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  1. Article ; Online: Development and application of a 3D image analysis strategy for focused ion beam - Scanning electron microscopy tomography of porous soft materials.

    Prochukhan, Nadezda / Rafferty, Aran / Canavan, Megan / Daly, Dermot / Selkirk, Andrew / Rameshkumar, Saranya / Morris, Michael A

    Microscopy research and technique

    2024  Volume 87, Issue 6, Page(s) 1335–1347

    Abstract: In recent years, the potential of porous soft materials in various device technologies has increased in importance due to applications in fields, such as wearable electronics, medicine, and transient devices. However, understanding the 3-dimensional ... ...

    Abstract In recent years, the potential of porous soft materials in various device technologies has increased in importance due to applications in fields, such as wearable electronics, medicine, and transient devices. However, understanding the 3-dimensional architecture of porous soft materials at the microscale remains a challenge. Herein, we present a method to structurally analyze soft materials using Focused Ion Beam - Scanning Electron Microscopy (FIB-SEM) tomography. Two materials, polymethyl methacrylate (PMMA) membrane and pine wood veneer were chosen as test-cases. FIB-SEM was successfully used to reconstruct the true topography of these materials in 3D. Structural and physical properties were subsequently deduced from the rendered 3D models. The methodology used segmentation, coupled with optimized thresholding, image processing, and reconstruction protocols. The 3D models generated pore size distribution, pore inter-connectivity, tortuosity, thickness, and curvature data. It was shown that FIB-SEM tomography provides both an informative and visual depiction of structure. To evaluate and validate the FIB-SEM reconstructions, porous properties were generated from the physical property analysis techniques, gas adsorption analysis using Brunauer-Emmett-Teller (BET) surface area analysis and mercury intrusion porosimetry (MIP) analysis. In general, the data obtained from the FIB-SEM reconstructions was well-matched with the physical data. RESEARCH HIGHLIGHTS: Porous specimens of both synthetic and biological nature, a poly(methyl methacrylate) membrane and a pine veneer respectively, are reconstructed via FIB-SEM tomography without resin-embedding. Different thresholding and reconstruction methods are explored whereby shadowing artifacts are present with the aid of free open-source software. Reconstruction data is compared to physical data: MIP, gas adsorption isotherms which are analyzed via BET and Barrett-Joyner-Halenda (BJH) analysis to yield a full picture of the materials.
    Language English
    Publishing date 2024-02-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1099714-3
    ISSN 1097-0029 ; 1059-910X
    ISSN (online) 1097-0029
    ISSN 1059-910X
    DOI 10.1002/jemt.24514
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Oxygen Consumption While Walking With Multijoint Neuromuscular Electrical Stimulation After Stroke.

    Makowski, Nathaniel S / Kobetic, Rudi / Foglyano, Kevin M / Lombardo, Lisa M / Selkirk, Stephen M / Pinault, Gilles / Triolo, Ronald J

    American journal of physical medicine & rehabilitation

    2020  Volume 99, Issue 12, Page(s) e138–e141

    Abstract: ... 28 ± 0.01 m/sec to 0.58 ± 0.04 m/sec, whereas average step length and cadence increased by 0.12 m and ...

    Abstract This case study evaluated the effect of implanted multijoint neuromuscular electrical stimulation gait assistance on oxygen consumption relative to walking without neuromuscular electrical stimulation after stroke. The participant walked slowly with an asymmetric gait pattern after stroke. He completed repeated 6-min walk tests at a self-selected walking speed with and without hip, knee, and ankle stimulation assistance. His walking speed with neuromuscular electrical stimulation more than doubled from 0.28 ± 0.01 m/sec to 0.58 ± 0.04 m/sec, whereas average step length and cadence increased by 0.12 m and 24 steps/min, respectively. As a result, energy cost of walking with neuromuscular electrical stimulation decreased by 0.19 ml O2/kg per meter as compared with walking without stimulation while oxygen consumption increased by 1.1 metabolic equivalent of tasks (3.9 ml O2/kg per minute). These metabolic demands are similar to those reported for stroke survivors capable of walking at equivalent speeds without stimulation, suggesting the increase in oxygen consumption and decreased energy cost result from improved efficiency of faster walking facilitated by neuromuscular electrical stimulation. Although the effect of neuromuscular electrical stimulation on gait economy has implications for community walking within the user's metabolic reserves, this case study's results should be interpreted with caution and the hypothesis that multijoint neuromuscular electrical stimulation improves metabolic efficiency should be tested in a wide population of stroke survivors with varied deficits.
    MeSH term(s) Aged ; Electric Stimulation Therapy ; Humans ; Joints ; Male ; Oxygen Consumption/physiology ; Stroke/complications ; Stroke/metabolism ; Stroke/physiopathology ; Stroke Rehabilitation ; Walking/physiology
    Language English
    Publishing date 2020-03-08
    Publishing country United States
    Document type Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 219390-5
    ISSN 1537-7385 ; 0002-9491 ; 0894-9115
    ISSN (online) 1537-7385
    ISSN 0002-9491 ; 0894-9115
    DOI 10.1097/PHM.0000000000001416
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Walking after incomplete spinal cord injury with an implanted neuromuscular electrical stimulation system and a hinged knee replacement: a single-subject study.

