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The management of municipal solid waste (MSW) in cities is one of the most complex tasks facing local administrations. For this reason, waste management performance measurement structures are increasingly implemented at local and national levels. These performance structures usually contain strategic objectives and associated action plans, as well as key performance indicators (KPIs) for organizations investing their resources in action plans. This study presents the results of applying a methodology to find a quantitative-based prioritization of MSW action plans for the City Council of Castelló de la Plana in Spain. In doing so, cause-effect relationships between the KPIs have been identified by applying the principal component analysis technique, and from these relationships it was possible to identify those action plans which should be addressed first to manage public services more efficiently. This study can be useful as a tool for local administrations when addressing the actions included in their local waste plans as it can lead to financial savings.Implications: This paper introduces and implements a methodology that uses principal component analysis to analyze real data from waste management KPIs and provide municipal solid waste managers with a decision-making tool for prioritizing action plans. The methodology saves financial resources and time, as well as reinforcing the probability of reaching the meta values of the main performance system KPIs.
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Municipal solid waste (MSW) management is vital in achieving sustainable development goals. It is a complex activity embracing collection, transport, recycling, and disposal; and whose management depends on proper strategic decision-making. The use of decision support methods such as multi-criteria decision-making (MCDM) is widespread in MSW management. However, their application mainly focuses on selecting plant locations and the best technologies for waste treatment. Despite the critical role played by transport in promoting sustainability, MCDM has seldom been applied for the selection of sustainable transport alternatives in the field of MSW management. There are a few MCDM studies about choosing waste collection vehicles, but none that include the most recent green vehicles among the options or consider feasible future scenarios. In this article, different engine technologies for collection trucks (diesel, compressed natural gas (CNG), hybrid CNG-electric, electric, and hydrogen) are evaluated under sustainability criteria in a Spanish city by applying the stratified best and worst method (SBWM). This method enables considering the uncertainty associated with future events to establish various feasible scenarios. The results show that the best-valued options are electric and diesel trucks, in that order, followed by CNG and hybrid CNG-electric, and with hydrogen-powered trucks coming last. The SBWM has proven helpful in defining a comprehensive framework for selecting the most suitable engine technology to support long-term MSW collection. Considering sustainability among the criteria and feasible future scenarios in waste management collection decision-making provides more comprehensive and conclusive results that help managers and policymakers make better informed and more reliable decisions.
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The European mink (Mustela lutreola) is one of Europe's most endangered species, and it is on the brink of extinction in the Iberian Peninsula. The species' precarious situation requires the application of new ex situ conservation methodologies that complement the existing ex situ and in situ conservation measures. Here, we report for the first time the establishment of a biobank for European mink mesenchymal stem cells (emMSC) and oocytes from specimens found dead in the Iberian Peninsula, either free or in captivity. New emMSC lines were isolated from different tissues: bone marrow (emBM-MSC), oral mucosa (emOM-MSc), dermal skin (emDS-MSC), oviduct (emO-MSc), endometrium (emE-MSC), testicular (emT-MSC), and adipose tissue from two different adipose depots: subcutaneous (emSCA-MSC) and ovarian (emOA-MSC). All eight emMSC lines showed plastic adhesion, a detectable expression of characteristic markers of MSCs, and, when cultured under osteogenic and adipogenic conditions, differentiation capacity to these lineages. Additionally, we were able to keep 227 Cumulus-oocyte complexes (COCs) in the biobank, 97 of which are grade I or II. The European mink MSC and oocyte biobank will allow for the conservation of the species' genetic variability, the application of assisted reproduction techniques, and the development of in vitro models for studying the molecular mechanisms of infectious diseases that threaten the species' precarious situation.
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Células-Tronco Mesenquimais , Vison , Animais , Diferenciação Celular , Células Cultivadas , Espécies em Perigo de Extinção , Feminino , Vison/genética , Oócitos , OsteogêneseRESUMO
Bovine mesenchymal stem cells are a relevant cell population found in the maternal reproductive tract that exhibits the immunomodulation capacity required to prevent embryo rejection. The phenotypic plasticity showed by both endometrial mesenchymal stem cells (eMSC) and embryonic trophoblast through mesenchymal to epithelial transition and epithelial to mesenchymal transition, respectively, is essential for embryo implantation. Embryonic trophoblast maintains active crosstalk via EVs and soluble proteins with eMSC and peripheral blood MSC (pbMSC) to ensure the retention of eMSC in case of pregnancy and induce the chemotaxis of pbMSC, critical for successful implantation. Early pregnancy-related proteins and angiogenic markers are detected as cargo in EVs and the soluble fraction of the embryonic trophectoderm secretome. The pattern of protein secretion in trophectoderm-EVs changes depending on their epithelial or mesenchymal phenotype and due to the uptake of MSC EVs. However, the changes in this EV-mediated communication between maternal and embryonic MSC populations infected by viruses that cause abortions in cattle are poorly understood. They are critical in the investigation of reproductive viral pathologies.
