Impact of intermediate to high doses of methylprednisolone on mortality rate in patients with COVID-19 pneumonia-induced severe systemic inflammation.

INTRODUCTION: In addition to respiratory support needs, patients' characteristics to guide indication or timing of corticosteroid treatment in COVID-19 patients are not completely established. This study aimed to evaluate the impact of methylprednisolone on mortality rate in patients with COVID-19 pneumonia-induced severe systemic inflammation (PI-SSI). METHODS: Between 9 March and 5 May 2020 (final follow-up on 2 July 2020), a retrospective cohort study was conducted in hospitalised patients with COVID-19 PI-SSI (≥2 inflammatory biomarkers [IBs]: temperature ≥38℃, lymphocyte ≤800 cell/µL, C-reactive protein ≥100 mg/L, lactate dehydrogenase ≥300 units/L, ferritin ≥1000 mcg/L, D-dimer ≥500 ng/mL). Patients received 0.5-1.0 mg/kg of methylprednisolone for 5-10 days or standard of care. The primary outcome was 28-day all-cause mortality. Secondary outcomes included ≥2 points improvement on a 7-item WHO-scale (Day 14), transfer to intensive care unit (ICU) (Day 28) and adverse effects. Kaplan-Meier method and Cox proportional hazard regression were implemented to analyse the time to event outcomes. RESULTS: A total of 142 patients (corticosteroid group n = 72, control group n = 70) were included. A significant reduction in 28-day all-cause mortality was shown with methylprednisolone in patients with respiratory support (HR: 0.15; 95% CI 0.03-0.71), with ≥3 (HR: 0.17; 95% CI 0.05-0.61) or ≥4 altered IB (HR: 0.15; 95% CI 0.04-0.54) and in patients with both respiratory support and ≥3 (HR: 0.11; 95% CI 0.02-0.53] or ≥4 altered IB (HR: 0.14; 95% CI 0.04-0.51). No significant differences were found in secondary outcomes. CONCLUSION: Intermediate to high doses of methylprednisolone, initiated between 5 and 12 days after symptom onset, was associated with a significant reduction in 28-day all-cause mortality in patients with COVID-19 pneumonia and ≥3 o ≥ 4 altered IB, independently of the need of respiratory support.

Plasticity resulted from phase transformation for monolayer molybdenum disulfide film during nanoindentation simulations.

Molecular dynamics simulations on nanoindentation of circular monolayer molybdenum disulfide (MoS2) film are carried out to elucidate the deformation and failure mechanisms. Typical force-deflection curves are obtained, and in-plane stiffness of MoS2 is extracted according to a continuum mechanics model. The measured in-plane stiffness of monolayer MoS2 is about 182 ± 14 N m-1, corresponding to an effective Young's modulus of 280 ± 21 GPa. More interestingly, at a critical indentation depth, the loading force decreases sharply and then increases again. The loading-unloading-reloading processes at different initial unloading deflections are also conducted to explain the phenomenon. It is found that prior to the critical depth, the monolayer MoS2 film can return to the original state after completely unloading, while there is hysteresis when unloading after the critical depth and residual deformation exists after indenter fully retracted, indicating plasticity. This residual deformation is found to be caused by the changed lattice structure of the MoS2, i.e. a phase transformation. The critical pressure to induce the phase transformation is then calculated to be 36 ± 2 GPa, consistent with other studies. Finally, the influences of temperature, the diameter and indentation rate of MoS2 monolayer on the mechanical properties are also investigated.

[Corticosteroids and metabolic resuscitation (hydrocortisone, ascorbic acid and thiamine) in sepsis and septic shock]. / Corticoides y resucitación metabólica (hidrocortisona, ácido ascórbico y tiamina) en la sepsis y el shock séptico.

