Cost-effectiveness of continuous glucose monitoring with FreeStyle Libre® in Brazilian insulin-treated patients with types 1 and 2 diabetes mellitus.

BACKGROUND: Hypoglycemia is a barrier to optimal glucose control in the treatment of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Blood glucose monitoring is essential in diabetes management. Inappropriate glucose management is associated with high mortality and morbidity. FreeStyle Libre® (FSL) is a continuous glucose monitoring (CGM) system that provides effective, safe, and convenient glucose monitoring, without routine finger pricking. This study aims to estimate the incremental cost-effectiveness ratio (ICER) of the FSL system in comparison to conventional Self-monitoring of blood glucose (SMBG) in T1DM and T2DM patients that require intensive insulin therapy. METHODS: A decision-tree model was developed to compare the cost-effectiveness ratio between FSL and conventional SMBG from the perspective of the Brazilian Public Healthcare System (SUS). The model captures the cumulative rates of acute complications such as severe hypoglicemia and diabetic ketoacidosis, per-event costs, and quality-adjusted life-years (QALYs) gained over a 1-year time horizon in adult and pediatric patients (≥ 4 years old) with T1DM or T2DM. Inputs from the Brazilian health databases, clinical trials, and real-world data were used in the study. RESULTS: The results demonstrated that, regarding solely severe hypoglicemia and diabetic ketoacidosis events, T1DM have a QALY difference of 0.276, a cost difference of R$ 7.255, and an ICER of R$ 26,267.69 per QALY gained for CGM with FSL, when compared to conventional SMBG. T2DM results demonstrated equally a QALY difference of 0.184, a cost difference of R$ 7290, and an ICER of R$ 39,692.67 per QALY gained, in favour of CGM with FSL. CONCLUSION: Our findings demonstrated that FSL is cost-effective in T1DM and T2DM for acute diabetic complications, from a SUS perspective. CGM with FSL can promote safe, convenient, and cost-effective glucose monitoring, therefore contributing to the improvement of the incidence of complications and quality of life.

Effect of Pyruvate Decarboxylase Knockout on Product Distribution Using Pichia pastoris (Komagataella phaffii) Engineered for Lactic Acid Production.

Lactic acid is the monomer unit of the bioplastic poly-lactic acid (PLA). One candidate organism for lactic acid production is Pichia pastoris, a yeast widely used for heterologous protein production. Nevertheless, this yeast has a poor fermentative capability that can be modulated by controlling oxygen levels. In a previous study, lactate dehydrogenase (LDH) activity was introduced into P. pastoris, enabling this yeast to produce lactic acid. The present study aimed to increase the flow of pyruvate towards the production of lactic acid in P. pastoris. To this end, a strain designated GLp was constructed by inserting the bovine lactic acid dehydrogenase gene (LDHb) concomitantly with the interruption of the gene encoding pyruvate decarboxylase (PDC). Aerobic fermentation, followed by micro-aerophilic culture two-phase fermentations, showed that the GLp strain achieved a lactic acid yield of 0.65 g/g. The distribution of fermentation products demonstrated that the acetate titer was reduced by 20% in the GLp strain with a concomitant increase in arabitol production: arabitol increased from 0.025 g/g to 0.174 g/g when compared to the GS115 strain. Taken together, the results show a significant potential for P. pastoris in producing lactic acid. Moreover, for the first time, physiological data regarding co-product formation have indicated the redox balance limitations of this yeast.

Novel homologous lactate transporter improves L-lactic acid production from glycerol in recombinant strains of Pichia pastoris.

