Evaluation of tolerance to mercaptopurine in patients with inflammatory bowel disease and gastrointestinal intolerance to azathioprine / Evaluación de la tolerancia a la mercaptopurina en los pacientes con enfermedad inflamatoria intestinal e intolerancia gastrointestinal a la azatioprina

Background Thiopurines such as azathioprine (AZA) and mercaptopurine (MP) are commonly utilized to treat inflammatory bowel disease (IBD). Their use is frequently restricted due to gastrointestinal intolerance (GI). Previous retrospective studies have reported that AZA-intolerant patients may benefit from a switch to MP; yet the effectiveness of this strategy has not been prospectively evaluated.AimsTo assess GI tolerance to MP in patients who are intolerant to AZA, and to identify clinical predictors of GI intolerance to AZA or MP.MethodsA prospective, observational, single-cohort study was performed in 92 thiopurine-naïve IBD patients. They were started on a 50mg dose of AZA and escalated to 2.5mg/kg per day by week 2. Those with GI intolerance were rechallenged with a 50% dose of AZA, after which another dose escalation attempt was made. If symptoms persisted, they were switched to MP.ResultsThirty (32.6%) of the recruited patients suffered from GI intolerance to AZA. Of these, 15 did not present recurrence of symptoms after rechallenge with lower doses. Of 15 intolerant patients, 14 were switched to MP. Within the MP cohort, 8 patients (57%) were also intolerant to MP, 5 (36%) had no symptoms, and 1 (7%) was lost to follow-up. Female gender was the only independent predictor of GI intolerance to AZA.ConclusionsUp to half of the AZA-intolerant patients tolerated a 50% dose rechallenge that was successfully escalated. A switch to MP was tolerated in over a third of cases whom rechallenge failed. Our strategy (challenge–rechallenge–switch) achieved an overall GI tolerance to thiopurines in most of the patients. (AU)

Antecedentes Las tiopurinas como la azatioprina (AZA) y la mercaptopurina (MP) se utilizan comúnmente para tratar la enfermedad inflamatoria intestinal (EII). Su uso está frecuentemente restringido debido a la intolerancia gastrointestinal. Estudios retrospectivos anteriores han informado que los pacientes intolerantes a la AZA pueden beneficiarse de un cambio a MP; sin embargo, la eficacia de esta estrategia no ha sido evaluada prospectivamente.ObjetivosEvaluar la tolerancia gastrointestinal a MP en pacientes que son intolerantes a AZA e identificar predictores clínicos de intolerancia gastrointestinal a AZA o MP.MétodosSe realizó un estudio prospectivo, observacional y de cohorte única en 92 pacientes con EII que nunca habían recibido tiopurinas. Comenzaron con una dosis de 50mg de AZA y se aumentó a 2,5mg/kg por día en la semana 2. En aquellos con intolerancia gastrointestinal se administró una dosis del 50% de AZA que se fue incrementando en función de la tolerancia. Si los síntomas persistían, se cambiaba a MP.ResultadosTreinta (32,6%) de los pacientes reclutados presentaron intolerancia gastrointestinal a la AZA. De estos, 15 no presentaron recurrencia de los síntomas después de la nueva exposición. De los 15 pacientes que no toleraron una dosis más baja, 14 recibieron MP. De los que recibieron MP, 8 pacientes (57%) también eran intolerantes a MP, 5 (36%) no tenían síntomas y uno (7%) se perdió durante el seguimiento. El género femenino fue el único predictor independiente de intolerancia gastrointestinal a la AZA.ConclusionesHasta la mitad de los pacientes intolerantes a la AZA toleran una nueva exposición al 50% de la dosis. Se toleró un cambio a MP en más de un tercio de los casos en los que la reexposición fracasó. Nuestra estrategia logró la tolerancia gastrointestinal a tiopurinas en la mayoría de los pacientes. (AU)

Evaluation of tolerance to mercaptopurine in patients with inflammatory bowel disease and gastrointestinal intolerance to azathioprine.