    Makowski, Nathaniel S / Lombardo, Lisa M / Foglyano, Kevin M / Kobetic, Rudi / Pinault, Gilles / Selkirk, Stephen M / Triolo, Ronald J

    Spinal cord series and cases

    2020  Volume 6, Issue 1, Page(s) 86

    Abstract: ... with the addition of stimulation again more than doubling her maximum walking distance from 214 to 513 m ...

    Abstract Study design: Single-subject repeated measures study.
    Objectives: Neuromuscular electrical stimulation (NMES) can enhance walking for people with partial paralysis from incomplete spinal cord injury (iSCI). This single-subject study documents an individual's experience who both received an experimental implanted NMES system and underwent clinical bilateral hinged total knee arthroplasty (TKA). She walked in the community with knee pain prior to either intervention. Walking performance improved with an implanted NMES system. Knee pain and instability continued to worsen over time and eventually required TKA. This study evaluates the effects of these interventions.
    Setting: Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland OH, USA.
    Methods: The differential and combined effects of NMES and hinged knee replacement were assessed in terms of walking speed, toe clearance, knee angle, and participant perceptions with and without stimulation assistance both before and after TKA.
    Results: The combined approach both reduced pain and restored walking ability to levels achieved prior to developing significant knee pain that prevented walking without NMES. There was an interaction effect between NMES and TKA on walking speed. Toe clearance consistently improved with stimulation assistance and TKA prevented significant knee hyperextension. The greatest impact was on endurance. Knee replacement re-enabled long distance walking with the addition of stimulation again more than doubling her maximum walking distance from 214 to 513 m.
    Conclusions: These data support further research of combined implantable interventions that may benefit people with iSCI. Furthermore, joint laxity and pain may not necessarily be contraindications to NMES if addressed with conventional clinical treatments.
    MeSH term(s) Arthroplasty, Replacement, Knee ; Electric Stimulation/methods ; Electric Stimulation Therapy/methods ; Humans ; Knee Joint/physiopathology ; Prostheses and Implants ; Spinal Cord Injuries/rehabilitation ; Walking/physiology
    Language English
    Publishing date 2020-09-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 2058-6124
    ISSN (online) 2058-6124
    DOI 10.1038/s41394-020-00336-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Gene therapy in clinical medicine.

    Selkirk, S M

    Postgraduate medical journal

    2004  Volume 80, Issue 948, Page(s) 560–570

    Abstract: Although the field of gene therapy has experienced significant setbacks and limited success, it is one of the most promising and active research fields in medicine. Interest in this therapeutic modality is based on the potential for treatment and cure of ...

    Abstract Although the field of gene therapy has experienced significant setbacks and limited success, it is one of the most promising and active research fields in medicine. Interest in this therapeutic modality is based on the potential for treatment and cure of some of the most malignant and devastating diseases affecting humans. Over the next decade, the relevance of gene therapy to medical practices will increase and it will become important for physicians to understand the basic principles and strategies that underlie the therapeutic intervention. This report reviews the history, basic strategies, tools, and several current clinical paradigms for application.
    MeSH term(s) Alzheimer Disease/therapy ; Arteriosclerosis/therapy ; Cystic Fibrosis/therapy ; Forecasting ; Gene Transfer Techniques ; Genetic Therapy/methods ; Genetic Therapy/trends ; Humans ; Neoplasms/therapy
    Language English
    Publishing date 2004-10
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 80325-x
    ISSN 1469-0756 ; 0032-5473
    ISSN (online) 1469-0756
    ISSN 0032-5473
    DOI 10.1136/pgmj.2003.017764
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: ILC3-derived acetylcholine promotes protease-driven allergic lung pathology.