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Vesículas Extracelulares , Células-Tronco Mesenquimais , Viroses , Animais , Bovinos , Comunicação , Transição Epitelial-Mesenquimal , Vesículas Extracelulares/metabolismo , Feminino , Células-Tronco Mesenquimais/metabolismo , Gravidez , Viroses/metabolismoRESUMO
Although the European rabbit is an "endangered" species and a notorious biological model, the analysis and comparative characterization of new tissue sources of rabbit mesenchymal stem cells (rMSCs) have not been well addressed. Here, we report for the first time the isolation and characterization of rMSCs derived from an animal belonging to a natural rabbit population within the native region of the species. New rMSC lines were isolated from different tissues: oral mucosa (rOM-MSC), dermal skin (rDS-MSC), subcutaneous adipose tissue (rSCA-MSC), ovarian adipose tissue (rOA-MSC), oviduct (rO-MSC), and mammary gland (rMG-MSC). The six rMSC lines showed plastic adhesion with fibroblast-like morphology and were all shown to be positive for CD44 and CD29 expression (characteristic markers of MSCs), and negative for CD34 or CD45 expression. In terms of pluripotency features, all rMSC lines expressed NANOG, OCT4, and SOX2. Furthermore, all rMSC lines cultured under osteogenic, chondrogenic, and adipogenic conditions showed differentiation capacity. In conclusion, this study describes the isolation and characterization of new rabbit cell lines from different tissue origins, with a clear mesenchymal pattern. We show that rMSC do not exhibit differences in terms of morphological features, expression of the cell surface, and intracellular markers of pluripotency and in vitro differentiation capacities, attributable to their tissue of origin.
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Células-Tronco Mesenquimais , Adipogenia , Animais , Biomarcadores/metabolismo , Diferenciação Celular , Células Cultivadas , Condrogênese , Células-Tronco Mesenquimais/metabolismo , Osteogênese , CoelhosRESUMO
Existing research recognizes the COVID-19 impact on waste generation. However, the preliminary studies were made at an early pandemic stage, focused on the household waste fraction, and employed descriptive statistics that lacked statistical support. This study tries to fill this gap by providing a reliable statistical analysis setting inferential confidence in the waste generation differences found in Castellón. Repeated measures ANOVA were carried out for all the waste fractions collected and recorded in the city landfill database from 2017 to 2020. Additionally, Bonferroni's multiple comparison test (p < 0.05) was used to assure confidence level correction and identify which pairs of years' differences appeared. The longitudinal study identified trends for each waste fraction before the pandemic and showed how they changed with the advent of the crisis. Compared to 2019, waste collection in 2020 significantly grew for glass and packaging; remained unchanged for beaches, paper and cardboard, and dropped substantially for households, streets, markets, bulky waste, hospitals, and recycling centres. Total waste showed no differences between 2017 and 2019 but dropped significantly in 2020. These findings may help us better understand the long-term implications of COVID-19 and improve municipal solid waste management in a similar crisis.
