From hardware store to hospital: a COVID-19-inspired, cost-effective, open-source, in vivo-validated ventilator for use in resource-scarce regions

AbstractResource-scarce regions with serious COVID-19 outbreaks do not have enough ventilators to support critically ill patients, and these shortages are especially devastating in developing countries. To help alleviate this strain, we have designed and tested the accessible low-barrier in vivo-validated economical ventilator (ALIVE Vent), a COVID-19-inspired, cost-effective, open-source, in vivo-validated solution made from commercially available components. The ALIVE Vent operates using compressed oxygen and air to drive inspiration, while two solenoid valves ensure one-way flow and precise cycle timing. The device was functionally tested and profiled using a variable resistance and compliance artificial lung and validated in anesthetized large animals. Our functional test results revealed its effective operation under a wide variety of ventilation conditions defined by the American Association of Respiratory Care guidelines for ventilator stockpiling. The large animal test showed that our ventilator performed similarly if not better than a standard ventilator in maintaining optimal ventilation status. The FiO2, respiratory rate, inspiratory to expiratory time ratio, positive-end expiratory pressure, and peak inspiratory pressure were successfully maintained within normal, clinically validated ranges, and the animals were recovered without any complications. In regions with limited access to ventilators, the ALIVE Vent can help alleviate shortages, and we have ensured that all used materials are publicly available. While this pandemic has elucidated enormous global inequalities in healthcare, innovative, cost-effective solutions aimed at reducing socio-economic barriers, such as the ALIVE Vent, can help enable access to prompt healthcare and life saving technology on a global scale and beyond COVID-19.

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Review: Tissue Engineering of Small-Diameter Vascular Grafts and Their In Vivo Evaluation in Large Animals and Humans

Cells ◽

10.3390/cells10030713 ◽

2021 ◽

Vol 10 (3) ◽

pp. 713

Author(s):

Shu Fang ◽

Ditte Gry Ellman ◽

Ditte Caroline Andersen

Keyword(s):

Animal Models ◽

Vascular Grafts ◽

Small Diameter ◽

Large Animal ◽

Large Animal Models ◽

Graft Outcome ◽

Limited Success ◽

Large Animals

To date, a wide range of materials, from synthetic to natural or a mixture of these, has been explored, modified, and examined as small-diameter tissue-engineered vascular grafts (SD-TEVGs) for tissue regeneration either in vitro or in vivo. However, very limited success has been achieved due to mechanical failure, thrombogenicity or intimal hyperplasia, and improvements of the SD-TEVG design are thus required. Here, in vivo studies investigating novel and relative long (10 times of the inner diameter) SD-TEVGs in large animal models and humans are identified and discussed, with emphasis on graft outcome based on model- and graft-related conditions. Only a few types of synthetic polymer-based SD-TEVGs have been evaluated in large-animal models and reflect limited success. However, some polymers, such as polycaprolactone (PCL), show favorable biocompatibility and potential to be further modified and improved in the form of hybrid grafts. Natural polymer- and cell-secreted extracellular matrix (ECM)-based SD-TEVGs tested in large animals still fail due to a weak strength or thrombogenicity. Similarly, native ECM-based SD-TEVGs and in-vitro-developed hybrid SD-TEVGs that contain xenogeneic molecules or matrix seem related to a harmful graft outcome. In contrast, allogeneic native ECM-based SD-TEVGs, in-vitro-developed hybrid SD-TEVGs with allogeneic banked human cells or isolated autologous stem cells, and in-body tissue architecture (IBTA)-based SD-TEVGs seem to be promising for the future, since they are suitable in dimension, mechanical strength, biocompatibility, and availability.

