Dually sensitive dextran-based micelles for methotrexate delivery

Temperature-sensitive polymeric micelles were prepared from dextran grafted with poly(N-isopropylacrylamide) (PNIPAAm) or polyethylene glycol methyl ether (PEGMA) via controlled radical polymerization and evaluated as delivery systems of the anticancer drug methotrexate (MTX). Polymer-grafting was carried out after introduction of initiating groups onto the polysaccharide backbone, without the need for protection of hydroxyl groups and avoiding the use of toxic solvents. Temperature-responsive dextran-based copolymers were designed to exhibit self-aggregation behaviour, affinity for MTX and high cellular internalization. In addition, some grafted polymers incorporated 2-aminoethyl methacrylate to reinforce MTX encapsulation in the micelles by means of ionic interactions. Dextran-based micelles were cytocompatible and had an appropriate size to be used as drug carriers. MTX release was dependent on the pH and temperature. The combination of poly(2-aminoethylmethacrylate) and PNIPAAm with the dextran backbone permitted the complete release of MTX at normal physiological temperature. Co-polymer micelles were highly internalized by tumour cells (CHO-K1) and, when loaded with MTX, led to enhanced cytotoxicity compared to the free drug

Applicability of Clinical Decision Support in Management among Patients Undergoing Cardiac Surgery in Intensive Care Unit: A Systematic Review

[Abstract] The advances achieved in recent decades regarding cardiac surgery have led to a new risk that goes beyond surgeons’ dexterity; postoperative hours are crucial for cardiac surgery patients and are usually spent in intensive care units (ICUs), where the patients need to be continuously monitored to adjust their treatment. Clinical decision support systems (CDSSs) have been developed to take this real-time information and provide clinical suggestions to physicians in order to reduce medical errors and to improve patient recovery. In this review, an initial total of 499 papers were considered after identification using PubMed, Web of Science, and CINAHL. Twenty-two studies were included after filtering, which included the deletion of duplications and the exclusion of titles or abstracts that were not of real interest. A review of these papers concluded the applicability and advances that CDSSs offer for both doctors and patients. Better prognosis and recovery rates are achieved by using this technology, which has also received high acceptance among most physicians. However, despite the evidence that well-designed CDSSs are effective, they still need to be refined to offer the best assistance possible, which may still take time, despite the promising models that have already been applied in real ICUs.Xunta de Galicia; ED431C 2018/4

Anti-biofilm multi drug-loaded 3D printed hearing aids

Over 5% of the world's population has disabling hearing loss, which affects approximately one third of individuals over 65 years. Hearing aids are commonly used in this population group, but prolonged use of these devices may cause ear infections. We describe for the first time, the use of 3D printing to fabricate hearing aids loaded with two antibiotics, ciprofloxacin and fluocinolone acetonide. Digital light processing 3D printing was employed to manufacture hearing aids from two polymer resins, ENG hard and Flexible. The inclusion of the antibiotics did not affect the mechanical properties of the hearing aids. All multi-drug-loaded devices exhibited a hydrophilic surface, excellent blood compatibility and anti-biofilm activity against P. aeruginosa and S. aureus. Hearing aids loaded with ciprofloxacin (6% w/w) and fluocinolone acetonide (0.5% w/w) sustained drug release for more than two weeks and inhibited biofilm formation on the surface of the devices and bacteria growth in the surrounding medium. In summary, this work highlights the potential of vat photopolymerization 3D printing as a versatile manufacturing approach to fabricate high-fidelity patient-specific medical devices with anti-bacterial properties

Aprender Arquitectura de Computadores con la herramienta Simula3MS

En este artículo se presenta la experiencia de uso de la herramienta Simula3MS en el laboratorio de las asignaturas de Arquitectura de Computadores en los estudios impartidos en la Facultad de Informática de la Universidade da Coruña y la Escuela Técnica Superior de Ingeniería de la Universidade de Santiago de Compostela. El objetivo de las prácticas es ilustrar, mediante un juego de ejercicios realizados sobre el simulador Simula3MS, cómo trabaja el procesador del computador. El simulador usa un subconjunto de instrucciones MIPS y varias configuraciones diferentes del procesador que se escogen según el objetivo de los ejercicios prácticos. En el artículo se describen los ejercicios que se proponen a los estudiantes en el laboratorio y se muestra un análisis sobre el impacto que ha tenido el uso del simulador en la actividad docente.Peer Reviewe