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COVID-19 , Eliminação de Resíduos , Gerenciamento de Resíduos , COVID-19/epidemiologia , Humanos , Estudos Longitudinais , Espanha/epidemiologiaRESUMO
Head and neck squamous cell carcinoma (HNSCC) ranks sixth in cancer incidence worldwide and has a 5-year survival rate of only 63%. Immunotherapies-principally immune checkpoint inhibitors (ICI), such as anti-PD-1 and anti-CTLA-4 antibodies that restore endogenous antitumor T-cell immunity-offer the greatest promise for HNSCC treatment. Anti-PD-1 has been recently approved for first-line treatment of recurrent and metastatic HNSCC; however, less than 20% of patients show clinical benefit and durable responses. In addition, the clinical application of ICI has been limited by immune-related adverse events (irAE) consequent to compromised peripheral immune tolerance. Although irAEs are often reversible, they can become severe, prompting premature therapy termination or becoming life threatening. To address the irAEs inherent to systemic ICI therapy, we developed a novel, local delivery strategy based upon an array of soluble microneedles (MN). Using our recently reported syngeneic, tobacco-signature murine HNSCC model, we found that both systemic and local-MN anti-CTLA-4 therapy lead to >90% tumor response, which is dependent on CD8 T cells and conventional dendritic cell type 1 (cDC1). However, local-MN delivery limited the distribution of anti-CTLA-4 antibody from areas distal to draining lymphatic basins. Employing Foxp3-GFPDTR transgenic mice to interrogate irAEs in vivo, we found that local-MN delivery of anti-CTLA-4 protects animals from irAEs observed with systemic therapy. Taken together, our findings support the exploration of MN-intratumoral ICI delivery as a viable strategy for HNSCC treatment with reduced irAEs, and the opportunity to target cDC1s as part of multimodal treatment options to boost ICI therapy.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Animais , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/etiologia , Humanos , Imunoterapia/efeitos adversos , Camundongos , Neoplasias Bucais/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológicoRESUMO
Resumen Introducción: El equilibrio dinámico (ED) es la base para todas las actividades motoras deportivas. Algunas variables como el tipo de pie y el mecanismo de Windlass (MW) están asociadas a dicho equilibrio y al riesgo de lesión en la extremidad inferior. Se hace necesario el reconocimiento de estos elementos en la población con el fin de identificar potenciales factores de riesgo y promover las respectivas medidas preventivas. Objetivo: Caracterizar el equilibrio dinámico, algunas variables sociodemográficas, antropométricas y anatómico-funcionales del pie en jóvenes futbolistas del Club Deportivo Cañasgordas Latinos. Materiales y métodos: Estudio cuantitativo, observacional y de corte transversal. Se incluyeron 10 futbolistas. Se evaluó ED por medio del Y-Balance Test. Se evaluó el MW por medio del Test de Jack. Para determinar la tipología del pie se utilizó el método HERZCO. Resultados: Se identificaron aspectos susceptibles en el equipo y posibles factores de riesgo de lesión como la prevalencia de pies cavos y la inactivación del mecanismo de Windlass en el 70% de la muestra. Ningún deportista presento riesgo de lesión asociado a asimetrías en el equilibrio dinámico. Conclusiones: Se sugiere complementar la evaluación del ED con factores anatómico-funcionales en futuros estudios para determinar el riesgo de lesión.
Abstract Introduction: Dynamic balance (ED) is at the base of all sports motor activity. Some variables such as the type of foot and the Windlass Mechanism (WM) are associated with this balance and the risk of injury on the lower limb. The recognition of these elements in the population is necessary to identify potential risk factors and promote the respective preventive measures. Objective: To characterize the dynamic balance sociodemographic, anthropometric and some anatomical-functional variables of the foot in young soccer players from the Canasgordas Latinos club. Materials and methods: Quantitative, observational, and cross-sectional study. A total of 10 soccer players were included. The ED was evaluated using the Y-Balance Test. MW was evaluated through the Jack's Test. The HERZCO method was used to determine the type of the foot. Results: Susceptible aspects of the equipment and possible risk factors for injury, such as the prevalence of pes cavus and the inactivation of the Windlass Mechanism in 70% of the sample were identified. Any athlete presented an injury risk associated with asymmetries in dynamic balance. Conclusions: It is suggested to complement the evaluation of ED with anatomical-functional factors in athletes to determine the risk of injury.
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Humanos , Masculino , Adulto , Reabilitação , Futebol , Pé , ColômbiaRESUMO
INTRODUCTION: Available data for biocomparable drugs are not enough to make clear decisions with respect to the potential consequences of a change for non-medical reasons in efficacy, security and inmunogenicity in patients. In the near future, options on biological treatments, biocomparable drugs, non biocomparable drugs and new chemical synthesis options will grow. Therefore, it is important to know how patients behave in persistence of treatment after a change for non- medical reasons, which already happens on a regular basis in social security institutions in Mexico. This information will help us to better understand the standard of treatment for patients with chronic immunomediated conditions. OBJECTIVE: The primary objective was to measure the impact of change for non-medical reasons in patients with rheumatoid arthritis (RA) treated with an innovative biological on persistence of treatment after changing to a biocomparable drug or a non-biocomparable drug, compared with those patients staying with the innovative biological. STUDY DESIGN: This is an observational study (non-interventionist) of paired cohorts, where an historic cohort obtained by review of clinical records of stable patients in which no modifications to treatment were made for at least six months is compared with two cohorts of patients whose treatments were switched to another treatment with the same therapeutic mechanism for-non-medical reasons (cycling). RESULTS: We included 264 RA patients (ACR/EULAR, 2010); 132 were switched for non-medical reasons, and 132 were not switched. Two-hundred and thirty (87.1%) were female. Average age was 53.9 years, ranging from 16 to 84 years. Two-hundred and sixty-three patients were Latino (99.6%); one was Caucasian. Persistence of treatment 12 months after the change was 84.8% (85.8% in Enbrel/Infinitam, 78.9% for Remicade/Remsima). No statistical difference was found with respect to RA clinical activity measured by DAS28 12 months after the switch (P > .05). In the 134 switched patients, 20 discontinued the new treatment due to lack of efficacy of the new drug and were changed to a different drug with a different biologic target. Although no differences were found in the cohorts of switched patients with respect to DAS 28 after 12 months of use, we did find differences in the frequency of adverse events. Forty-two patients had an adverse event in the drug switch cohorts: 33 in the Enbrel-Infinitam group and 9 in the Remicade-Remsima group. CONCLUSIONS: The persistence of treatment after switching from an innovative drug to a biocomparable or a non- biocomparable in RA patients did not show statistically significative differences in our cohorts, but we did find a higher number of adverse events when comparing those who were changed with those who continued on an innovative drug. Twenty patients in the switch groups had to receive a new drug with a different biological target due to lack of efficacy of the switched drug.
