scholarly journals Vent-Lock: A 3D Printed Ventilator Multiplexer to Enhance the Capacity of Treating Patients with COVID-19

2020 ◽  
Author(s):  
Helen Xun ◽  
Christopher Shallal ◽  
Justin Unger ◽  
Runhan Tao ◽  
Alberto Torres ◽  
...  
Keyword(s):  
Distress Syndrome ◽  
De Novo ◽  
Cost Effective ◽  
The Novel ◽  
Proof Of Concept ◽  
Mechanical Ventilators ◽  
Respiratory Therapists ◽  
Flow Restriction ◽  
3D Printed ◽  
Critical Components

Mechanical ventilators are essential to patients who become critically ill from acute respiratory distress syndrome (ARDS), and shortages have been reported due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We utilized cost-effective, on-demand 3D printing (3DP) technology to produce critical components for a novel ventilator multiplexer system, Vent-Lock, to split one ventilator or anesthesia gas machine between two patients. FloRest, a novel 3DP flow restrictor, provides clinicians control of tidal volumes and positive end expiratory pressure (PEEP), using the 3DP manometer adaptor to monitor pressures. We tested the ventilator splitter circuit in simulation centers between artificial lungs and used an anesthesia gas machine to successfully ventilate two swines. As one of the first studies to demonstrate splitting one anesthesia gas machine between two swines, we present proof-of-concept of a de novo, closed, multiplexing system, with flow restriction for individualized patient therapy. Our studies underscore that while possible, ventilator multiplexing is a complicated synergy between machine settings, circuit modification, and patient monitoring. Consequently, ventilator multiplexing is reserved only as a last emergency resource, by trained clinicians and respiratory therapists with ventilator operative experience.

scholarly journals The Vent-Lock Protocol: 3D Printing and Testing of A Ventilator Multiplexer to Enhance the Capacity of Treating Patients with COVID-19 

2020 ◽  
Author(s):  
Helen Xun ◽  
Christopher Shallal ◽  
Justin Unger ◽  
Runhan Tao ◽  
Alberto Torres ◽  
...  
Keyword(s):  
3D Printing ◽  
Distress Syndrome ◽  
De Novo ◽  
Cost Effective ◽  
The Novel ◽  
Proof Of Concept ◽  
Mechanical Ventilators ◽  
Respiratory Therapists ◽  
Flow Restriction ◽  
Critical Components

Abstract Mechanical ventilators are essential to patients who become critically ill from acute respiratory distress syndrome (ARDS), and shortages have been reported due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We utilized cost-effective, on-demand 3D printing (3DP) technology to produce critical components for a novel ventilator multiplexer system, Vent-Lock, to split one ventilator or anesthesia gas machine between two patients. FloRest, a novel 3DP flow restrictor, provides clinicians control of tidal volumes and positive end expiratory pressure (PEEP), using the 3DP manometer adaptor to monitor pressures. We tested the ventilator splitter circuit in simulation centers between artificial lungs and used an anesthesia gas machine to successfully ventilate two swines. As one of the first studies to demonstrate splitting one anesthesia gas machine between two swines, we present proof-of-concept of a de novo, closed, multiplexing system, with flow restriction for individualized patient therapy. Our studies underscore that while possible, ventilator multiplexing is a complicated synergy between machine settings, circuit modification, and patient monitoring. Consequently, ventilator multiplexing is reserved only as a last emergency resource, by trained clinicians and respiratory therapists with ventilator operative experience.

scholarly journals Enhancement and Validation of a 3D-Printed Solid Target Holder at a Cyclotron Facility in Perth, Australia

Instruments ◽  
2019 ◽  
Vol 3 (1) ◽  
pp. 12 ◽  
Author(s):  
Sun Chan ◽  
David Cryer ◽  
Roger I. Price
Keyword(s):  
Thermal Conductivity ◽  
Cast Alloy ◽  
Cost Effective ◽  
Solid Target ◽  
Cooling Efficiency ◽  
Proof Of Concept ◽  
Proton Bombardment ◽  
Target Holder ◽  
3D Printed ◽  
Target Design