BACKGROUND: Thiopurines such as azathioprine (AZA) and mercaptopurine (MP) are commonly utilized to treat inflammatory bowel disease (IBD). Their use is frequently restricted due to gastrointestinal intolerance (GI). Previous retrospective studies have reported that AZA-intolerant patients may benefit from a switch to MP; yet the effectiveness of this strategy has not been prospectively evaluated. AIMS: To assess GI tolerance to MP in patients who are intolerant to AZA, and to identify clinical predictors of GI intolerance to AZA or MP. METHODS: A prospective, observational, single-cohort study was performed in 92 thiopurine-naïve IBD patients. They were started on a 50mg dose of AZA and escalated to 2.5mg/kg per day by week 2. Those with GI intolerance were rechallenged with a 50% dose of AZA, after which another dose escalation attempt was made. If symptoms persisted, they were switched to MP. RESULTS: Thirty (32.6%) of the recruited patients suffered from GI intolerance to AZA. Of these, 15 did not present recurrence of symptoms after rechallenge with lower doses. Of 15 intolerant patients, 14 were switched to MP. Within the MP cohort, 8 patients (57%) were also intolerant to MP, 5 (36%) had no symptoms, and 1 (7%) was lost to follow-up. Female gender was the only independent predictor of GI intolerance to AZA. CONCLUSIONS: Up to half of the AZA-intolerant patients tolerated a 50% dose rechallenge that was successfully escalated. A switch to MP was tolerated in over a third of cases whom rechallenge failed. Our strategy (challenge-rechallenge-switch) achieved an overall GI tolerance to thiopurines in most of the patients.

Bioderived Pickering Emulsion Based on Chitosan/Trialkyl Phosphine Oxides Applied to Selective Recovery of Rare Earth Elements.

A novel biobased pickering emulsion (PE) material was prepared by the encapsulation of Cyanex 923 (Cy923) into chitosan (CS) to selectively recover rare earth elements (REEs) from the aqueous phase. The preparation of PE was optimized through sequentially applying a 23 full factorial design, followed by a 33 Box-Behnken design varying the Cy923 content, CS concentration, and pH of CS. The material was characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), optical microscopy, rheological, compositional, and stability measurements. The resultant material was evaluated in the removal of yttrium by pH influence, nitrate concentration, kinetics, equilibrium isotherms, reusability, and a comparison with liquid-liquid (L-L) extraction and tested in a real scenario to extract Y from a fluorescent lamp powder waste. In addition, the selectivity of PE for REE was investigated with Y/Ca, Gd/Ca, and La/Ni systems. PE extracts REE at 1 ≤ pH ≤ 5 at nitrate concentrations up to 2 mol/L. The kinetics and equilibrium studies showed reaction times <5 min and a maximum sorption capacity of 89.98 mg/g. Compared with L-L extraction, PE consumed 48% less Cy923 without using organic diluents. PE showed a remarkable selectivity for REE in the systems evaluated, showing separation factors of 22.62, 9.35, and 504.64 for the blends Y/Ca, Gd/Ca/Mg, and La/Ni, respectively. PE showed excellent selectivity extracting Y from a real aqueous liquor from the fluorescent lamp powder. PE demonstrates to be an effective and sustainable alternative for REE recovering due to its excellent efficiency in harsh conditions, favorable green chemistry metrics, and use of a biopolymer material in its composition avoiding the use of organic solvents used in L-L extraction.

Engineering a Point-of-Care Paper-Microfluidic Electrochemical Device Applied to the Multiplexed Quantitative Detection of Biomarkers in Sputum.

Health initiatives worldwide demand affordable point-of-care devices to aid in the reduction of morbidity and mortality rates of high-incidence infectious and noncommunicable diseases. However, the production of robust and reliable easy-to-use diagnostic platforms showing the ability to quantitatively measure several biomarkers in physiological fluids and that could in turn be decentralized to reach any relevant environment remains a challenge. Here, we show the particular combination of paper-microfluidic technology, electrochemical transduction, and magnetic nanoparticle-based immunoassay approaches to produce a unique, compact, and easily deployable multiplex device to simultaneously measure interleukin-8, tumor necrosis factor-α, and myeloperoxidase biomarkers in sputum, developed with the aim of facilitating the timely detection of acute exacerbations of chronic obstructive pulmonary disease. The device incorporates an on-chip electrochemical cell array and a multichannel paper component, engineered to be easily aligned into a polymeric cartridge and exchanged if necessary. Calibration curves at clinically relevant biomarker concentration ranges are produced in buffer and artificial sputum. The analysis of sputum samples of healthy individuals and acutely exacerbated patients produces statistically significant biomarker concentration differences between the two studied groups. The device can be mass-produced at a low cost, being an easily adaptable platform for measuring other disease-related target biomarkers.

