Pathophysiology and Imaging Findings of COVID-19 Infection: An Organ-system Based Review.

BACKGROUND: COVID-19 commonly presents with upper respiratory symptoms; however, studies have shown that SARS-CoV-2 infection affects multiple organ systems. Here, we review the pathophysiology and imaging characteristics of SARS-CoV-2 infection in organ systems throughout the body and explore commonalities. OBJECTIVE: Familiarity with the underlying pathophysiology and imaging characteristics is essential for the radiologist to recognize these findings in patients with COVID-19 infection. Though pulmonary findings are the most prevalent presentation, COVID-19 may have multiple manifestations and recognition of the extrapulmonary manifestations is especially important because of the potential serious and long-term effects of COVID-19 on multiple organ systems.

Slowing the Spread of Grapevine Leafroll-Associated Viruses in Commercial Vineyards With Insecticide Control of the Vector, Pseudococcus maritimus (Hemiptera: Pseudococcidae).

Vineyards were surveyed for grapevine leafroll-associated viruses and their insect vectors in New York State's Finger Lakes region in 2006-2008. Grape mealybug, Pseudococcus maritimus (Erhorn) (Hemiptera: Pseudococcidae), European Fruit Lecanium, Parthenolecanium corni (Bouche), and Cottony Maple Scale, Pulvinaria acericola (Walsh and Riley) (Hemiptera: Coccidae) were identified as vector species in this region. An increase in the incidence of Grapevine leafroll-associated virus 1 (GLRaV-1) and GLRaV-3 was observed in 8 of the 20 vineyards surveyed, which implies transmission by these insect vectors. Two of the vineyards for which a temporal increase in disease incidence was documented were then used to evaluate the efficacy of foliar applications of horticultural oil and two classes of insecticides for control of P. maritimus and for slowing virus spread over 2 years of vine protection. Delayed dormant applications of horticultural oil contributed to control of early season crawlers; however, this was not the case for control of summer populations. Applications of acetamiprid and spirotetramat achieved control in summer populations; however, spirotetramat outperformed acetamiprid in percent reduction of treated compared with control vines and in a side-by-side trial. Vines treated with spirotetramat had a lower percentage of new vines testing positive for GLRaV-1 than control vines after 2 years, while no other spray program altered the increase in incidence of GLRaV-1 or -3.

Use of a virtual integrated environment in prosthetic limb development and phantom limb pain.

Patients face two major difficulties following limb loss: phantom limb pain (PLP) in the residual limb and limited functionality in the prosthetic limb. Many studies have focused on decreasing PLP with mirror therapy, yet few have examined the same visual ameliorating effect with a virtual or prosthetic limb. Our study addresses the following key questions: (1) does PLP decrease through observation of a 3D limb in a virtual integration environment (VIE) and (2) can consistent surface electromyography (sEMG) signals from the VIE drive an advanced modular prosthetic limb (MPL)? Recorded signals from the residual limb were correlated to the desired motion of the phantom limb, and changes in PLP were scored during each VIE session. Preliminary results show an overall reduction in PLP and a trend toward improvement in signal-to-motion accuracy over time. These signals allowed MPL users to perform a wide range of hand motions.

Toward Perceiving Robots as Humans: Three Handshake Models Face the Turing-Like Handshake Test.

In the Turing test a computer model is deemed to "think intelligently" if it can generate answers that are indistinguishable from those of a human. We developed an analogous Turing-like handshake test to determine if a machine can produce similarly indistinguishable movements. The test is administered through a telerobotic system in which an interrogator holds a robotic stylus and interacts with another party - artificial or human with varying levels of noise. The interrogator is asked which party seems to be more human. Here, we compare the human-likeness levels of three different models for handshake: (1) Tit-for-Tat model, (2) λ model, and (3) Machine Learning model. The Tit-for-Tat and the Machine Learning models generated handshakes that were perceived as the most human-like among the three models that were tested. Combining the best aspects of each of the three models into a single robotic handshake algorithm might allow us to advance our understanding of the way the nervous system controls sensorimotor interactions and further improve the human-likeness of robotic handshakes.

Using a virtual integration environment in treating phantom limb pain.