A 3D-printed metal solid target using additive manufacturing process is a cost-effective production solution to complex and intricate target design. The initial proof-of-concept prototype solid target holder was 3D-printed in cast alloy, Al–7Si–0.6Mg (A357). However, given the relatively low thermal conductivity for A357 (max, 160 W/m·K), replication of the solid target holder in sterling silver (SS925) with higher thermal conductivity (max, 361 W/m·K) was investigated. The SS925 target holder enhances the cooling efficiency of the target design, thus achieving higher target current during irradiation. A validation production of 64Cu using the 3D-printed SS925 target holder indicated no loss of enriched 64Ni from proton bombardment above 80 µA, at 11.5 MeV.

Mimicking LysC Proteolysis by ‘Arginine-Modification-cum-Trypsin digestion’: Comparison of Bottom-Up & Middle-Down Proteomic Approaches by ESI-QTOF-MS

2021 ◽  
Vol 28 ◽  
Author(s):  
P. Boomathi Pandeswari ◽  
R. Nagarjuna Chary ◽  
A.S. Kamalanathan ◽  
Sripadi Prabhakar ◽  
Varatharajan Sabareesh
Keyword(s):  
Mass Spectrometry ◽  
De Novo ◽  
Cost Effective ◽  
Peptide Sequencing ◽  
Trypsin Digestion ◽  
Ionization Mass ◽  
Proof Of Concept ◽  
Tryptic Peptides ◽  
Esi Ms ◽  
Arginine Modification

Background: Middle-down (MD) proteomics is an emerging approach for reliable identification of post- translational modifications and isoforms, as this approach focuses on proteolytic peptides containing > 25 - 30 amino acid residues (a.a.r.), which are longer than typical tryptic peptides. Such longer peptides can be obtained by AspN, GluC, LysC proteases. Additionally, some special proteases were developed specifically to effect MD approach, e.g., OmpT, Sap9, etc. However, these proteases are expensive. Herein we report a cost-effective strategy, ‘arginine modification-cum trypsin digestion’, which can produce longer tryptic peptides resembling LysC peptides derived from proteins. Objective:: To obtain proteolytic peptides that resemble LysC peptides, by using 'trypsin', which is an less expensive protease. Methods: This strategy is based on the simple principle that trypsin cannot act at the C-termini of those arginines in proteins, whose sidechain guanidine groups are modified by 1,2-cyclohexanedione or phenylglyoxal. Results: As a proof of concept, we demonstrate this strategy on four models: -casein (bovine), - lactoglobulin (bovine), ovalbumin (chick) and transferrin (human), by electrospray ionization-mass spectrometry (ESI-MS) involving hybrid quadrupole time-of-flight. From the ESI-MS of these models, we obtained several arginine modified tryptic peptides, whose lengths are in the range, 30 - 60 a.a.r. The collision-induced dissociation MS/MS characteristics of some of the arginine modified longer tryptic peptides are compared with the unmodified standard tryptic peptides. Conclusion: The strategy followed in this proof-of-concept study, not only helps in obtaining longer tryptic peptides that mimic LysC proteolytic peptides, but also facilitates in enhancing the probability of missed cleavages by the trypsin. Hence, this method aids in evading the possibility of obtaining very short peptides that are < 5 - 10 a.a.r. Therefore, this is indeed an cost-effective alternative/substitute for LysC proteolysis and in turn, for those MD proteomic studies that utilize LysC. Additionally, this methodology can be fruitful for mass spectrometry based de novo protein and peptide sequencing.