Are we ready for telemonitoring inflammatory bowel disease? A review of advances, enablers, and barriers.

This review summarizes the evidence about telemonitoring in patients with inflammatory bowel disease (IBD). To give an overview of the advances performed, as well as the enablers and barriers which favoured/hindered telemonitoring implementation. We performed a literature search in PubMed, EMBASE, MEDLINE, Cochrane Database, Web of Science and Conference Proceedings. Titles and abstracts published up to September 2022 were screened for a set of inclusion criteria: telemonitoring intervention, IBD as the main disease, and a primary study performed. Ninety-seven reports were selected for full review. Finally, 20 were included for data extraction and critical appraisal. Most studies used telemonitoring combined with tele-education, and programs evolved from home telemanagement systems towards web portals through mHealth applications. Web systems demonstrated patients' acceptance, improvement in quality of life, disease activity and knowledge, with a good cost-effectiveness profile in the short-term. Initially, telemonitoring was almost restricted to ulcerative colitis, but new patient reported outcome measures, home-based tests and mobile devices favoured its expansion to different patients´ categories. However, technological and knowledge advances led to legal, ethical, economical and logistic issues. Standardization of remote healthcare is necessary, to improve the interoperability of systems as well as to address liability concerns and users´ preferences. Telemonitoring IBD is well accepted and improves clinical outcomes at a lower cost in the short-term. Funders, policymakers, providers, and patients need to align their interests to overcome the emerging barriers for its full implementation.

Changes in the management of IBD patients since the onset of COVID-19 pandemic. A path toward the implementation of telemedicine in Spain? / Cambios en el manejo de la EII desde la pandemia por COVID-19. ¿Un nuevo inicio de la telemedicina en España?

Background: COVID-19 pandemic increased medical services demand aside from interrupting daily clinical practice for other diseases such as inflammatory bowel disease (IBD). Here we present the results of a survey to gain the perception of IBD specialists in their patient-management using telemedicine in their daily practice. Methods: This was an observational survey study among physicians focused on IBD (gastroenterologist, surgeons, and pediatricians) members of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU), the Spanish Association of Gastroenterology (AEG), and the Spanish Association of Coloproctology (AECP), regarding changes of management of IBD patients. Results: We received a total of 269 responses to the survey (from May to June 2020). Before the pandemic, nearly all the respondents reported performing very frequently their visits face-to-face (n=251, 93.3%) while, during the pandemic, the telephone visits were the most frequent visits performed (n=138, 51.3%). Regarding communication difficulties, 157 (58.4%) respondents reported the impossibility of performing a proper examination as the most relevant issue. Also, 114 (42.4%) respondents considered remote visits more time-consuming than face-to-face visits. Most gastroenterologists (n=188, 83.2%) considered patients with active perianal disease in special need of face-to-face consultation and more than half of the surgeons (n=35, 50.7%) reported having performed an immediate postoperative follow-up remotely. Conclusions: Most IBD units have implemented remote visits during the pandemic, but most professionals found them more time-consuming and unsuitable for some disease profiles. Therefore, there is a need for the development of better telemedicine systems that can meet professionals’ and patients’ requirements.(AU)

Introducción: La pandemia por COVID-19ha supuesto un incremento en la demanda de atención sanitaria y ha modificado el modelo asistencial de algunas patologías como la enfermedad inflamatoria intestinal (EII). Presentamos los resultados de una encuesta sobre el papel de la telemedicina en el manejo de pacientes con EII. Material y métodos: Estudio observacional mediante encuesta dirigida a gastroenterólogos, cirujanos y pediatras especializados en EII, miembros del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa, la Asociación Española de Gastroenterología y/o la Asociación Española de Coloproctología. Resultados: Recibimos un total de 269 respuestas (mayo a junio de 2020). Antes de la pandemia, el 93,3% de los participantes afirmó llevar a cabo la mayor parte de sus consultas de manera presencial. Durante la pandemia, la consulta telefónica se ha convertido en la modalidad preferida por el 51,3%. El principal inconveniente de la asistencia telemática fue la imposibilidad de llevar a cabo una exploración física según el 58,4%. Además, el 42,4% aseguró emplear más tiempo en este tipo de consultas. Entre gastroenterólogos, el 83,2% consideró que el paciente que más puede beneficiarse de la visita presencial es aquel con enfermedad perianal activa. Y, por último, el 50,7% de los cirujanos afirmó haber realizado controles remotos en el postoperatorio inmediato. Conclusiones: Si bien las unidades de EII han implementado durante la pandemia herramientas de telemedicina, muchos de los encuestados encontraron dificultades en su implementación. Es necesario adecuar y mejorar estos nuevos canales de asistencia remota para satisfacer las necesidades de profesionales y pacientes.(AU)

Ionic Liquids as Biocompatible Antibacterial Agents: A Case Study on Structure-Related Bioactivity on Escherichia coli.

