Imaging Sarcomeres of Extensor Carpi Radialis Brevis in Humans Using Minimally Invasive Microendoscopy

2009 ◽  
Author(s):  
Melinda J. Cromie ◽  
Gabriel N. Sanchez ◽  
Mark J. Schnitzer ◽  
Scott L. Delp
Keyword(s):  
Minimally Invasive ◽  
Fluorescent Dyes ◽  
Second Harmonic ◽  
Human Subjects ◽  
The Body ◽  
Biomechanical Analysis ◽  
Capacity Measurement ◽  
Generating Capacity ◽  
Extensor Carpi Radialis

Sarcomeres are the smallest contractile elements of muscle. Muscle generates force when overlapping myosin and actin filaments within the sarcomere interact to generate force. The amount of force these interactions generate depends on sarcomere length. The range of sarcomere lengths over which a muscle normally operates in the body is an important factor in analyzing a muscle’s force generating capacity. Measurement of sarcomere lengths in vivo is limited by their small size (2–4 μm) and the inability to use fluorescent dyes in humans. We recently developed a microendoscopy system to image sarcomeres in humans via Second Harmonic Generation (SHG) [1]. Here we demonstrate the use of this microendoscopy system as a robust, minimally-invasive tool for biomechanical analysis by measuring sarcomere lengths of the forearm muscle extensor carpi radialis brevis (ECRB) in 5 human subjects.

scholarly journals Ferromagnetic soft catheter robots for minimally invasive bioprinting

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Cheng Zhou ◽  
Youzhou Yang ◽  
Jiaxin Wang ◽  
Qingyang Wu ◽  
Zhuozhi Gu ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
The Body ◽  
Magnetic Actuation ◽  
Internal Organs ◽  
Planar Surfaces ◽  
Reinforced Polymer ◽  
Direct Fabrication ◽  
Digitally Controlled

AbstractIn vivo bioprinting has recently emerged as a direct fabrication technique to create artificial tissues and medical devices on target sites within the body, enabling advanced clinical strategies. However, existing in vivo bioprinting methods are often limited to applications near the skin or require open surgery for printing on internal organs. Here, we report a ferromagnetic soft catheter robot (FSCR) system capable of in situ computer-controlled bioprinting in a minimally invasive manner based on magnetic actuation. The FSCR is designed by dispersing ferromagnetic particles in a fiber-reinforced polymer matrix. This design results in stable ink extrusion and allows for printing various materials with different rheological properties and functionalities. A superimposed magnetic field drives the FSCR to achieve digitally controlled printing with high accuracy. We demonstrate printing multiple patterns on planar surfaces, and considering the non-planar surface of natural organs, we then develop an in situ printing strategy for curved surfaces and demonstrate minimally invasive in vivo bioprinting of hydrogels in a rat model. Our catheter robot will permit intelligent and minimally invasive bio-fabrication.

Clock gene-independent daily regulation of haemoglobin oxidation in red blood cells

2021 ◽  
Author(s):  
Andrew D. Beale ◽  
Priya Crosby ◽  
Utham K. Valekunja ◽  
Rachel S. Edgar ◽  
Johanna E. Chesham ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Human Subjects ◽  
Developmental Regulation ◽  
Physiological Role ◽  
Cell Types ◽  
The Body

AbstractCellular circadian rhythms confer daily temporal organisation upon behaviour and physiology that is fundamental to human health and disease. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body. Being naturally anucleate, RBC circadian rhythms share key elements of post-translational, but not transcriptional, regulation with other cell types. The physiological function and developmental regulation of RBC circadian rhythms is poorly understood, however, partly due to the small number of appropriate techniques available. Here, we extend the RBC circadian toolkit with a novel biochemical assay for haemoglobin oxidation status, termed “Bloody Blotting”. Our approach relies on a redox-sensitive covalent haem-haemoglobin linkage that forms during cell lysis. Formation of this linkage exhibits daily rhythms in vitro, which are unaffected by mutations that affect the timing of circadian rhythms in nucleated cells. In vivo, haemoglobin oxidation rhythms demonstrate daily variation in the oxygen-carrying and nitrite reductase capacity of the blood, and are seen in human subjects under controlled laboratory conditions as well as in freely-behaving humans. These results extend our molecular understanding of RBC circadian rhythms and suggest they serve an important physiological role in gas transport.

scholarly journals Recommendations for Nanomedicine Human Subjects Research Oversight: An Evolutionary Approach for an Emerging Field