Design and Fabrication of Hierarchical Multi-Stable Structures Through Multi-Material Additive Manufacturing

2016 ◽  
Author(s):  
Tian Chen ◽  
Kristina Shea
Keyword(s):  
Additive Manufacturing ◽  
Design Procedure ◽  
The Novel ◽  
Proof Of Concept ◽  
Form Finding ◽  
Out Of Plane ◽  
3D Printed ◽  
Novel Structures ◽  
Design For Am ◽  
Stable Structures

The design and fabrication of hierarchical multi-stable structures using multi-material Additive Manufacturing (AM) is presented. First a reversible bistable unit actuator is designed to serve as the basis of the design hierarchy. With this unit actuator, the authors present monolithically printed proof-of-concept structures that can transform to multiple activated states, all of which are stable without the need for continuous energy input. The equilibrium positions of these hierarchical designs are found through iterative form finding when necessary. The novel structures illustrated in this paper are only made possible through design for AM that exploits the capabilities of a multi-material, inkjet 3D printer. The design procedure is illustrated through two concepts. The first consists of a series of tetrahedra fabricated as tiled deployable triangles with the out-of-plane members consisting of the actuators in the retracted configuration. The second concept consists of multiple shape changing square unit modules tiled in a grid to achieve complex 3D activated states including a hemisphere, a hyperbolic paraboloid, a star and a cube. Their design and prototyping form the foundation for new types of active and deployable 3D printed structures.

Recent Advances in Drug Repurposing for Parkinson’s Disease

2019 ◽  
Vol 26 (28) ◽  
pp. 5340-5362 ◽  
Author(s):  
Xin Chen ◽  
Giuseppe Gumina ◽  
Kristopher G. Virga
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Discovery ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Cost Effective ◽  
New Drugs ◽  
Recent Advances ◽  
Clinical Drugs

:As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson’s disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progression. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson’s disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and timeefficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson’s disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson’s disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson’s disease will be discussed.

scholarly journals Direct antivirals working against the novel coronavirus: azithromycin (DAWn-AZITHRO), a randomized, multicenter, open-label, adaptive, proof-of-concept clinical trial of new antivirals working against SARS-CoV-2—azithromycin trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Iwein Gyselinck ◽  
◽  
Laurens Liesenborghs ◽  
Ewout Landeloos ◽  
Ann Belmans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Cytokine Signaling ◽  
Nasopharyngeal Swab ◽  
The Novel ◽  
Proof Of Concept ◽  
Open Label ◽  
Novel Coronavirus

Abstract Background The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19. Methods DAWn-AZITHRO is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID wards are eligible for study inclusion when they are symptomatic (i.e., clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 h through PCR (nasopharyngeal swab or bronchoalveolar lavage) or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. The primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days. Discussion The trial investigates the urgent and still unmet global need for drugs that may impact the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN consortium will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context. Trial registration EU Clinical trials register EudraCT Nb 2020-001614-38. Registered on 22 April 2020

scholarly journals 3D printed microfluidic lab-on-a-chip device for fiber-based dual beam optical manipulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haoran Wang ◽  
Anton Enders ◽  
John-Alexander Preuss ◽  
Janina Bahnemann ◽  
Alexander Heisterkamp ◽  
...  
Keyword(s):  
Optical Fibers ◽  
Single Cells ◽  
Lab On A Chip ◽  
Cost Effective ◽  
Optical Manipulation ◽  
Hydrodynamic Focusing ◽  
Trapping Region ◽  
Dual Beam ◽  
3D Printed ◽  
On Chip

Abstract3D printing of microfluidic lab-on-a-chip devices enables rapid prototyping of robust and complex structures. In this work, we designed and fabricated a 3D printed lab-on-a-chip device for fiber-based dual beam optical manipulation. The final 3D printed chip offers three key features, such as (1) an optimized fiber channel design for precise alignment of optical fibers, (2) an optically clear window to visualize the trapping region, and (3) a sample channel which facilitates hydrodynamic focusing of samples. A square zig–zag structure incorporated in the sample channel increases the number of particles at the trapping site and focuses the cells and particles during experiments when operating the chip at low Reynolds number. To evaluate the performance of the device for optical manipulation, we implemented on-chip, fiber-based optical trapping of different-sized microscopic particles and performed trap stiffness measurements. In addition, optical stretching of MCF-7 cells was successfully accomplished for the purpose of studying the effects of a cytochalasin metabolite, pyrichalasin H, on cell elasticity. We observed distinct changes in the deformability of single cells treated with pyrichalasin H compared to untreated cells. These results demonstrate that 3D printed microfluidic lab-on-a-chip devices offer a cost-effective and customizable platform for applications in optical manipulation.