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An open-source control system for in vivo fluorescence measurements from deep-brain structures

10.1101/399329 ◽

2018 ◽

Cited By ~ 1

Author(s):

Scott F. Owen ◽

Anatol C. Kreitzer

Keyword(s):

Open Source ◽

Optical Fibers ◽

Dorsal Striatum ◽

Cost Effective ◽

Brain Structures ◽

Source Control ◽

Optical Components ◽

Fluorescence Measurements ◽

Deep Brain

ABSTRACTBackgroundIntracranial photometry through chronically implanted optical fibers is a widely adopted technique for measuring signals from fluorescent probes in deep-brain structures. The recent proliferation of bright, photo-stable, and specific genetically-encoded fluorescent reporters for calcium and for other neuromodulators has greatly increased the utility and popularity of this technique.New MethodHere we describe an open-source, cost-effective, microcontroller-based solution for controlling optical components in an intracranial photometry system and processing the resulting signal.ResultsWe show proof-of-principle that this system supports high quality intracranial photometry recordings from dorsal striatum in freely moving mice. A single system supports simultaneous fluorescence measurements in two independent color channels, but multiple systems can be integrated together if additional fluorescence channels are required. This system is designed to work in combination with either commercially available or custom-built optical components. Parts can be purchased for less than one tenth the cost of commercially available alternatives and complete assembly takes less than one day for an inexperienced user.Comparison with Existing Method(s)Currently available hardware draws on a variety of commercial, custom-built, or hybrid elements for both optical and electronic components. Many of these hardware systems are either specialized and inflexible, or over-engineered and expensive.ConclusionsThis open-source system increases experimental flexibility while reducing cost relative to current commercially available components. All software and firmware are open-source and customizable, affording a degree of experimental flexibility that is not available in current commercial systems.

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Open-source, cost-effective system for low-light in vivo fiber photometry

Neurophotonics ◽

10.1117/1.nph.5.2.025006 ◽

2018 ◽

Vol 5 (02) ◽

pp. 1 ◽

Cited By ~ 5

Author(s):

Kathryn Simone ◽

Tamás Füzesi ◽

David Rosenegger ◽

Jaideep Bains ◽

Kartikeya Murari

Keyword(s):

Open Source ◽

Cost Effective ◽

Low Light ◽

Effective System

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Increasing Access to Medical Training With Three-Dimensional Printing: Creation of an Endotracheal Intubation Model (Preprint)

10.2196/preprints.12626 ◽

2018 ◽

Author(s):

Lily Park ◽

Steven Price-Williams ◽

Alireza Jalali ◽

Kashif Pirzada

Keyword(s):

Open Source ◽

Endotracheal Intubation ◽

Medical Training ◽

Three Dimensional ◽

Simulation Models ◽

Cost Effective ◽

Ease Of Use ◽

Life Saving ◽

3D Printers ◽

Simulation Center

BACKGROUND Endotracheal intubation (ETI) is a crucial life-saving procedure, where more than 2 failed attempts can lead to further complications or even death. Like all technical skills, ETI requires sufficient practice to perform adequately. Currently, the models used to practice ETI are expensive and, therefore, difficult to access, particularly in the developing world and in settings that lack a dedicated simulation center. OBJECTIVE This study aimed to improve access to ETI training by creating a comparable yet cost-effective simulation model producible by 3-dimensional (3D) printers. METHODS Open-source mesh files of relevant anatomy from BodyParts3D were modified through the 3D modeling programs Meshlab (ISTI-CNR) and Blender (Blender Foundation). Several prototypes with varying filaments were tried to optimize the ETI simulation. RESULTS We have created the novel 3D-printed pediatric ETI model for learners at all levels to practice this airway management skill at negligible costs compared with current simulation models. It is an open-source design available for all medical trainees. CONCLUSIONS Revolutions in cost and ease of use have allowed home and even desktop 3D printers to become widespread. Therefore, open-source access to the ETI model will improve accessibility to medical training in the hopes of optimizing patient care.

