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Progressive stiffening of the extracellular matrix (ECM) is observed in tissue development as well as in pathologies such as cancer, cardiovascular disease, and fibrotic disease. However, methods to recapitulate this phenomenon in vitro face critical limitations. Here, we present a poly(ethylene glycol)-based peptide-functionalized ECM-mimetic hydrogel platform capable of facile, user-controlled dynamic stiffening. This platform leverages supramolecular interactions between inverse-electron demand Diels-Alder tetrazine-norbornene click products (TNCP) to create pendant moieties that undergo non-covalent crosslinking, stiffening a pre-existing network formed via thiol-ene click chemistry over the course of 6 h. Pendant TNCP moieties have a concentration-dependent effect on gel stiffness while still being cytocompatible and permissive of cell-mediated gel degradation. The robustness of this approach as well as its simplicity and ease of translation give it broad potential utility.
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Hidrogéis , Polietilenoglicóis , Materiais Biocompatíveis , Química Click , Matriz ExtracelularRESUMO
The blood-brain barrier (BBB) limits the efficacy of treatments for malignant brain tumors, necessitating innovative approaches to breach the barrier. This study introduces burst sine wave electroporation (B-SWE) as a strategic modality for controlled BBB disruption without extensive tissue ablation and compares it against conventional pulsed square wave electroporation-based technologies such as high-frequency irreversible electroporation (H-FIRE). Using an in vivo rodent model, B-SWE and H-FIRE effects on BBB disruption, tissue ablation, and neuromuscular contractions are compared. Equivalent waveforms were designed for direct comparison between the two pulsing schemes, revealing that B-SWE induces larger BBB disruption volumes while minimizing tissue ablation. While B-SWE exhibited heightened neuromuscular contractions when compared to equivalent H-FIRE waveforms, an additional low-dose B-SWE group demonstrated that a reduced potential can achieve similar levels of BBB disruption while minimizing neuromuscular contractions. Repair kinetics indicated faster closure post B-SWE-induced BBB disruption when compared to equivalent H-FIRE protocols, emphasizing B-SWE's transient and controllable nature. Additionally, finite element modeling illustrated the potential for extensive BBB disruption while reducing ablation using B-SWE. B-SWE presents a promising avenue for tailored BBB disruption with minimal tissue ablation, offering a nuanced approach for glioblastoma treatment and beyond.
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There is evidence that healthcare can be executed differentially depending on the gender of patients, researchers, and clinicians. The aim was to analyze the possible existence of nursing gender differences in pain management produced by arterial puncture for blood gas analysis. A cross-sectional, multicenter study designed was conducted in Castilla-la Mancha (Spain). Variables of interest were collected from nurses in the public health system of a European region through a questionnaire. Data were collected for four months; the primary outcome was the use of any intervention to reduce pain and the explanatory variable was the nurse's gender. Bivariate analysis was carried out to assess associations between gender and pain-reducing interventions and a multivariate model was created with those factors that were relevant using logistic regression. A significantly higher proportion of men reported using some form of intervention (45% vs. 30%) and had more specific training (45.9% vs. 32.4%). The adjusted probability of using pain-reducing interventions by men was 71% higher than women. Thus, we found gender differences in the management of pain caused by arterial punctures performed by nurses as the main healthcare providers.
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The 4th World Congress of Electroporation (Copenhagen, 9-13 October 2022) provided a unique opportunity to convene leading experts in pulsed electric fields (PEF). PEF-based therapies harness electric fields to produce therapeutically useful effects on cancers and represent a valuable option for a variety of patients. As such, irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumour-treating fields (TTF) are on the rise. Still, their full therapeutic potential remains underappreciated, and the field faces fragmentation, as shown by parallel maturation and differences in the stages of development and regulatory approval worldwide. This narrative review provides a glimpse of PEF-based techniques, including key mechanisms, clinical indications, and advances in therapy; finally, it offers insights into current research directions. By highlighting a common ground, the authors aim to break silos, strengthen cross-functional collaboration, and pave the way to novel possibilities for intervention. Intriguingly, beyond their peculiar mechanism of action, PEF-based therapies share technical interconnections and multifaceted biological effects (e.g., vascular, immunological) worth exploiting in combinatorial strategies.
