A soft computing approach to kidney diseases evaluation

Kidney renal failure means that one’s kidney have unexpectedly stopped functioning, i.e., once chronic disease is exposed, the presence or degree of kidney dysfunction and its progression must be assessed, and the underlying syndrome has to be diagnosed. Although the patient’s history and physical examination may denote good practice, some key information has to be obtained from valuation of the glomerular filtration rate, and the analysis of serum biomarkers. Indeed, chronic kidney sickness depicts anomalous kidney function and/or its makeup, i.e., there is evidence that treatment may avoid or delay its progression, either by reducing and prevent the development of some associated complications, namely hypertension, obesity, diabetes mellitus, and cardiovascular complications. Acute kidney injury appears abruptly, with a rapid deterioration of the renal function, but is often reversible if it is recognized early and treated promptly. In both situations, i.e., acute kidney injury and chronic kidney disease, an early intervention can significantly improve the prognosis.The assessment of these pathologies is therefore mandatory, although it is hard to do it with traditional methodologies and existing tools for problem solving. Hence, in this work, we will focus on the development of a hybrid decision support system, in terms of its knowledge representation and reasoning procedures based on Logic Programming, that will allow one to consider incomplete, unknown, and even contradictory information, complemented with an approach to computing centered on Artificial Neural Networks, in order to weigh the Degree-of-Confidence that one has on such a happening. The present study involved 558 patients with an age average of 51.7 years and the chronic kidney disease was observed in 175 cases. The dataset comprise twenty four variables, grouped into five main categories. The proposed model showed a good performance in the diagnosis of chronic kidney disease, since the sensitivity and the specificity exhibited values range between 93.1 and 94.9 and 91.9–94.2 %, respectively

Digital clinical guidelines modelling

Oliveira T., Costa A., Neves J., Novais P., Digital Clinical Guidelines Modelling, Modelling and Simulation 2011, Novais P., Machado J., Analide C., Abelha A., (Eds.) (ESM’2011 – The 2011 European Simulation and Modelling Conference, Guimarães, Portugal) EUROSIS Publisher, ISBN: 978-9077381-66-3, pp 392-398, 2011.Healthcare environments are very demanding, because practitioners are required to consult many patients in a short period of time, increasing the levels of stress which usually harms the outcome of healthcare processes. The short time practitioners have with their patients does not facilitate informed decision making and checking all possibilities. A possible solution is the use of guideline-based applications, because they have the potential of being an effective means of both changing the process of healthcare and improving its outcomes. However, current Clinical Guidelines are available in text format as long documents, which render them difficult to consult and to integrate in clinical Decision Support Systems. With this paper we present a new model for guideline interpretation, in order to facilitate de development of guideline-based Decision Support Systems and to increase the availability of Clinical Guidelines at the moment of the clinical process. This model will also provide mechanisms to comply with cases where incomplete and uncertain information is present. The development and implementation of this model will be presented in the following pages

Novel 1-hydroxy-1,1-bisphosphonates derived from indazole: synthesis and characterization

Bisphosphonates (BPs) are an important class of drugs used in the treatment of abnormal calcium metabolism diseases. The first syntheses of bisphosphonates derived from indazole, substituted at the N-1, N-2 and C-3 positions are reported. The 1-hydroxy-1,1-bisphosphonates were synthesized from the corresponding carboxylic acid or acyl chloride compounds, by two different methods. These BPs have a side chain with different lengths ((CH2)n, n = 0-5) between the indazole ring and the bisphosphonate group

Sustainable lysis of Bacillus subtilis biomass to recover the biopharmaceutical L-asparaginase

The first-line biopharmaceutical used to treat Acute lymphoblastic leukemia (ALL), Oncaspar, is based on the enzyme L-asparaginase (ASNase), and has annual sales of ca. USD $100 million. In addition to other sources, genetically modified Bacillus subtilis is regarded as one of the most promising hosts for the ASNase production. The Aliivibrio fischeri ASNase type II, which has anti-tumour activity due its higher specific affinity for L-asparagine, expressed in B. subtillis is located in the periplasm. Therefore, cell lysis is required for the ASNase recovery. Nevertheless, typical cell lysis approaches, e.g. chemical methods with surfactants lead to some biocompatibility concerns and the need of extra purification steps. To overcome this drawback, in this work, ultrasound sonication (USS) conditions were studied to develop a greener and more biocompatible method for ASNase recovery from B. subtilis cell lysis. The USS cell lysis was optimized regarding the amplitude of USS pulse, number of lysis cycles and mass of cells/volume of solvent ratio. The identification and quantification of ASNase and major impurities present in the cell extract after lysis were investigated by sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE) and size exclusion high-performance liquid chromatography (SE-HPLC). ASNase activity was determined by monitoring the hydrolysis of the substrate, L-asparagine. The results obtained show that the ideal conditions for B. subtilis cell lysis are an amplitude of USS pulse of 60%, 40 cycles of lysis and 10 mL of phosphatebuffered saline (PBS) per 1 g of cells. Overall, an optimized sustainable B. subtilis cell lysis method was developed, avoiding the use of surfactants and with low energy consumption.publishe

Overview on protein extraction and purification using ionic-liquid-based processes