In accordance with the recommendations of, among others, the Surviving Sepsis Campaign, adjunctive therapies may play a role in the treatment and the prognosis in sepsis patients. Corticosteroids, ascorbic acid, and thiamine has been identified as a potential therapy for septic shock alone or in combination. Since many years, low-dosis corticosteroids has been proposed as adjuvant therapies for these patients. However, there are still many controversies regarding the role of systemic low-dose corticosteroids as a part of the treatment of septic shock. In recent clinical and experimental investigations, mitochondrion-target therapy bic acid and thiamine) for sepsis has been suggested to reduce MODS severity and mortality although their clinical results are not yet convincing for their use. In the present article, we have performed a narrative review of the current literature including pathophysiologic rationale and the current evidence for such therapies in septic patients.

Superplastic Deformation of Alumina Composites Reinforced with Carbon Nanofibers and with Graphene Oxide Sintered by SPS-Experimental Testing and Theoretical Interpretation.

The superplastic behavior of alumina-based nanostructured ceramics (Al2O3) is an important issue in the world of materials. The main body of this paper is an analysis of the creep behavior of polycrystals, with grain boundary sliding as the main deformation mechanism at high temperatures. Concomitant accommodation of grain shapes to preserve spatial continuity has a comparatively small effect on the strain rate. The constitutive equations for small deformations, relating strain and strain rate, derived from two models for grain sliding, are compared with the experimental data with their respective uncertainties. The data follow from experiments on the plastic deformation of alumina composites reinforced, on the one hand by graphene oxide, and on the other hand by carbon nanofibers sintered by SPS. The results show good agreement between experiment and theory for these advanced ceramics, particularly for one of the assumed models. The values obtained of ξ2 for model A were in the interval 0.0002-0.1189, and for model B were in the interval 0.000001-0.0561. The values obtained of R2 for model A were in the interval 0.9122-0.9994, and for model B were in the interval 0.9586-0.9999. The threshold stress was between (3.05 · 10-15-25.68) MPa.

Fabrication of Porous Alumina Structures by SPS and Carbon Sacrificial Template for Bone Regeneration.

In this work, a procedure for fabricating porous alumina with the use of a carbon sacrificial template has been tested in order to optimize the fabrication of porous structures mimicking the porosity and mechanical properties of the human cortical bone. Two different sources of sacrificial carbon were used and compared, and different sintering and calcination routes were considered. The porosity of the alumina structures studied by Hg porosimetry revealed that the amount of porosity and the size and shape of the pores are still below the required values, although some acicular pores were clearly observed by SEM. Moreover, measured mechanical properties (Young's modulus) remained below that of the bone, suggesting the need for further consolidation treatments. In summary, these encouraging results drive the optimization of future fabrication routes.

Biodosimetry and assessment of radiation dose.

AIM: When investigating radiation accidents, it is very important to determine the exposition dose to the individuals. In the case of exposures over 1 Gy, clinicians may expect deterministic effects arising the following weeks and months, in these cases dose estimation will help physicians in the planning of therapy. Nevertheless, for doses below 1 Gy, biodosimetry data are important due to the risk of developing late stochastic effects. Finally, some accidental overexposures are lack of physical measurements and the only way of quantifying dose is by biological dosimetry. BACKGROUND: The analysis of chromosomal aberrations by different techniques is the most developed method of quantifying dose to individuals exposed to ionising radiations.(1,2) Furthermore, the analysis of dicentric chromosomes observed in metaphases from peripheral lymphocytes is the routine technique used in case of acute exposures to assess radiation doses. MATERIALS AND METHODS: Solid stain of chromosomes is used to determine dicentric yields for dose estimation. Fluorescence in situ hybridization (FISH) for translocations analysis is used when delayed sampling or suspected chronically irradiation dose assessment. Recommendations in technical considerations are based mainly in the IAEA Technical Report No. 405.(2.) RESULTS: Experience in biological dosimetry at Gregorio Marañón General Hospital is described, including own calibration curves used for dose estimation, background studies and real cases of overexposition. CONCLUSION: Dose assessment by biological dosimeters requires a large previous standardization work and a continuous update. Individual dose assessment involves high qualification professionals and its long time consuming, therefore requires specific Centres. For large mass casualties cooperation among specialized Institutions is needed.

The Possible Detriment of Oxygen in Creep of Alumina and Zirconia Ceramic Composites Reinforced with Graphene.

