Drug-related problems in patients admitted for SARS-CoV-2 infection during the COVID-19 pandemic.

Introduction: Drug-related problems (DRP) are events or circumstances in which drug therapy does or could interfere with desired health outcomes. In December 2019, a new coronavirus, SARS-CoV-2, appeared. Little knowledge about this type of infection resulted in the administration of various drugs with limited use in other pathologies. Evidence about DRP in patients with COVID-19 is lacking. Objective: The aim of the present study is to describe identified cases of DRP and those drugs involved in the first wave of patients with COVID-19, and evaluate associated risk factors. Material and methods: Observational, retrospective study performed in a tertiary university hospital between 14th March 2020 and 31 May 2020 (corresponding to the first COVID-19 wave). We recruited patients admitted during the study period. Exclusion criteria included age < 18 years; admission to critically ill units; and care received either in the emergency room, at-home hospitalization or a healthcare center. Results: A total of 817 patients were included. The mean age was 62.5 years (SD 16.4) (range 18-97), and 453 (55.4%) were male. A total of 516 DRP were detected. Among the patients, 271 (33.2%) presented at least one DRP. The mean DRP per patient with an identified case was 1.9. The prevailing DRPs among those observed were: incorrect dosage (over or underdosage) in 145 patients (28.2%); wrong drug combination in 131 (25.5%); prescriptions not in adherence to the then COVID-19 treatment protocol in 73 (14.1%); prescription errors due to the wrong use of the computerized physician order entry in 47 (9.2%); and incorrect dosage due to renal function in 36 (7%). The logistic regression analysis showed that patients who received only prescriptions of antibacterials for systemic use (J01 ATC group) faced a higher likelihood of experiencing a DRP (OR 2.408 (1.071-5.411), p = 0.033). Conclusion: We identified several factors associated with an increased risk of DRPs, similar to those reported in other pre-pandemic studies, including a prolonged length of stay, higher number of prescribed drugs and antimicrobial administration. The relevance of pharmacists and tools like pharmacy warning systems can help prevent, identify and resolve DRP efficiently.

Superconducting spintronic tunnel diode.

Diodes are key elements for electronics, optics, and detection. Their evolution towards low dissipation electronics has seen the hybridization with superconductors and the realization of supercurrent diodes with zero resistance in only one direction. Here, we present the quasi-particle counterpart, a superconducting tunnel diode with zero conductance in only one direction. The direction-selective propagation of the charge has been obtained through the broken electron-hole symmetry induced by the spin selection of the ferromagnetic tunnel barrier: a EuS thin film separating a superconducting Al and a normal metal Cu layer. The Cu/EuS/Al tunnel junction achieves a large rectification (up to ∼40%) already for a small voltage bias (∼200 µV) thanks to the small energy scale of the system: the Al superconducting gap. With the help of an analytical theoretical model we can link the maximum rectification to the spin polarization (P) of the barrier and describe the quasi-ideal Shockley-diode behavior of the junction. This cryogenic spintronic rectifier is promising for the application in highly-sensitive radiation detection for which two different configurations are evaluated. In addition, the superconducting diode may pave the way for future low-dissipation and fast superconducting electronics.

Magnetization reversal in circular vortex dots of small radius.

We present a detailed study of the magnetic behavior of Permalloy (Ni80Fe20 alloy) circular nanodots with small radii (30 nm and 70 nm) and different thicknesses (30 nm or 50 nm). Despite the small size of the dots, the measured hysteresis loops manifestly display the features of classical vortex behavior with zero remanence and lobes at high magnetic fields. This is remarkable because the size of the magnetic vortex core is comparable to the dot diameter, as revealed by magnetic force microscopy and micromagnetic simulations. The dot ground states are close to the border of the vortex stability and, depending on the dot size, the magnetization distribution combines attributes of the typical vortex, single domain states or even presents features resembling magnetic skyrmions. An analytical model of the dot magnetization reversal, accounting for the large vortex core size, is developed to explain the observed behavior, providing a rather good agreement with the experimental results. The study extends the understanding of magnetic nanodots beyond the classical vortex concept (where the vortex core spins have a negligible influence on the magnetic behavior) and can therefore be useful for improving emerging spintronic applications, such as spin-torque nano-oscillators. It also delimits the feasibility of producing a well-defined vortex configuration in sub-100 nm dots, enabling the intracellular magneto-mechanical actuation for biomedical applications.