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Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fatores Biológicos/uso terapêutico , Etanercepte/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , México , Pessoa de Meia-IdadeRESUMO
RESUMEN El consumo de pescado contaminado con mercurio representa un grave problema para la salud humana, en especial, en poblaciones, en las cuales, forma parte de su dieta diaria. Este problema requiere un seguimiento de la concentración de mercurio en peces depredadores y no depredadores de agua dulce, especialmente, en zonas poco estudiadas, como la región de la Orinoquia colombiana. Por lo tanto, el objetivo de este estudio fue determinar la concentración de mercurio total en muestras de bagre rayado (Pseudoplatystoma fasciatum metaense) y de bocachico (Prochilodus mariae), de la parte alta del río Meta, Colombia, peces muy consumidos por las poblaciones aledañas. Ocho muestras de cada especie de pez se analizaron por duplicado, por espectrofotometría de absorción atómica, con generador de hidruros. Se estableció, que el método aplicado es trazable al material de referencia certificado Dorm-4; también, se realizó la validación del método. El valor promedio de mercurio total en bagre rayado fue de 0,055 ± 0,0107 mg/kg y para el bocachico, 0,026 ± 0,0054 mg/kg de pescado fresco. Las muestras analizadas no sobrepasan el valor límite establecido por la Organización Mundial de la Salud y Environmental Protection Agency; sin embargo, el índice de riesgo por efectos no cancerígenos, en algunas muestras de bagre rayado, presentan un valor superior a uno, por lo que su consumo representa un riesgo para la salud, especialmente, durante la gestación y la primera infancia, así como de pescadores y aquellas comunidades de la región, que dependen del consumo de este alimento.
ABSTRACT The consumption of fish contaminated with mercury represents a serious problem for human health, especially in populations in which it is part of their daily diet. This problem requires the monitoring of mercury concentration in freshwater predatory and non-predatory fish, especially in poorly studied areas such as the Orinoquia region of Colombia. The aim of this study was to determine total mercury concentration in samples of catfish (Pseudoplatystoma fasciatum metaense) and bocachico (Prochilodus mariae) from the river Meta, Meta-Colombia. Fishes very much consumed by the adjacent populations. Eight samples of each fish species were analyzed in duplicate by atomic absorption spectrophotometry with a hydride generator. It was established that the applied method is traceable to the Dorm-4 certified reference material; the method was also validated. The average value of total mercury in striped catfish was 0.055 ± 0.0107 mg / kg, and for bocachico 0.026 ± 0.0054 mg / kg of fresh fish. These data obtained do not exceed the limit value established by the World Health Organization and Environmental Protection Agency. However, the risk index for non-carcinogenic effects in some samples of striped catfish have a value greater than one, therefore their consumption represents a health risk, especially during pregnancy and early childhood, as well as for fishermen and those communities in the area that depend on the consumption of this food.