Microemulsions for colorectal cancer treatments: general considerations and formulation of methotrexate

[Abstract] Microemulsions combine the advantages of emulsions with those of nanocarriers, overcoming the stability problems of the former and providing facile scalable systems with compartments adequate for high drug loadings. Recently, microemulsions are gaining attention in the formulation of anticancer drugs not only for topical treatment, but also for systemic delivery as well as for the development of theranostic systems. The aim of this paper is two-fold. First, an updated review about general features, preparation, characterization and pharmaceutical applications, with a special focus on colorectal cancer, is provided. Second, a case study of formulation of methotrexate in microemulsions is presented. Various essential oils (menthol, trans-anethole, α-tocopherol) and surfactants (TPGS-l000, Maxemul 6112, Noigen RN-20) were investigated for the preparation of o/w microemulsions for the delivery of methotrexate, and the ability of methotrexate-loaded microemulsions to inhibit cancer cell growth was then evaluated. Disregarding the surfactants used, menthol and trans-anethole led to cytotoxic microemulsions, whereas α-tocopherol based-formulations induced cell proliferation. These findings highlight the role that the oily component may play in the efficacy and safety of the microemulsions.México. Consejo Nacional de Ciencia y Tecnologia; No. CB-2011/ 168472Ministerio de Economia y Competitividad; SAF2014-52632-RRed Gallega de Investigación sobre Cáncer Colorrectal; R2014/03

Technologies for participatory medicine and health promotion in the elderly population

Study protocol clinical trial[Abstract] Introduction: The progressive aging of the population is a socio-demographic phenomenon experienced by most countries in the world in recent decades, especially in Japan and in many European Union countries. During this process, so-called “geriatric syndromes” frequently occur. The focus of this study is the quality of life of the elderly in relation to these 3 factors: risk of falls, urinary incontinence, and insomnia. Objective: The main purpose is to determine the impact of a multifactorial intervention program implemented with institutionalized elderly people. The program is focused on the treatment of the aforementioned factors. Methods and Analysis: The study will be carried out with elderly people living in three residences for the elderly in A Coruña Province (Galicia, Spain).It is a prospective and longitudinal study, with a temporary series design of a “quasi-experimental” type that evaluates the effect of an intervention in 1 given population by doing assessments pre- and post-intervention, but there is no comparison with a control group. The intervention will be based on a multifactorial program, including the following phases: the use of wearable devices (wearable fitness trackers to register physical activity and sleep), the use of an App on a Tablet to record the participants’ occupations and activities, counseling about performance in activities of daily living, the implementation of a physical activity program, and the treatment of the pelvic floor (according to each research line). The Quality of Life (QoL) will be assessed before and after the intervention, with the use of the questionnaire EuroQol-5D-5L. Data analysis will be applied with all registered variables through a quantitative perspective. Ethics and Dissemination: The protocol has been approved by the host institution's ethics committee (Research Ethics Committee of Galicia) under the number 2017/106. Results will be disseminated via peer-reviewed journal articles and conferences. This clinical trial is registered at ClinicalTrials.gov identifier: NCT03504813.Xunta de Galicia; IN852A 2016/10Xunta de Galicia; R2014/039Xunta de Galicia; ED431G/0

Acylcarnitine profile in neonatal hypoxic-ischemic encephalopathy: The value of butyrylcarnitine as a prognostic marker