The potential of ionic liquids (ILs) to be used as antimicrobial agents for biomedical applications has been hindered by the fact that most of them are cytotoxic toward mammalian cells. Understanding the mechanism of bacterial and mammalian cellular damage of ILs is key to their safety design. In this work, we evaluate the antimicrobial activity and mode of action of several ILs with varying anions and cations toward the clinically relevant Gram-negative Escherichia coli. Langmuir monolayer technique was used to evaluate if the IL's mode of action was related to the bacterial cell membrane interaction for an effective E. coli killing. 1-Decyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide [DMIM][TFSI] and trihexyltetradecyl phosphonium bis(trifluoromethylsulfonyl) imide [P6,6,6,14][TFSI] were surface-active and induced bacterial cell lysis, through a membrane-disruption phenomenon on bacteria, in a mechanism that was clearly related to the long alkyl chains of the cation. 1-Ethyl-3-methylimidazolium hydrogen sulfate [EMIM][HSO4] was highly antimicrobial toward E. coli and found suitable for biological applications since it was harmless to mammalian cells at most of the tested concentrations. The results suggest that the imidazolium cation of the ILs is mostly responsible not only for their antimicrobial activity but also for their cytotoxicity, and the inclusion of different anions may tailor the ILs' biocompatibility without losing the capacity to kill bacteria, as is the case of [EMIM][HSO4]. Importantly, this IL was found to be highly antimicrobial even when incorporated in a polymeric matrix.

Rapid Colorimetric Detection of Wound Infection with a Fluidic Paper Device.

Current procedures for the assessment of chronic wound infection are time-consuming and require complex instruments and trained personnel. The incidence of chronic wounds worldwide, and the associated economic burden, urge for simple and cheap point-of-care testing (PoCT) devices for fast on-site diagnosis to enable appropriate early treatment. The enzyme myeloperoxidase (MPO), whose activity in infected wounds is about ten times higher than in non-infected wounds, appears to be a suitable biomarker for wound infection diagnosis. Herein, we develop a single-component foldable paper-based device for the detection of MPO in wound fluids. The analyte detection is achieved in two steps: (i) selective immunocapture of MPO, and (ii) reaction of a specific dye with the captured MPO, yielding a purple color with increasing intensity as a function of the MPO activity in infected wounds in the range of 20-85 U/mL. Ex vivo experiments with wound fluids validated the analytic efficiency of the paper-based device, and the results strongly correlate with a spectrophotometric assay.

Nano-Formulation Endows Quorum Quenching Enzyme-Antibiotic Hybrids with Improved Antibacterial and Antibiofilm Activities against Pseudomonas aeruginosa.

The emergence of antibiotic resistant bacteria coupled with the shortage of efficient antibacterials is one of the most serious unresolved problems for modern medicine. In this study, the nano-hybridization of the clinically relevant antibiotic, gentamicin, with the bacterial pro-pathological cell-to-cell communication-quenching enzyme, acylase, is innovatively employed to increase its antimicrobial efficiency against Pseudomonas aeruginosa planktonic cells and biofilms. The sonochemically generated hybrid gentamicin/acylase nano-spheres (GeN_AC NSs) showed a 16-fold improved bactericidal activity when compared with the antibiotic in bulk form, due to the enhanced physical interaction and disruption of the P. aeruginosa cell membrane. The nano-hybrids attenuated 97 ± 1.8% of the quorum sensing-regulated virulence factors' production and inhibited the bacterium biofilm formation in an eight-fold lower concentration than the stand-alone gentamicin NSs. The P. aeruginosa sensitivity to GeN_AC NSs was also confirmed in a real time assay monitoring the bacterial cells elimination, using a quartz crystal microbalance with dissipation. In protein-enriched conditions mimicking the in vivo application, these hybrid nano-antibacterials maintained their antibacterial and antibiofilm effectiveness at concentrations innocuous to human cells. Therefore, the novel GeN_AC NSs with complementary modes of action show potential for the treatment of P. aeruginosa biofilm infections at a reduced antibiotic dosage.