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In order to predict the high mortality due to COVID-19, simple, useful and remote instruments are required. To assess the validity of the baseline Barthel Index score as a predictor of in-hospital mortality among COVID-19 patients, a validation study of a clinical prediction tool in a cohort of patients with COVID-19 was conducted. The primary variable was mortality and the Barthel Index was the main explanatory variable. Demographic, clinical and laboratory variables were collected. Other mortality predictor scores were also assessed: Pneumonia Severity Index, CURB-65 and A-DROP. The Receiver Operating Characteristic Area under the Curve (ROC AUC), sensitivity and specificity were calculated for both the Barthel Index and the other predictor scores. An analysis of the association between the main variables was conducted, adjusting by means of three multivariate models. Three hundred and twelve patients were studied. Mortality was 16.4%. A mortality Odds Ratio (OR) of 5.95 was associated with patients with a Barthel Index ≤ 90. The model number 3 was developed to predict in-hospital mortality before COVID-19 infection occurs. It exhibits an OR of 3.44, a ROC AUC of 0.792, a sensitivity of 74.5% and a specificity of 73.9%. The Baseline Barthel Index proved useful in our population as a predictor of in-hospital mortality due to COVID-19.
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The treatment of CNS disorders suffers from the inability to deliver large therapeutic agents to the brain parenchyma due to protection from the blood-brain barrier (BBB). Herein, we investigated high-frequency pulsed electric field (HF-PEF) therapy of various pulse widths and interphase delays for BBB disruption while selectively minimizing cell ablation. Eighteen male Fisher rats underwent craniectomy procedures and two blunt-tipped electrodes were advanced into the brain for pulsing. BBB disruption was verified with contrast T1W MRI and pathologically with Evans blue dye. High-frequency irreversible electroporation cell death of healthy rodent astrocytes was investigated in vitro using a collagen hydrogel tissue mimic. Numerical analysis was conducted to determine the electric fields in which BBB disruption and cell ablation occur. Differences between the BBB disruption and ablation thresholds for each waveform are as follows: 2-2-2 µs (1028 V/cm), 5-2-5 µs (721 V/cm), 10-1-10 µs (547 V/cm), 2-5-2 µs (1043 V/cm), and 5-5-5 µs (751 V/cm). These data suggest that HF-PEFs can be fine-tuned to modulate the extent of cell death while maximizing peri-ablative BBB disruption. Furthermore, numerical modeling elucidated the diffuse field gradients of a single-needle grounding pad configuration to favor large-volume BBB disruption, while the monopolar probe configuration is more amenable to ablation and reversible electroporation effects.
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INTRODUCTION: Introduction: the situations of stress among which physical exercise is included imply the possibility of an excessive production of free radicals and, by their action, an oxidative stress in the cells. To combat these effects, cells have defense mechanisms called antioxidant systems. Objectives: the objective of this study is to analyze the possible physiological changes in relation to parameters related to oxidative stress (MDA) and antioxidant activity (vitamin A, vitamin C and vitamin E) in the erythrocytes of professional soccer players, in comparison with untrained subjects. Methods: forty-two men divided into 21 soccer players (SG) (24.95 ± 3.03 years) and 21 sedentary students (CG) (23.71 ± 2.42 years) participated in the study. Their basal levels of MDA, vitamin C, vitamin A and vitamin E in erythrocytes, as well as their anthropometric characteristics and VO2max, were evaluated. Results: significant differences were observed in the anthropometric characteristics (p < 0.05) and VO2max (p > 0.01). SG presented statistically lower levels of MDA (p > 0.01), vitamin C (p > 0.05), vitamin E (p > 0.05) and vitamin A (p > 0.01). Conclusions: there is higher oxidative stress in soccer players than in sedentary players and it may be necessary to supplement with antioxidants in this group.
INTRODUCCIÓN: Introducción: cualquier situación de estrés, entre las cuales se incluye la realización de ejercicio físico, implica la posibilidad de una excesiva producción de radicales libres y, por acción de estos, un estrés oxidativo en las células. Para combatir estos efectos, las células disponen de unos mecanismos de defensa denominados sistemas antioxidantes. Objetivos: el objetivo del presente estudio se basa en analizar los posibles cambios fisiológicos en relación a parámetros relacionados con el estrés oxidativo (MDA) y con la actividad antioxidante (vitamina A, vitamina C y vitamina E) en los eritrocitos de jugadores profesionales de fútbol, en comparación con sujetos no entrenados. Métodos: cuarenta y dos varones divididos en 21 jugadores de fútbol (SG) (24,95 ± 3,03 años) y 21 estudiantes sedentarios (CG) (23,71 ± 2,42 años) participaron en el estudio. Se les evaluaron los niveles basales de MDA, vitamina C, vitamina A y vitamina E en eritrocitos, así como las características antropométricas y el VO2max. Resultados: se observaron diferencias significativas en las características antropométricas (p < 0,05) y VO2max (p > 0,01). SG presentó niveles estadísticamente inferiores de MDA (p > 0,01), vitamina C (p > 0,05), vitamina E (p > 0,05) y vitamina A (p > 0,01). Conclusiones: existe un mayor estrés oxidativo en jugadores de fútbol que en sedentarios, por lo que puede ser necesaria una suplementación con antioxidantes en este grupo.
