in the model. CONCLUSION: Persistent AKI was common in ALF patients and associated with more severe AKI, worst systemic complications and a higher 30-day mortality, compared to transient and no AKI patients.