Performance of emergency mechanical ventilators in response to the covid-19 pandemic: an intercomparison study.

Emergency mechanical ventilators developed during the pandemic were used to meet the high demand in intensive care units to care for COVID-19 patients. An example of such ventilators is Masi, developed in Peru and installed in more than 15 hospitals around the country. This study aimed to compare Masi's performance with other emergency mechanical ventilators manufactured during the covid-19 pandemic such as Neyün, Spiro Wave and a prototype developed by the Faculty of Engineering of the National University of Asuncion (FIUNA). Three configurations of a test lung were used, combining different values of resistance and compliance (C1, C2 and C3). Ventilators were set to volume-controlled ventilation with tidal volume = 400 mL, respiratory rate = 12 breaths/minute, and positive end-expiratory pressure (PEEP) = 8 cm H2O. These parameters were measured in a series of ten two-minute tests which then were evaluated through a two-way analysis of variance, considering the type of ventilator and test lung configuration as the two independent variables. For target values, MASI delivered VT that ranged from 319 to 432 ml (-20 to +8%), respiratory rate of 12 bpm, and PEEP from 8.4 to 9.5 cm H2O (+5 to +20%). In contrast, for instance, Neyün delivered VT that ranged from 199 to 543 ml (-50 to +35%) and PEEP from 7.05 to 9.21 cm H2O (--11 to +15%), with p<0.05. The analysis of variance showed that he differences between preset and delivered parameters were influenced by the type of ventilator and, significantly, by the test lung configuration.Clinical Relevance- This establishes the most advantageous conditions in which three emergency mechanical ventilators work and a quantitative perspective in this topic.

Temporal Evaluation of the Surface Area of Treated Skin Ulcers Caused by Cutaneous Leishmaniasis and Relation with Optical Parameters in an Animal Model: A Proof of Concept.

Cutaneous leishmaniasis (CL) is a neglected disease caused by an intracellular parasite of the Leishmania genus. CL lacks tools that allow its understanding and treatment follow-up. This article presents the use of metrical and optical tools for the analysis of the temporal evolution of treated skin ulcers caused by CL in an animal model. Leishmania braziliensis and L. panamensis were experimentally inoculated in golden hamsters, which were treated with experimental and commercial drugs. The temporal evolution was monitored by means of ulcers' surface areas, as well as absorption and scattering optical parameters. Ulcers' surface areas were obtained via photogrammetry, which is a procedure that allowed for 3D modeling of the ulcer using specialized software. Optical parameters were obtained from a spectroscopy study, representing the cutaneous tissue's biological components. A one-way ANOVA analysis was conducted to identify relationships between both the ulcers' areas and optical parameters. As a result, ulcers' surface areas were found to be related to the following optical parameters: epidermis thickness, collagen, keratinocytes, volume-fraction of blood, and oxygen saturation. This study is a proof of concept that shows that optical parameters could be associated with metrical ones, giving a more reliable concept during the assessment of a skin ulcer's healing.

COVOX: Providing oxygen during the COVID-19 health emergency.

We introduce an autonomous oxygen concentrator that was designed in Peru to fight the oxygen shortage produced worldwide as a consequence of the COVID-19 pandemic. Oxygen concentrators represent a suitable and favorable option for administering this gas at the patient's bedside in developing countries, especially when cylinders and tubed systems are unavailable or when access to them is restricted by lack of accessories, inadequate power supply, or shortage of qualified personnel. Our system uses a pressure swing adsorption technique to provide oxygen to patients at a flow rate of up to 15 l/min ± 1,5 l/min and a concentration of 93 % ± 3 %, offering robustness, safety and functionality. The quality measurements obtained from the validation process demonstrate repeatability and accuracy. The complete design files are provided in the source file repository to facilitate oxygen concentrator production in low and middle income countries, where access to oxygen is still a major problem even after the pandemic. Oxygen is part of the World Health Organization Model List of Essential Medicines and is perhaps the only medicine that has no substitute. This device can provide a reliable supply of oxygen for critically ill patients and improve their chances of survival.

Extension of Non-invasive Ventilation Capabilities of MASI for the Care of Patients Affected by COVID-19.