2012 ◽  
Vol 40 (4) ◽  
pp. 716-750 ◽  
Author(s):  
Leili Fatehi ◽  
Susan M. Wolf ◽  
Jeffrey McCullough ◽  
Ralph Hall ◽  
Frances Lawrenz ◽  
...  
Keyword(s):  
Medical Devices ◽  
Human Subjects ◽  
High Surface ◽  
The Body ◽  
Biologically Active ◽  
Implantable Medical Devices ◽  
Research Oversight ◽  
Insoluble Drugs ◽  
Drug Eluting

Nanomedicine is yielding new and improved treatments and diagnostics for a range of diseases and disorders. Nanomedicine applications incorporate materials and components with nanoscale dimensions (often defined as 1-100 nm, but sometimes defined to include dimensions up to 1000 nm, as discussed further below) where novel physiochemical properties emerge as a result of size-dependent phenomena and high surface-to-mass ratio. Nanotherapeutics and in vivo nanodiagnostics are a subset of nanomedicine products that enter the human body. These include drugs, biological products (biologics), implantable medical devices, and combination products that are designed to function in the body in ways unachievable at larger scales. Nanotherapeutics and in vivo nanodiagnostics incorporate materials that are engineered at the nanoscale to express novel properties that are medicinally useful. These nanomedicine applications can also contain nanomaterials that are biologically active, producing interactions that depend on biological triggers. Examples include nanoscale formulations of insoluble drugs to improve bioavailability and pharmacokinetics, drugs encapsulated in hollow nanoparticles with the ability to target and cross cellular and tissue membranes (including the bloodbrain barrier) and to release their payload at a specific time or location, imaging agents that demonstrate novel optical properties to aid in locating micrometastases, and antimicrobial and drug-eluting components or coatings of implantable medical devices such as stents.

scholarly journals Variability of in vivo sarcomere length measures in the upper limb obtained with second harmonic generation microendoscopy

2021 ◽  
Author(s):  
Amy N Adkins ◽  
Ryan Fong ◽  
Julius P. A. Dewald ◽  
Wendy M. Murray
Keyword(s):  
Second Harmonic Generation ◽  
Harmonic Generation ◽  
Upper Limb ◽  
Sarcomere Length ◽  
Second Harmonic ◽  
Human Subjects ◽  
Measurement Techniques ◽  
Muscle Adaptation ◽  
Limb Muscles

The lengths of a muscle's sarcomeres are a primary determinant of its ability to contract and produce force. In addition, sarcomere length is a critical parameter that is required to make meaningful comparisons of both the force-generating and excursion capacities of different muscles. Until recently, in vivo sarcomere length data have been limited to invasive or intraoperative measurement techniques. With the advent of second harmonic generation microendosopy, minimally invasive measures of sarcomere length can be made for the first time. This imaging technique expands our ability to study muscle adaptation due to changes in stimulus, use, or disease. However, due to the prior inability to measure sarcomeres outside of surgery or biopsy, little is known about the natural, anatomical variability in sarcomere length in living human subjects. To develop robust experimental protocols that ensure data provide accurate representations of a muscle's sarcomere lengths, we sought to quantify experimental uncertainty associated with in vivo measures of sarcomere lengths. Specifically, we assessed the variability in sarcomere length measured 1) within a single image, along a muscle fiber, 2) across images captured within a single trial, across trials, and across days, as well as 3) across locations in the muscle using second harmonic generation in two upper limb muscles with different muscle architectures, functions, and sizes. Across all of our measures of variability we estimate that the magnitude of the uncertainty in in vivo sarcomere length are on the order of 0.25 microns. In the two upper limb muscles studied we found larger variability in sarcomere length within a single insertion than across locations. We also developed custom code to make measures of sarcomere length variability across a single fiber and determined that this codes' accuracy is an order of magnitude smaller than our measurement uncertainty due to sarcomere variability. Together, our findings provide guidance for the development of robust experimental design and analysis of in vivo sarcomere lengths in the upper limb.