High-yield fabrication of 60 nm Permalloy nanodiscs in well-defined magnetic vortex state for biomedical applications.

Permalloy disc structures in magnetic vortex state constitute a promising new type of magnetic nanoparticles for biomedical applications. They present high saturation magnetisation and lack of remanence, which ease the remote manipulation of the particles by magnetic fields and avoid the problem of agglomeration, respectively. Importantly, they are also endowed with the capability of low-frequency magneto-mechanical actuation. This effect has already been shown to produce cancer cell destruction using functionalized discs, about 1 µm in diameter, attached to the cell membrane. Here, Permalloy nanodiscs down to 60 nm in diameter are obtained by hole-mask colloidal lithography, which is proved to be a cost-effective method for the uniform patterning of large substrate areas, with a high production yield of nanostructures. The characterisation of the magnetic behaviour of the nanodiscs, complemented with micromagnetic simulations, confirms that they present a very well defined magnetic vortex configuration, unprecedented, to our knowledge, for nanostructures of this size prepared by a high-yield method. The successful detachment of the gold-covered nanodiscs from the substrate is also demonstrated by the use of sacrificial layers.

Phosphorus cycling. Major role of planktonic phosphate reduction in the marine phosphorus redox cycle.

Phosphorus in the +5 oxidation state (i.e., phosphate) is the most abundant form of phosphorus in the global ocean. An enigmatic pool of dissolved phosphonate molecules, with phosphorus in the +3 oxidation state, is also ubiquitous; however, cycling of phosphorus between oxidation states has remained poorly constrained. Using simple incubation and chromatography approaches, we measured the rate of the chemical reduction of phosphate to P(III) compounds in the western tropical North Atlantic Ocean. Colonial nitrogen-fixing cyanobacteria in surface waters played a critical role in phosphate reduction, but other classes of plankton, including potentially deep-water archaea, were also involved. These data are consistent with marine geochemical evidence and microbial genomic information, which together suggest the existence of a vast oceanic phosphorus redox cycle.

Analgesia epidural en una mujer con neuroestimulación medular para síndrome regional complejo tipo I. Caso clínico y revisión de la literatura / Epidural analgesia in a woman with spinal neurostimulation for complex regional pain syndrome type 1. A clinical case and a literature review

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Estimating the capability of different phytoplankton groups to adapt to contamination: herbicides will affect phytoplankton species differently.

• Investigating the differential capacity of the response of phytoplankton to human-induced environmental forcing has become a key issue to understanding further the future repercussions on the functioning of aquatic ecosystems. • The initial tolerance to the widely dispersed herbicide simazine was measured in diverse phytoplankton species. An experimental ratchet system maintaining large populations of dividing cells (which ensures the occurrence of rare spontaneous mutations that confer adaptation) and a strong selection pressure (which ensures the preservation of such mutations within the population) was later applied to estimate the capability of different groups of phytoplankton to adapt to simazine. • Initially, simazine doses between 0.05 and 0.15 ppm were able to inhibit 100% growth in all the species tested. However, a significant increase in simazine resistance was achieved in all derived populations during the ratchet experiment. The differential capacity for simazine adaptation was observed among the different species. • The capacity of different species to adapt to simazine can be explained in relation to taxonomic group, ploidy, growth rate and habitat preference. Haploid populations of continental Chlorophyta showed the greatest capacity to adapt to simazine. By contrast, populations of Haptophyta of open ocean regions were the group least capable of adapting to the herbicide.