This paper is aims to give an answer to the following question: is the oxidation of graphene a critical issue for high-temperature plasticity in graphene-reinforced ceramics? To give a convincing reply, we will focus on two very different graphene-based ceramic composites: reduced graphene oxide (rGO)-reinforced alumina (α-Al2O3) and reduced graphene oxide (rGO)-reinforced yttria tetragonal zirconia (t-ZrO2). The processing of the powders has been made using a colloidal route, and after that, a spark plasma sintering process was performed in order to densify the samples. Creep tests were performed at temperatures between 1200-1250 °C in an argon atmosphere. The microstructure obtained by an SEM of the sintered and tested specimens was characterized quantitatively to elucidate the deformation mechanism. Raman spectroscopy was carried out to check the integrity of the graphene. The average grain size was in the order of 1 µm and the shape factor was 0.7 for all the studied materials. The integrity of the graphene was checked before and after the creep experiments. The careful analysis of the creep tests shows that graphene oxide or its reduced version are not efficient phases for creep resistance improvement in general, contrary to what is reported elsewhere. However, the results permit the suggestion of a creep improvement in nanocomposites at a very high temperature regime due to an enhanced reactivity of oxygen between carbon and alumina interfaces. In the case of zirconia, the results give us the conclusion that the oxidation of graphene is a highly detrimental issue regarding the improvement of high-temperature plasticity.

[Relationships with microbiology: the view from other specialties]. / Las relaciones con la microbiología: la visión desde otras especialidades.

The major advances produced in infectious diseases, partly favored by technological development in the last few years, together with current changes in healthcare, have led to a new scenario in which, far from the control of infectious diseases, clinical microbiology has acquired an undoubted leading role. This new panorama implies collaboration among distinct health professionals within the same healthcare setting, with common and occasionally conflicting interests. Setting aside the individual differences that can be produced in the daily life of our hospitals, all health professionals should understand one another, not only because such cooperation is required for optimal patient care but also because synergistic collaboration among professions would improve professional development. Based on this principle of a multidisciplinary approach, collaboration and mutual respect, the moment seems opportune for the various professionals involved in infectious diseases (infectologists, internists, pediatricians and intensivists) to express their view of the specialty of clinical microbiology. The present article includes reflections, from a highly liberal and personal point of view, on how mutual relationships can be approached and on how greater knowledge of infectious diseases can continue to be gained in Spain. In all these reflections, the questions of where we come from and where we are going are explicit or implicit.

High levels of population genetic differentiation in the American crocodile (Crocodylus acutus).

The American crocodile (Crocodylus acutus) is a widely distributed species across coastal and brackish areas of the Neotropical region of the Americas and the Greater Antilles. Available information on patterns of genetic differentiation in C. acutus shows a complex structuring influenced by interspecific interactions (mainly hybridization) and anthropogenic actions (mostly historical hunting, recent poaching, habitat loss and fragmentation, and unintentional translocation of individuals). In this study, we used data on mitochondrial DNA control region and 11 nuclear polymorphic microsatellite loci to assess the degree of population structure of C. acutus in South America, North America, Central America and the Greater Antilles. We used traditional genetic differentiation indices, Bayesian clustering and multivariate methods to create a more comprehensive picture of the genetic relationships within the species across its range. Analyses of mtDNA and microsatellite loci show evidence of a strong population genetic structure in the American crocodile, with unique populations in each sampling locality. Our results support previous findings showing large degrees of genetic differentiation between the continental and the Greater Antillean C. acutus. We report three new haplotypes unique to Venezuela, which are considerably less distant from the Central and North American haplotypes than to the Greater Antillean ones. Our findings reveal genetic population differentiation between Cuban and Jamaican C. acutus and offer the first evidence of strong genetic differentiation among the populations of Greater Antillean C. acutus.

[Future role of micafungin in the treatment of invasive mycoses caused by filamentous fungi]. / Papel futuro de la micafungina en el tratamiento de las micosis invasoras por hongos filamentosos.

