Use of Crotalidae equine immune F(ab')2 antivenom for treatment of an Agkistrodon envenomation.

INTRODUCTION: Anavip (F(ab')2AV) is a lyophilized F(ab')2 immunoglobulin fragment derived from horses immunized with venom from Bothrops asper and Crotalus durissus. It was approved by the FDA in 2015 for treatment of North American rattlesnake envenomation but not for Agkistrodon envenomation. Published data regarding the efficacy and safety of Anavip in treating Agkistrodon envenomations is limited. We present a case of a patient treated with Anavip after confirmed Agkistrodon laticinctus envenomation. CASE DETAILS: A 77 year-old man was bitten on his fifth finger by a captive A. laticinctus. He was taken to a local emergency department where he received a 10 vial initial dose of F(ab')2AV for pain and swelling and was transferred. At the receiving facility, his pain had improved and his swelling had not progressed. Over the next 30 h, his platelets declined to 132,000/mm3 and he received an additional 4 vials of F(ab')2AV. The remainder of his course was unremarkable with complete recovery by 3 months. DISCUSSION: This case provides an additional published datapoint on the use of this F(ab')2AV in the treatment of envenomation by Agkistrodon.

Intentional use of carbapenem antibiotics for valproic acid toxicity: A case report.

WHAT IS KNOWN AND OBJECTIVE: The interaction between valproic acid (VPA) and carbapenem antibiotics is well described with previous reports suggesting a reduction in VPA half-life between 47% and 90%. As described in this case, this interaction might be beneficial in the setting of toxic VPA ingestion. CASE DESCRIPTION: An intubated, unresponsive patient arrived via emergency medical services after toxic VPA ingestion. Meropenem was prescribed for a suspected pneumonia and to take advantage of the VPA interaction. We observed a 56% decline in half-life with short-term meropenem dosing and an improvement in mental status shortly after administration. WHAT IS NEW AND CONCLUSION: Our findings suggest a potential role for short-term carbapenem therapy for VPA overdose.

Cardiac Sodium Channel Mutations: Why so Many Phenotypes?

The cardiac Na(+) channel (Nav1.5) conducts a depolarizing inward Na(+) current that is responsible for the generation of the upstroke Phase 0 of the action potential. In heart tissue, changes in Na(+) currents can affect conduction velocity and impulse propagation. The cardiac Nav1.5 is also involved in determination of the action potential duration, since some channels may reopen during the plateau phase, generating a persistent or late inward current. Mutations of cardiac Nav1.5 can induce gain or loss of channel function because of an increased late current or a decrease of peak current, respectively. Gain-of-function mutations cause Long QT syndrome type 3 and possibly atrial fibrillation, while loss-of-function channel mutations are associated with a wider variety of phenotypes, such as Brugada syndrome, cardiac conduction disease, dilated cardiomyopathy, and sick sinus node syndrome. The penetrance and phenotypes resulting from Nav1.5 mutations also vary with age, gender, body temperature, circadian rhythm, and between regions of the heart. This phenotypic variability makes it difficult to correlate genotype-phenotype. We propose that mutations are only one contributor to the phenotype and additional modifications on Nav1.5 lead to the phenotypic variability. Possible modifiers include other genetic variations and alterations in the life cycle of Nav1.5 such as gene transcription, RNA processing, translation, posttranslational modifications, trafficking, complex assembly, and degradation. In this chapter, we summarize potential modifiers of cardiac Nav1.5 that could help explain the clinically observed phenotypic variability. Consideration of these modifiers could help improve genotype-phenotype correlations and lead to new therapeutic strategies.

Gene and cell therapies for the failing heart to prevent sudden arrhythmic death.