Electrochemical quantification of biomarker myeloperoxidase.

Point of care testing (PoCT) devices permit precise and rapid detection of disease-related biomarkers contributing to an early disease diagnosis and administration of an appropriate treatment. The enzyme myeloperoxidase (MPO) is a relevant biomarker for infection and inflammation events assessment; however its direct electrochemical quantification is hindered by the limited accessibility to the iron atom in its active center. Herein, such hindrance of the MPO biomolecule is overcome using the redox mediator 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS). The charge involved in the electrochemical reduction of the MPO-oxidized ABTS is correlated with the concentration of MPO. The use of ABTS allowed for the electrochemical assessment of a wide range of MPO concentrations (10-1000 nM) including those reported for wound infections, chronic obstructive pulmonary disease and early adverse cardiac events. The developed electroanalytical approach is rapid and inexpensive, and thus suitable for implementation in PoCT devices.

Changes in the management of IBD patients since the onset of COVID-19 pandemic. A path toward the implementation of telemedicine in Spain?

BACKGROUND: COVID-19 pandemic increased medical services demand aside from interrupting daily clinical practice for other diseases such as inflammatory bowel disease (IBD). Here we present the results of a survey to gain the perception of IBD specialists in their patient-management using telemedicine in their daily practice. METHODS: This was an observational survey study among physicians focused on IBD (gastroenterologist, surgeons, and pediatricians) members of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU), the Spanish Association of Gastroenterology (AEG), and the Spanish Association of Coloproctology (AECP), regarding changes of management of IBD patients. RESULTS: We received a total of 269 responses to the survey (from May to June 2020). Before the pandemic, nearly all the respondents reported performing very frequently their visits face-to-face (n=251, 93.3%) while, during the pandemic, the telephone visits were the most frequent visits performed (n=138, 51.3%). Regarding communication difficulties, 157 (58.4%) respondents reported the impossibility of performing a proper examination as the most relevant issue. Also, 114 (42.4%) respondents considered remote visits more time-consuming than face-to-face visits. Most gastroenterologists (n=188, 83.2%) considered patients with active perianal disease in special need of face-to-face consultation and more than half of the surgeons (n=35, 50.7%) reported having performed an immediate postoperative follow-up remotely. CONCLUSIONS: Most IBD units have implemented remote visits during the pandemic, but most professionals found them more time-consuming and unsuitable for some disease profiles. Therefore, there is a need for the development of better telemedicine systems that can meet professionals' and patients' requirements.

Lipid artificial tears at a mimetic ocular interface.

We studied the behaviour of three lipid tear products, commercialised by the same brand, as Langmuir films at the air/liquid interface to simulate the ocular environment. No significant differences were observed in the surface behaviour of two of them disclosing the same composition, but commercialised for different applications. The interaction of several subphases, namely sodium chloride, glucose, albumin and lysozyme present in the natural tear, with the lipid films was assessed at room temperature and the temperature of human tear using surface pressure-area isotherms and elastic modulus plots. There is a notable influence of sodium chloride and the proteins albumin and lysozyme on the surface pressure-area isotherm of the lipid Langmuir films. Albumin shifted this isotherm to lower areas while an opposite shift was caused by lysozyme. These studies could be useful for the formulation of new lipid-containing artificial tears, and for increasing the confidence of the customers in commercial eye care formulations.

Novel Lignin-Capped Silver Nanoparticles against Multidrug-Resistant Bacteria.