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BACKGROUND: Diabetic neuropathy represents a polyneuropathy with electrophiosiological alterations. Electroneuromyography (NMD) plays an important role in the evaluation of patient with diabetes mellitus type 2 (DM2) and doubtful neuropathy. OBJECTIVE: To determine clinical manifestations in patients with distal symmetrical sensory polyneuropathy (DSSP) and to correlate them with electromyographic alterations. MATERIAL AND METHODS: Transversal, analytical study. 138 patients over 18 years old, with DM2 and PSSD were selected. They underwent physical examination, laboratory studies and electromyography (EM) with 4-channel Nicolet electromyograph. Measures of central tendency and their dispersion were analyzed; data normality with Kolmogorov-Smirnov; Student's t test and Spearman's correlation. RESULTS: Thalar hyperkeratosis was the most frequent clinical finding in 103 (74%) patients. The most frequent symptoms were paresthesia in 132 (95.7%) patients and tingling in 93 (67.4%) patients. Exploration of superficial sensitivity determined neuropathy in 42 (30.4%) patients finding greater insensitivity in the medial plantar nerve territory. In the EM, the nerve with the greatest absent response was the left lateral plantar nerve in 51 (59%) patients. A significant correlation (p < 0.05) was found between the variables of EM with age, years of evolution and levels of glycated hemoglobin A1c. CONCLUSIONS: The higher the lack of glycemic control, the chronobiology of the patient and the time of illness, the greater the electromyographic affection.
INTRODUCCIÓN: la neuropatía diabética representa una polineuropatía con alteración electrofiosiológica. La electroneuromiografía (ENM) desempeña un papel importante en la evaluación del paciente con diabetes mellitus tipo 2 (DM2) y neuropatía dudosa. OBJETIVO: determinar las manifestaciones clínicas en pacientes con polineuropatía sensitiva simétrica distal (PSSD) y correlacionarlas con alteraciones electroneuromiográficas. MATERIAL Y MÉTODOS: estudio transversal, analítico. Se seleccionaron 138 pacientes mayores de 18 años, con DM2 y PSSD. Se les realizó exploración física, estudios de laboratorio y ENM con electromiógrafo Nicolet de 4 canales. Se analizaron las medidas de tendencia central y su dispersión; normalidad de datos con Kolmogorov-Smirnov; t de Student y correlación de Spearman. RESULTADOS: la hiperqueratosis talar fue el hallazgo clínico más frecuente en 74% de los pacientes. Los síntomas más frecuentes fueron parestesias en 95.7% y hormigueo en 67.4%. La exploración de sensibilidad superficial determinó neuropatía en 30.4%, encontrando mayor insensibilidad en el territorio del nervio plantar medial. En la ENM, el nervio con mayor respuesta ausente fue el plantar lateral izquierdo en 59%. Se encontró correlación significativa (p < 0.05) entre las variables electroneuromiograficas con la edad, años de evolución y niveles de hemoglobina glucosilada A1c (HbA1c). CONCLUSIONES: a mayor descontrol glucémico, cronobiología del paciente y tiempo del padecimiento, mayor es la afección electroneuromiográfica.
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Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Polineuropatias , Adolescente , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/diagnóstico , Hemoglobinas Glicadas , Humanos , Condução NervosaRESUMO
Embryonic implantation is a key step in the establishment of pregnancy. In the present work, we have carried out an in-depth proteomic analysis of the secretome (extracellular vesicles and soluble proteins) of two bovine blastocysts embryonic trophectoderm primary cultures (BBT), confirming different epithelial-mesenchymal transition stages in these cells. BBT-secretomes contain early pregnancy-related proteins and angiogenic proteins both as cargo in EVs and the soluble fraction. We have demonstrated the functional transfer of protein-containing secretome between embryonic trophectoderm and maternal MSC in vitro using two BBT primary cultures eight endometrial MSC (eMSC) and five peripheral blood MSC (pbMSC) lines. We observed that eMSC and pbMSC chemotax to both the soluble fraction and EVs of the BBT secretome. In addition, in a complementary direction, we found that the pattern of expression of implantation proteins in BBT-EVs changes depending on: (i) their epithelial-mesenchymal phenotype; (ii) as a result of the uptake of eMSC- or pbMSC-EV previously stimulated or not with embryonic signals (IFN-); (iii) because of the stimulation with the endometrial cytokines present in the uterine fluid in the peri-implantation period.
