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Hydrogel-based local drug delivery strategies for spinal cord repair

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Neural Regeneration Research 2021年第2期16卷 247-253页

作者： robert b.shultz Yinghui Zhong School of biomedical Engineering Science and Health SystemsDrexel UniversityPhiladelphiaPAUSA Department of Neurosurgery University of PennsylvaniaPhiladelphiaPAUSA Department of bioengineering University of PennsylvaniaPhiladelphiaPAUSA New Jersey Center for biomaterials Rutgers–The State University of New JerseyPiscatawayNJUSA Center for Neurotrauma Neurodegeneration&RestorationCorporal Michael J.Crescenz Veterans Affairs Medical CenterPhiladelphiaPAUSA

Spinal cord injury results in significant loss of motor, sensory, and autonomic functions. Although a wide range of therapeutic agents have been shown to attenuate secondary injury or promote regeneration/repair in animal models of spinal cord injury, clinical translation of these strategies has been limited, in part due to difficulty in safely and effectively achieving therapeutic concentrations in the injured spinal cord tissue. Hydrogelbased drug delivery systems offer unique opportunities to locally deliver drugs to the injured spinal cord with sufficient dose and duration, while avoiding deleterious side effects associated with systemic drug administration. Such local drug delivery systems can be readily fabricated from biocompatible and biodegradable materials. In this review, hydrogel-based strategies for local drug delivery to the injured spinal cord are extensively reviewed, and recommendations are made for implementation.

关键词： drug carriers drug delivery hydrogels microparticles nanoparticles neurotrophic factors scaffolds spinal cord injury

Engineered neuronal microtissue provides exogenous axons for delayed nerve fusion and rapid neuromuscular recovery in rats

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bioactive Materials 2022年第12期7卷 339-353页

作者： Justin C.burrell Suradip Das Franco A.Laimo Kritika S.Katiyar Kevin D.browne robert b.shultz Vishal J.Tien Phuong T.Vu Dmitriy Petrov Zarina SAli Joseph M.Rosen D.Kacy Cullen Center for brain Injury&Repair Department of NeurosurgeryPerelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA Department of bioengineering School of Engineering&Applied ScienceUniversity of PennsylvaniaPhiladelphiaPAUSA Center for Neurotrauma Neurodegeneration&RestorationCorporal Michael J.Crescenz Veterans Affairs Medical CenterPhiladelphiaPA19104USA Axonova Medical LLCPhiladelphiaPAUSA Dartmouth-Hitchcock Medical Center Division of Plastic SurgeryDartmouth CollegeLebanonNHUSA

Nerve injury requiring surgical repair often results in poor functional recovery due to the inability of host axons to re-grow long distances and reform meaningful connections with the target muscle. While surgeons can re-route local axon fascicles to the target muscle, there are no technologies to provide an exogenous source of axons without sacrificing healthy nerves. Accordingly, we have developed tissue engineered neuromuscular interfaces (TE-NMIs) as the first injectable microtissue containing motor and sensory neurons in an anatomically-inspired architecture. TE-NMIs provide axon tracts that are intended to integrate with denervated distal structures and preserve regenerative capacity during prolonged periods without host innervation. Following implant, we found that TE-NMI axons promoted Schwann cell maintenance, integrated with distal muscle, and preserved an evoked muscle response out to 20-weeks post nerve transection in absence of innervation from host axons. by repopulating the distal sheath with exogenous axons, TE-NMIs also enabled putative delayed fusion with proximal host axons, a phenomenon previously not achievable in delayed repair scenarios due to distal axon degeneration. Here, we found immediate electrophysiological recovery after fusion with proximal host axons and improved axon maturation and muscle reinnervation at 24-weeks post-transection (4-weeks following delayed nerve fusion). These findings show that TE-NMIs provide the potential to improve functional recovery following delayed nerve repair.

关键词： Nerve regeneration Neuromuscular injury Muscle preservation Tissue engineering Microtissue Axon fusion

Invasion syndromes:hypotheses on relationships among invasive species attributes and characteristics of invaded sites

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Journal of Arid Land 2013年第3期5卷 275-283页

作者： Lora b PERKINS robert S NOWAK Department of Natural Resource Management South Dakota State UniversityBrookings SD 57007USA Department of Natural Resources & Environmental Science University of NevadaReno NV 89557USA