The Revolutionizing Prosthetics 2009 program conducted by the Defense Advanced Research Projects Agency (DARPA) has resulted in a Virtual Integration Environment (VIE) that provides a common development platform for researchers and clinicians that design, model and build prosthetic limbs and then integrate and test them with patients. One clinical need that arose during the VIE development was a feature to easily create and model animations that represent patient activities of daily living (ADLs) and simultaneously capture real-time surface EMG activity from the residual limb corresponding to the ADLs. An application of this feature is being made by the Walter Reed Military Amputee Research Program (MARP) where they are utilizing the VIE to investigate methods of reducing upper extremity amputee phantom limb pain (PLP).

Diversity of ampeloviruses in mealybug and soft scale vectors and in grapevine hosts from leafroll-affected vineyards.

The occurrence and diversity of Grapevine leafroll-associated virus 1 (GLRaV-1) and Grapevine leafroll-associated virus 3 (GLRaV-3) in the soft scales Parthenolecanium corni and Pulvinaria innumerabilis and in the mealybug Pseudococcus maritimus was determined in leafroll-affected vineyards in the Finger Lakes region of New York. Groups of 1 to 4 specimens were collected under loose grapevine bark and tested by reverse-transcription polymerase chain reaction (RT-PCR) for segments of the second diverged copy of the GLRaV-1 coat protein gene or GLRaV-3 heat-shock protein 70-homologue gene. Virus-specific RT-PCR products were amplified from immature insect vectors and adult mealybugs. Single viral amplicons were obtained mostly from immature vectors (35%, 30 of 85) and dual viral amplicons from immature (16%, 10 of 61) and adult (100%, 14 of 14) mealybugs, including individuals. These observations suggested a simultaneous uptake of GLRaV-1 and GLRaV-3 by individual mealybugs. Furthermore, a comparative nucleotide sequence analysis of viral amplicons from soft scales, mealybugs, and grapevines from which vectors were collected showed identical or highly similar haplotypes, indicating that uptake of GLRaV-1 and GLRaV-3 likely occurred by direct feeding of vectors on their host plants.

Force estimation from ensembles of Golgi tendon organs.

Golgi tendon organs (GTOs) located in the skeletal muscles provide the central nervous system with information about muscle tension. The ensemble firing of all GTO receptors in the muscle has been hypothesized to represent a reliable measure of the whole muscle force but the precision and accuracy of that information are largely unknown because it is impossible to record activity simultaneously from all GTOs in a muscle. In this study, we combined a new mathematical model of force sampling and transduction in individual GTOs with various models of motor unit (MU) organization and recruitment simulating various normal, pathological and neural prosthetic conditions. Our study suggests that in the intact muscle the ensemble GTO activity accurately encodes force information according to a nonlinear, monotonic relationship that has its steepest slope for low force levels and tends to saturate at the highest force levels. The relationship between the aggregate GTO activity and whole muscle tension under some pathological conditions is similar to one seen in the intact muscle during rapidly modulated, phasic excitation of the motor pool (typical for many natural movements) but quite different when the muscle is activated slowly or held at a given force level. Substantial deviations were also observed during simulated functional electrical stimulation.

Survey for the Three Major Leafroll Disease-Associated Viruses in Finger Lakes Vineyards in New York.

Vineyards in the Finger Lakes region in New York were surveyed for the three major viruses associated with leafroll disease, i.e., Grapevine leafroll-associated virus 1 (GLRaV-1), Grapevine leafroll-associated virus 2 (GLRaV-2), and Grapevine leafroll-associated virus 3 (GLRaV-3). Target viruses were detected in nearly two-thirds (68%, 65 of 95) of the vineyard blocks surveyed by enzyme-linked immunosorbent assay. Single infections by GLRaV-1, GLRaV-2, and GLRaV-3 occurred in 10% (113 of 1,124), 3% (36 of 1,124), and 15% (173 of 1,124) of the samples tested, respectively, whereas mixed infections affected 3.6% (40 of 1,124) of them, essentially with GLRaV-1 and GLRaV-3 (2.5%, 28 of 1,124). Presence of the target viruses was confirmed in selected samples by reverse transcription-polymerase chain reaction and sequencing. Comparative analysis indicated moderate to high nucleotide sequence identities in the second diverged copy of the GLRaV-1 coat protein gene (81.0 to 86.7%), GLRaV-2 coat protein gene (87.6 to 99.2%), and GLRaV-3 heat shock protein 70 homologue gene (91.5 to 98.3%) of New York isolates with corresponding virus reference strains. The prevalence of the three major leafroll disease-associated viruses in Finger Lakes vineyards results likely from poor sanitary status of planting materials, stressing the need to reinstate a certification program in New York.