    Darby, Matthew / Roberts, Luke B / Mackowiak, Claire / Chetty, Alisha / Tinelli, Sasha / Schnoeller, Corinna / Quesniaux, Valerie / Berrard, Sylvie / Togbe, Dieudonnée / Selkirk, Murray E / Ryffel, Bernhard / Horsnell, William G C

    The Journal of allergy and clinical immunology

    2021  Volume 147, Issue 4, Page(s) 1513–1516.e4

    MeSH term(s) Acetylcholine/immunology ; Animals ; Bronchial Hyperreactivity/immunology ; Bronchial Hyperreactivity/physiopathology ; Bronchoalveolar Lavage Fluid/cytology ; Cytokines/immunology ; Hypersensitivity/immunology ; Hypersensitivity/physiopathology ; Immunity, Innate ; Lung/drug effects ; Lung/immunology ; Lymphocytes/drug effects ; Lymphocytes/immunology ; Mice, Inbred C57BL ; Mice, Transgenic ; Papain/pharmacology ; Mice
    Chemical Substances Cytokines ; Papain (EC 3.4.22.2) ; Acetylcholine (N9YNS0M02X)
    Language English
    Publishing date 2021-01-19
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2020.10.038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Absorption, Metabolism, and Excretion, In Vitro Pharmacology, and Clinical Pharmacokinetics of Ozanimod, a Novel Sphingosine 1-Phosphate Receptor Modulator.

    Surapaneni, Sekhar / Yerramilli, Usha / Bai, April / Dalvie, Deepak / Brooks, Jennifer / Wang, Xiaomin / Selkirk, Julie V / Yan, Yingzhuo Grace / Zhang, Peijin / Hargreaves, Richard / Kumar, Gondi / Palmisano, Maria / Tran, Jonathan Q

    Drug metabolism and disposition: the biological fate of chemicals

    2021  Volume 49, Issue 5, Page(s) 405–419

    Abstract: Ozanimod is approved for the treatment of relapsing forms of multiple sclerosis. Absorption, metabolism, and excretion of ozanimod were investigated after a single oral dose of 1.0 mg [ ...

    Abstract Ozanimod is approved for the treatment of relapsing forms of multiple sclerosis. Absorption, metabolism, and excretion of ozanimod were investigated after a single oral dose of 1.0 mg [
    MeSH term(s) Administration, Oral ; Adult ; Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Humans ; Indans/administration & dosage ; Indans/metabolism ; Male ; Middle Aged ; Oxadiazoles/administration & dosage ; Oxadiazoles/metabolism ; Sphingosine 1 Phosphate Receptor Modulators/administration & dosage ; Sphingosine 1 Phosphate Receptor Modulators/metabolism ; Sphingosine-1-Phosphate Receptors/metabolism
    Chemical Substances Indans ; Oxadiazoles ; Sphingosine 1 Phosphate Receptor Modulators ; Sphingosine-1-Phosphate Receptors ; ozanimod (Z80293URPV)
    Language English
    Publishing date 2021-03-04
    Publishing country United States
    Document type Clinical Trial ; Journal Article
    ZDB-ID 186795-7
    ISSN 1521-009X ; 0090-9556
    ISSN (online) 1521-009X
    ISSN 0090-9556
    DOI 10.1124/dmd.120.000220
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Deconstructing the Pharmacological Contribution of Sphingosine-1 Phosphate Receptors to Mouse Models of Multiple Sclerosis Using the Species Selectivity of Ozanimod, a Dual Modulator of Human Sphingosine 1-Phosphate Receptor Subtypes 1 and 5.

    Selkirk, Julie V / Dines, Kevin C / Yan, Yingzhuo Grace / Ching, Nathan / Dalvie, Deepak / Biswas, Shameek / Bortolato, Andrea / Schkeryantz, Jeffrey M / Lopez, Carlos / Ruiz, Iliana / Hargreaves, Richard

    The Journal of pharmacology and experimental therapeutics

    2021  Volume 379, Issue 3, Page(s) 386–399

    Abstract: Ozanimod, a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity selectively to S1P receptor subtypes 1 ( ... ...