The MASI mechanical ventilator was developed in a state of emergency to meet the demand for ventilators caused by COVID-19. Although it has obtained positive results in its use with patients in intensive care units, not having an optimal quality non-invasive ventilation (NIV) modality prevents it from being used in the early treatment of patients, which has been shown to prevent admission to the ICU and reduce mortality. Therefore, the following study focuses on evaluating MASI's ability to provide NIV using different accessories in order to compare their performance and determine which one would work best with MASI, and under which conditions. To do this, the high-flow nasal cannula, facial mask, and ventilation helmet accessories were tested under different pressure parameter settings. The data was collected using a gas flow analyzer. After that, a statistical analysis of the results was carried out, which showed that the face mask is the best accessory to use for NIV with MASI, and that it performs with optimal accuracy and precision when the peak inspiratory pressure is set at a value lower than 25 cmH20. Clinical Relevance- This study presents an optimization of the non-invasive ventilation (NIV) modality of the MASI me-chanical ventilator by evaluating its performance with different accessories.

Cytotoxicity and Genotoxicity of Azobenzene-Based Polymeric Nanocarriers for Phototriggered Drug Release and Biomedical Applications.

Drug nanoencapsulation increases the availability, pharmacokinetics, and concentration efficiency for therapeutic regimes. Azobenzene light-responsive molecules experience a hydrophobicity change from a polar to an apolar tendency by trans-cis photoisomerization upon UV irradiation. Polymeric photoresponse nanoparticles (PPNPs) based on azobenzene compounds and biopolymers such as chitosan derivatives show prospects of photodelivering drugs into cells with accelerated kinetics, enhancing their therapeutic effect. PPNP biocompatibility studies detect the safe concentrations for their administration and reduce the chance of side effects, improving the effectiveness of a potential treatment. Here, we report on a PPNP biocompatibility evaluation of viability and the first genotoxicity study of azobenzene-based PPNPs. Cell line models from human ventricular cardiomyocytes (RL14), as well as mouse fibroblasts (NIH3T3) as proof of concept, were exposed to different concentrations of azobenzene-based PPNPs and their precursors to evaluate the consequences on mitochondrial metabolism (MTT assay), the number of viable cells (trypan blue exclusion test), and deoxyribonucleic acid (DNA) damage (comet assay). Lethal concentrations of 50 (LC50) of the PPNPs and their precursors were higher than the required drug release and synthesis concentrations. The PPNPs affected the cell membrane at concentrations higher than 2 mg/mL, and lower concentrations exhibited lesser damage to cellular genetic material. An azobenzene derivative functionalized with a biopolymer to assemble PPNPs demonstrated biocompatibility with the evaluated cell lines. The PPNPs encapsulated Nile red and dofetilide separately as model and antiarrhythmic drugs, respectively, and delivered upon UV irradiation, proving the phototriggered drug release concept. Biocompatible PPNPs are a promising technology for fast drug release with high cell interaction opening new opportunities for azobenzene biomedical applications.

PytuTester: RaspberryPi open-source ventilator tester.

PytuTester is an open-source ventilator tester developed to help bio-engineers in the design and verification of new ventilator prototypes. A ventilator tester allows measuring the flow, pressure, volume, and oxygen concentration provided to the patient. During the global pandemic COVID-19, several open-source ventilators prototypes were developed; however, due to high cost and demand testers, they were not available. In this context, a low-cost tester was developed using a Raspberry Pi and medical-grade sensors for the test ventilators prototypes. This paper presents the design files, software interface, and validations tests. Our results indicate that the tester has good accuracy to evaluate the efficacy and performance of new prototypes. When tested on two ventilator designs developed in Paraguay, PytuTester reported flow profiles that were concordant with the industry-standard VT650 Gas Flow Analyzer. PytuTester was then field deployed to test several DIY ventilator designs in low-resource areas.

Quality characteristics of the Masi Peruvian mechanical ventilator manufacturing process.

Three hundred and ten rapid-manufactured mechanical ventilators, named Masi, were produced and validated in Peru, according to applicable standards. From these, a sample of 30 was taken and two ventilation parameters, tidal volume and peak inspiratory pressure, were statically analyzed using control charts and histograms. Results show that several points were outside estimated limits for Shewhart means and ranges charts, which could possibly be due to the quantity of equipment used for data recollection and the fact that the Masi team had over 20 engineers. Nevertheless, Masi ventilators met the tolerance required by their user´s manual and MHRA standard and Peruvian DIGEMID for every parameter.Clinical Relevance-This article shows the performance in the validation stage of the peruvian mechanical ventilator MASI built as an emergency response for the COVID-19 crisis.

