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Extracellular vesicle-based therapeutics: natural versus engineered targeting and trafficking
Daniel E. Murphy,Olivier G. de Jong,Maarten Brouwer,Matthew J. Wood,Grégory Lavieu,Raymond M. Schiffelers,Pieter Vader 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-
Extracellular vesicles (EVs) are increasingly being recognized as mediators of intercellular signaling via the delivery of effector molecules. Interestingly, certain types of EVs are also capable of inducing therapeutic responses. For these reasons, the therapeutic potential of EVs is a topic of intense research, both in the context of drug delivery and regenerative medicine. However, to fully utilize EVs for therapeutic purposes, an improved understanding of the mechanisms by which they function would be highly advantageous. Here, the current state of knowledge regarding the cellular uptake and trafficking of EVs is reviewed, along with a consideration of how these pathways potentially influence the functions of therapeutic EVs. Furthermore, the natural cell-targeting abilities, biodistribution profiles, and pharmacokinetics of exogenously administered EVs, along with the components responsible for these features are discussed. An overview of the potential clinical applications and preclinical examples of their successful use is also provided. Finally, examples of EV modifications that have successfully been employed to improve their therapeutic characteristics receive a particular focus. We suggest that, in addition to investigation of EV cell targeting and routes of uptake, future research into the routes of intracellular trafficking in recipient cells is required to optimally utilize EVs for therapeutic purposes.
Daniel R. Schmitt,Cameron Killen,Michael Murphy,Michael Perry,Joseph Romano,Nicholas Brown 대한정형외과학회 2020 Clinics in Orthopedic Surgery Vol.12 No.3
Background: Antibiotic-loaded bone cement (ALBC) is commonly used in total knee arthroplasty (TKA), especially among high-risk patients. While previous studies have reported on the efficacy of ALBC in reducing the rate of periprosthetic joint infection (PJI), its impact on antibiotic resistance has not been determined. The purpose of this study was to investigate antibiotic resistance among organisms causing PJIs after TKA in which ALBC was utilized. Methods: A retrospective review from December 1998 through December 2017 identified 36 PJIs that met inclusion criteria. Patients with culture-negative infection and unknown cement type were excluded. Patient characteristics, infecting organism, and antibiotic susceptibilities were recorded. ABLC included an aminoglycoside in all cases. Results: There was no difference in the type of PJI between the 2 groups. Staphylococcus species was the most commonly isolated, with 9 of 16 cases (56.3%) using non-ALBC and 14 of 20 (65.0%) cases using ALBC. Of those infected with Staphylococcus , there was no significant difference in antibiotic susceptibilities between groups. Overall, there were only 3 cases where the infecting organism was aminoglycoside resistant (standard cement, 1; ALBC, 2). Conclusions: These results suggest that the use of ALBC does not increase the risk of antibiotic resistance or affect the pattern of infection, even as the use of ALBC continues to increase, particularly among high-risk patients.
Wireless sensor networks for permanent health monitoring of historic buildings
Daniele Zonta,Huayong Wu,Matteo Pozzi,Paolo Zanon,Matteo Ceriotti,Luca Mottola,Gian Pietro Picco,Amy L. Murphy,Stefan Guna,Michele Corrà 국제구조공학회 2010 Smart Structures and Systems, An International Jou Vol.6 No.6
This paper describes the application of a wireless sensor network to a 31 meter-tall medieval tower located in the city of Trento, Italy. The effort is motivated by preservation of the integrity of a set of frescoes decorating the room on the second floor, representing one of most important International Gothic artworks in Europe. The specific application demanded development of customized hardware and software. The wireless module selected as the core platform allows reliable wireless communication at low cost with a long service life. Sensors include accelerometers, deformation gauges, and thermometers. A multi-hop data collection protocol was applied in the software to improve the system flexibility and scalability. The system has been operating since September 2008, and in recent months the data loss ratio was estimated as less than 0.01%. The data acquired so far are in agreement with the prediction resulting a priori from the 3-dimensional FEM. Based on these data a Bayesian updating procedure is employed to real-time estimate the probability of abnormal condition states. This first period of operation demonstrated the stability and reliability of the system, and its ability to recognize any possible occurrence of abnormal conditions that could jeopardize the integrity of the frescos.