    Abstract Ozanimod, a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity selectively to S1P receptor subtypes 1 (S1P
    MeSH term(s) Amino Acid Sequence ; Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Disease Models, Animal ; Dogs ; Dose-Response Relationship, Drug ; Encephalomyelitis, Autoimmune, Experimental/drug therapy ; Encephalomyelitis, Autoimmune, Experimental/genetics ; Encephalomyelitis, Autoimmune, Experimental/metabolism ; Female ; Humans ; Indans/metabolism ; Indans/pharmacology ; Indans/therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis/genetics ; Multiple Sclerosis/metabolism ; Oxadiazoles/metabolism ; Oxadiazoles/pharmacology ; Oxadiazoles/therapeutic use ; Rats ; Species Specificity ; Sphingosine 1 Phosphate Receptor Modulators/metabolism ; Sphingosine 1 Phosphate Receptor Modulators/pharmacology ; Sphingosine 1 Phosphate Receptor Modulators/therapeutic use ; Sphingosine-1-Phosphate Receptors/chemistry ; Sphingosine-1-Phosphate Receptors/genetics ; Sphingosine-1-Phosphate Receptors/metabolism
    Chemical Substances Indans ; Oxadiazoles ; Sphingosine 1 Phosphate Receptor Modulators ; Sphingosine-1-Phosphate Receptors ; ozanimod (Z80293URPV)
    Language English
    Publishing date 2021-09-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3106-9
    ISSN 1521-0103 ; 0022-3565
    ISSN (online) 1521-0103
    ISSN 0022-3565
    DOI 10.1124/jpet.121.000741
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Impact of an implanted neuroprosthesis on community ambulation in incomplete SCI.

    Lombardo, Lisa M / Kobetic, Rudolf / Pinault, Gilles / Foglyano, Kevin M / Bailey, Stephanie N / Selkirk, Stephen / Triolo, Ronald J

    The journal of spinal cord medicine

    2017  Volume 41, Issue 2, Page(s) 165–173

    Abstract: ... from baseline. However, average walking speed was significantly faster (0.22 m/s) with stimulation over longer ... distances than volitional walking (0.12 m/s). In addition, there was a 413% increase in walking distance ... from 95 m volitionally to 488 m with stimulation while oxygen consumption and maximum upper extremity ...

    Abstract Objective: Test the effect of a multi-joint control with implanted electrical stimulation on walking after spinal cord injury (SCI).
    Design: Single subject research design with repeated measures.
    Setting: Hospital-based biomechanics laboratory and user assessment of community use.
    Participants: Female with C6 AIS C SCI 30 years post injury.
    Interventions: Lower extremity muscle activation with an implanted pulse generator and gait training.
    Outcome measures: Walking speed, maximum distance, oxygen consumption, upper extremity (UE) forces, kinematics and self-assessment of technology.
    Results: Short distance walking speed at one-year follow up with or without stimulation was not significantly different from baseline. However, average walking speed was significantly faster (0.22 m/s) with stimulation over longer distances than volitional walking (0.12 m/s). In addition, there was a 413% increase in walking distance from 95 m volitionally to 488 m with stimulation while oxygen consumption and maximum upper extremity forces decreased by 22 and 16%, respectively. Stimulation also produced significant (P ≤ 0.001) improvements in peak hip and knee flexion, ankle angle at foot off and at mid-swing.
    Conclusion: An implanted neuroprosthesis enabled a subject with incomplete SCI to walk longer distances with improved hip and knee flexion and ankle dorsiflexion resulting in decreased oxygen consumption and UE support. Further research is required to determine the robustness, generalizability and functional implications of implanted neuroprostheses for community ambulation after incomplete SCI.
    MeSH term(s) Electric Stimulation Therapy/instrumentation ; Female ; Gait ; Hip Joint ; Humans ; Knee Joint ; Middle Aged ; Prostheses and Implants ; Range of Motion, Articular ; Spinal Cord Injuries/rehabilitation ; Walking/physiology
    Language English
    Publishing date 2017-02-03
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1223949-5
    ISSN 2045-7723 ; 1079-0268
    ISSN (online) 2045-7723
    ISSN 1079-0268
    DOI 10.1080/10790268.2016.1275448
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  9. Article ; Online: Accelerometer-based step initiation control for gait-assist neuroprostheses.