As invasion science accepts that there is no single causal factor for biological invasion, the identification of groups of traits that are often associated, or ＂syndromes＂, is a logical move forward. Invasion syndromes are proposed to identify suites of site conditions （biotic and environmental） that render a site vulnerable to invasion by different types of invaders. This paper proposed four invasion syndromes which relate invader attributes （competitive ability, niche construction, phenotypic plasticity, and phenological niche separation） to the biotic characteristics （biodiversity and enemies） and environmental conditions （resource abundance and fluctuation） of invaded sites. The four invasion syndromes described in this paper are a development of hypotheses of how the many factors that influence species invasion might be associated. Invasion Syndrome 1 proposes that sites with relatively high resource abundance and high diversity should be vulnerable to invasion by species with high competitive ability. Invasion Syndrome 2 hypothesizes that sites with relatively low resource abundance and low diversity should be vulnerable to invasion by species with niche construction ability. Invasion Syndrome 3 postulates that sites with moderate or fluctuating resources and moderate diversity should be vulnerable to invasion by species with high phenotypic plasticity. Invasion Syndrome 4 hypothesizes that species introduced into a site where it has phenological niche separation from natives will not have to contend with interference from the biotic community at a site （diversity or natural enemies） and may invade where ever site environmental conditions suit its life history. Further work is needed to support, contradict, or refine these hypotheses and almost certainly will identify more invasion syndromes.

关键词： non-native competitive ability niche construction ecosystem engineering phenotypic plasticity phenological niche separation

Performance evaluation of near real-time condition monitoring in haul trucks

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International Journal of Mining Science and Technology 2020年第6期30卷 909-915页

作者： Hemanth Reddy Alla robert Hall Derek b.Apel University of Alberta Edmonton T6G 2H5Canada

Strategic maintenance plays a key role in ensuring high availability and utilization of the haul trucks,and as equipment began to grow more complex towards the end of the 20th century,there was a need for a proactive maintenance strategy,which led to the development of condition-based *** condition monitoring(RTCM)is the ability to perform condition monitoring in real-time and has the ability to alert maintenance and operations of abnormal *** alarms can be used as an indication leading to a problem,and if a suitable corrective action is initiated in time,it could result in significant savings of equipment downtime and repair *** study aims to compare some maintenance performance indicators prior to and after implementation of RTCM strategy at a mine site using some tests of statistical *** study also indicated the presence of seasonality in the data,and thus the data was deseasonalized and detrended prior to being subjected to the statistical ***,the results indicated that RTCM strategy has proven to be successful in improving the availability for some of the failure categories chosen in this study.

关键词： Haul trucks Real-time condition monitoring Performance indicators

Regulatory T cells in viral hepatitis

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World Journal of Gastroenterology 2007年第36期13卷 4858-4864页

作者： Eva billerbeck Tobias bttler robert Thimme Department of Medicine Ⅱ University Hospital Freiburg Germany

The pathogenesis and outcome of viral infections are significantly influenced by the host immune response. The immune system is able to eliminate many viruses in the acute phase of infection. However, some viruses, like hepatitis C virus (HCV) and hepatitis b virus (HbV), can evade the host immune responses and establish a persistent infection. HCV and HbV persistence is caused by various mechanisms, like subversion of innate immune responses by viral factors, the emergence of T cell escape mutations, or T cell dysfunction and suppression. Recently, it has become evident that regulatory T cells may contribute to the pathogenesis and outcome of viral infections by suppressing antiviral immune responses. Indeed, the control of HCV and HbV specific immune responses mediated by regulatory T cells may be one mechanism that favors viral persistence, but it may also prevent the host from overwhelming T cell activity and liver damage. This review will focus on the role of regulatory T cells in viral hepatitis.

关键词： Regulatory T cells Viral hepatitis Immunoregulation

Guizhou Province, China: the birthplace of modern Medical Geology

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Acta Geochimica 2020年第1期39卷 155-159页

作者： robert b.Finkelman Jose A.Centeno University of Texas at Dallas RichardsonTX 75080USA International Medical Geology Association GaithersburgMD 20879USA

Medical Geology,the emerging discipline that focuses on the health impacts of geologic materials and geologic processes,has its roots in Guizhou Province,*** the 1980 s *** baoshan and his students recognized that a large number of people in Guizhou Province had clinical symptoms of arsenic poisoning,fluorine exposure,selenosis,and other diseases caused by exposure to potentially toxic trace elements or due to deficiency of essential *** publications and invitations to scientists to visit the Province ultimately resulted in increased attention to the health impacts of the natural environment and the formation of scientific societies,the publication of at least a dozen books,and thousands of technical articles on what is now called Medical Geology.