Tratamiento epidural del dolor en isquemia vascular periférica. Parte II. Revisión bibliográfi ca basada en la evidencia del tratamiento epidural en la isquemia vascular periférica / Epidural pain treatment in peripheral vascular ischemia (II)

Introducción: La isquemia arterial periférica puede ser el resultado de diversas enfermedades que afectan la vascularización de los miembros, generando dolor, discapacidad y deterioro de la calidad de vida del paciente, y en los casos de isquemia crítica, produciendo una considerable morbimortalidad y dolor crónico. Objetivo: Realizar una revisión histórica y crítica de publicaciones científicas sobre la analgesia epidural como método de control del dolor por isquemia vascular periférica y de sus efectos tróficos vasculares, y compararlos con otras técnicas analgésicas, así como recopilar diversas pautas de analgesia epidural y sus resultados. Material y métodos: Búsqueda en Medline, recopilación de datos y posterior análisis crítico, siguiendo los criterios de la medicina basada en la evidencia, de las publicaciones científicas sobre analgesia epidural y el dolor en el contexto de la isquemia arterial periférica. Resultados: a) La analgesia con infusión de fármacos epidurales en isquemia de miembros sólo alcanzó un nivel de evidencia 4 en la presente revisión; b) la anestesia epidural lumbar para cirugía de revascularización de miembros inferiores se relaciona con unas menores tasas de trombosis postoperatoria y de reintervenciones de revascularización que la anestesia general (nivel de evidencia 2b); c) no hay evidencia científica concluyente que apoye la utilización de analgesia epidural preventiva de los síndromes de dolor crónico postamputación de extremidades con isquemia, y d) la aplicación de neuroestimulación epidural medular en la isquemia crítica de origen ateroclusivo de miembros no reconstruibles mediante técnicas quirúrgicas está apoyada por un nivel de evidencia 1. En la enfermedad de Buerger, la enfermedad de Raynaud y trastornos vaso espásticos, la aplicación de la neuro-estimulación eléctrica epidural viene avalada por un nivel de evidencia 4 (...) (AU)

Introduction: Peripheral arterial ischemia can be caused by several diseases that compromise limb vascularization, leading to pain and disability and impairing quality of life. Critical ischemia produces substantial morbidity and mortality, as well as chronic pain. Objective: To perform a critical literature review of scientific publications on epidural analgesia to control pain due to peripheral vascular ischemia and on its vascular trophic effects, to compare this treatment modality with other analgesic techniques, and to describe several epidural analgesia strategies and their results. Material and methods: We searched MEDLINE for articles on epidural analgesia and pain in the context of peripheral arterial ischemia to gather data for subsequent critical analysis, following the criteria of evidence-based medicine. Results: a) Analgesia with epidural drug infusion in limb ischemia only reached level 4evidence in the present review; b) lumber epidural anesthesia for surgical revascularization of the lower extremities is associated with lower rates of postoperative thrombosis and revascularization reinterventions than general anesthesia (level 2b evidence); c) there is no conclusive scientific evidence supporting the use of preventive epidural analgesia of chronic pain syndromes after amputation of ischemic limbs, and d) the application of epidural spinal cord stimulation in critical atherosclerotic occlusive ischemia of non reconstructible limbs using surgical techniques is supported by level I evidence. In Buerger’s disease, Raynaud’s disease and vasospastic disorders, the application of epidural electrical stimulation is supported by level 4 evidence (...) (AU)

Toxic effect and adaptation in Scenedesmus intermedius to anthropogenic chloramphenicol contamination: genetic versus physiological mechanisms to rapid acquisition of xenobiotic resistance.