scholarly journals Safety and efficacy of the treatment of in-stent restenosis and de novo complex lesions with the novel paclitaxel-coated scoring balloon (Angiosculpt X)

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D.P Agip Fustamante ◽  
S Ortiz Cruces ◽  
S Camacho Freire ◽  
A Gutierrez Barrios ◽  
A Gomez Menchero ◽  
...  
Keyword(s):  
Real World ◽  
Cardiac Death ◽  
De Novo ◽  
Funding Source ◽  
The Novel ◽  
Safety And Efficacy ◽  
Stent Restenosis ◽  
Scoring Balloon ◽  
In Stent Restenosis ◽  
Complex Lesions

Abstract Background The AngioSculpt X (Spectranetics) is a novel paclitaxel-coated scoring balloon with encouraging preliminary data for the treatment of in-stent restenosis or de novo complex lesions. Purpose To assess the safety and efficacy of real-world patients with in-stent restenosis (ISR) or de novo complex lesions (vessels &lt;2.5 mm, calcified lesions, bifurcation lesions...) treated with the novel paclitaxel-coated scoring balloon. Methods A “real-world”, prospective registry from two centers was performed including consecutive patients presenting with ISR or de novo complex lesions and treated with AngioSculpt X. Their clinical data were prospectively registered. Major adverse cardiac events (MACE) were defined as a composite of cardiac death, stent thrombosis, nonfatal myocardial infarction, target lesion revascularization (TLR) and target vessel revascularization (TVR). Results Overall, 87 real-world patients and 93 lesions (73% male, 68±10 years, 46% smoker, 83% hypertensive, 62% diabetic, 71% hyperlipidemic, 35% LVEF &lt;60% impairment) were enrolled in the study. Clinical presentation was stable angina in 19%, unstable angina in 33%, NSTEMI in 29% and STEMI in 5%. Radial access account 84%. The median fluoroscopy time was 17 (IQ range 10,0 - 37.5) min. De novo complex lesions were treated in 35% (n=32) while ISR in 63% (n=57), (Prior BMS 19%; Sirolimus DES 9%; Everolimus DES 26%; Biolimus/Anfilimus DES 20%; Zotarolimus DES 26%) with a median time to ISR of 3.6 (IQ range 1.1 - 10.7) years. Total stent length was 28±18 mm, with an overlap spot affected in 18%, and 27% had &gt;1 treatment for ISR. The most frequent artery treated was left anterior descending (41%) followed by left circumflex (35%) and right coronary artery (17%). Quantitative coronary angiography reference diameter of lesions was 2.7±0.5 mm and length 9.0±4.8 mm, with a % stenosis of 75±20. Predilatation/postdilatation was performed in 60/24% respectively. Device diameter was 2.9±0.4 mm and length 13.6±3.9 mm, deployed at 16±3 atmospheres, with an inflation time of 33±16 seconds. The balloon/artery ratio was 0.99±0.03. Crossover was decided on 18 cases (19%) due to remaining intimal flap, but the success rate (residual stenosis &lt;30%) was 100%. Intracoronary imaging technique was performed in 12% (OCT=7, IVUS=4). At 7±6 month follow-up, there were 10 MACE (cardiac death=1, nonfatal myocardial infarction =4, TLR=4 and TVR=1). Conclusions Paclitaxel-coated scoring balloon offers a safe and valuable treatment option for ISR and de novo complex lesions. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Juan Ramόn Jiménez University Hospital

scholarly journals The aiming device for cervical distractor pin insertion: a proof-of-concept, feasibility study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Torphong Bunmaprasert ◽  
Sittichai Luangkittikong ◽  
Menghong Tosinthiti ◽  
Supachoke Nivescharoenpisan ◽  
Raphi Raphitphan ◽  
...  
Keyword(s):  
Radiation Exposure ◽  
Feasibility Study ◽  
Vertebral Body ◽  
The Novel ◽  
Cervical Lordosis ◽  
Proof Of Concept ◽  
Entry Points ◽  
Free Hand Technique ◽  
Anterior Discectomy And Fusion ◽  
Vertebral Endplates