BACKGROUND: Micafungin is a echinocandin. It inhibits beta-1,3-D-glucan synthesis, thus achieving fungicidal activity against virtually all Candida spp., including those resistant to fluconazole, and fungistatic activity against Aspergillus spp., as well as several but not all pathogenic molds. Results from in vitro studies, animal models, small clinical trials, hint at possible future indications such as invasive aspergillosis and empirical viantifungal therapy, although currently there is little information published. AIMS: To describe published data of micafungin as treatment against invasive mold infections, specially analysing its role in the inmunodepressed host and critical care setting. METHODS: A systematic review of literature using the principal medical search engines was performed. Terms such as micafungin, aspergillosis, zygomycosis, invasive fungal infections, emerging fungal infections, antifungal treatment or therapy, antifungal prophylaxis, empiric or pre-emptive therapy were crossed. Febrile neutropenia patients were excluded. RESULTS: Several studies in these setting were identified and were described in this review. Although there were no blinded randomized clinical trials published, treatment or prophylaxis of invasive aspergillosis and other invasive mould infections with micafungin described in open clinical studies were analyzed. CONCLUSIONS: Micafungin could play a future important role as a primary or rescue therapy, alone or in combination, in the treatment or prophylaxis of invasive fungal infections caused by moulds. New randomized clinical trials are needed to confirm their efficacy.

Stiffening of graphene oxide films by soft porous sheets.

Graphene oxide (GO) sheets have been used as a model system to study how the mechanical properties of two-dimensional building blocks scale to their bulk form, such as paper-like, lamellar-structured thin films. Here, we report that the modulus of multilayer GO films can be significantly enhanced if some of the sheets are drastically weakened by introducing in-plane porosity. Nanometer-sized pores are introduced in GO sheets by chemical etching. Membrane-deflection measurements at the single-layer level show that the sheets are drastically weakened as the in-plane porosity increases. However, the mechanical properties of the corresponding multilayer films are much less sensitive to porosity. Surprisingly, the co-assembly of pristine and etched GO sheets yields even stiffer films than those made from pristine sheets alone. This is attributed to the more compliant nature of the soft porous sheets, which act as a binder to improve interlayer packing and load transfer in the multilayer films.

An Adaptable Human-Like Gait Pattern Generator Derived From a Lower Limb Exoskeleton.

Walking rehabilitation processes include many repetitions of the same physical movements in order to replicate, as close as possible, the normal gait trajectories, and kinematics of all leg joints. In these conventional therapies, the therapist's ability to discover patient's limitations-and gradually reduce them-is key to the success of the therapy. Lower-limb robotic exoskeletons have strong deficiencies in this respect as compared to an experienced therapist. Most of the currently available robotic solutions are not able to properly adapt their trajectories to the biomechanical limitations of the patient. With this in mind, much research and development is still required in order to improve artificial human-like walking patterns sufficiently for valuable clinical use. The work herein reported develops and presents a method to acquire and saliently analyze subject-specific gait data while the subject dons a passive lower-limb exoskeleton. Furthermore, the method can generate adjustable, yet subject-specific, kinematic gait trajectories useful in programming controllers for future robotic rehabilitation protocols. A human-user study with ten healthy subjects provides the experimental setup to validate the proposed method. The experimental protocol consists in capturing kinematic data while subjects walk, with the donned H2 lower-limb exoskeleton, across three experimental conditions: walking with three different pre-determined step lengths marked on a lane. The captured ankle trajectories in the sagittal plane were found by normalizing all trials of each test from one heel strike to the next heel strike independent of the specific gait features of each individual. Prior literature suggests analyzing gait in phases. A preliminary data analysis, however, suggests that there exist six key events of the gait cycle, events that can adequately characterize gait for the purposes required of robotic rehabilitation including gait analysis and reference trajectory generation. Defining the ankle as an end effector and the hip as the origin of the coordinate frame and basing the linear regression calculations only on the six key events, i.e., Heel Strike, Toe Off, Pre-Swing, Initial Swing, Mid-Swing, and Terminal Swing, it is possible to generate a new calculated ankle trajectory with an arbitrary step length. The Leave-One-Out Cross Validation algorithm was used to estimate the fitting error of the calculated trajectory vs. the characteristic captured trajectory per subject, showing a fidelity average value of 95.2, 96.1, and 97.2%, respectively, for each step-length trial including all subjects. This research presents method to capture ankle trajectories from subjects and generate human-like ankle trajectories that could be scaled and computed on-line, could be adjusted to different gait scenarios, and could be used not only to generate reference trajectories for gait controllers, but also as an accurate and salient benchmark to test the human likeness of gait trajectories employed by existing robotic exoskeletal devices.