Current therapies for treatment and prevention of sudden cardiac death have certain limitations, and a search for new therapeutic approaches is desirable to reduce the burden of sudden arrhythmic death. Gene therapy and stem cell therapy have been investigated as new, valuable tools in treating cardiac diseases such as arrhythmias. In this review, the basics of each modality, important related experimental and clinical studies, and potential advantages and limitations of these treatments will be discussed. The future success of gene and cell therapy to become practical clinical tools greatly depends on our understanding of the mechanisms of ventricular arrhythmia and the mechanisms of action of gene and cell therapy.

Investigations of roll-over shape: implications for design, alignment, and evaluation of ankle-foot prostheses and orthoses.

PURPOSE: The purpose of this article is to provide an overview of our previous work on roll-over shapes, which are the effective rocker shapes that the lower limb systems conform to during walking. METHOD: This article is a summary of several recently published articles from the Northwestern University Prosthetics Research Laboratory and Rehabilitation Engineering Research Program on the topic of roll-over shapes. The roll-over shape is a measurement of centre of pressure of the ground reaction force in body-based coordinates. This measurement is interpreted as the effective rocker shape created by lower limb systems during walking. RESULTS: Our studies have shown that roll-over shapes in able-bodied subjects do not change appreciably for conditions of level ground walking, including walking at different speeds, while carrying different amounts of weight, while wearing shoes of different heel heights, or when wearing shoes with different rocker radii. In fact, results suggest that able-bodied humans will actively change their ankle movements to maintain the same roll-over shapes. CONCLUSIONS: The consistency of the roll-over shapes to level surface walking conditions has provided insight for design, alignment and evaluation of lower limb prostheses and orthoses. Changes to ankle-foot and knee-ankle-foot roll-over shapes for ramp walking conditions have suggested biomimetic (i.e. mimicking biology) strategies for adaptable ankle-foot prostheses and orthoses.

Net external energy of the biologic and prosthetic ankle during gait initiation.

The net external energy of the biologic human ankle joint and of some lower limb prosthetic ankle-foot systems was examined during gait initiation. The purpose of the study was to better understand the ankle's behavior during the acceleration phase of walking for use in the design of improved lower limb prostheses and orthoses. Quantitative gait data were collected from 10 able-bodied subjects and 10 persons with unilateral transtibial amputations during gait initiation. The behaviors of the biologic and prosthetic 'ankle' joints were examined by analyzing the relationship between sagittal plane ankle angles and moments. Net external energy at the ankle was estimated by calculating the area under the moment versus angle curves (hysteresis) created during the loading and unloading phases. Results indicate that able-bodied persons utilize energy input from the trailing ankle after the first step is made in gait initiation, most likely to help transition the body into steady-state walking. The passive prosthetic ankle-foot systems tested were unable to put energy into the system during gait initiation.

Language assessment in Wada test: comparison of methohexital and amobarbital.

INTRODUCTION: Methohexital has replaced amobarbital during Wada testing at many centers. The objective of our study was to compare the use of methohexital and amobarbital during Wada testing regarding language and memory lateralization quotients as well as speech arrest times. METHODS: A chart review of 582 consecutive patients undergoing 1041 Wada-procedures was performed (left=60, right=63, bilateral=459). Language lateralization was calculated based on duration of speech arrest using a laterality index, defined as (L-R)/(L+R). Memory lateralization was expressed as percentage of retained objects and laterality quotient. RESULTS: Language and memory lateralization revealed a similar distribution with amobarbital and methohexital. Speech arrest after left and right-sided injection was significantly longer in the amobarbital group as compared to the methohexital group. Language lateralization did not differ in the two groups. Percentage of retained memory items was higher in the methohexital group and there were fewer presented test items in the methohexital group. DISCUSSION: Language and memory testing during the Wada test can successfully be performed with methohexital instead of amobarbital. The shorter half-life of methohexital allows repeated injections and shorter interhemispheric testing intervals, but also shortens the testing window.

Phenotypic selection on leaf ecophysiological traits in Helianthus.