Influence of leaf trichomes on predatory mite (Typhlodromus pyri) abundance in grape varieties.

Non-glandular leaf trichomes positively influence the abundance of many phytoseiid mites. We characterized the influence of grape leaf trichomes (domatia, hairs, and bristles) on Typhlodromus pyri Scheuten abundance over two years in a common garden planting of many grape varieties and 2 years of sampling in a commercial vineyard. In general, a lack of trichomes was associated with much lower predator numbers and in the case of Dechaunac, a cultivar with almost no trichomes, very few T. pyri were found. Phytoseiid abundance was best predicted by a model where domatia and hair had an additive effect (r (2) = 0.815). Over two years of sampling at a commercial vineyard there were T. pyri present on all of the 5 cultivars except Dechaunac. At the same time, European red mite prey were present on Dechaunac alone. These results suggest that on grape cultivars lacking leaf trichomes, T. pyri likely will not attain sufficient densities to provide biological control of European red mite, despite presence of the mite food source. The relationship between leaf trichomes and phytoseiid abundance that is observed at the scale of single vines in a garden planting appears to also be manifest at the scale of a commercial vineyard. Because persistence of predatory mites in or nearby the habitats of prey mites is important for effective mite biological control, leaf trichomes, through their influence on phytoseiid persistence, may be critical for successful mite biological control in some systems.

Computationally efficient models of neuromuscular recruitment and mechanics.

We have improved the stability and computational efficiency of a physiologically realistic, virtual muscle (VM 3.*) model (Cheng et al 2000 J. Neurosci. Methods 101 117-30) by a simpler structure of lumped fiber types and a novel recruitment algorithm. In the new version (VM 4.0), the mathematical equations are reformulated into state-space representation and structured into a CMEX S-function in SIMULINK. A continuous recruitment scheme approximates the discrete recruitment of slow and fast motor units under physiological conditions. This makes it possible to predict force output during smooth recruitment and derecruitment without having to simulate explicitly a large number of independently recruited units. We removed the intermediate state variable, effective length (Leff), which had been introduced to model the delayed length dependency of the activation-frequency relationship, but which had little effect and could introduce instability under physiological conditions of use. Both of these changes greatly reduce the number of state variables with little loss of accuracy compared to the original VM. The performance of VM 4.0 was validated by comparison with VM 3.1.5 for both single-muscle force production and a multi-joint task. The improved VM 4.0 model is more suitable for the analysis of neural control of movements and for design of prosthetic systems to restore lost or impaired motor functions. VM 4.0 is available via the internet and includes options to use the original VM model, which remains useful for detailed simulations of single motor unit behavior.

Model-based sensorimotor integration for multi-joint control: development of a virtual arm model.

An integrated, sensorimotor virtual arm (VA) model has been developed and validated for simulation studies of control of human arm movements. Realistic anatomical features of shoulder, elbow and forearm joints were captured with a graphic modeling environment, SIMM. The model included 15 musculotendon elements acting at the shoulder, elbow and forearm. Muscle actions on joints were evaluated by SIMM generated moment arms that were matched to experimentally measured profiles. The Virtual Muscle (VM) model contained appropriate admixture of slow and fast twitch fibers with realistic physiological properties for force production. A realistic spindle model was embedded in each VM with inputs of fascicle length, gamma static (gamma(stat)) and dynamic (gamma(dyn)) controls and outputs of primary (I(a)) and secondary (II) afferents. A piecewise linear model of Golgi Tendon Organ (GTO) represented the ensemble sampling (I(b)) of the total muscle force at the tendon. All model components were integrated into a Simulink block using a special software tool. The complete VA model was validated with open-loop simulation at discrete hand positions within the full range of alpha and gamma drives to extrafusal and intrafusal muscle fibers. The model behaviors were consistent with a wide variety of physiological phenomena. Spindle afferents were effectively modulated by fusimotor drives and hand positions of the arm. These simulations validated the VA model as a computational tool for studying arm movement control. The VA model is available to researchers at website http://pt.usc.edu/cel .

Flexible communication and control protocol for injectable neuromuscular interfaces.

BION2 is a system based on injectable neuromuscular implants whose main goal is to restore the functional movement of paralyzed limbs. To achieve this objective, the functional requirements of the implanted interfaces include not only stimulation but also integrated sensors in order to detect patient intention, to provide servocontrol of muscle activation and to sense posture to inform more global motor planning and coordination. The technical constraints for managing the system include the efficient use of forward and reverse telemetry channels with limited capacity, minimization of adverse consequences from errors in data transmission or intermittent loss of power to the implants, and ability to adjust stimulation rates and phases to achieve efficient fine control of muscle force while minimizing fatigue. This paper describes a communication and control architecture with several novel features that address these requirements.