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Quimiotaxia , Ectoderma/metabolismo , Implantação do Embrião , Embrião de Mamíferos/metabolismo , Endométrio/metabolismo , Células-Tronco Mesenquimais/metabolismo , Animais , Bovinos , Linhagem Celular , Feminino , ProteômicaRESUMO
INTRODUCTION: Available data for biocomparable drugs are not enough to make clear decisions with respect to the potential consequences of a change for non-medical reasons in efficacy, security and inmunogenicity in patients. In the near future, options on biological treatments, biocomparable drugs, non biocomparable drugs and new chemical synthesis options will grow. Therefore, it is important to know how patients behave in persistence of treatment after a change for non-medical reasons, which already happens on a regular basis in social security institutions in Mexico. This information will help us to better understand the standard of treatment for patients with chronic immunomediated conditions. OBJECTIVE: The primary objective was to measure the impact of change for non-medical reasons in patients with rheumatoid arthritis (RA) treated with an innovative biological on persistence of treatment after changing to a biocomparable drug or a non-biocomparable drug, compared with those patients staying with the innovative biological. STUDY DESIGN: This is an observational study (non-interventionist) of paired cohorts, where an historic cohort obtained by review of clinical records of stable patients in which no modifications to treatment were made for at least six months is compared with two cohorts of patients whose treatments were switched to another treatment with the same therapeutic mechanism for-non-medical reasons (cycling). RESULTS: We included 264 RA patients (ACR/EULAR, 2010); 132 were switched for non-medical reasons, and 132 were not switched. Two-hundred and thirty (87.1%) were female. Average age was 53.9years, ranging from 16 to 84years. Two-hundred and sixty-three patients were Latino (99.6%); one was Caucasian. Persistence of treatment 12months after the change was 84.8% (85.8% in Enbrel/Infinitam, 78.9% for Remicade/Remsima). No statistical difference was found with respect to RA clinical activity measured by DAS28 12months after the switch (P>.05). In the 134 switched patients, 20 discontinued the new treatment due to lack of efficacy of the new drug and were changed to a different drug with a different biologic target. Although no differences were found in the cohorts of switched patients with respect to DAS28 after 12months of use, we did find differences in the frequency of adverse events. Forty-two patients had an adverse event in the drug switch cohorts: 33 in the Enbrel-Infinitam group and 9 in the Remicade-Remsima group. CONCLUSIONS: The persistence of treatment after switching from an innovative drug to a biocomparable or a non-biocomparable in RA patients did not show statistically significative differences in our cohorts, but we did find a higher number of adverse events when comparing those who were changed with those who continued on an innovative drug. Twenty patients in the switch groups had to receive a new drug with a different biological target due to lack of efficacy of the switched drug.
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Cyclic products can be obtained through the intramolecular version of the Nicholas reaction, which requires having the nucleophile connected to the alkyne unit. Here, we report the synthesis of 1-oxa-3-cyclooctynes starting from commercially available (1R,3S)-camphoric acid. The strategy is based on the initial preparation of propargylic alcohols, complexation of the triple bond with Co2(CO)8, and treatment with BF3·Et2O to induce an intramolecular Nicholas reaction with the free hydroxyl group as nucleophile. Finally, oxidative deprotection of the alkyne afforded the cyclooctynes in good yields. Notably, large-sized R substituents at the chiral center connected to the O atom were oriented in such a way that steric interactions were minimized in the cyclization, allowing the formation of cyclooctynes exclusively with (R) configuration, in good agreement with theoretical predictions. Moreover, preliminary studies demonstrated that these cyclooctynes were reactive in the presence of azides yielding substituted triazoles.
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The administration of extracellular vesicles (EV) from mesenchymal stromal cells (MSC) is a promising cell-free nanotherapy for tissue repair after myocardial infarction (MI). However, the optimal EV delivery strategy remains undetermined. Here, we designed a novel MSC-EV delivery, using 3D scaffolds engineered from decellularised cardiac tissue as a cell-free product for cardiac repair. EV from porcine cardiac adipose tissue-derived MSC (cATMSC) were purified by size exclusion chromatography (SEC), functionally analysed and loaded to scaffolds. cATMSC-EV markedly reduced polyclonal proliferation and pro-inflammatory cytokines production (IFNγ, TNFα, IL12p40) of allogeneic PBMC. Moreover, cATMSC-EV recruited outgrowth endothelial cells (OEC) and allogeneic MSC, and promoted angiogenesis. Fluorescently labelled cATMSC-EV were mixed with peptide hydrogel, and were successfully retained in decellularised scaffolds. Then, cATMSC-EV-embedded pericardial scaffolds were administered in vivo over the ischemic myocardium in a pig model of MI. Six days from implantation, the engineered scaffold efficiently integrated into the post-infarcted myocardium. cATMSC-EV were detected within the construct and MI core, and promoted an increase in vascular density and reduction in macrophage and T cell infiltration within the damaged myocardium. The confined administration of multifunctional MSC-EV within an engineered pericardial scaffold ensures local EV dosage and release, and generates a vascularised bioactive niche for cell recruitment, engraftment and modulation of short-term post-ischemic inflammation.