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The CSF p-tau181/Aβ42 Ratio Offers a Good Accuracy “In Vivo” in the Differential Diagnosis of Alzheimer’s Dementia

Current Alzheimer Research ◽

10.2174/1567205016666190725150836 ◽

2019 ◽

Vol 16 (7) ◽

pp. 587-595 ◽

Cited By ~ 7

Author(s):

Roberto Santangelo ◽

Alessandro Dell'Edera ◽

Arianna Sala ◽

Giordano Cecchetti ◽

Federico Masserini ◽

...

Keyword(s):

Clinical Practice ◽

Clinical Diagnosis ◽

Fdg Pet ◽

Amyloid Β ◽

Cost Effective ◽

Daily Clinical Practice ◽

Different Types ◽

Experimental Trials ◽

Csf Findings

Background: The incoming disease-modifying therapies against Alzheimer’s disease (AD) require reliable diagnostic markers to correctly enroll patients all over the world. CSF AD biomarkers, namely amyloid-β 42 (Aβ42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-tau181), showed good diagnostic accuracy in detecting AD pathology, but their real usefulness in daily clinical practice is still a matter of debate. Therefore, further validation in complex clinical settings, that is patients with different types of dementia, is needed to uphold their future worldwide adoption. Methods: We measured CSF AD biomarkers’ concentrations in a sample of 526 patients with a clinical diagnosis of dementia (277 with AD and 249 with Other Type of Dementia, OTD). Brain FDG-PET was also considered in a subsample of 54 patients with a mismatch between the clinical diagnosis and the CSF findings. Results: A p-tau181/Aβ42 ratio higher than 0.13 showed the best diagnostic performance in differentiating AD from OTD (86% accuracy index, 74% sensitivity, 81% specificity). In cases with a mismatch between clinical diagnosis and CSF findings, brain FDG-PET partially agreed with the p-tau181/Aβ42 ratio, thus determining an increase in CSF accuracy. Conclusions: The p-tau181/Aβ42 ratio alone might reliably detect AD pathology in heterogeneous samples of patients suffering from different types of dementia. It might constitute a simple, cost-effective and reproducible in vivo proxy of AD suitable to be adopted worldwide not only in daily clinical practice but also in future experimental trials, to avoid the enrolment of misdiagnosed AD patients.

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Polyamines and Related Nitrogen Compounds in the Chemotherapy of Neglected Diseases Caused by Kinetoplastids

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666180427151338 ◽

2018 ◽

Vol 18 (5) ◽

pp. 321-368 ◽

Cited By ~ 2

Author(s):

Juan A. Bisceglia ◽

Maria C. Mollo ◽

Nadia Gruber ◽

Liliana R. Orelli

Keyword(s):

Drug Targets ◽

Redox Homeostasis ◽

Cost Effective ◽

Structural Features ◽

Mammalian Host ◽

Neglected Diseases ◽

Nitrogen Compounds ◽

Chemical Structures

Neglected diseases due to the parasitic protozoa Leishmania and Trypanosoma (kinetoplastids) affect millions of people worldwide, and the lack of suitable treatments has promoted an ongoing drug discovery effort to identify novel nontoxic and cost-effective chemotherapies. Polyamines are ubiquitous small organic molecules that play key roles in kinetoplastid parasites metabolism, redox homeostasis and in the normal progression of cell cycles, which differ from those found in the mammalian host. These features make polyamines attractive in terms of antiparasitic drug development. The present work provides a comprehensive insight on the use of polyamine derivatives and related nitrogen compounds in the chemotherapy of kinetoplastid diseases. The amount of literature on this subject is considerable, and a classification considering drug targets and chemical structures were made. Polyamines, aminoalcohols and basic heterocycles designed to target the relevant parasitic enzyme trypanothione reductase are discussed in the first section, followed by compounds directed to less common targets, like parasite SOD and the aminopurine P2 transporter. Finally, the third section comprises nitrogen compounds structurally derived from antimalaric agents. References on the chemical synthesis of the selected compounds are reported together with their in vivo and/or in vitro IC50 values, and structureactivity relationships within each group are analyzed. Some favourable structural features were identified from the SAR analyses comprising protonable sites, hydrophobic groups and optimum distances between them. The importance of certain pharmacophoric groups or amino acid residues in the bioactivity of polyamine derived compounds is also discussed.