Investigation of Murine Vaginal Creep Response to Altered Mechanical Loads

2021 ◽  
Author(s):  
Gabrielle L. Clark ◽  
Jeffrey McGuire ◽  
Laurephile Desrosiers ◽  
Leise R. Knoepp ◽  
Raffaella De Vita ◽  
...  
Keyword(s):  
Axial Length ◽  
Second Harmonic ◽  
Viscoelastic Behavior ◽  
Primary Objective ◽  
The Body ◽  
Multiaxial Loading ◽  
Axial Loads ◽  
Viscoelastic Creep ◽  
Second Harmonic Generation Imaging

Abstract The vagina is a viscoelastic fibromuscular organ that provides support to the pelvic organs. The viscoelastic properties of the vagina are understudied but may be critical for pelvic stability. Most studies evaluate vaginal viscoelasticity under a single uniaxial load; however, the vagina is subjected to dynamic multiaxial loading in the body. It is unknown how varied multiaxial loading conditions affect vaginal viscoelastic behavior and which microstructural processes dictate this. Therefore, the primary objective was to develop methods using extension-inflation protocols to quantify vaginal viscoelastic creep under various circumferential and axial loads. The second objective was to quantify vaginal creep and collagen microstructure in the fibulin-5 wildtype and haploinsufficient vaginas. To evaluate pressure-dependent creep, the fibulin-5 wildtype and haploinsufficient vaginas (n=7/genotype) were subjected to various constant pressures at the physiologic length for 100 seconds. For axial length-dependent creep, the vaginas (n=7/genotype) were extended to various fixed axial lengths then subjected to the mean in vivo pressure for 100 seconds. Second harmonic generation imaging was performed to quantify collagen fiber organization and undulation (n=3/genotype). Increased pressure significantly increased creep strain in the wildtype, but not the haploinsufficient vagina. Axial length did not significantly affect the creep rate or strain in both genotypes. Collagen undulation varied through the depth of the subepithelium but not between genotypes. These findings suggest that the response to loading may vary with biological processes and pathologies, therefore, evaluating vaginal creep under various circumferential loads may be important.

scholarly journals 3249 Defining the Extracellular Vesicle Content of Interstitial Fluid for Blood-Free Diagnostics; Extraction Methods and Initial Characterization

2019 ◽  
Vol 3 (s1) ◽  
pp. 7-7
Author(s):  
Justin Baca Robert Taylor ◽  
Srinivasa Rao Gadam ◽  
Lauren Perez
Keyword(s):  
Electron Microscopy ◽  
Minimally Invasive ◽  
Intercellular Communication ◽  
Interstitial Fluid ◽  
Human Subjects ◽  
Extracellular Vesicle ◽  
Vis Spectroscopy ◽  
Initial Characterization

OBJECTIVES/SPECIFIC AIMS: Recent advances in microneedle technology have enabled practical, in vivo dermal interstitial fluid (ISF) sampling. These minimally-invasive techniques allow for collection of ISF without damage to adjacent tissues and do not rely on blister formation. Initial reports of extracellular vesicle (EV) isolation from dermal ISF and paired blood samples suggest that EVs may be more abundant in ISF. Analysis of ISF-derived EVs may allow for more detailed study of intercellular communication at the tissue level, particularly in acute inflammatory conditions. The objective of this study is to describe the isolation and initial characterization of interstitial fluid-derived exosomes. METHODS/STUDY POPULATION: We apply electron microscopy, nanoparticle tracking analysis (NTA), immuochemical, and sequencing methods to describe and distinguish the EV content of interstitial fluid. We include apparently healthy adult human subjects with no active skin disease. We also study immunocompetent, CD-hairless rats to demonstrate the generalizability of the methods. RESULTS/ANTICIPATED RESULTS: We successfully isolated EVs from human and rat interstitial fluid using commercially available precipitation methods. The EVs were initially characterized using UV/Vis spectroscopy, electron microscopy, and NTA. While the study is ongoing, initial results suggest that the concentration and size distribution of EVs differs significantly between blood fractions and ISF. Further immunochemical and sequencing characterization is ongoing. DISCUSSION/SIGNIFICANCE OF IMPACT: We present here the initial characterization of EVs isolated from dermal interstitial fluid. This appears to be the first report of EV characterization using ISF collection methods that do not perturb adjacent tissues (such as with blister or microdialysis methods). The present study lays a foundation for further examination of ISF-derived EVs in acute inflammatory disease such as cellulitis or infectious neuritis. This may enable minimally invasive diagnostics and new research tools to understand intercellular communication in living organisms with increased spatial and temporal resolution.

scholarly journals Highly sensitive scent-detection of COVID-19 patients in vivo by trained dogs

