Chagas disease, caused by the protozoan Trypanosoma cruzi, constitutes a substantial public health concern due to its high morbidity and mortality rates among people typically in low-income ...populations who often do not have access to timely medical diagnosis and treatment. Despite successful and sustained vector control policies and screening of blood and organs for donation, more than 6 million people still live with Chagas disease in the Americas, most of them unaware of their infection.1 About 28 000 new cases result each year from vector transmission, with an additional 8000 new cases resulting from congenital transmission.1,2 Moreover, 12 000 people die each year from the disease and its complications.3 Globally, the annual burden is US$627·46 million in health-care costs and 806 170 disability-adjusted life-years.4 The economic burden of Chagas disease is similar to or exceeds those of other prominent infectious diseases globally—eg, rotavirus $2·0 billion or Lyme disease $2·5 billion.4–6 The main region that bears the burden of Chagas disease is the Americas, where the disease originated. Some of this information would be useful for inexperienced health teams. ...for clinical management in areas where health teams are not used to managing patients with Chagas disease, complementary guidelines should be available to clarify these topics.
The environmental impact of fluorinated gases (F-gases) necessitates the development of green technologies to mitigate them. Fluorinated ionic liquids (FIL/ILs) emerged as an alternative absorbent ...due to their unique and exceptional properties. In this work, a COSMO-based/Aspen Plus methodology was used to evaluate the performance of FIL/ILs as absorbents in the process scale of two F-gases: 1,1,1,2-tetrafluoroethane (R-134a) and difluoromethane (R-32). Results of the absorption column in equilibrium mode revealed that the behavior of FIL/ILs is similar under the same conditions, reaching higher efficiencies in the case of absorbing R-134a at a high F-gas partial pressure. Rate-based calculations in packing column demonstrated a kinetic control with highly viscous FIL/ILs, revealing higher performance differences between FIL/IL absorbents. The regeneration stage was also evaluated in near-industrial conditions. Operating conditions of the absorption column were optimized with a column of height 10 m and diameter ranging from 1.1 to 1.2 m at 10 bar total pressure, reaching 90% F gas recovery with an L/G range of 6-10. Finally, preliminary economic analysis revealed operating costs to recover 90% of F-gas of 70 $/ton (R-134a) and 130 $/ton (R-32) with the FIL/IL that revealed the best behavior, 1-ethyl-3-methylimidazolium triflate.
On an absolute basis, Argentina is the country with the largest affected population with Chagas Disease (ChD). This constitutes a significant public health issue. As a consequence of Argentina's ...migratory patterns, there has been a significant increase of affected population in urban centers. An innovative project for early diagnosis and timely treatment of ChD was designed for Municipal Primary Care Facilities of La Plata City, a non- endemic area, in line with a proposal from the Pan-American Health Organization. The project was a public -private intervention. The objectives of this study were to demonstrate the feasibility of the primary healthcare level for early diagnosis and timely treatment of ChD; to design and implement a tailor made program and to innovate in a public-private association.
The healthcare barriers for early diagnosis and timely treatment for the population with ChD of La Plata were analyzed. The four dimensions described by Peters et al. (Ann N Y Acad Sci 1136:161-71, 2008) were used. The baseline was measured during a previous pilot project and the same items were evaluated at the end of 2017. The model from Damschroder et al. (Implement Sci 4:50, 2009) was used during the implementation process.
With all the information gathered during this investigation, a "patient-centered" model was designed. During the program, 17,894 people were serologically tested for ChD, 1,394 were positive and 1,035 were treated. Additionally, 3,750 children from 46 public schools were evaluated for risk factors of ChD.
This project showed the feasibility of the primary healthcare level for early diagnosis and timely treatment of ChD. Tailor made programs and public-private associations should be considered for vulnerable populations in emerging economies in order to enhance efforts and obtain better results. This program may be replicated in other countries of Latin America were Chagas is a main public health issue and, with the corresponding adaptations, for other neglected diseases as well.