Optimal prognostic markers evaluating early neuroprotective interventions in neonatal hypoxic-ischemic encephalopathy (HIE) are lacking. This study was designed to assess the prognostic value of acylcarnitines in neonatal HIE.An observational cohort study was conducted over 10 years in 67 HIE. Variables analyzed included sex, blood cord pH, Apgar score, hypothermia treatment (yes/no), neuron-specific enolase (NSE) levels, and clinical outcome (neurological examination, brain magnetic resonance imaging [MRI], and electroencephalogram) before discharge and at 6 months. Acylcarnitine profiles were analyzed by tandem-mass spectrometry on dried-blood spots collected on day 3 for newborn screening. A cohort of healthy newborns was used as control group.HIE patients had significantly increased C4, C5, C5:1, C6, C6-OH, C8 levels (all P < .01) and decreased long-chain acylcarnitine levels (P < .03). Hypothermia treatment was associated with a decrease in C4 levels (p = 0.005) and an increase in most long-chain acylcarnitine levels (P < .01). A significant association was found between C4 levels and NSE on day 1 of hypothermia treatment (P = .002) and abnormal brain magnetic resonance imaging (MRI) at discharge (P = .037). In the hypothermia group, C4 levels decreased in patients with favorable outcomes but remained high in those who progressed unfavorably.C4 appears to be a good prognostic marker in HIE, as blood levels correlated with NSE levels and abnormal MRI findings. Furthermore, hypothermia did not lead to decreased levels in patients with adverse outcomes

Supercritical fluid (SCF)-assisted preparation of cyclodextrin-based poly(pseudo)rotaxanes for transdermal purposes

This study aims to investigate the effect of the preparation of solid dispersions using supercritical CO2 (scCO2) on the physicochemical properties and the performance of supramolecular gels based on polymer-cyclodextrin (CD) interactions (named poly(pseudo)rotaxanes, PPR) envisaging a transdermal administration. Solid dispersions containing Soluplus®, the antihypertensive drug carvedilol (CAR), and CD (αCD or HPβCD) were prepared and characterized by HPLC, XRPD, FTIR, and DSC. PPRs prepared from solid dispersions (SCF gels) and the corresponding physical mixtures (PM gels) were analyzed regarding rheology, morphology, in vitro drug diffusion, and ex vivo drug skin permeation. The application of scCO2 led to the loss of the crystalline lattice of CAR while preserving its chemical identity. On the contrary, αCD crystals were still present in the SCF solid dispersions. SCF gels were more uniform than their corresponding PM, and the supercritical treatment resulted in changes in the rheological behavior, reducing the viscosity. CAR in vitro diffusion was significantly higher (p < 0.05) for the αCD-based SCF gel than its corresponding PM gel. Drug skin permeation showed a significant increase in drug flux from CD-based SCF gels (containing αCD or HPβCD) compared to corresponding PM gels. Additionally, the pretreatment of the skin with αCD exhibited increased CAR permeation, suggesting an interaction between αCD and the skin membrane. Results evidenced that SCF processing decisively modified the properties of the supramolecular gels, particularly those prepared with αCDOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This research was partially supported by the Brazilian agency Fundação de Apoio à Pesquisa do Estado de Goiás (FAPEG). The work was supported by MCIN/AEI/10.13039/501100011033 (PID 2020-113881RB-I00), Spain, Xunta de Galicia (ED431C 2020/17), and FEDERS

Accuracy of transcutaneous bilirubin on covered skin in preterm and term newborns receiving phototherapy using a JM-105 bilirubinometer

OBJECTIVE: Determine the suitability of transcutaneous bilirubin (TCB) as a tool to assess the effectiveness of phototherapy on patched skin. STUDY DESIGN: A prospective observational study was conducted. We covered a fragment of skin (sternum) with a photo-opaque patch. Several simultaneous TCB and TSB measurements were performed with the JM-105 bilirubinometer. Bland and Altman test evaluated the agreement between bilirubin levels. RESULT: A total of 217 patients were studied, 48.8% were preterm. The mean difference between TSB and TCB before the start of treatment was 1.07 mg/dL. During phototherapy, differences on covered skin were 0.52, 0.27, and 0.39 mg/dL at 24, 48, and 72 h of therapy respectively. The best correlation was observed at 48 h in preterm infants. CONCLUSION: The measurement of TCB on patched skin (PTCB) is useful for monitoring the response to phototherapy in term and preterm infants. We use a patch with a removable flap that eases successive measures without disturbing the patients