The Potential Role of Ocular and Otolaryngological Mucus Proteins in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness associated with a constellation of other symptoms. While the most common symptom is unrelenting fatigue, many individuals also report suffering from rhinitis, dry eyes and a sore throat. Mucin proteins are responsible for contributing to the formation of mucosal membranes throughout the body. These mucosal pathways contribute to the body's defense mechanisms involving pathogenic onset. When compromised by pathogens the epithelium releases numerous cytokines and enters a prolonged state of inflammation to eradicate any particular infection. Based on genetic analysis, and computational theory and modeling we hypothesize that mucin protein dysfunction may contribute to ME/CFS symptoms due to the inability to form adequate mucosal layers throughout the body, especially in the ocular and otolaryngological pathways leading to low grade chronic inflammation and the exacerbation of symptoms.

A First Assessment of an Aerodynamic Barrier Layer for Filtering Airborne Hygroscopic Particles.

In this work, consideration is given to an aerodynamic concept to boost the filtration in face masks of airborne hygroscopic particles such as those caused by an infected person when coughs or sneezes. Nowadays, increasing the filtration efficiency of face masks implies either increasing the number of crisscrossing fiber layers or decreasing the equivalent hydraulic diameter of the pore, however, both measures are in clear detriment of its breathability. Here, a novel strategy is proposed in which the filtration of an airborne particle is boosted by increasing its diameter. We called properly this concept as the aerodynamic barrier layer. In this concept, a traditional crisscrossing fiber layer is replaced by a parallel rearranged of the fibers in the direction of the flow. This rearrangement will promote central lift forces which will push the particles toward the center of the channel where after clustering they will coalesce resulting in a bigger particle that can be now easily captured by a conventional fiber crisscrossing layer. Utilizing a simplified geometrical model, an expression for the required length of the aerodynamic barrier layer was derived. It is shown that an aerodynamic barrier layer with a length of only a few millimeters can aerodynamically focus water droplets around 1 µm-diameter and the penetration of airborne particles can be reduced up to 55%.

Modeling Neuroimmune Interactions in Human Subjects and Animal Models to Predict Subtype-Specific Multidrug Treatments for Gulf War Illness.

Gulf War Illness (GWI) is a persistent chronic neuroinflammatory illness exacerbated by external stressors and characterized by fatigue, musculoskeletal pain, cognitive, and neurological problems linked to underlying immunological dysfunction for which there is no known treatment. As the immune system and the brain communicate through several signaling pathways, including the hypothalamic-pituitary-adrenal (HPA) axis, it underlies many of the behavioral and physiological responses to stressors via blood-borne mediators, such as cytokines, chemokines, and hormones. Signaling by these molecules is mediated by the semipermeable blood-brain barrier (BBB) made up of a monocellular layer forming an integral part of the neuroimmune axis. BBB permeability can be altered and even diminished by both external factors (e.g., chemical agents) and internal conditions (e.g., acute or chronic stress, or cross-signaling from the hypothalamic-pituitary-gonadal (HPG) axis). Such a complex network of regulatory interactions that possess feed-forward and feedback connections can have multiple response dynamics that may include several stable homeostatic states beyond normal health. Here we compare immune and hormone measures in the blood of human clinical samples and mouse models of Gulf War Illness (GWI) subtyped by exposure to traumatic stress for subtyping this complex illness. We do this via constructing a detailed logic model of HPA-HPG-Immune regulatory behavior that also considers signaling pathways across the BBB to neuronal-glial interactions within the brain. We apply conditional interactions to model the effects of changes in BBB permeability. Several stable states are identified in the system beyond typical health. Following alignment of the human and mouse blood profiles in the context of the model, mouse brain sample measures were used to infer the neuroinflammatory state in human GWI and perform treatment simulations using a genetic algorithm to optimize the Monte Carlo simulations of the putative treatment strategies aimed at returning the ill system back to health. We identify several ideal multi-intervention strategies and potential drug candidates that may be used to treat chronic neuroinflammation in GWI.