The Role of Water in Mediating Interfacial Adhesion and Shear Strength in Graphene Oxide.

Graphene oxide (GO), whose highly tunable surface chemistry enables the formation of strong interfacial hydrogen-bond networks, has garnered increasing interest in the design of devices that operate in the presence of water. For instance, previous studies have suggested that controlling GO's surface chemistry leads to enhancements in interfacial shear strength, allowing engineers to manage deformation pathways and control failure mechanisms. However, these previous reports have not explored the role of ambient humidity and only offer extensive chemical modifications to GO's surface as the main pathway to control GO's interfacial properties. Herein, through atomic force microscopy experiments on GO-GO interfaces, the adhesion energy and interfacial shear strength of GO were measured as a function of ambient humidity. Experimental evidence shows that adhesion energy and interfacial shear strength can be improved by a factor of 2-3 when GO is exposed to moderate (∼30% water weight) water content. Furthermore, complementary molecular dynamics simulations uncovered the mechanisms by which these nanomaterial interfaces achieve their properties. They reveal that the strengthening mechanism arises from the formation of strongly interacting hydrogen-bond networks, driven by the chemistry of the GO basal plane and intercalated water molecules between two GO surfaces. In summary, the methodology and findings here reported provide pathways to simultaneously optimize GO's interfacial and in-plane mechanical properties, by tailoring the chemistry of GO and accounting for water content, in engineering applications such as sensors, filtration membranes, wearable electronics, and structural materials.

Engineering the Mechanical Properties of Monolayer Graphene Oxide at the Atomic Level.

The mechanical properties of graphene oxide (GO) are of great importance for applications in materials engineering. Previous mechanochemical studies of GO typically focused on the influence of the degree of oxidation on the mechanical behavior. In this study, using density functional-based tight binding simulations, validated using density functional theory simulations, we reveal that the deformation and failure of GO are strongly dependent on the relative concentrations of epoxide (-O-) and hydroxyl (-OH) functional groups. Hydroxyl groups cause GO to behave as a brittle material; by contrast, epoxide groups enhance material ductility through a mechanically driven epoxide-to-ether functional group transformation. Moreover, with increasing epoxide group concentration, the strain to failure and toughness of GO significantly increases without sacrificing material strength and stiffness. These findings demonstrate that GO should be treated as a versatile, tunable material that may be engineered by controlling chemical composition, rather than as a single, archetypical material.

Plasticity and ductility in graphene oxide through a mechanochemically induced damage tolerance mechanism.

The ability to bias chemical reaction pathways is a fundamental goal for chemists and material scientists to produce innovative materials. Recently, two-dimensional materials have emerged as potential platforms for exploring novel mechanically activated chemical reactions. Here we report a mechanochemical phenomenon in graphene oxide membranes, covalent epoxide-to-ether functional group transformations that deviate from epoxide ring-opening reactions, discovered through nanomechanical experiments and density functional-based tight binding calculations. These mechanochemical transformations in a two-dimensional system are directionally dependent, and confer pronounced plasticity and damage tolerance to graphene oxide monolayers. Additional experiments on chemically modified graphene oxide membranes, with ring-opened epoxide groups, verify this unique deformation mechanism. These studies establish graphene oxide as a two-dimensional building block with highly tuneable mechanical properties for the design of high-performance nanocomposites, and stimulate the discovery of new bond-selective chemical transformations in two-dimensional materials.