Functional electrical stimulation using microstimulators to correct foot drop: a case study.

This paper presents a case study that tested the feasibility and efficacy of using injectable microstimulators (BIONs) in a functional electrical stimulation (FES) device to correct foot drop. Compared with surface stimulation of the common peroneal nerve, stimulation with BIONs provides more selective activation of specific muscles. For example, stimulation of the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles with BIONs produces ankle flexion without excessive inversion or eversion of the foot (i.e., balanced flexion). Efficacy was assessed using a 3-dimensional motion analysis of the ankle and foot trajectories during walking with and without stimulation. Without stimulation, the toe on the affected leg drags across the ground. BION stimulation of the TA muscle and deep peroneal nerve (which innervates TA and EDL) elevates the foot such that the toe clears the ground by 3 cm, which is equivalent to the toe clearance in the less affected leg. The physiological cost index (PCI) measured effort during walking. The PCI equals the change in heart rate (from rest to activity) divided by the walking speed; units are beats per metre. The PCI is high without stimulation (2.29 +/- 0.37, mean +/- SD) and greatly reduced with surface (1.29 +/- 0.10) and BIONic stimulation (1.46 +/- 0.24). Also, walking speed increased from 9.4 +/- 0.4 m/min without stimulation to 19.6 +/- 2.0 m/min with surface and 17.8 +/- 0.7 m/min with BIONic stimulation. These results suggest that FES delivered by a BION is an alternative to surface stimulation and provides selective control of muscle activation.

RF-powered BIONs for stimulation and sensing.

Virtually all bodily functions are controlled by electrical signals in nerves and muscles. Electrical stimulation can restore missing signals but this has been difficult to achieve practically because of limitations in the bioelectric interfaces. Wireless, injectable microdevices are versatile, robust and relatively inexpensive to implant in a variety of sites and applications. Several variants are now in clinical use or under development to perform stimulation and/or sensing functions and to operate autonomously or with continuous coordination and feedback control.

BIONic WalkAide for correcting foot drop.

The goal of this study was to test the feasibility and efficacy of using microstimulators (BIONs) to correct foot drop, the first human application of BIONs in functional electrical stimulation (FES). A prototype BIONic foot drop stimulator was developed by modifying a WalkAide2 stimulator to control BION stimulation of the ankle dorsiflexor muscles. BION stimulation was compared with surface stimulation of the common peroneal nerve provided by a normal WalkAide2 foot drop stimulator. Compared to surface stimulation, we found that BION stimulation of the deep peroneal nerve produces a more balanced ankle flexion movement without everting the foot. A 3-D motion analysis was performed to measure the ankle and foot kinematics with and without stimulation. Without stimulation, the toe on the affected leg drags across the ground. The BIONic WalkAide elevates the foot such that the toe clears the ground by 3 cm, which is equivalent to the toe clearance in the unaffected leg. The physiological cost index (PCI) was used to measure effort during walking. The PCI is high without stimulation (2.29 +/- 0.37; mean +/- S.D.) and greatly reduced with surface (1.29 +/- 0.10) and BION stimulation (1.46 +/- 0.24). Also, walking speed is increased from 9.4 +/- 0.4 m/min. without stimulation to 19.6 +/- 2.0 m/min. with surface and 17.8 +/- 0.7 m/min. with BION stimulation. We conclude that functional electrical stimulation with BIONs is a practical alternative to surface stimulation and provides more selective control of muscle activation.

First subject evaluated with simulated BION treatment in genioglossus to prevent obstructive sleep apnea.

We are using percutaneous electrical stimulation to simulate BION activation of posterior genioglossus during sleep to prevent occurrences of obstructive sleep apnea (OSA). Patients with OSA due to tongue prolapse are recruited in this ongoing clinical study for an overnight session in a sleep laboratory. Bipolar hooked wires are inserted percutaneously into the tongue muscle, from under the chin at midline, and used for neuromuscular stimulation. Data are collected with polysomnography and analyzed to compare the efficacy of proposed treatment to conventional CPAP or the untreated state. Encouraging preliminary results from the first study participant are described.

Development of clinician-friendly software for musculoskeletal modeling and control.