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Facile sonochemical-assisted synthesis of orthorhombic phase black phosphorus/rGO hybrids for effective photothermal therapy

Nanophotonics ◽

10.1515/nanoph-2019-0476 ◽

2020 ◽

Vol 9 (9) ◽

pp. 3023-3034

Author(s):

Weiyuan Liang ◽

Dou Wang ◽

Xiaohui Ren ◽

Chenchen Ge ◽

Hanyue Wang ◽

...

Keyword(s):

Electrode Materials ◽

Orthorhombic Phase ◽

Cost Effective ◽

Black Phosphorus ◽

Antitumor Effects ◽

Covalent Bonds ◽

Preparation Conditions ◽

Reduced Graphene

AbstractTwo-dimensional black phosphorus (BP) has been demonstrated to be promising in photoelectronic devices, electrode materials, and biomedicine owing to its outstanding properties. However, the application of BP has been hindered by harsh preparation conditions, high costs, and easy degradation in ambient condition. Herein, we report a facile and cost-effective strategy for synthesis of orthorhombic phase BP and a kind of BP-reduced graphene oxide (BP/rGO) hybrids in which BP remains stable for more than 4 weeks ascribed to the formation of phosphorus-carbon covalent bonds between BP and rGO as well as the protection effect of the unique wrinkle morphology of rGO nanosheets. Surface modification BP/rGO hybrids (PEGylated BP/rGO) exhibit excellent photothermal performance with photothermal conversion efficiency as high as 57.79% at 808 nm. The BP/rGO hybrids exhibit enhanced antitumor effects both in vitro and in vivo, showing promising perspectives in biomedicine.

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Myocardial fibrosis reversion via rhACE2-electrospun fibrous patch for ventricular remodeling prevention

npj Regenerative Medicine ◽

10.1038/s41536-021-00154-y ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Zeping Qiu ◽

Jingwen Zhao ◽

Fanyi Huang ◽

Luhan Bao ◽

Yanjia Chen ◽

...

Keyword(s):

Myocardial Infarction ◽

Myocardial Fibrosis ◽

Ventricular Remodeling ◽

Cardiac Fibroblasts ◽

Cost Effective ◽

Intramyocardial Injection ◽

Undesirable Consequence ◽

Adverse Remodeling

AbstractMyocardial fibrosis and ventricular remodeling were the key pathology factors causing undesirable consequence after myocardial infarction. However, an efficient therapeutic method remains unclear, partly due to difficulty in continuously preventing neurohormonal overactivation and potential disadvantages of cell therapy for clinical practice. In this study, a rhACE2-electrospun fibrous patch with sustained releasing of rhACE2 to shape an induction transformation niche in situ was introduced, through micro-sol electrospinning technologies. A durable releasing pattern of rhACE2 encapsulated in hyaluronic acid (HA)—poly(L-lactic acid) (PLLA) core-shell structure was observed. By multiple in vitro studies, the rhACE2 patch demonstrated effectiveness in reducing cardiomyocytes apoptosis under hypoxia stress and inhibiting cardiac fibroblasts proliferation, which gave evidence for its in vivo efficacy. For striking mice myocardial infarction experiments, a successful prevention of adverse ventricular remodeling has been demonstrated, reflecting by improved ejection fraction, normal ventricle structure and less fibrosis. The rhACE2 patch niche showed clear superiority in long term function and structure preservation after ischemia compared with intramyocardial injection. Thus, the micro-sol electrospun rhACE2 fibrous patch niche was proved to be efficient, cost-effective and easy-to-use in preventing ventricular adverse remodeling.