2021 ◽  
Author(s):  
Omar Vesga ◽  
Maria Agudelo ◽  
Andres F Valencia-Jaramillo ◽  
Alejandro Mira-Montoya ◽  
Ivan Felipe Ossa-Ospina ◽  
...  
Keyword(s):  
Positive Predictive Value ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Limit Of Detection ◽  
Human Subjects ◽  
Real Life ◽  
The Body ◽  
Scent Detection

Timely and accurate diagnostics are essential to fight the COVID-19 pandemic, but no test satisfies both conditions. Dogs can scent-identify the unique odors of the volatile organic compounds generated during infection by interrogating specimens or, ideally, the body of a patient. After training 6 dogs to detect SARS-CoV-2 in human respiratory secretions (in vitro scent-detection), we retrained 5 of them to diagnose the infection by scenting the patient directly (in vivo scent-detection). Then, efficacy trials were designed to compare the diagnostic performance of the dogs against that of the rRT-PCR in 848 human subjects: 269 hospitalized patients (COVID-19 prevalence 30.1%), 259 hospital staff (prevalence 2.7%), and 320 government employees (prevalence 1.25%). The limit of detection in vitro was lower than 10-12 copies ssRNA/mL. In vivo, all dogs detected 92 COVID-19 patients present among the 848 study subjects. Detection was immediate, and independent of prevalence, time post-exposure, or presence of symptoms, with 95.2% accuracy and high sensitivity (95.9%; 95% C.I. 93.6-97.4), specificity (95.1%; 94.4-95.8), positive predictive value (69.7%; 65.9-73.2), and negative predictive value (99.5%; 99.2-99.7). To determine real-life performance, we waited 75 days to carry out an effectiveness assay among the riders of the Metro System of Medellin, deploying the human-canine teams without previous training or announcement. Three dogs (one of each breed) scent-interrogated 550 citizens who volunteered for simultaneous canine and rRT-PCR testing. Negative predictive value remained at 99.0% (95% C.I. 98.3-99.4), but positive predictive value dropped to 28.2% (95% C.I. 21.1-36.7). Canine scent-detection in vivo is a highly accurate screening test for COVID-19, and it detects more than 99% of infected individuals independently of the key variables. However, real-life conditions increased substantially the number of false positives, indicating the necessity of training a threshold for the limit of detection to discriminate environmental odoriferous contamination from infection.

Differential Expression of RANKL and Osteoprotegerin in Gingival Crevicular Fluid of Patients with Periodontitis

2004 ◽  
Vol 83 (2) ◽  
pp. 166-169 ◽  
Author(s):  
M. Mogi ◽  
J. Otogoto ◽  
N. Ota ◽  
A. Togari
Keyword(s):  
Periodontal Disease ◽  
Gingival Crevicular Fluid ◽  
Human Subjects ◽  
Bone Destruction ◽  
Osteoclast Formation ◽  
The Body ◽  
Il Interleukin ◽  
Receptor Activator ◽  
Crevicular Fluid

The receptor activator for NF-κB ligand (RANKL) plays an important role in osteoclast formation. A recent study with animal models suggests the involvement of RANKL in the pathogenesis of this periodontal disease. However, no one has examined the level of RANKL in the body fluid of human subjects. This communication reports on the in vivo concentrations of RANKL and the RANKL decoy receptor osteoprotegerin (OPG) in the gingival crevicular fluid (GCF) of periodontal subjects with severe, moderate, and mild forms of the disease. An increased concentration of RANKL and a decreased concentration of OPG were detected in GCF from patients with periodontitis (*p < 0.05 vs. control subjects). The ratio of the concentration of RANKL to that of OPG in the GCF was significantly higher for periodontal disease patients than for healthy subjects (*p < 0.01). Taken together, these data suggest that RANKL and OPG contribute to osteoclastic bone destruction in periodontal disease. Abbreviations: GCF, gingival crevicular fluid; IL, interleukin; OPG, osteoprotegerin; RANKL, receptor activator for NF-κB ligand.

scholarly journals A Quantitative Look Inside the Body: Minimally Invasive Infrared Analysis in Vivo

2014 ◽  
Vol 86 (21) ◽  
pp. 10511-10514 ◽  
Author(s):  
Christian Vrančić ◽  
Niels Kröger ◽  
Norbert Gretz ◽  
Sabine Neudecker ◽  
Annemarie Pucci ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
The Body ◽  
Infrared Analysis
Sign in / Sign up

Export Citation Format

Share Document