The emergence of bacteria resistant to antibiotics and the resulting infections are increasingly becoming a public health issue. Multidrug-resistant (MDR) bacteria are responsible for infections leading to increased morbidity and mortality in hospitals, prolonged time of hospitalization, and additional burden to financial costs. Therefore, there is an urgent need for novel antibacterial agents that will both treat MDR infections and outsmart the bacterial evolutionary mechanisms, preventing further resistance development. In this study, a green synthesis employing nontoxic lignin as both reducing and capping agents was adopted to formulate stable and biocompatible silver-lignin nanoparticles (NPs) exhibiting antibacterial activity. The resulting silver-lignin NPs were approximately 20 nm in diameter and did not agglomerate after one year of storage at 4 °C. They were able to inhibit the growth of a panel of MDR clinical isolates, including Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii, at concentrations that did not affect the viability of a monocyte-derived THP-1 human cell line. Furthermore, the exposure of silver-lignin NPs to the THP-1 cells led to a significant increase in the secretion of the anti-inflammatory cytokine IL-10, demonstrating the potential of these particles to act as an antimicrobial and anti-inflammatory agent simultaneously. P. aeruginosa genes linked with efflux, heavy metal resistance, capsular biosynthesis, and quorum sensing were investigated for changes in gene expression upon sublethal exposure to the silver-lignin NPs. Genes encoding for membrane proteins with an efflux function were upregulated. However, all other genes were membrane proteins that did not efflux metals and were downregulated.

Hybrid Tellurium-Lignin Nanoparticles with Enhanced Antibacterial Properties.

The surge of antibiotic-resistant bacteria is leading to the loss of effectiveness of antibiotic treatment, resulting in prolonged infections and even death. Against this healthcare threat, antimicrobial nanoparticles that hamper the evolution of resistance mechanisms are promising alternatives to antibiotics. Herein, we used Kraft lignin, a poorly valorized polymer derived from plant biomass, to develop novel hybrid tellurium-lignin nanoparticles (TeLigNPs) as alternative antimicrobial agents. The sonochemically synthesized TeLigNPs are comprised of a lignin matrix with embedded Te clusters, revealing the role of lignin as both a reducing agent and a structural component. The hybrid NPs showed strong bactericidal effects against the Gram-negative Escherichia coli and Pseudomonas aeruginosa, achieving more than 5 log bacteria reduction, while they only slightly inhibited the growth of the Gram-positive Staphylococcus aureus. Exposure of TeLigNPs to human cells did not cause morphological changes or reduction in cell viability. Studies on the antimicrobial mechanism of action demonstrated that the novel TeLigNPs were able to disturb bacterial model membranes and generate reactive oxygen species (ROS) in Gram-negative bacteria.

Implementing telemedicine in inflammatory bowel disease: Is COVID-19 the definitive trigger? / Implementación de la telemedicina en la enfermedad inflamatoria intestinal: ¿es la COVID-19 el impulso definitivo?

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A Fungal Ascorbate Oxidase with Unexpected Laccase Activity.

Ascorbate oxidases are an enzyme group that has not been explored to a large extent. So far, mainly ascorbate oxidases from plants and only a few from fungi have been described. Although ascorbate oxidases belong to the well-studied enzyme family of multi-copper oxidases, their function is still unclear. In this study, Af_AO1, an enzyme from the fungus Aspergillus flavus, was characterized. Sequence analyses and copper content determination demonstrated Af_AO1 to belong to the multi-copper oxidase family. Biochemical characterization and 3D-modeling revealed a similarity to ascorbate oxidases, but also to laccases. Af_AO1 had a 10-fold higher affinity to ascorbic acid (KM = 0.16 ± 0.03 mM) than to ABTS (KM = 1.89 ± 0.12 mM). Furthermore, the best fitting 3D-model was based on the ascorbate oxidase from Cucurbita pepo var. melopepo. The laccase-like activity of Af_AO1 on ABTS (Vmax = 11.56 ± 0.15 µM/min/mg) was, however, not negligible. On the other hand, other typical laccase substrates, such as syringaldezine and guaiacol, were not oxidized by Af_AO1. According to the biochemical and structural characterization, Af_AO1 was classified as ascorbate oxidase with unusual, laccase-like activity.

Antibody-Enabled Antimicrobial Nanocapsules for Selective Elimination of Staphylococcus aureus.

