Formation of Iron Phosphide Nanobundles from an Iron Oxyhydroxide Precursor.

Iron phosphide (FeP) nanoparticles have excellent properties such as fast charge transfer kinetics, high electrical conductivity, and high stability, making them a promising catalyst for hydrogen evolution reaction (HER). A challenge to the wide use of iron phosphide nanomaterials for this application is the available synthesis protocols that limit control over the resulting crystalline phase of the product. In this study, we report a method for synthesizing FeP through a solution-based process. Here, we use iron oxyhydroxide (ß-FeOOH) as a cost-effective, environmentally friendly, and air-stable source of iron, along with tri-n-octylphosphine (TOP) as the phosphorus source and solvent. FeP is formed in a nanobundle morphology in the solution phase reaction at a temperature of 320 °C. The materials were characterized by pXRD and transmission electron microscopy (TEM). The optimization parameters evaluated to produce the phosphorus-rich FeP phase included the reaction rate, time, amount of TOP, and reaction temperature. Mixtures of Fe2P and FeP phases were obtained at shorter reaction times and slow heating rates (4.5 °C /min), while longer reaction times and faster heating rates (18.8 °C/min) favored the formation of phosphorus-rich FeP. Overall, the reaction lever that consistently yielded FeP as the predominant crystalline phase was a fast heat rate.

Expression of Inhibitory Receptors TIGIT, TIM-3, and LAG-3 on CD4+ T Cells from Patients with Different Clinical Forms of Chronic Chagas Disease.

T cells are central to the adaptive immune response against Trypanosoma cruzi infection. In chronic Chagas disease (CCD), circulating parasite-specific memory T cells show reduced functionality and increased expression of inhibitory receptors as a result of persistent antigenic stimulation. This phenotype has been linked to progression of cardiac pathology, whereas the presence of polyfunctional T cells shows association with therapeutic success. In this study, we demonstrate that T. cruzi-specific human CD4+ T cells can be identified by their expression of OX40 and CD25 upon in vitro stimulation. We characterized the expression of the inhibitory receptors T cell immunoreceptor with Ig and ITIM domains (TIGIT), T cell Ig and mucin-domain containing-3 (TIM-3), and lymphocyte activation gene 3 (LAG-3) in CD4+ T cells from CCD patients with and without cardiac alterations. Our results show that, independently of their clinical stage, CCD patients present an increased frequency of CD4+ T cells expressing TIGIT in comparison with non-T. cruzi-infected donors. Exposure to parasite Ags increases the expression of TIM-3 in CD4+ T cells from CCD patients, especially in those with cardiac compromise. Upregulation of LAG-3 was also detected in CCD individuals without cardiac manifestations, predominantly within the subpopulation of cells that did not become activated upon stimulation. Further differences were found between groups in the coexpression of these receptors. Blockade of each individual receptor did not affect activation or the production of IFN-γ and IL-10 by CD4+ T cells in response to parasite Ags. Our results suggest a role for TIGIT, TIM-3, and LAG-3 in the modulation of inflammatory phenomena thought to ultimately lead to tissue damage and cardiac pathology.

Activation-induced marker assays for identification of Trypanosoma cruzi-specific CD4 or CD8 T cells in chronic Chagas disease patients.

Antigen-specific T cells are central to the adaptive immune response against T. cruzi infection and underpin the efficacy of on-going vaccine strategies. In this context, the present study focuses on T-cell assays that define the parasite-specificity on the basis of upregulation of TCR stimulation-induced surface markers. For this purpose, we tested different dual marker combinations (OX40, CD25, CD40L, CD137, CD69, PD-L1, CD11a, CD49d, HLA-DR, CD38) to reliably identify activated CD4+ and CD8+ T-cell populations from PBMCs of chronic Chagas disease (CCD) patients after 12 or 24 h of stimulation with T. cruzi lysate. Results demonstrated that activation-induced markers (AIM) assays combining the expression of OX40, CD25, CD40L, CD137, CD69 and/or PD-L1 surface markers are efficient at detecting T. cruzi-specific CD4+ T cells in CCD patients, in comparison to non-infected donors, after both stimulation times. For CD8+ T cells, only PD-L1/OX40 after 24 h of antigen exposure resulted to be useful to track a parasite-specific response. We also demonstrated that the agnostic activation is mediated by different T. cruzi strains, such as Dm28c, CL Brener or Sylvio. Additionally, we successfully used this approach to identify the phenotype of activated T lymphocytes based on the expression of CD45RA and CCR7. Overall, our results show that different combinations of AIM markers represent an effective and simple tool for the detection of T. cruzi-specific CD4+ and CD8+ T cells.