The mechanical effect of moisturization on airborne COVID-19 transmission and its potential use as control technique.

Mounting evidence from scientific community seems to suggest that COVID-19 virus can potentially spread by airborne transmission. As a result, methods and techniques for preventing environmental contagious, such as ventilation or air filtration have been proposed. Here, it is investigated the effect of moisturization on airborne COVID-19 transmission from a mechanical point of view in which comparatively large water droplets promote the growth -by collision and coalescence, of suspended airborne COVID-19 and then accelerating its gravitational settling. Utilizing a classical raindrop collisional model from cloud science and the available experimental data an expression for the removal time of suspended airborne COVID-19 as function of the relative humidity was derived. The mechanical model is in good agreement with the recent reported experimental research in which high temperature and high relative humidity reduce COVID-19 contagious and then is a point in favor of the mechanic model of the effect of moisture in the COVID-19 airborne transmission. The results encourage further research on the deliberate moisturization of room air (by using ceiling mounted humidifiers) as a potential technique for control of airborne COVID-19 transmission.

Are Runners More Prone to Become Infected with COVID-19? An Approach from the Raindrop Collisional Model.

It is known that COVID-19 spread mainly from person-to-person through respiratory droplets produced when an infected person coughs or sneezes, and as a result certain ideas about contagious of COVID-19 have been spread. One of them is the widespread belief that close runners, owing to the stronger exhalation, can be more prone to be infected with COVID-19 because the collision with the suspended respiratory droplets should the runner in front be infected. However, because of the low Stokes number this idea cannot be generalized without carefully thought and in fact can be put into question. Utilizing the raindrop collisional model and with the help of computational fluid dynamics (CFD), it is shown that the probability of collision with respiratory droplets is not always increasing with the approaching velocity of the runner but rather there is a maximum velocity threshold at which the efficiency of collision drops.

The Effects of Videogaming with a Brain-Computer Interface on Mood and Physiological Arousal.

Objective: In recent years, immersive videogame technologies such as virtual reality have been shown to affect psychological welfare in such way that they can be applied to clinical psychology treatments. However, the effects of videogaming with other immersive gaming apparatuses such as commercial electroencephalography (EEG)-based brain-computer interfaces (BCIs) on psychological welfare have not been extensively researched. Thus, we aimed at providing early insights into some of these effects by looking at how videogaming with a commercial EEG-based BCI would impact mood and physiological arousal. Materials and Methods: A total of 26 participants were sampled. Participants were randomly assigned to either a BCI condition or a traditional condition wherein they played an action videogame with a commercial EEG-based BCI or a standard keyboard and mouse interface for 20 minutes. In both conditions, participants filled out the profile of mood states to assess mood and the perceived stress scale to control for stress. We also measured heart rate, heart rate variability as measured by the root mean square of successive differences, and galvanic skin response (GSR) amplitude differences. Results: Participants in the BCI condition overall reported a significantly higher total mood disturbance (P < 0.05), tension (P < 0.05), confusion (P < 0.05), and significantly less vigor (P < 0.05). We also found that participants in the BCI condition had significantly lower GSR amplitude differences between gaming and baseline (P < 0.05). Conclusion: The results suggest that the use of commercial EEG-based BCIs for playing with videogames can induce greater frustration and negative moods than playing with a traditional keyboard and mouse interface, possibly limiting their use in clinical psychology settings.

The behavior of radiogenic particles at solidification fronts.

The thermal behavior of insoluble radiogenic particles at the solid-liquid interface of an advancing solidification front and its significance with regard to environmental impact are discussed. It is shown that, unlike classical particles, where the most probable behavior is engulfing by the solidification front, radiogenic particles are more likely to be rejected by the solidification front. Utilizing a simplified physical model, an adaptation of classical theoretical models is performed, where it is shown that, unlike classical particles, for radiogenic particles the mechanism is thermally driven. An analytical expression for the critical velocity of the solidification front for engulfing/rejection to occur is derived. The study could be potentially important to several fields, e.g. in engineering applications where technological processes for the physical removal of radionuclide particles dispersed throughout another substance by inducing solidification could be envisaged, in planetary science where the occurrence of radiogenic concentration could result in the possibility of the eruption of primordial comet/planetoids, or, if specific conditions are suitable, particle ejection may result in an increase in concentration as the front moves, which can translate into the formation of hot spots.