Research and development in various fields dealing with human movement has been hampered by the lack of adequate software tools. We have formed a core development team to organize a collective effort by the research community to develop musculoskeletal modeling software that satisfies the requirements of both researchers and clinicians. We have identified initial requirements and have developed some of the basic components. We are developing common standards to facilitate sharing and reuse of musculoskeletal models and their component parts. Free distribution of the software and its source code will allow users to contribute to further development of the software as new models and data become available in the future.

Leaf pubescence mediates the abundance of non-prey food and the density of the predatory mite Typhlodromus pyri.

Plants with leaves having numerous trichomes or domatia frequently harbor greater numbers of phytoseiid mites than do plant with leaves that lack these structures. We tested the hypothesis that this pattern occurs, in part, with Typhlodromus pyri because trichomes increase the capture of pollen or fungal spores that serve as alternative food. Using a common garden orchard, we found that apple varieties with trichome-rich leaves had 2-3 times more pollen and fungal spores compared to varieties with trichome-sparse leaves. We also studied the effects of leaf trichome density and pollen augmentation on T. pyri abundance to test the hypothesis that leaf trichomes mediate pollen and fungal spore capture and retention and thereby influence phytoseiid numbers. Cattail pollen (Typha sp.) was applied weekly to mature 'McIntosh' and 'Red Delicious' trees grown in an orchard and, in a separate experiment, to potted trees of the same varieties. 'McIntosh' trees have leaves with many trichomes whereas leaves on the 'Red Delicious' trees have roughly half as many trichomes. With both field-grown and potted trees, adding cattail pollen to 'Red Delicious' trees increased T. pyri numbers compared to 'Red Delicious' trees without pollen augmentation. In contrast, cattail pollen augmentation had no effect on T. pyri populations on 'McIntosh' trees. Augmentation with cattail pollen most likely supplemented a lower supply of naturally available alternative food on 'Red Delicous' leaves and thereby enhanced predator abundance. These studies indicate that larger populations of T. pyri on pubescent plants are due, in part, to the increased capture and retention of pollen and fungal spores that serve as alternative foods.

Advanced modeling environment for developing and testing FES control systems.

Realistic models of neuromusculoskeletal systems can provide a safe and convenient environment for the design and evaluation of controllers for functional electrical stimulation (FES) prior to clinical trials. We have developed a set of integrated musculoskeletal modeling tools to facilitate the model building process. Simulink models of musculoskeletal systems are created using two software packages developed in our laboratory, Musculoskeletal Modeling in Simulink (MMS) and virtual muscle, in addition to one software package available commercially, SIMM (Musculographics Inc., USA). MMS converts anatomically accurate musculoskeletal models generated by SIMM into Simulink(R) blocks. It also removes run-time constraints on kinetic simulations in SIMM, and allows the development of complex musculoskeletal models without writing a line of code. Virtual muscle builds realistic Simulink models of muscles responding to either natural recruitment or FES. Models of sensorimotor control systems can be developed using various Matlab (Mathworks Inc., USA) toolboxes and integrated easily with these musculoskeletal blocks in the graphical environment of Simulink.

Neck muscles in the rhesus monkey. II. Electromyographic patterns of activation underlying postures and movements.

Electromyographic (EMG) activity was recorded in < or = 12 neck muscles in four alert monkeys whose heads were unrestrained to describe the spatial and temporal patterns of neck muscle activation accompanying a large range of head postures and movements. Some head postures and movements were elicited by training animals to generate gaze shifts to visual targets. Other spontaneous head movements were made during orienting, tracking, feeding, expressive, and head-shaking behaviors. These latter movements exhibited a wider range of kinematic patterns. Stable postures and small head movements of only a few degrees were associated with activation of a small number of muscles in a reproducible synergy. Additional muscles were recruited for more eccentric postures and larger movements. For head movements during trained gaze shifts, movement amplitude, velocity, and acceleration were correlated linearly and agonist muscles were recruited without antagonist muscles. Complex sequences of reciprocal bursts in agonist and antagonist muscles were observed during very brisk movements. Turning movements of similar amplitudes that began from different initial head positions were associated with systematic variations in the activities of different muscles and in the relative timings of these activities. Unique recruitment synergies were observed during feeding and head-shaking behaviors. Our results emphasize that the recruitment of a given muscle was generally ordered and consistent but that strategies for coordination among various neck muscles were often complex and appeared to depend on the specifics of musculoskeletal architecture, posture, and movement kinematics that differ substantially among species.