Trypanosoma cruzi Induces Regulatory B Cell Alterations in Patients With Chronic Chagas Disease.

The clinical evolution of patients with chronic Chagas disease (CCD) is mainly associated with an excessive inflammation and a defective immunomodulatory profile caused by the interaction between T. cruzi and the host. Regulatory B (Breg) cells exert immune suppression mostly through IL-10 production (B10 cells), but also through IL-10-independent mechanisms. Previously, we demonstrated that CCD patients with cardiomyopathy show changes in the ex vivo Breg cell phenotypic distribution although maintain IL-10 production capacity. Here, we sought to identify potential alterations on Breg cells upon in vitro stimulation. Isolated B cells from CCD patients with or without cardiomyopathy and non-infected (NI) donors were stimulated with T. cruzi lysate or CpG + CD40L, and characterized by flow cytometry based on the expression of CD24, CD27, CD38, and the regulatory molecules IL-10 and PD-L1. IL-10 and IL-17 secretion in the supernatant of B cells was evaluated by ELISA. Data showed that T. cruzi stimulation diminished the expression of CD24 and CD38 on CD27- B cells while reducing the percentage of CD24high inside CD27+ B cells. Furthermore, T. cruzi induced a regulatory B cell phenotype by increasing B10 cells and IL-10 secretion in all the groups. The innate-like B10 cells expansion observed in patients with cardiomyopathy would be associated with CD27- B10 cell subsets, while no predominant phenotype was found in the other groups. Patients with cardiomyopathy also displayed higher IL-17 secretion levels in T. cruzi-activated B cells. CpG + CD40L stimulation revealed that B cells from CCD patients and NI donors had the same ability to differentiate into B10 cells and secrete IL-10 in vitro. Additionally, CCD patients showed an increased frequency of CD24-CD27- B cells and a reduction in the percentage of CD24highCD27+ Breg cells, which appeared to be inversely correlated with the presence of T. cruzi DNA in blood. Finally, CCD patients exhibited a higher frequency of PD-L1+ B cells in T. cruzi-stimulated samples, suggesting that IL-10-independent mechanisms could also be tangled in the control of inflammation. Altogether, our results provide evidence about the potential role of Breg cells in the immune response developed against T. cruzi and its contribution to chronic Chagas cardiomyopathy.

A Bimodal Nanosensor for Probing Influenza Fusion Protein Activity Using Magnetic Relaxation.

Viral fusion is a critical step in the entry pathway of enveloped viruses and remains a viable target for antiviral exploration. The current approaches for studying fusion mechanisms include ensemble fusion assays, high-resolution cryo-TEM, and single-molecule fluorescence-based methods. While these methods have provided invaluable insights into the dynamic events underlying fusion processes, they come with their own limitations. These often include extensive data and image analysis in addition to experimental time and technical requirements. This work proposes the use of the spin-spin T2 relaxation technique as a sensitive bioanalytical method for the rapid quantification of interactions between viral fusion proteins and lipids in real time. In this study, new liposome-coated iron oxide nanosensors (LIONs), which mimic as magnetic-labeled host membranes, are reported to detect minute interactions occurring between the membrane and influenza's fusion glycoprotein, hemagglutinin (HA). The influenza fusion protein's interaction with the LION membrane is detected by measuring changes in the sensitive spin-spin T2 magnetic relaxation time using a bench-top NMR instrument. More data is gleaned from including the fluorescent dye DiI into the LION membrane. In addition, the effects of environmental factors on protein-lipid interaction that affect fusion such as pH, time of incubation, trypsin, and cholesterol were also examined. Furthermore, the efficacy and sensitivity of the spin-spin T2 relaxation assay in quantifying similar protein/lipid interactions with more native configurations of HA were demonstrated using virus-like particles (VLPs). Shorter domains derived from HA were used to start a reductionist path to identify the parts of HA responsible for the NMR changes observed. Finally, the known fusion inhibitor Arbidol was employed in our spin-spin T2 relaxation-based fusion assay to demonstrate the application of LIONs in real-time monitoring of this aspect of fusion for evaluation of potential fusion inhibitors.