    Foglyano, Kevin M / Schnellenberger, John R / Kobetic, Rudi / Lombardo, Lisa / Pinault, Gilles / Selkirk, Stephen / Makowski, Nathaniel S / Triolo, Ronald J

    Journal of rehabilitation research and development

    2017  Volume 53, Issue 6, Page(s) 919–932

    Abstract: Electrical activation of paralyzed musculature can generate or augment joint movements required for walking after central nervous system trauma. Proper timing of stimulation relative to residual volitional control is critical to usefully affecting ... ...

    Abstract Electrical activation of paralyzed musculature can generate or augment joint movements required for walking after central nervous system trauma. Proper timing of stimulation relative to residual volitional control is critical to usefully affecting ambulation. This study evaluates three-dimensional accelerometers and customized algorithms to detect the intent to step from voluntary movements to trigger stimulation during walking in individuals with significantly different etiologies, mobility limitations, manual dexterities, and walking aids. Three individuals with poststroke hemiplegia or partial spinal cord injury exhibiting varying gait deficits were implanted with multichannel pulse generators to provide joint motions at the hip, knee, and ankle. An accelerometer integrated into the external control unit was used to detect heel strike or walker movement, and wireless accelerometers were used to detect crutch strike. Algorithms were developed for each sensor location to detect intent to step to progress through individualized stimulation patterns. Testing these algorithms produced detection accuracies of at least 90% on both level ground and uneven terrain. All participants use their accelerometer-triggered implanted gait systems in the community; the validation/system testing was completed in the hospital. The results demonstrated that safe, reliable, and convenient accelerometer-based step initiation can be achieved regardless of specific gait deficits, manual dexterities, and walking aids.
    MeSH term(s) Accelerometry ; Algorithms ; Gait ; Humans ; Prostheses and Implants ; Spinal Cord Injuries/therapy ; Walking
    Language English
    Publishing date 2017-05-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 605796-2
    ISSN 1938-1352 ; 0007-506X ; 0748-7711 ; 0742-3241 ; 0898-2732
    ISSN (online) 1938-1352
    ISSN 0007-506X ; 0748-7711 ; 0742-3241 ; 0898-2732
    DOI 10.1682/JRRD.2015.09.0188
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  10. Article: Primary care physician experiences with integrated pharmacogenomic testing in a community health system.

    Lemke, Amy A / Hutten Selkirk, Christina G / Glaser, Nicole S / Sereika, Annette W / Wake, Dyson T / Hulick, Peter J / Dunnenberger, Henry M

    Personalized medicine

    2017  Volume 14, Issue 5, Page(s) 389–400

    Abstract: Aim: To explore primary care physicians' views of the utility and delivery of direct access to pharmacogenomics (PGx) testing in a community health system.: Methods: This descriptive study assessed the perspectives of 15 healthcare providers ... ...

    Abstract Aim: To explore primary care physicians' views of the utility and delivery of direct access to pharmacogenomics (PGx) testing in a community health system.
    Methods: This descriptive study assessed the perspectives of 15 healthcare providers utilizing qualitative individual interviews.
    Results: Three main themes emerged: perceived value and utility of PGx testing; challenges to implementation in practice; and provider as well as patient needs.
    Conclusion: While providers in this study viewed benefits of PGx testing as avoiding side effects, titrating doses more quickly, improving shared decision-making and providing psychological reassurance, challenges will need to be addressed such as privacy concerns, cost, insurance coverage and understanding the complexity of PGx test results.
    MeSH term(s) Attitude of Health Personnel ; Community Health Planning ; Health Personnel ; Humans ; Pharmacogenetics/methods ; Pharmacogenomic Testing/trends ; Pharmacogenomic Testing/utilization ; Physicians, Primary Care ; Precision Medicine/methods ; Public Health ; Surveys and Questionnaires
    Language English
    Publishing date 2017-08-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2299146-3
    ISSN 1744-828X ; 1741-0541
    ISSN (online) 1744-828X
    ISSN 1741-0541
    DOI 10.2217/pme-2017-0036
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