Elastin-like recombinamers with acquired functionalities for gene-delivery applications.

In this work, well-defined elastin-like recombinamers (ELRs) were studied as a choice to the existing nonviral vectors due to their biocompatibility and ease of scale-up. Functional motifs, namely penetratin and LAEL fusogenic peptides were incorporated into a basic ELR sequence, and imidazole groups were subsequently covalently bound obtaining ELRs with new functionalities. Stable polyplexes composed of plasmid DNA and ELRs were formed. A particle size around 200 nm and a zeta potential up to nearly +24 mV made them suitable for gene delivery purposes. Additionally, viability and transfection assays with C6 rat glioma cell line showed an increase in the cellular uptake and transfection levels for the construction containing the LAEL motif. This study highlights the importance of controlling the polymer functionality using recombinant techniques and establishes the utility of ELRs as biocompatible nonviral systems for gene-therapy applications.

Efficient cell and cell-sheet harvesting based on smart surfaces coated with a multifunctional and self-organizing elastin-like recombinamer.

A wide range of smart surfaces with novel properties relevant for biomedical applications have been developed recently. Herein we focus on thermoresponsive surfaces that switch between cell-adherent and nonadherent states and their applications for cell harvesting. These smart surfaces are obtained by covalently coupling a tailored elastin-like recombinamer onto glass surfaces by means of the well-known and widely applied Click Chemistry methodology. The resulting recombinamer-functionalized surfaces have been characterized by means of water contact angle measurements, XPS and TOF-SIMS. A cell-based analysis of these surfaces with human fibroblasts showed a high degree of adhesion to the surface in its adherent state (37 °C), thus, promoting cell viability and proliferation. A temperature decrease triggers reorganization of the recombinamer, thus, markedly increasing the number of nonadherent domains and masking the adherent ones. This process allows a specific and efficient temporal control of cell adhesion and cell detachment. After determination of the properties required for a suitable cell-harvesting system, optimization of the process allows single cells or cell sheets from at least two types of cells (HFF-1 and ADSCs) to be rapidly harvested.

Nanostructured and thermoresponsive recombinant biopolymer-based microcapsules for the delivery of active molecules.

Multilayer capsules conceived at the nano- and microscales are receiving increasing interest due to their potential role as carriers of biomolecules for drug delivery and tissue engineering. Herein we report the construction of microcapsules by the sequential adsorption of chitosan and a biomimetic elastin-like recombinamer into nanostructured layers on inorganic microparticle templates. The release profile of bovine serum albumin, which was studied at 25 and 37 °C, shows higher retention and Fickian diffusion at physiological temperature. The self-assembled multilayers act as a barrier and allowed for sustained release over 14 days. The capsules studied are non-cytotoxic towards L929 cells, thereby suggesting multiple applications in the fields of biotechnology and bioengineering, where high control of the delivery of therapeutics and growth/differentiation factors is required. FROM THE CLINICAL EDITOR: In this paper, the construction of microcapsules by sequential adsorption of chitosan and a biomimetic, elastin-like recombinamer into nanostructured layers on inorganic microparticle templates is reported. The layers demonstrated sustained drug release over 14 days. These microcapsules are non-cytotoxic toward L929 cells, suggesting multiple applications where high control of drug or growth factor delivery is required.

Elastin-like recombinamers: biosynthetic strategies and biotechnological applications.