Speckle tracking echocardiography in the indeterminate form of Chagas disease.

BACKGROUND: Chagas disease is one of the most common diseases in Latin-America, and cardiac involvement is a significant cause of death. Assessment of myocardial strain may detect early myocardial damage. OBJECTIVES: To determine differences in longitudinal strain using speckle tracking to assess regional and global left ventricular function in patients with the indeterminate form of Chagas disease, in comparison with a control group. METHODS: This is a retrospective matched case-control study, conducted in a single center. We evaluated 45 adult patients with Chagas disease, diagnosed with 2 serological methods, without evidence of cardiac involvement, who were compared with 45 healthy control subjects, who were sex- and age-matched. All patients underwent Doppler echocardiography and longitudinal strain with speckle tracking. RESULTS: Median age was 59 years, and 60% were female. Echocardiographic parameters were similar in patients with Chagas and control subjects. In patients with Chagas, global strain differed significantly from that of control subjects (-17 vs -20.3, P < .001). Segmental strain showed 7 abnormal segments in patients with Chagas (P < .05). CONCLUSIONS: In patients with the indeterminate form of Chagas disease, global and segmental longitudinal peak systolic strain is reduced compared with healthy subjects, thus suggesting that it could be a sensitive technique to detect early myocardial damage. These findings could provide useful information regarding the pathophysiology of cardiac involvement and understand whether they might have prognostic usefulness or help develop strategies to modify the course and prognosis of patients with Chagas disease. A longitudinal prospective study would be necessary to validate our findings.

Synthesis of Magnetite Nanorods from the Reduction of Iron Oxy-Hydroxide with Hydrazine.

Nanowires and nanorods of magnetite (Fe3O4) are of interest due to their varied biological applications but most importantly for their use as magnetic resonance imaging contrast agents. One-dimensional (1D) structures of magnetite, however, are more challenging to synthesize because the surface energy favors the formation of isotropic structures. Synthetic protocols can be dichotomous, producing either the 1D structure or the magnetite phase but not both. Here, superparamagnetic Fe3O4 nanorods were prepared in solution by the reduction of iron oxy-hydroxide (ß-FeOOH) nanoneedles with hydrazine (N2H4). The amount of hydrazine and the reaction time affected the phase and morphology of the resulting iron oxide nanoparticles. One-dimensional nanostructures of Fe3O4 could be produced consistently from various aspect ratios of ß-FeOOH nanoneedles, although the length of the template was not retained. Fe3O4 nanorods were characterized by transmission electron microscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, and SQUID magnetometry.

Simulation and control of dissolved air flotation and column froth flotation with simultaneous sedimentation.

Flotation is a separation process where particles or droplets are removed from a suspension with the aid of floating gas bubbles. Applications include dissolved air flotation (DAF) in industrial wastewater treatment and column froth flotation (CFF) in wastewater treatment and mineral processing. One-dimensional models of flotation have been limited to steady-state situations for half a century by means of the drift-flux theory. A newly developed dynamic one-dimensional model formulated in terms of partial differential equations can be used to predict the process of simultaneous flotation of bubbles and sedimentation of particles that are not attached to bubbles. The governing model is a pair of first-order conservation laws for the aggregate and solids volume fractions as functions of height and time. An analysis of nonlinear ingredients of the governing equations helps to identify desired steady-state operating conditions. These can be chosen by means of operating charts, which are diagrams that visualize regions of admissible values of the volumetric flows of the feed input and underflow outlet. This is detailed for the DAF thickening process. Dynamic simulations are obtained with a recently developed numerical method. Responses to control actions are demonstrated with scenarios in CFF and DAF.