Interferon alpha-2b (IFN-α2b) is an essential cytokine widely used in the treatment of chronic hepatitis C and hairy cell leukemia, and serum albumin is the most abundant plasma protein with numerous ...physiological functions. Effective single-step aqueous biphasic system (ABS) extraction for the simultaneous purification of IFN-α2b and BSA (serum albumin protein) was developed in this work. Effects of the ionic liquid (IL)-based ABS functionalization, fluorinated ILs (FILs; C2C1ImC4F9SO3 and N1112(OH)C4F9SO3) vs. mere fluoro-containing IL (C4C1ImCF3SO3), in combination with sucrose or N1112(OH)H2PO4 (well-known globular protein stabilizers), or high-charge-density salt K3PO4 were investigated. The effects of phase pH, phase water content (%wt), phase composition (%wt), and phase volume ratio were investigated. The phase pH was found to have a significant effect on IFN-α2b and BSA partition. Experimental results show that simultaneous single-step purification was achieved with a high yield (extraction efficiency up to 100%) for both proteins and a purification factor of IFN-α2b high in the enriched IFN-α2b phase (up to 23.22) and low in the BSA-enriched phase (down to 0.00). SDS-PAGE analysis confirmed the purity of both recovered proteins. The stability and structure of IFN-α2b and BSA were preserved or even improved (FIL-rich phase) during the purification step, as evaluated by CD spectroscopy and DSC. Binding studies of IFN-α2b and BSA with the ABS phase-forming components were assessed by MST, showing the strong interaction between FILs aggregates and both proteins. In view of their biocompatibility, customizable properties, and selectivity, FIL-based ABSs are suggested as an improved purification step that could facilitate the development of biologics.
This work unfolds functionalized ABSs composed of FILs (C2C1ImC4F9SO3 and N1112(OH)C4F9SO3), mere fluoro-containing ILs (C2C1ImCF3SO3 and C4C1ImCF3SO3), known globular protein stabilizers (sucrose ...and N1112(OH)C4F9SO3), low-molecular-weight carbohydrate (glucose), and even high-charge density salt (K3PO4). The ternary phase diagrams were determined, stressing that FILs highly increased the ability for ABS formation. The functionalized ABSs (FILs vs. mere fluoro-containing ILs) were used to extract lysozyme (Lys). The ABSs’ biphasic regions were screened in terms of protein biocompatibility, analyzing the impact of ABS phase-forming components in Lys by UV-VIS spectrophotometry, CD spectroscopy, fluorescence spectroscopy, DSC, and enzyme assay. Lys partition behavior was characterized in terms of extraction efficiency (% EE). The structure, stability, and function of Lys were maintained or improved throughout the extraction step, as evaluated by CD spectroscopy, DSC, enzyme assay, and SDS-PAGE. Overall, FIL-based ABSs are more versatile and amenable to being tuned by the adequate choice of the phase-forming components and selecting the enriched phase. Binding studies between Lys and ABS phase-forming components were attained by MST, demonstrating the strong interaction between Lys and FILs aggregates. Two of the FIL-based ABSs (30 %wt C2C1ImC4F9SO3 + 2 %wt K3PO4 and 30 %wt C2C1ImC4F9SO3 + 25 %wt sucrose) allowed the simultaneous purification of Lys and BSA in a single ABS extraction step with high yield (extraction efficiency up to 100%) for both proteins. The purity of both recovered proteins was validated by SDS-PAGE analysis. Even with a high-charge density salt, the FIL-based ABSs developed in this work seem more amenable to be tuned. Lys and BSA were purified through selective partition to opposite phases in a single FIL-based ABS extraction step. FIL-based ABSs are proposed as an improved extraction step for proteins, based on their biocompatibility, customizable properties, and selectivity.
The use of fluorinated ionic liquids (FILs) as novel materials in biological and pharmaceutical applications is an emerging research field. The knowledge of their cytotoxicity and that of ...1-octanol/water partition coefficients are essential to assess their environmental risks, to estimate their toxicity and activity, or the hydrophilic/lipophilic balance, as well as to explore their properties as solvents in extraction processes or for successful drug design. The study of the cytotoxicity in four different human cell lines and the experimental measurement of the partition coefficient between 1-octanol and water (Po/w), using the slow-stirring method, were carried out for several FILs. In both studies, the effect of the cation (C2C1Im+, C2C1py+, C4C1pyr+, N1112(OH)+, or N4444+), the cationic alkyl side-chain length (CnC1Im+, with n = 2, 6, 8 or 12), and the anionic fluorinated chain length/anionic fluorinated domain size (C4F9SO3¯, C8F17SO3¯, or N(C4F9SO3)2¯) were analysed. The results reveal that both toxicity and partition properties are mainly influenced by the size of the cationic hydrogenated alkyl side-chain and that of the anionic fluorinated domain. The intrinsic tuneability of the FILs allows for their selection according to the lipophilic or hydrophilic character of the target biological system under consideration. The toxicity studies corroborate the biocompatible nature of some FILs tested in this work. Along, for all the FILs under study Po/w < 1.00. Accordingly, a decadic logarithm of the bioconcentration factor in fish of 0.5 would be estimated, which is below the regulatory endpoint used by regulatory agencies.
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•Human Cytotoxicity of FILs using MTS colorimetric assay.•Po/w of FILs using the experimental slow-stirring method.•FILs intrinsic tuneability allows to fine-tune the hydrophilic/lipophilic balance.•For all the FILs under study Po/w < 1.00 and consequently log BCF = 0.5.•Biocompatible FILs can be designed using short hydrogenated and fluorinated chains.
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