Performance of the Masi Peruvian ventilator at high altitude.

In response to Covid-19 crisis, 310 Masi ventilators were produced and validated in Lima, Peru, according to applicable standards. Four of them, were transported to Puno, in order to strengthen ICU Services there, but this set a major challenge to Masi team as effects of altitude on ventilators were unknown. Once there, ventilators were acclimated and calibrated. Volume tidal, I:E ratio, respiratory frequency and PEEP were tested, all of them presenting errors under 15%, except for tidal volume, for which a 25% negative correction was applied. After the installation of a new version of Masi software, parameters were tested again, all of them presenting results with errors below 15%, which allowed the Masi team to take them to ICU services for use.Clinical Relevance- Masi Peruvian Ventilators are able to perform according to their specifications at extremely high altitude, after the adequate calibration. These devices are an alternative to treat COVID-19 patients in the middle of the crisis.

Masi: A mechanical ventilator based on a manual resuscitator with telemedicine capabilities for patients with ARDS during the COVID-19 crisis.

In this article, we introduce a portable and low-cost ventilator that could be rapidly manufactured, to meet the increasing demand of ventilators worldwide produced by COVID-19 pandemic. These ventilators should be rapidly deployable and with functional capabilities to manage COVID-19 patients with severe acute respiratory distress syndrome (ARDS). Our implementation offers robustness, safety and functionality absent in existing solutions to the ventilator shortage (i.e., telemonitoring, easy-to-disinfect, modularity) by maintaining simplicity. The design makes use of a manual resuscitator as the core respiration component activated by a compression mechanism which consist of two electronically controlled paddles. The quality measurements obtained after testing on a calibrated artificial lung demonstrate repeatability and accuracy exceeding human capabilities of manual ventilation. The complete design files are provided in the supplementary materials to facilitate ventilator production even in resource-limited settings. The implementation of this mechanical ventilator could eliminate device rationing or splitting to serve multiple patients on ICUs.

Photosensitive nanocarriers for specific delivery of cargo into cells.

Nanoencapsulation is a rapidly expanding technology to enclose cargo into inert material at the nanoscale size, which protects cargo from degradation, improves bioavailability and allows for controlled release. Encapsulation of drugs into functional nanocarriers enhances their specificity, targeting ability, efficiency, and effectiveness. Functionality may come from cell targeting biomolecules that direct nanocarriers to a specific cell or tissue. Delivery is usually mediated by diffusion and erosion mechanisms, but in some cases, this is not sufficient to reach the expected therapeutic effects. This work reports on the development of a new photoresponsive polymeric nanocarrier (PNc)-based nanobioconjugate (NBc) for specific photo-delivery of cargo into target cells. We readily synthesized the PNcs by modification of chitosan with ultraviolet (UV)-photosensitive azobenzene molecules, with Nile red and dofetilide as cargo models to prove the encapsulation/release concept. The PNcs were further functionalized with the cardiac targeting transmembrane peptide and efficiently internalized into cardiomyocytes, as a cell line model. Intracellular cargo-release was dramatically accelerated upon a very short UV-light irradiation time. Delivering cargo in a time-space controlled fashion by means of NBcs is a promising strategy to increase the intracellular cargo concentration, to decrease dose and cargo side effects, thereby improving the effectiveness of a therapeutic regime.

Azopolymer based nanoparticles for phototriggered drug delivery.

Controlled release by stimulus-responsive nanoparticles is oriented to increase the specificity of drug delivery, to improve the therapy effectiveness and minimizing side effects. This work presents the synthesis of photosensitive-polymeric nanoparticles as a potential system for localized drug delivery. First, the photoisomerizable amphiphilic-copolymer poly2-[4-phenylazophenoxy]ethyl acrylate-co-acrylic acid (PPAPE), was synthesized. Then, PPAPE was employed to prepare micellar nanoparticles by the nanoprecipitation method. Characterizations of the polymer were performed by proton nuclear magnetic resonance, X-ray photoelectron spectroscopy and FTIR spectroscopy. The morphology of the nanoparticles was analyzed by dynamic light scattering and transmission electron microscopy. Also, photostimulation response was confirmed by UV-VIS spectroscopy. Results indicate that the obtained photoresponsive nanoparticles have the size and photoisomerization necessary to perform the specific release of drugs.