Iron Pyrite Nanocrystals: A Potential Catalyst for Selective Transfer Hydrogenation of Functionalized Nitroarenes.

We report a solution-based synthetic method to produce shape-tunable iron pyrite (FeS2) nanocrystals using iron oxy-hydroxide (ß-FeOOH) as a precursor and their application for selective reduction of functionalized nitroarenes to aniline derivatives with formic acid-triethylamine (HCOOH-Et3N) as a hydrogen donor system.

Circulating T Follicular Helper Cell Abnormalities Associated to Different Clinical Forms of Chronic Chagas Disease.

Multiple perturbations of the immune response affecting a range of cells have been reported in Trypanosoma cruzi-infected individuals and associated to clinical manifestations of chronic Chagas disease. There is a paucity of knowledge about the role of T follicular helper (Tfh) cells in this infection. Here, we sought to characterize circulating Tfh (cTfh) cells in chronic Chagas disease patients and to identify potential associations with disease severity in humans. cTfh cells were characterized by flow cytometry in freshly isolated PBMCs from 7 T. cruzi-infected asymptomatic patients (ASYMP), 5 patients with chronic chagasic dilated cardiomyopathy (CCC) and 8 healthy controls, using antibodies against chemokine receptors CXCR5, CXCR3, CCR6, and CCR7. Our results showed significant expansion of CD4+CD45RO+CXCR5+CCR6+ cells in ASYMP and CCC patients, along with a contraction of CD4+CD45RO+CXCR5+CXCR3-CCR6- (cTfh2) cells. ASYMP patients further exhibited decreased CD4+CD45RO+CXCR5+CXCR3+CCR6- (cTfh1) cells and expanded CD4+CD45RO+CXCR5+CXCR3-CCR6+ (cTfh17) cells while CCC patients exhibited significantly increased frequencies of CD4+CD45RO+CXCR5+CCR7+ cells. Linear regression analysis revealed a positive trend of CD4+CD45RO+CXCR5+CXCR3+CCR6+ (cTfh1/17) cells and negative trends of cTfh1 and cTfh2 cells as disease was more severe. There was no correlation between the frequencies of cTfh cells and circulating CD19+IgD-IgG+ cells or serum levels of T. cruzi-specific IgG. These results demonstrate that the cTfh compartment of humans chronically infected with T. cruzi comprises expanded CCR6-expressing cells and reduced cTfh2 cells. The association of discrete phenotypic changes in cTfh subsets with different clinical forms suggests the potential contribution of T follicular helper cells to Chagas heart disease progression.

Cellular Uptake and Cytotoxicity of Varying Aspect Ratios of Gold Nanorods in HeLa Cells.

Gold nanorods (GNRs) have received broad attention due to their tunable surface plasmonic resonance modes, which make them an attractive candidate for biomedical applications in drug and gene delivery, biological imaging, and cancer treatment. In this study, we highlight the interactions of four different aspect ratios (ARs), 2.6, 3.2, 5.4 and 11.5, of GNRs with HeLa cells with respect to cellular uptake and cellular viability while also considering the effects of other parameters such as the surface stabilizer, supernatant, and serum proteins present in the medium. From this work, it was determined that the cell viability depended on the chemical composition of the supernatant, especially the amount of excess surfactant, hexadecyltrimethylammonium bromide (CTAB), used for the synthesis of GNRs; thus, the effect of aspect ratio of GNRs on endocytosis could not be directly discerned. For example, when exposed to GNRs of aspect ratio 11.5, HeLa cells showed higher cellular uptake compared to the shorter aspect ratios and a lower cytotoxicity simply because of the lower concentration of CTAB used during the synthesis, and a gentler purification method, such as sedimentation, also appeared to be a factor. Overall, the synthesis protocols, functionalization, purification processes, and the stability of GNRs in media have a major effect on cellular uptake and viability. Our results suggest that perhaps AR does play a role in endocytosis although an overall trend could not be unequivocally established, and sedimentation, contact time, and internalization kinetics need to be probed further using more biocompatible ligands in future studies.