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Transdermal microneedle (MN) drug delivery patches, comprising water-soluble polymers, have played an essential role in diverse biomedical applications, but with limited development towards fast deep release or sustained delivery applications. The effectiveness of such MN delivery patches strongly depends on the materials from which they are constructed. Herein, we present a dual-action combinatorial programmable MN patch, comprising of fast and sustained-release MN zones, with tunable release kinetics towards delivering a wide range of therapeutics over different timeframes in single application. We demonstrate the fine tuning of MN materials; the patches can be tailored to deliver a first payload faster and deeper within minutes, while simultaneously delivering a second payload over long times ranging from weeks to months. The active and rapid burst release relies on embedding biodegradable Mg microparticle 'engines' in dissolvable MNs while the sustained release is attributed to biocompatible polymers that allow prolonged release in a controllable tunable manner. In addition, the patches are characterized and optimized for their design, materials and mechanical properties. These studies indicate that such programmable dual-action versatile MN platform is expected to improve therapeutic efficacy and patient compliance, achieving powerful benefits by single patch application at low manufacturing cost.
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Sistemas de Liberação de Medicamentos/instrumentação , Microtecnologia/instrumentação , Agulhas , Preparações de Ação Retardada , Desenho de Equipamento , Cinética , Fenômenos Mecânicos , Solubilidade , Água/químicaRESUMO
Mesenchymal stem cells (MSCs) have a great potential in regenerative medicine because of their multipotential and immunoregulatory capacities, while in early pregnancy they could participate in the immunotolerance of the mother towards the embryo. Peripheral blood constitutes an accessible source of MSCs. We successfully isolated peripheral blood MSC (pbMSCs) lines, with or without previous bone marrow mobilization. All pbMSCs lines obtained in both conditions presented classical MSC markers and properties, alkaline phosphatase activity and multipotent capacity to differentiate among adipogenic, osteogenic or chondrogenic lineages, and suppressed the proliferation of T cells. pbMSCs showed migratory capacity without cytokine stimulation while increasing their migration rate in the presence of inflammatory or embryo implantation stimuli. Interestingly, in contrast to MSCs derived from endometrial tissue, three pbMSCs lines also showed increased migration towards the IFN-τ implantation cytokine. Moreover, the secretome produced by an early implantation stage embryonic trophectoderm cell line showed a chemoattractant effect in pbMSCs. Our results suggest that circulating MSCs are present in the peripheral blood under healthy conditions. The fact that both the inflammation and implantation signals induced pbMSCs chemotaxis highlights MSC heterogeneity and suggests that their migratory capacity may differ according to their tissue of origin and would suggest the possible active recruitment of MSCs from bone marrow during pregnancy to repress the immune response to prevent the embryo rejection by the maternal organism.
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Quimiotaxia/genética , Inflamação/genética , Células-Tronco Mesenquimais/metabolismo , Medicina Regenerativa , Adipogenia/genética , Animais , Bovinos , Diferenciação Celular/genética , Proliferação de Células/genética , Células Cultivadas , Condrogênese/genética , Implantação do Embrião/genética , Feminino , Humanos , Inflamação/patologia , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Relações Materno-Fetais/fisiologia , Células-Tronco Mesenquimais/fisiologia , Osteogênese/genéticaRESUMO
Introducción El reemplazo total de rodilla (RTR) es una de las cirugías con mayor tasa de éxito, y la funcionalidad y calidad de vida dependen en gran medida de la rehabilitación física adecuada. En Colombia no existe una Guía de rehabilitación física registrada ante el Ministerio de Salud. Por lo anterior el presente estudio tuvo como objetivo general determinar el efecto de la intervención fisioterapéutica en la funcionalidad y calidad de vida en pacientes sometidos a RTR. Materiales & métodos Estudio de cohorte transversal, que consto de tres evaluaciones (prequirúrgica, a los 3 y 6 meses) aplicando WOMAC, SF12, evaluación fisioterapéutica; y 36 sesiones de fisioterapia domiciliaria a 10 adultos mayores de 65 años. La muestra fue tomada de la lista de espera del cirujano participante entre noviembre de 2017 y junio de 2018. Resultados Al aplicar el cuestionario WOMAC la rigidez y el dolor obtuvieron un valor p=0.00 y 0,01 respectivamente. En la capacidad funcional se encontró una significancia de 0,009 entre el 1 y el 3 momento de la evaluación. Los resultados obtenidos al aplicar el cuestionario SF12 refirieron un mejor estado de salud, con poca limitación al realizar esfuerzos moderados o subir escaleras. En el 80% de la población la fuerza paso de 3- a 4+. En amplitud de movimiento articular se alcanzaron rangos funcionales que superan los 90° de flexión. Discusión Los resultados en la funcionalidad y calidad de vida están en consonancia con lo reportado en la literatura internacional.