Wireless sensor networks for permanent health monitoring of historic buildings
Zonta, Daniele,Wu, Huayong,Pozzi, Matteo,Zanon, Paolo,Ceriotti, Matteo,Mottola, Luca,Picco, Gian Pietro,Murphy, Amy L.,Guna, Stefan,Corra, Michele Techno-Press 2010 Smart Structures and Systems, An International Jou Vol.6 No.5
This paper describes the application of a wireless sensor network to a 31 meter-tall medieval tower located in the city of Trento, Italy. The effort is motivated by preservation of the integrity of a set of frescoes decorating the room on the second floor, representing one of most important International Gothic artworks in Europe. The specific application demanded development of customized hardware and software. The wireless module selected as the core platform allows reliable wireless communication at low cost with a long service life. Sensors include accelerometers, deformation gauges, and thermometers. A multi-hop data collection protocol was applied in the software to improve the system's flexibility and scalability. The system has been operating since September 2008, and in recent months the data loss ratio was estimated as less than 0.01%. The data acquired so far are in agreement with the prediction resulting a priori from the 3-dimensional FEM. Based on these data a Bayesian updating procedure is employed to real-time estimate the probability of abnormal condition states. This first period of operation demonstrated the stability and reliability of the system, and its ability to recognize any possible occurrence of abnormal conditions that could jeopardize the integrity of the frescos.
Bioresorbable silicon electronic sensors for the brain
Kang, Seung-Kyun,Murphy, Rory K. J.,Hwang, Suk-Won,Lee, Seung Min,Harburg, Daniel V.,Krueger, Neil A.,Shin, Jiho,Gamble, Paul,Cheng, Huanyu,Yu, Sooyoun,Liu, Zhuangjian,McCall, Jordan G.,Stephen, Manu Nature Publishing Group, a division of Macmillan P 2016 Nature Vol.530 No.7588
<P>Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury(1,2). However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions(3,4). The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications(5-8). Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action(9-12), eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury(2,13); the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body's abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine.</P>
Non-invasive estimation of relative pressure in turbulent flow using virtual work-energy
Marlevi, David,Ha, Hojin,Dillon-Murphy, Desmond,Fernandes, Joao F.,Fovargue, Daniel,Colarieti-Tosti, Massimiliano,Larsson, Matilda,Lamata, Pablo,Figueroa, C. Alberto,Ebbers, Tino,Nordsletten, David A. Elsevier 2020 Medical image analysis Vol.60 No.-
<P><B>Abstract</B></P> <P>Vascular pressure differences are established risk markers for a number of cardiovascular diseases. Relative pressures are, however, often driven by turbulence-induced flow fluctuations, where conventional non-invasive methods may yield inaccurate results. Recently, we proposed a novel method for non-turbulent flows, <I>ν</I>WERP, utilizing the concept of virtual work-energy to accurately probe relative pressure through complex branching vasculature. Here, we present an extension of this approach for turbulent flows: <I>ν</I>WERP-t. We present a theoretical method derivation based on flow covariance, quantifying the impact of flow fluctuations on relative pressure. <I>ν</I>WERP-t is tested on a set of <I>in-vitro</I> stenotic flow phantoms with data acquired by 4D flow MRI with six-directional flow encoding, as well as on a patient-specific <I>in-silico</I> model of an acute aortic dissection. Over all tests <I>ν</I>WERP-t shows improved accuracy over alternative energy-based approaches, with excellent recovery of estimated relative pressures. In particular, the use of a guaranteed divergence-free virtual field improves accuracy in cases where turbulent flows skew the apparent divergence of the acquired field. With the original <I>ν</I>WERP allowing for assessment of relative pressure into previously inaccessible vasculatures, the extended <I>ν</I>WERP-t further enlarges the method's clinical scope, underlining its potential as a novel tool for assessing relative pressure <I>in-vivo</I>.</P> <P><B>Highlights</B></P> <P> <UL> <LI> vWERP-t uses virtual work-energy to accurately assess turbulent relative pressure. </LI> <LI> In-vitro, vWERP-t shows 1:1 agreement with invasive measurements of relative pressure. </LI> <LI> In transient flow, vWERP-t shows significant improvement compared to other approaches. </LI> <LI> vWERP-t guarantees divergence free flow even in turbulent fields, improving accuracy. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>