Targeted bactericide nanosystems hold significant promise to improve the efficacy of existing antimicrobials for treatment of severe bacterial infections, minimizing the side effects and lowering the risk of the development of antibiotic resistance. In this work, we developed antibody-functionalized nanocapsules (NCs) containing antibacterial essential oil (EO) for selective and effective eradication of Staphylococcus aureus. Antibacterial EO NCs were produced via self-assembly nanoencapsulation in the plant-derived protein zein. The obtained EO NCs were decorated with aminocellulose to provide more reactive surface groups for carboxyl-to-amine immobilization of a antibody that is specific against S. aureus. The antibody-enabled EO NCs (Ab@EO NCs) demonstrated 2-fold higher bactericidal efficacy against the targeted bacterium compared to the pristine EO NCs at the same concentrations. The improved antibacterial effect of the Ab@EO NCs toward S. aureus was also confirmed in a real-time assay by monitoring bacterial cells elimination using a quartz crystal microbalance. Furthermore, the Ab@EO NCs selectively decreased the load and changed the cell morphology of the targeted S. aureus in a mixed inoculum with nontargeted Pseudomonas aeruginosa. Applying the nanoformulated antibacterial actives to an in vitro coculture model of the bacteria and skin fibroblasts resulted in suppression of S. aureus growth while preserving the human cells viability. The novel antibody-enabled antibacterial NCs showed potential for improving the treatment efficacy of staphylococcal infections, minimally affecting the beneficial microbial and human cells.

Early treatment with anti-tumor necrosis factor agents improves long-term effectiveness in symptomatic stricturing Crohn's disease.

BACKGROUND: There is limited evidence on the effectiveness of biological therapy in stricturing complications in patients with Crohn's disease. AIM: The study aims to determine the effectiveness of anti-tumor necrosis factor (TNF) agents in Crohn's disease complicated with symptomatic strictures. METHODS: In this multicentric and retrospective study, we included adult patients with symptomatic stricturing Crohn's disease receiving their first anti-TNF therapy, with no previous history of biological, endoscopic or surgical therapy. The effectiveness of the anti-TNF agent was defined as a composite outcome combining steroid-free drug persistence with no use of new biologics or immunomodulators, hospital admission, surgery or endoscopic therapy during follow-up. RESULTS: Overall, 262 patients with Crohn's disease were included (53% male; median disease duration, 35 months, 15% active smokers), who received either infliximab (N = 141, 54%) or adalimumab (N = 121, 46%). The treatment was effective in 87% and 73% of patients after 6 and 12 months, respectively, and continued to be effective in 26% after a median follow-up of 40 months (IQR, 19-85). Nonetheless, 15% and 21% of individuals required surgery after 1 and 2 years, respectively, with an overall surgery rate of 32%. Postoperative complications were identified in 15% of patients, with surgical site infection as the most common. Starting anti-TNF therapy in the first 18 months after the diagnosis of Crohn's disease or the identification of stricturing complications was associated with a higher effectiveness (HR 1.62, 95% CI 1.18-2.22; and HR 1.55, 95% CI 1.1-2.23; respectively). Younger age, lower albumin levels, strictures located in the descending colon, concomitant aminosalicylates use or presence of lymphadenopathy were associated with lower effectiveness. CONCLUSIONS: Anti-TNF agents are effective in approximately a quarter of patients with Crohn's disease and symptomatic intestinal strictures, and 68% of patients are free of surgery after a median of 40 months of follow-up. Early treatment and some potential predictors of response were associated with treatment success in this setting.

A potential lignocellulosic biomass based on banana waste for critical rare earths recovery from aqueous solutions.

Rare earth elements (REE) present multiple applications in technological devices but also drawbacks (scarcity and water contaminant). The current study aims to valorise the banana wastes - banana rachis (BR), banana pseudo-stem (BPS) and banana peel (BP) as sustainable adsorbent materials for the recovery of REE (Nd3+, Eu3+, Y3+, Dy3+ and Tb3+). The adsorbent materials were characterized using analytical techniques such as: Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, zeta potential and scanning electron microscopy with energy dispersive X-ray probe. The adsorption performance and mechanisms were studied by pH dependence, equilibrium isotherms, kinetics, thermodynamics, ion-exchange and desorption evaluation. The results show good adsorption capacities for the three materials, highlighting BR that presents ∼100 mg/g for most of the REE. The adsorption process (100 mg REE/L) reaches the 60% uptake in 8 min and the equilibrium within 50 min. On the other hand, the thermodynamic study indicates that the adsorption is spontaneous and exothermic (ΔH° < 40 kJ/mol). The adsorption mechanism is based on the presence of carboxylic groups that induce electrostatic interactions and facilitate the surface nucleation of REE microcrystals coupled to an ion exchange process as well as the presence of other oxygen containing groups that establish weak intermolecular forces. The recovery of REE from the adsorbent (∼97%) is achieved using EDTA as desorbing solution. This research indicates that banana waste and particularly BR is a new and promising renewable bioresource to recover REE with high adsorption capacity and moderated processing cost.