The past few decades have witnessed the development of novel naturally inspired biomimetic materials, such as polysaccharides and proteins. Likewise, the seemingly exponential evolution of genetic-engineering techniques and modern biotechnology has led to the emergence of advanced protein-based materials with multifunctional properties. This approach allows extraordinary control over the architecture of the polymer, and therefore, monodispersity, controlled physicochemical properties, and high sequence complexity that would otherwise be impossible to attain. Elastin-like recombinamers (ELRs) are emerging as some of the most prolific of these protein-based biopolymers. Indeed, their inherent properties, such as biocompatibility, smart nature, and mechanical qualities, make these recombinant polymers suitable for use in numerous biomedical and nanotechnology applications, such as tissue engineering, "smart" nanodevices, drug delivery, and protein purification. Herein, we present recent progress in the biotechnological applications of ELRs and the most important genetic engineering-based strategies used in their biosynthesis.

Layer-by-layer assembly of chitosan and recombinant biopolymers into biomimetic coatings with multiple stimuli-responsive properties.

In this work, biomimetic smart thin coatings using chitosan and a recombinant elastin-like recombinamer (ELR) containing the cell attachment sequence arginine-glycine-(aspartic acid) (RGD) are fabricated through a layer-by-layer approach. The synthetic polymer is characterized for its molecular mass and composition using mass spectroscopy and peptide sequencing. The adsorption of each polymeric layer is followed in situ at room temperature and pH 5.5 using a quartz-crystal microbalance with dissipation monitoring, showing that both polymers can be successfully combined to conceive nanostructured, multilayered coatings. The smart properties of the coatings are tested for their wettability by contact angle (CA) measurements as a function of external stimuli, namely temperature, pH, and ionic strength. Wettability transitions are observed from a moderate hydrophobic surface (CAs approximately from 62° to 71°) to an extremely wettable one (CA considered as 0°) as the temperature, pH, and ionic strength are raised above 50 °C, 11, and 1.25 M, respectively. Atomic force microscopy is performed at pH 7.4 and pH 11 to assess the coating topography. In the latter, the results reveal the formation of large and compact structures upon the aggregation of ELRs at the surface, which increase water affinity. Cell adhesion tests are conducted using a SaOs-2 cell line. Enhanced cell adhesion is observed in the coatings, as compared to a coating with a chitosan-ending film and a scrambled arginine-(aspartic acid)-glycine (RDG) biopolymer. The results suggest that such films could be used in the future as smart biomimetic coatings of biomaterials for different biomedical applications, including those in tissue engineering or in controlled delivery systems.

Alteración de superficies de implantes de ti comercialmente puro a través de métodos físicos y / o químicos. Estudios experimentales: una revisión de literatura / Implants surface alteration of commercial pure through chemical and/or physical methods. Experimental studies: a review of literature

La obtimización de la calidad de interfase creada entre huesos de implante, ha sido objeto de múltiples investigaciones debido a la demanda funcional y biomecnica que esta interfase tiene a ser sometida a cargas oclusales. Dicho mejoramiento se ha hecho a costa del manejo de diferentes biomateriales para cubrimiento de la superficie y de la alteración de las características microestructurales de la superficie de los implantes de Ti comercialmente puro. Esto último se ha realizado con el fin de eliminar o aumentar la cantidad de rugosidad superficial de tal manera que se modifique la cantidad de superficie de contacto entre el hueso e implante para que se produzca un ancláje adecuado del implante al hueso que le permita soportar cargas. Las alteraciones de la topografía superficial se realiza a través de procedimientos físicos tales como el arenodo con partículas de dixido de titanio o de dixido de aluminio de diferentes tamaños, electropulimiento, o por medio de grabado cido con diferentes soluciones y diferentes tiempos. La eficacia de dichos procedimientos sobre las interfase hueso-implante ha sido evaluada por medio de cultivos celulares invitro, análisis histomorfomátricos, y análisis de resistencia al torque reverso. Observando en la mayoria de los estudios que la reacción de rugosidades con diferentes tratamientos puede aumentar la superficie de contacto entre hueso e implante, mejorando a su vez las propiedades biomecánicas de dicha interfase.