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Eritrócitos/fisiologia , Exercício Físico/fisiologia , Estresse Oxidativo/fisiologia , Futebol/fisiologia , Adulto , Ácido Ascórbico/metabolismo , Estudos de Casos e Controles , Eritrócitos/metabolismo , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Comportamento Sedentário , Vitamina A/metabolismo , Vitamina E/metabolismo , Adulto JovemAssuntos
Anestésicos Locais , Punções , Humanos , Dor/tratamento farmacológico , Dor/etiologia , GasometriaRESUMO
The study of Irish Mesostigmata extends back for more than 100 years, and most of the principal Irish habitat types have been studied. In this paper we provide a catalogue of the species of Mesostigmata (Arachnida, Acari, Parasitiformes) recorded from Ireland over that time. The catalogue includes 329 species, information on the habitats and locations where they occurred and provides a comprehensive list of the literature related to the Irish fauna. This catalogue increases the number of Mesostigmata species known in Ireland by 40% over the number recorded in the most recent catalogue (Luxton, 1998).
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Ácaros e Carrapatos , Aracnídeos , Animais , Ecossistema , Irlanda , ÁcarosAssuntos
Antibacterianos/farmacologia , Fosfomicina/farmacologia , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Polimixina B/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Fosfomicina/uso terapêutico , Humanos , Infecções por Klebsiella/urina , Klebsiella pneumoniae/isolamento & purificação , Pessoa de Meia-Idade , Polimixina B/uso terapêutico , Falha de Tratamento , Infecções Urinárias/tratamento farmacológicoRESUMO
El ayuno intermitente es una estrategia nutricional de creciente interés para el control del peso y mejora de la salud metabólica. El objetivo del presente estudio fue evaluar el efecto de un protocolo de ayuno intermitente sobre la composición corporal, perfil lipídico y los biomarcadores de riesgo cardiovascular en estudiantes universitarios. En este estudio experimental participaron 30 sujetos varones y fueron divididos aleatoriamente en dos grupos, 15 sujetos constituían el grupo experimental (GE) (edad: 20,83±0,98 años) y 15 el grupo control (GC) (edad: 23,71±5,55 años). El GE realizó un protocolo de ayuno 16/8, dieciséis horas de ayuno y ocho horas de ingesta calórica sin limitaciones, dos días consecutivos a la semana durante cinco semanas. Se evaluó la composición corporal, la ingesta calórica, el perfil lipídico y los biomarcadores del riesgo cardiovascular al inicio, mitad y final del protocolo. Se observaron descensos significativos en el GE en pliegues cutáneos, perímetro cintura, porcentaje de grasa, perfil lipídico y biomarcadores del riesgo cardiovascular en comparación con GC (p<0,05). Se encontraron incrementos significativos en la ingesta de colesterol y ácidos grasos poliinsaturados en el GE al final del estudio (p<0,05). Se observaron descensos en el colesterol total, triglicéridos, lipoproteínas de baja densidad y biomarcadores del riesgo cardiovascular a lo largo del protocolo en el GE (p<0,05). Un protocolo de ayuno intermitente 16/8, dos días consecutivos por semana, durante cinco semanas, parece efectivo para mejorar parámetros de composición corporal y perfil lipídico, así como para mejorar los biomarcadores relacionados con el riesgo cardiovascular(AU)
Intermittent fasting is a nutritional strategy of high interest in weight control and improvement of metabolic health. The objective of this study was to evaluate the effect of an intermittent fasting protocol on body composition, lipid profile and biomarkers of cardiovascular risk in university students. In this experimental study thirty male subjects participated and were randomly divided into two groups; fifteen subjects constituted the experimental group (GE) (age: 20.83 ± 0.98 years) and fifteen the control group (GC) (age: 23.71 ± 5.55 years). The GE performed a fasting protocol 16/8, sixteen hours of fasting and eight hours of caloric intake without limitations, two consecutive days per week for five weeks. Body composition, calorie intake, lipid profile and biomarkers of cardiovascular risk were evaluated at the beginning, middle and at the end of the protocol. Significant decreases were found in GE in skinfolds, waist perimeter, % fat, lipid profile and biomarkers of cardiovascular risk as compared to GC (p <0.05). There were significant increases in the intake of cholesterol and polyunsaturated fatty acids in the GE at the end of the study (p <0.05). There were decreases in total cholesterol, triglycerides, low-density lipoproteins, and biomarkers of cardiovascular risk throughout the study in GE (p<0.05). An intermittent fasting protocol 16/8, two consecutive days per week, for five weeks, seems effective to improve parameters of body composition and lipid profile, as well as to improving biomarkers related to cardiovascular risk(AU)