Introduction Total knee replacement (TKR) has one of the highest success rates, and functionality and quality of life depend largely on appropriate physical rehabilitation. There is no physical rehabilitation guideline registered with the Ministry of Health in Colombia. Therefore, the general objective of this study was to determine the effect of physiotherapy intervention on functionality and quality of life in patients undergoing TKR. Materials & methods A cross-sectional cohort study, comprising three assessments (preoperative, at 3 and at 6 months) using the WOMAC and SF12 questionnaires, physiotherapy assessment, and 36 sessions of home physiotherapy in 10 adults over 65 years of age. The sample was taken from the participating surgeon's waiting list between November 2017 and June 2018. Results. Stiffness and pain obtained p-values of .00 and .01 respectively from the WOMAC questionnaire. A significance level of .009 was found in functional ability between the 1st and 3rd assessments. The SF12 questionnaire results reflected a better state of health, with little limitation on moderate effort or climbing stairs. Strength went from 3- to 4+ in 80% of the population. Functional ranges exceeding 90Ì of flexion were achieved in joint range of motion. Discussion Outcomes in terms of functionality and quality of life are in line with those reported in the international literature.
Assuntos
Humanos , Artroplastia do Joelho , Medicina Física e Reabilitação , Qualidade de VidaRESUMO
Abstract This work aimed to investigate the prevalence of Trichinella infection in horses (Equus ferus caballus) handled by rural slaughterhouses across five distinctive socioeconomic regions in Mexico. Serum samples were obtained by non-probabilistic convenience sampling in the Eastern, Southern Central and Western regions (100 samples of each). Additionally, muscle tissue samples were collected from the East (n = 45), Southeastern (n = 88), Southern Central (n = 39) and Southwestern (n = 11) regions. Antibodies were determined by Western blot and the muscle tissue was examined by artificial digestion. A global antibody prevalence of 2% was obtained. Regionally, a prevalence of 5% was observed in the East and 1% in the Southern Central region. No antibodies were detected in the West region and no larvae were found in the muscle tissue samples. These findings support the low presence of Trichinella in Mexican horses, which can positively impact the Mexican horse meat trade.
Resumen Se investigó la prevalencia de Trichinella en caballos (Equus ferus caballus) demataderos rurales en cinco regiones socioeconómicas de México. Los sueros se obtuvieron por Trichinella muestreo de conveniencia no probabilístico en las regiones Este, Centrosur y Oeste (100 muestras de cada una). Además se colectaron muestras de tejido muscular de animales de las regionesEste (n = 45), Centro Sur (n = 39), Sudeste (n = 88) y Sudoeste (n = 11). Los anticuerpos se determinaron por Western blot y el tejido muscular se examinó por digestión artificial. Se obtuvo una prevalencia global de anticuerpos del 2%. A nivel regional se observó una prevalencia del 5% enel Este y del 1% en el Centrosur. No se detectaron anticuerpos en el Oeste y no se encontraron larvas en el tejido muscular. Los datos respaldan la baja presencia de Trichinella en caballos mexicanos, lo que puede impactar positivamente en su comercio.
Assuntos
Animais , Trichinella , Triquinelose , Doenças dos Cavalos , Fatores Socioeconômicos , Triquinelose/veterinária , Triquinelose/epidemiologia , Matadouros , Doenças dos Cavalos/epidemiologia , Cavalos , Carne , México/epidemiologiaRESUMO
Maritime transport is responsible for 13% of the Greenhouse Gases (GHG) emissions of the transport sector. Port authorities, terminals, shipping companies, and other stakeholders have joined efforts to improve this sector's environmental performance. In Spain, the Ministry for Ecological Transition and Demographic Challenge has developed a methodology to assess the carbon footprint. This methodology has been adapted to ports and applied to processes under the Port Authority of Valencia's umbrella achieving scopes 1, 2, and 3. The results highlight that ship traffic, within the port, of containers and cruises (categorized in scope 3) had a major impact on the carbon footprint. Buildings lighting managed by the terminals has a significant effect on scope 2. Diesel consumption shares with gasoline consumption the primary representation in scope 1. The carbon footprint between 2008 and 2016 was maintained, although traffic in the port increased by 24% during this period. The results show a decrease of 17% when emissions are compared using the base year's emissions factors to avoid external factors. Future projects that include self-consumption or renewable energy policies seem to be the next step in a port that shows good results but still has room for improvement in activities of scope 3.