Monocyte glycolysis determines CD8+ T cell functionality in human Chagas disease.

Chagas disease is a lifelong pathology resulting from Trypanosoma cruzi infection. It represents one of the most frequent causes of heart failure and sudden death in Latin America. Herein, we provide evidence that aerobic glycolytic pathway activation in monocytes drives nitric oxide (NO) production, triggering tyrosine nitration (TN) on CD8+ T cells and dysfunction in patients with chronic Chagas disease. Monocytes from patients exhibited a higher frequency of hypoxia-inducible factor 1α and increased expression of its target genes/proteins. Nonclassical monocytes are expanded in patients' peripheral blood and represent an important source of NO. Monocytes entail CD8+ T cell surface nitration because both the frequency of nonclassical monocytes and that of NO-producing monocytes positively correlated with the percentage of TN+ lymphocytes. Inhibition of glycolysis in in vitro-infected peripheral blood mononuclear cells decreased the inflammatory properties of monocytes/macrophages, diminishing the frequency of IL-1ß- and NO-producing cells. In agreement, glycolysis inhibition reduced the percentage of TN+CD8+ T cells, improving their functionality. Altogether, these results clearly show that glycolysis governs oxidative stress on monocytes and modulates monocyte-T cell interplay in human chronic Chagas disease. Understanding the pathological immune mechanisms that sustain an inflammatory environment in human pathology is key to designing improved therapies.

Formation of Stem Cell Aggregates and Their Differentiation on Surface-Patterned Hydrogels Based on Poly(2-hydroxyethyl Methacrylate).

Micropillar patterns were fabricated and used to study cell adhesion, morphology, and function. Micropillars were produced in poly(2-hydroxyethyl methacrylate (HEMA)/N,N-(dimethylaminoethyl)methacrylate (DMAEMA)/tetraethylene glycol dimethacrylate (TEGDMA)) hydrogels using soft lithography, had dimensions of 1 µm diameter, and were either 2.05 or 4.91 µm tall. The patterned hydrogel substrates increased adhesion and induced the formation of cellular aggregates. Digital micrographs were used to quantify aggregate size and number. Differentiation of hMSCs toward adipocytes and chondrocytes was performed using the respective complete culture and differentiation medium for 2 weeks. Cells were stained for Oil red O, Alcian blue, and Type II collagen. Hydrogel substrates supported the differentiation of hMSCs to adipocytes and chondrocytes. The taller micropillar patterns supported the attachment and growth of larger aggregates and were more amenable to aid chondrogenic differentiation.

Phenotypic diversity and drug susceptibility of Trypanosoma cruzi TcV clinical isolates.

Trypanosoma cruzi is a genetically heterogeneous group of organisms that cause Chagas disease. It has been long suspected that the clinical outcome of the disease and response to therapeutic agents are, at least in part, related to the genetic characteristics of the parasite. Herein, we sought to validate the significance of the genotype of T. cruzi isolates recovered from patients with different clinical forms of Chagas disease living in Argentina on their biological behaviour and susceptibility to drugs. Genotype identification of the newly established isolates confirmed the reported predominance of TcV, with a minor frequency of TcI. Epimastigote sensitivity assays demonstrated marked dissimilar responses to benznidazole, nifurtimox, pentamidine and dihydroartemisinin in vitro. Two TcV isolates exhibiting divergent response to benznidazole in epimastigote assays were further tested for the expression of anti-oxidant proteins. Benznidazole-resistant BOL-FC10A epimastigotes had decreased expression of Old Yellow Enzyme and cytosolic superoxide dismutase, and overexpression of mitochondrial superoxide dismutase and tryparedoxin- 1, compared to benznidazole-susceptible AR-SE23C parasites. Drug sensitivity assays on intracellular amastigotes and trypomastigotes reproduced the higher susceptibility of AR-SE23C over BOL-FC10A parasites to benznidazole observed in epimastigotes assays. However, the susceptibility/resistance profile of amastigotes and trypomastigotes to nifurtimox, pentamidine and dihydroartemisinin varied markedly with respect to that of epimastigotes. C3H/He mice infected with AR-SE23C trypomastigotes had higher levels of parasitemia and mortality rate during the acute phase of infection compared to mice infected with BOL-FC10A trypomastigotes. Treatment of infected mice with benznidazole or nifurtimox was efficient to reduce patent parasitemia induced by either isolate. Nevertheless, qPCR performed at 70 dpi revealed parasite DNA in the blood of mice infected with AR-SE23C but not in BOL-FC10A infected mice. These results demonstrate high level of intra-type diversity which may represent an important obstacle for the testing of chemotherapeutic agents.