BACKGROUND: Crude glycerol is the main byproduct of the biodiesel industry. Although it can have different applications, its purification is costly. Therefore, in this study a biotechnological route has been proposed for further utilization of crude glycerol in the fermentative production of lactic acid. This acid is largely utilized in food, pharmaceutical, textile, and chemical industries, making it the hydroxycarboxylic acid with the highest market potential worldwide. Currently, industrial production of lactic acid is done mainly using sugar as the substrate. Thus here, for the first time, Pichia pastoris has been engineered for heterologous L-lactic acid production using glycerol as a single carbon source. For that, the Bos taurus lactate dehydrogenase gene was introduced into P. pastoris. Moreover, a heterologous and a novel homologous lactate transporter have been evaluated for L-lactic acid production. RESULTS: Batch fermentation of the P. pastoris X-33 strain producing LDHb allowed for lactic acid production in this yeast. Although P. pastoris is known for its respiratory metabolism, batch fermentations were performed with different oxygenation levels, indicating that lower oxygen availability increased lactic acid production by 20 %, pushing the yeast towards a fermentative metabolism. Furthermore, a newly putative lactate transporter from P. pastoris named PAS has been identified by search similarity with the lactate transporter from Saccharomyces cerevisiae Jen1p. Both heterologous and homologous transporters, Jen1p and PAS, were evaluated in one strain already containing LDH activity. Fed-batch experiments of P. pastoris strains carrying the lactate transporter were performed with the batch phase at aerobic conditions followed by an aerobic oxygen-limited phase where production of lactic acid was favored. The results showed that the strain containing PAS presented the highest lactic acid titer, reaching a yield of approximately 0.7 g/g. CONCLUSIONS: We showed that P. pastoris has a great potential as a fermentative organism for producing L-lactic acid using glycerol as the carbon source at limited oxygenation conditions (below 0.05 % DO in the bioreactor). The best strain had both the LDHb and the homologous lactate transporter encoding genes expressed, and reached a titer 1.5 times higher than the strain with the S. cerevisiae transporter. Finally, it was also shown that increased lactic acid production was concomitant to reduction of acetic acid formation by half.

Iontophoresis: principles and applications / Iontoforese: princípios e aplicações

Introduction Iontophoresis is a noninvasive technique used to increase transdermal penetration of substances through the skin layer (epidermis, dermis and hypodermis) in a controlled manner. Technological advance in recent decades have provided reduced cost of equipment needed for implementation, which allowed for the expansion of this technique. Objective The aim of this paper is to present the state of the art on iontophoresis, ranging from the atomic characteristics of the ion formation to the current applications of the technique. Methods Were researched papers from databases: IOP publishing, ScienceDirect, Pubmed, Springer, IEEE Xplore, Google Scholar and books with keywords iontophoresis, ions, topical applications between 1967 and 2010. Results Were selected (number of papers and database) 1 IOP Publishing, 1 from ScienceDirect, Central, 1 from Springer, 2 from PubMed, 11 from IEEE Xplore, 35 from Google Scholar, and 15 books, totaling 66 references and websites with nationally marketed electrotherapy products. Conclusion Iontophoresis is suitable for applications such as acetic acid (calcific tendinitis and myositis ossificans), calcium chloride and magnesium sulfate (control of musculoskeletal spasms), dexamethasone (inflammation), lidocaine (inflammation of soft tissues), zinc oxide (rheumatoid arthritis). It is also used in cosmetic applications with devices attached to the skin and for eye treatment aimed at specific tissues of the eye, providing a treatment option for various eye diseases, reducing the complications secondary to traditional methods of treatment. The advantages are the significant increase in the release and control of therapeutic agents, including drugs with high molecular weight. The disadvantages of iontophoresis are the complexity of the drug release system and prolonged exposure of the skin to an electrical current. .

Introdução A iontoforese é uma técnica não invasiva utilizada para aumentar, de forma controlada, a penetração transdermal de substâncias através das camadas da pele (epiderme, derme e hipoderme). O avanço tecnológico nas últimas décadas proporcionou uma redução no custo dos equipamentos necessários à sua aplicação, o que possibilitou a expansão dessa técnica. Objetivo Apresentar o estado da arte sobre iontoforese, abrangendo desde as características atômicas da formação do íon até as atuais aplicações da técnica. Métodos Foram pesquisados artigos das bases de pesquisa: IOP publishing, ScienceDirect, Pubmed, Springer, IEEE Xplore, Google Scholar e livros com os unitermos: iontophoresis, ions, topical applications entre os anos de 1967 e 2010. Resultados Foram selecionados (número de artigos e base de pesquisa) 1 da IOP Publishing, 1 da ScienceDirect, 1 da Springer, 2 da PubMed, 11 da IEEE Xplore, 35 do Google Scholar e 15 livros, totalizando 66 referências, além de websites com produtos comerciais nacionais de eletroterapia. Conclusão A iontoforese é indicada para aplicações como de ácido acético (tendinite calcificante e miosite ossificante), cloreto de cálcio e sulfato de magnésio (controle de espasmos musculoesqueléticos), dexametasona (inflamação), lidocaína (inflamação de tecidos moles), óxido de zinco (artrite reumatóide). Também é utilizada em aplicações cosméticas com dispositivos aderidos à pele e em tratamento ocular visando tecidos específicos do olho, oferecendo uma forma de tratamento para diversas doenças oculares, diminuindo as complicações apresentadas em métodos clássicos de tratamento. As vantagens ...