Proteins are one the most widely studied biomolecules with diverse functions and applications. Aiming at overcoming the current drawbacks of purification processes of proteins, the introduction of ionic liquids (ILs) has been a hot topic of research. ILs have been applied in the creation of aqueous biphasic systems (IL-based ABS), solid-phase extractions through poly(ionic liquid)s (PILs) and supported ionic-liquid phases (SILPs), and in the crystallization of proteins. In this sense, ILs have emerged as solvents, electrolytes or adjuvants, or as supported materials to tune the adsorption/affinity capacity aiming at developing an efficient, cost-effective, sustainable and green IL-based process for protein extraction. This review discusses different IL-based processes in the extraction and purification of proteins in the past years, namely IL-based aqueous biphasic systems (IL-based ABS), solid-phase extractions through PILs and SILPs, and protein crystallization. The type and structure of ILs applied and their influence in the different processes performance are also discussed.publishe

Reusability of L-asparaginase immobilized on silica-based supported ionic liquids

L-asparaginase (ASNase) is an aminohydrolase enzyme used as an anticancer drug, e.g. in the treatment of acute lymphoblastic leukemia, in acrylamide reduction and in biosensing. Nevertheless, its low stability and thermolability, and susceptibility to proteases, hinder its application in the health and food industries. Hence, the improvement of its properties through efficient immobilization methods is in high demand. Thus, this work aims the development of silica-based supported ionic liquids (SILs) for the ASNase immobilization to improve its stability and enable its reusability. While activated silica with no ILs only kept total initial ASNase activity during the first cycle of reaction, SILs allowed 5 cycles of reaction, keeping 82% of initial ASNase activity, reinforcing their potential as alternative enzymatic supports.publishe

Selective separation of manganese, cobalt, and nickel in a fully aqueous system

The continued electrification of society and the related growing demand for rechargeable batteries require in turn the elaboration of efficient and sustainable recycling strategies for their recovery and valorization. An important separation relevant to nickel metal hydride (NiMH) and lithium-ion battery recycling is the intertransition element separation between Ni(II), Co(II), and Mn(II). In this work, a fully aqueous process for the recovery of Mn(II) and Co(II) from concentrated Ni(II) effluents typical of NiMH battery leachate is disclosed consuming only Na2CO3. In the first instance, Mn is selectively precipitated as Mn(IV) by oxidation using ozone as an oxidant, resulting in a significant enrichment of Mn in the precipitate relative to its original solution concentration. Second, a thermo- and acid-responsive aqueous biphasic system (ABS) based on the ionic liquid (IL) tributyltetradecylphosphonium chloride ([P44414]Cl) and NiCl2 was used to recover Co(II). By using the high NiCl2 content found in NiMH leachates both as the ABS phase former and salting-out agent, no additional salt is required. Through careful manipulation of the Co(II) to Ni(II) and the IL to Co(II) molar ratios, an effective and selective separation of Co(II) from Ni(II) was achieved. Finally, Co(II) is precipitated from the IL-rich phase and the IL is regenerated in one step by the addition of Na2CO3 to induce a new phase separation.publishe

L-asparaginase-based biosensors

L-asparaginase (ASNase) is an aminohydrolase enzyme widely used in the pharmaceutical and food industries. Although currently its main applications are focused on the treatment of lymphoproliferative disorders such as acute lymphoblastic leukemia (ALL) and acrylamide reduction in starch-rich foods cooked at temperatures above 100 ºC, its use as a biosensor in the detection and monitoring of L-asparagine levels is of high relevance. ASNase-based biosensors are a promising and innovative technology, mostly based on colorimetric detection since the mechanism of action of ASNase is the catalysis of the L-asparagine hydrolysis, which releases L-aspartic acid and ammonium ions, promoting a medium pH value change followed by color variation. ASNase biosensing systems prove their potential for L-asparagine monitoring in ALL patients, along with L-asparagine concentration analysis in foods, due to their simplicity and fast response.publishe

Purification of antileukemic drugs through silica-based supported ionic liquids

L-asparaginase (LA) is an enzyme used as a biopharmaceutical for the treatment of acute lymphoblastic leukemia. LA can be produced via fermentation and its purification usually comprises several steps including precipitation, liquid-liquid extraction and chromatography techniques. Among these, ion exchange chromatography, which is often preceded by precipitation with salts as a first pre-chromatographic step, is the most used. However, theses common strategies for protein purification result in low yields and purity, requiring long processing times, while leading to a consequent increase of the process costs. Therefore, the demand for new cost-effective production/purification processes play now a priority role. This work aims the development of cost-effective technologies to purify LA from the complex fermentation medium from Bacillus Subtillis. Silica-based supported ionic liquids (SILs) are investigated as cost-effective purification materials for the target enzyme. The concentration of the extract from the fermentation, material/ extract from fermentation ratio and contact time effects in the purity and yield of LA were optimized. With this strategy, process costs, energy consumed, and waste generated, may be significantly decreased, which may lead to this biopharmaceutical price decrease and wider application.publishe

Purification of antileukemic drugs through silica-based supported ionic liquids

L-asparaginase (LA) is an enzyme used as a biopharmaceutical for the treatment of acute lymphoblastic leukemia. LA can be produced via fermentation and its purification usually comprises ion exchange chromatography, which is often preceded by precipitation with salts as a first pre-chromatographic step. However, this purification strategy result in low yields and purity, requires long processing times, while leading to a consequent increase of the process costs. Therefore, the demand for new cost-effective purification processes play now a priority role. In this work silica-based supported ionic liquids (SILs) are investigated as an alternative technology to purify LA from the complex fermentation medium from Bacillus subtillis. The concentration of the extract from the fermentation, material/ extract from fermentation ratio and contact time effects in the purity and yield of LA were optimized. With this strategy, process costs, energy consumed, and waste generated, may be significantly decreased, which may lead to this biopharmaceutical price decrease and wider application.publishe