Abstract Background Restoration of cervical lordosis after anterior discectomy and fusion is a desirable goal. Proper insertion of the vertebral distraction or Caspar pin can assist lordotic restoration by either putting the tips divergently or parallel to the index vertebral endplates. With inexperienced surgeons, the traditional free-hand technique for Caspar pin insertion may require multiple insertion attempts that may compromise the vertebral body and increase radiation exposure during pin localization. Our purpose is to perform a proof-of-concept, feasibility study to evaluate the effectiveness of a pin insertion aiming device for vertebral distraction pin insertion. Methods A Smith-Robinson approach and anterior cervical discectomy were performed from C3 to C7 in 10 human cadaveric specimens. Caspar pins were inserted using a novel pin insertion aiming device at C3-4, C4-5, C5-6, and C6-7. The angles between the cervical endplate slope and Caspar pin alignment were measured with lateral cervical imaging. Results The average Superior Endplate-to-Caspar Pin angle (SE-CP) and the average Inferior Endplate-to-Caspar Pin angle (IE-CP) were 6.2 ± 2.0° and 6.3 ± 2.2° respectively. For the proximal pins, the SE-CP and the IE-CP were 4.0 ± 1.1°and 5.2 ± 2.4° respectively. For the distal pins, the SE-CP and the IE-CP were 7.7 ± 1.4° and 6.2 ± 2.0° respectively. No cervical endplate violations occurred. Conclusion The novel Caspar pin insertion aiming device can control the pin entry points and pin direction with the average SE-CP and average IE-CP of 6.2 ± 2.0° and 6.3 ± 2.2°, respectively. The study shows that the average different angles between the Caspar pin and cervical endplate are less than 7°.

scholarly journals Preparation and Performance Evaluation of Duotone 3D-Printed Polyetheretherketone as Oral Prosthetic Materials: A Proof-of-Concept Study

Polymers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 1949
Author(s):  
Ling Ding ◽  
Wei Lu ◽  
Jiaqi Zhang ◽  
Chuncheng Yang ◽  
Guofeng Wu
Keyword(s):  
Titanium Dioxide ◽  
Performance Evaluation ◽  
Mechanical Performance ◽  
Mechanical Tests ◽  
Flexural Properties ◽  
Proof Of Concept ◽  
Tooth Color ◽  
Dental Application ◽  
3D Printed ◽  
And Performance

Literature has reported the successful use of 3D printed polyetheretherketone (PEEK) to fabricate human body implants and oral prostheses. However, the current 3D printed PEEK (brown color) cannot mimic the vivid color of oral tissues and thus cannot meet the esthetical need for dental application. Therefore, titanium dioxide (TiO2) and ferric oxide (Fe2O3) were incorporated into PEEK to prepare a series of tooth-color and gingival-color PEEK composites in this study. Through color measurements and mechanical tests, the color value and mechanical performance of the 3D printed PEEK composites were evaluated. In addition, duotone PEEK specimens were printed by a double nozzle with an interface between tooth-color and gingival-color parts. The mechanical performance of duotone PEEK with two different interfaces (horizontal and vertical) was investigated. With the addition of TiO2 and Fe2O3, the colors of 3D printed PEEK composites become closer to that of dental shade guides. 3D printed PEEK composites generally demonstrated superior tensile and flexural properties and hence have great potential in the dental application. In addition, duotone 3D printed PEEK with a horizontal interfacial orientation presented better mechanical performance than that with a vertical one.

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