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Assessment of Electrospun Pellethane-Based Scaffolds for Vascular Tissue Engineering

Materials ◽

10.3390/ma14133678 ◽

2021 ◽

Vol 14 (13) ◽

pp. 3678

Author(s):

Vera Chernonosova ◽

Alexandr Gostev ◽

Ivan Murashov ◽

Boris Chelobanov ◽

Andrey Karpenko ◽

...

Keyword(s):

Vascular Tissue ◽

Ex Vivo ◽

Vascular Grafts ◽

Wistar Rat ◽

Graft Occlusion ◽

Suitable Candidate ◽

Large Animals ◽

Cell Adhesion And Proliferation

We examined the physicochemical properties and the biocompatibility and hemocompatibility of electrospun 3D matrices produced using polyurethane Pellethane 2363-80A (Pel-80A) blends Pel-80A with gelatin or/and bivalirudin. Two layers of vascular grafts of 1.8 mm in diameter were manufactured and studied for hemocompatibility ex vivo and functioning in the infrarenal position of Wistar rat abdominal aorta in vivo (n = 18). Expanded polytetrafluoroethylene (ePTFE) vascular grafts of similar diameter were implanted as a control (n = 18). Scaffolds produced from Pel-80A with Gel showed high stiffness with a long proportional limit and limited influence of wetting on mechanical characteristics. The electrospun matrices with gelatin have moderate capacity to support cell adhesion and proliferation (~30–47%), whereas vascular grafts with bivalirudin in the inner layer have good hemocompatibility ex vivo. The introduction of bivalirudin into grafts inhibited platelet adhesion and does not lead to a change hemolysis and D-dimers concentration. Study in vivo indicates the advantages of Pel-80A grafts over ePTFE in terms of graft occlusion, calcification level, and blood velocity after 6 months of implantation. The thickness of neointima in Pel-80A–based grafts stabilizes after three months (41.84 ± 20.21 µm) and does not increase until six months, demonstrating potential for long-term functioning without stenosis and as a suitable candidate for subsequent preclinical studies in large animals.

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Development of a porcine model of emergency resternotomy at a low-volume cardiac surgery centre

Interactive CardioVascular and Thoracic Surgery ◽

10.1093/icvts/ivaa191 ◽

2020 ◽

Vol 31 (6) ◽

pp. 803-805

Author(s):

Timothy M Guenther ◽

Sarah A Chen ◽

Joshua D Gustafson ◽

Curtis J Wozniak ◽

Bob Kiaii

Keyword(s):

Intensive Care Unit ◽

Cardiac Surgery ◽

Porcine Model ◽

Comfort Level ◽

Large Animal Model ◽

Large Animal ◽

Training Environment ◽

Life Saving ◽

Simulation Scenario ◽

Low Volume

Abstract Emergency resternotomy in the intensive care unit (ICU) is a rarely performed, yet potentially life-saving intervention. Success relies on recognition of a deteriorating clinical condition, timely deployment of equipment/personnel and rapid execution. Given how infrequently it is performed, we sought to develop a large animal model of resternotomy to prepare ICU nurses and technicians at our low-volume cardiac surgery military centre. A porcine model of resternotomy was developed at the end of an already-scheduled trauma lab. Participants worked their way through a pre-planned simulation scenario, culminating in the need for resternotomy. Pre-simulation surveys assessing knowledge and comfort level with aspects of resternotomy were compared to post-simulation surveys. Participants improved their knowledge of resternotomy by 20.4% (P < 0.0001; 14.7% for nurses and 26.9% for technicians). Improvements were seen in all aspects assessed relating to subjective comfort/preparedness of resternotomy. The model was an effective and realistic method to augment training of ICU staff about resternotomy. Costs associated with this model can be reduced when used in conjunction with large animal labs. This model should be used together with mannequin-based methods of resternotomy training to provide a realistic training environment and assessment of skills at capable institutions.

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