Evaluation of the immune response against Trypanosoma cruzi cytosolic tryparedoxin peroxidase in human natural infection.

Trypanosoma cruzi, the aetiological agent of Chagas disease, has a highly efficient detoxification system to deal with the oxidative burst imposed by its host. One of the antioxidant enzymes involved is the cytosolic tryparedoxin peroxidase (c-TXNPx), which catalyses the reduction to hydrogen peroxide, small-chain organic hydroperoxides and peroxynitrite. This enzyme is present in all parasite stages, and its overexpression renders parasites more resistant to the oxidative defences of macrophages, favouring parasite survival. This work addressed the study of the specific humoral and cellular immune response triggered by c-TXNPx in human natural infection. Thus, sera and peripheral blood mononuclear cells (PBMC) were collected from chronically infected asymptomatic and cardiac patients, and non-infected individuals. Results showed that levels of IgG antibodies against c-TXNPx were low in sera from individuals across all groups. B-cell epitope prediction limited immunogenicity to a few, small regions on the c-TXNPx sequence. At a cellular level, PBMC from asymptomatic and cardiac patients proliferated and secreted interferon-γ after c-TXNPx stimulation, compared with mock control. However, only proliferation was higher in asymptomatic patients compared with cardiac and non-infected individuals. Furthermore, asymptomatic patients showed an enhanced frequency of CD19+ CD69+ cells upon exposure to c-TXNPx. Overall, our results show that c-TXNPx fails to induce a strong immune response in natural infection, being measurable only in those patients without any clinical symptoms. The low impact of c-TXNPx in the human immune response could be strategic for parasite survival, as it keeps this crucial antioxidant enzyme activity safe from the mechanisms of adaptive immune response.

ZnO Microstructures as Flame-Retardant Coatings on Cotton Fabrics.

In this study, we report a unique strategy that utilizes ZnO and ZnS microparticles and rods as fire-retardant materials when coated onto cotton fabrics. ZnO and ZnO/ZnS microparticles or rods were grown or adsorbed to the surface of cotton fibers. Properties such as heat release rate, total smoke release, and mass loss rate of the materials were tested using a cone calorimeter. ZnO and ZnO/ZnS rods were able to reduce the heat release rate and total smoke release from 118 kW/m2 and 18.3 m2/m2 to about 70.0 kW/m2 and 6.00 m2/m2, respectively. The maximum average rate of heat emission and fire growth rate index, which is used to evaluate the fire spread rate, the size of the fire, and the propensity of fire development, were improved with these coatings and indicate that there are potential applications of these materials as fire retardants.

A three-dimensional in vitro model to demonstrate the haptotactic effect of monocyte chemoattractant protein-1 on atherosclerosis-associated monocyte migration.

Monocyte transendothelial migration is a multi-step process critical for the initiation and development of atherosclerosis. The chemokine monocyte chemoattractant protein-1 (MCP-1) is overexpressed during atheroma and its concentration gradients in the extracellular matrix (ECM) is critical for the transendothelial recruitment of monocytes. Based on prior observations, we hypothesize that both free and bound gradients of MCP-1 within the ECM are involved in directing monocyte migration. The interaction between a three-dimensional (3D), cell-free, collagen matrix and MCP-1; and its effect on monocyte migration was measured in this study. Our results showed such an interaction existed between MCP-1 and collagen, as 26% of the total MCP-1 added to the collagen matrix was bound to the matrix after extensive washes. We also characterized the collagen-MCP-1 interaction using biophysical techniques. The treatment of the collagen matrix with MCP-1 lead to increased monocyte migration, and this phenotype was abrogated by treating the matrix with an anti-MCP-1 antibody. Thus, our results indicate a binding interaction between MCP-1 and the collagen matrix, which could elicit a haptotactic effect on monocyte migration. A better understanding of such mechanisms controlling monocyte migration will help identify target cytokines and lead to the development of better anti-inflammatory therapeutic strategies.