Anthropogenic water pollution is producing a challenge to the survival of phytoplankton populations. From an ecological point of view, the tolerance of these microorganisms to water pollution is of paramount importance since they are the principal primary producers of aquatic ecosystems. The adaptation of a common chlorophyta species (Scenedesmus intermedius) exposed to selected dose-response chloramphenicol (CAP) concentrations has been analyzed. A fluctuation analysis demonstrated that CAP-resistant cells arise due to spontaneous mutation which occurs randomly prior to the antibiotic exposure. CAP-inhibited growth and photosynthetic performance of algal cells at 0.28 mg/l, and the IC(50(72)) value was established in 0.10 mg/l for both parameters. The mutation rate from CAP sensitivity to resistance was 1.01 x 10(-5) mutations per cell division, while the frequency of CAP-resistant allele in non-polluted environment was estimated to be 5.5 CAP-resistant mutants per 10(3) sensitive-cells. These results demonstrate that resistant mutants exhibit a diminished fitness until 5 mg/l of CAP, thus enabling the survival of microalgae population.

Tratamiento epidural del dolor en la isquemia vascular periférica (I) / Treatment of epidural pain in peripheral vascular ischemia (I)

La isquemia arterial periférica puede ser el resultado de diversas enfermedades que afectan la vascularización de los miembros, generando dolor, discapacidad y deterioro dela calidad de vida del paciente, y en los casos de isquemia crítica produciendo una considerable morbimortalidad y dolor crónico. El objetivo ha sido realizar una revisión histórica de publicaciones científicas acerca de los distintos tipos de isquemia periférica, del dolor derivado, de su tratamiento analgésico por vía epidural y de las peculiaridades que hay que tener en cuenta en dicha patología. Se ha realizado una búsqueda en MEDLINE y se han recopilado los principales datos respecto a la evolución y las principales líneas de investigación científicas publicadas en las áreas de la analgesia epidural y el dolor en el contexto de la isquemia arterial periférica. Desde su introducción terapéutica en la isquemia periférica, la analgesia con perfusión de fármacos epidurales ha constituido un método eficaz analgésico, que en el caso de los anestésicos locales, además, aporta efectos hemorreológicos positivos a través de un bloqueo simpático. La neuroestimulación eléctrica epidural (NEE) medular es una modalidad analgésica crónica con indicaciones específicas dentro de la isquemia periférica, con potencial efecto trófico y capacidad de preservación de miembros, incluso en isquemia crítica atero-oclusiva. El efecto, tanto analgésico como trófico de las distintas modalidades analgésicas epidurales, varía según sus características técnicas y según los distintos tipos de isquemia periférica. Se deben tener en cuenta las limitaciones y riesgos del tratamiento analgésico epidural en la isquemia de miembros (...) (AU)

Peripheral arterial ischemia can result from various diseases that compromise limb vascularization, leading to pain, disability, and reduced quality of life; critical limb ischemia can cause substantial morbidity and mortality and chronic pain. The present article aims to provide a historical review of the scientific literature on the distinct types of peripheral ischemia, pain due to this disease, epidural analgesic treatment, and the particular features that should be taken into account in this disease. A MEDLINE search was performed and the main data on the evolution and main lines of research in epidural analgesia and pain in peripheral arterial ischemia were gathered. Since its introduction in peripheral ischemia, epidural infusion has been an effective analgesic method, which in the case of local anesthetics also provides positive hemorheological effects through sympathetic block. Epidural spinal cord stimulation is used to treat chronic pain and has specific indications in peripheral ischemia, with a potential trophic effect and limb salvage capacity even in critical limb ischemia due to atherosclerotic occlusive disease. Indeed, both the analgesic and trophic effects of the various epidural analgesic modalities vary according to their technical characteristics and the distinct types of peripheral ischemia. The limitations and risks of epidural analgesia in limb ischemia should be taken into account. Scientific studies evaluating the efficiency and effectiveness of epidural spinal cord stimulation in non-atherosclerotic occlusive peripheral ischemia, as well as research into the clinical vascular parameters that can act as predictors of limb preservation in critical limb ischemia during the test phase of spinal cord stimulation are required (AU)