关键词： Coal Fluorosis Arsenic poisoning Selenosis Health impacts Environmental health

Endoscopic management of refractory gastrointestinal non-variceal bleeding using Histoacryl(N-butyl-2-cyanoacrylate)glue

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Gastroenterology Report 2016年第3期4卷 232-236,I0002,I0003页

作者： Damien CK Loh robert b Wilson Department of Upper Gastrointestinal Surgery Liverpool HospitalSydneyAustralia

background:Histoacryl glue(N-butyl-2-cyanoacrylate)has well-established utility in the endoscopic management of gastrointestinal variceal *** role of Histoacryl glue in non-variceal bleeding is less clear,and there are few articles describing its use in this ***:Six patients with intractable non-variceal gastrointestinal bleeding were managed using injection of Histoacryl *** patients had previously failed conventional endostasis and/or interventional angioembolization and were not suitable for emergency salvage surgery due to serious comorbidities or unacceptable anaesthetic *** endoscopic Lipiodol-Histoacryl-Lipiodol sandwich injection technique was used in these *** clinical outcomes and complications were ***:There were four females and two males with a mean age of 55 *** lesions included gastric ulcers(n=2),duodenal ulcers(n=2),duodenal gastrointestinal stromal tumor(GIST)(n=1)and rectal ulcers(n=1).All patients had successful Histoacryl endostasis without the requirement for salvage *** was no treatment-related morbidity and no *** patients had further bleeding after initial Histoacryl endostasis,which was successfully controlled with further endoscopic Histoacryl ***:Histoacryl endostasis should be included in the treatment algorithm for refractory non-variceal gastrointestinal bleeding.

关键词： Histoacryl glue N-butyl-2-cyanoacrylate endoscopy non-variceal upper gastrointestinal bleeding

Toward three-dimensional in vitro models to study neurovascular unit functions in health and disease

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Neural Regeneration Research 2021年第11期16卷 2132-2140页

作者： Tara M.Caffrey Emily b.button Jerome robert Djavad Mowafaghian Center for brain Health University of British ColumbiaVancouverBCCanada Department of Pathology University of British ColumbiaVancouverBCCanada Institute of Clinical Chemistry University Hospital of ZurichZurichSwitzerland

The high metabolic demands of the brain require an efficient vascular system to be coupled with neural activity to supply adequate nutrients and *** supply is coordinated by the action of neurons,glial and vascular cells,known collectively as the neurovascular unit,which temporally and spatially regulate local cerebral blood flow through a process known as neurovascular *** many neurodegenerative diseases,changes in functions of the neurovascular unit not only impair neurovascular coupling but also permeability of the blood-brain barrier,cerebral blood flow and clearance of waste from the *** order to study disease mechanisms,we need improved physiologicallyrelevant human models of the neurovascular *** towards modeling the cellular complexity of the neurovascular unit in vitro have been made using stem-cell derived organoids and more recently,vascularized organoids,enabling intricate studies of non-cell autonomous *** and design innovations in microfluidic devices and tissue engineering are progressing our ability to interrogate the *** advanced models are being used to gain a better understanding of neurodegenerative disease processes and potential *** innovation is required to build more physiologically-relevant models of the neurovascular unit encompassing both the cellular complexity and designed features to interrogate neurovascular unit functionality.

关键词： Alzheimer’s disease cerebrovasculature in vitro model neurodegeneration neurovascular unit

A Simple Kinetic Monte Carlo Approach for Epitaxial Submonolayer Growth

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Communications in Computational Physics 2008年第4期3卷 822-833页

作者： robert Deak Zoltan Neda Peter b.barna Eotvos Lor and University Department of Materials ScienceH-1117 BudapestHungary babe¸s-bolyai University Department of Theoretical and Computational PhysicsCluj-NapocaRO-400084Romania Research Institute for Technical Physics and Materials Science H-1525BudapestP.O box 49Hungary

Two-component submonolayer growth on triangular lattice is qualitatively studied by kinetic Monte Carlo *** hopping barrier governing surface diffusion of the atoms is estimated using pair interaction *** degrees of freedoms enhancing the surface diffusion of atoms are also *** main advantages of the presented technique are the reduced number of free parameters and the clear diffusion activated mechanism for the segregation of different types of *** potential of this method is exemplified by reproducing(i)phase-boundary creation and dynamics related to vacancies and stacking faults;(ii)a special co-deposition and segregation process where the segregated atoms of the second component surround the islands formed by the first type of atoms.

关键词： Submonolayer epitaxial growth kinetic Monte Carlo pattern formation twocomponent systems segregation.