In vitro evaluation of sustained released matrix tablets containing ibuprofen: a model poorly water-soluble drug

ABSTRACT A matrix system was developed that releases ibuprofen (IB) over a 12-hour period and the influence of the polymer type and concentration on the release rate of the drug was evaluated. Tablets containing different concentrations of Carbopol (CP), hydroxypropyl methylcellulose (HPMC), or ethyl cellulose (EC) were prepared using direct compression and the drug content, content uniformity, hardness, friability, dissolution performance, and in vitro release kinetics were examined. Formulated tablets were found to be within acceptable limits for physical and chemical parameters. The release kinetics of the Carbopol(r)971P 8% formulation showed the best linearity (r 2 =0.977) in fitting zero-order kinetics, suggesting the release rate was time independent. The drug release from tablets containing 8% CP was extended over approximately 18 hours and the release kinetics were nearly linear, suggesting that this system has the potential to maintain constant plasma drug concentrations over 12 hours, which could reduce the frequency of administration and the occurrence of adverse effects associated with repeated administration of conventional IB tablets.

An aptamer-functionalized chemomechanically modulated biomolecule catch-and-release system.

The efficient extraction of (bio)molecules from fluid mixtures is vital for applications ranging from target characterization in (bio)chemistry to environmental analysis and biomedical diagnostics. Inspired by biological processes that seamlessly synchronize the capture, transport and release of biomolecules, we designed a robust chemomechanical sorting system capable of the concerted catch and release of target biomolecules from a solution mixture. The hybrid system is composed of target-specific, reversible binding sites attached to microscopic fins embedded in a responsive hydrogel that moves the cargo between two chemically distinct environments. To demonstrate the utility of the system, we focus on the effective separation of thrombin by synchronizing the pH-dependent binding strength of a thrombin-specific aptamer with volume changes of the pH-responsive hydrogel in a biphasic microfluidic regime, and show a non-destructive separation that has a quantitative sorting efficiency, as well as the system's stability and amenability to multiple solution recycling.

An analysis of unused and expired medications in Mexican households.

BACKGROUND: Unsafe storage of unused medications at home leads to an increased risk of toxicity, accidental childhood poisoning or risk for suicide, whereas an improper disposal of unwanted/expired medications from household raises concern about environmental pollution. OBJECTIVE: The aim of the study was to characterize expired medications collected according to the types of therapeutic groups, pharmaceutical dosage forms, expiration dates and were prescribed or over the counter drugs, and whether they came from Mexican health system or purchased by patients themselves. SETTING: The study was conducted in the metropolitan area of Monterrey during a 12-month period from March 2012 to February 2013. METHOD: Unused/expired drugs were collected according to the collection and disposal of expired medication program instituted by the Department of Health of the State of Nuevo León. Pharmacists and students from The Autonomous University of Nuevo León recorded types of therapeutic groups, total of medicines in each group, among other classification criteria. MAIN OUTCOME MEASURE: The proportion of every collected therapeutic group, type of dosage forms, and expiration date. RESULTS: The amount of medications classified was 22,140 items corresponding to a 30 % of the total collected medications in that period of time; most of them belonged to the non-steroidal anti-inflammatory drugs (16.11 %). According to the pharmaceutical dosage forms, results showed that a high percentage were solid dosage forms (73.39 %), of the total unused/expired medications, most of them were prescription drugs (91 %) which were purchased at private pharmacies. Expiration date of medications ranges from 1995 to 2016, being 2011 the outstanding year (36.66 %). CONCLUSION: Addressing the aspect of unused drug disposition constitutes a challenge for Mexican government, due to health implications related to inadequate disposition. No matter how efficient the programs of collection and disposal of expired drugs are, none of them can collect all unused or expired drugs, that is the reason why the best approach might be to prevent this need.