Habitats that differ in soil resource availability are expected to differ for selection on resource-related plant traits. Here, we examined spatial and temporal variation in phenotypic selection on leaf ecophysiological traits for 10 Helianthus populations, including two species of hybrid origin, Helianthus anomalus and Helianthus deserticola, and artificial hybrids of their ancestral parents. Leaf traits assessed were leaf size, succulence, nitrogen (N) concentration and water-use efficiency (WUE). Biomass and leaf traits of artificial hybrids indicate that the actively moving dune habitat of H. anomalus was more growth limiting, with lower N availability but higher relative water availability than the stabilized dune habitat of H. deserticola. Habitats differed for direct selection on leaf N and WUE, but not size or succulence, for the artificial hybrids. However, within the H. anomalus habitat, direct selection on WUE also differed among populations. Across years, direct selection on leaf traits did not differ. Leaf N was the only trait for which direct selection differed between habitats but not within the H. anomalus habitat, suggesting that nutrient limitation is an important selective force driving adaptation of H. anomalus to the active dune habitat.

CIR Casting System for making transtibial sockets.

This paper describes a new casting system for transtibial socket fabrication. Like the earlier CIR Sand Casting System, the CIR Casting System is based on the 'dilatancy' principle that is similar to the packaging process for coffee beans by which loose beans become a solid mass when a vacuum is applied. The main difference from the CIR Sand Casting System is that the CIR Casting System uses light-weight, polystyrene beads in place of silica sand as the primary material for casting the negative mold. The formed negative mold can be converted into a positive sand model for modification and socket formation. With the new plaster-less casting system, the prosthetist can fabricate a transtibial prosthesis in about one hour. It reduces the set-up cost, overall weight and size of the casting system, and increases portability for service in remote areas. The System also creates minimal waste and is energy-conserving and environmentally-friendly.

A uniaxial bioMEMS device for imaging single cell response during quantitative force-displacement measurements.

A microfabricated device has been developed for imaging of a single, adherent cell while quantifying force under an applied displacement. The device works in a fashion similar to that of a displacement-controlled uniaxial tensile machine. The device was calibrated using a tipless atomic force microscope (AFM) cantilever and shows excellent agreement with the calculated spring constant. A step input was applied to a single, adherent fibroblast cell and the viscoelastic response was characterized with a mechanical model. The adherent fibroblast was imaged by use of epifluorescence and phase contrast techniques.

Biocompatibility of atomic layer-deposited alumina thin films.

Presented in this paper is a study of the biocompatibility of an atomic layer-deposited (ALD) alumina (Al2O3) thin film and an ALD hydrophobic coating on standard glass cover slips. The pure ALD alumina coating exhibited a water contact angle of 55 degrees +/- 5 degrees attributed, in part, to a high concentration of -OH groups on the surface. In contrast, the hydrophobic coating (tridecafluoro-1,1,2,2-tetrahydro-octyl-methyl-bis(dimethylamino)silane) had a water contact angle of 108 degrees +/- 2 degrees. Observations using differential interference contrast microscopy on human coronary artery smooth muscle cells showed normal cell proliferation on both the ALD alumina and hydrophobic coatings when compared to cells grown on control substrates. These observations suggested good biocompatibility over a period of 7 days in vitro. Using a colorimetric assay technique to assess cell viability, the cellular response between the three substrates can be differentiated to show that the ALD alumina coating is more biocompatible and that the hydrophobic coating is less biocompatible when compared to the control. These results suggest that patterning a substrate with hydrophilic and hydrophobic groups can control cell growth. This patterning can further enhance the known advantages of ALD alumina, such as conformality and excellent dielectric properties for bio-micro electro mechanical systems (Bio-MEMS) in sensors, actuators, and microfluidics devices.

Roll-over shapes of the able-bodied knee-ankle-foot system during gait initiation, steady-state walking, and gait termination.

A few investigators have described the movement of the center of pressure (COP) of the ground reaction force and the activation patterns of the lower limb muscles during gait initiation and termination. This study examines the effective rocker (roll-over shape) behavior of the knee-ankle-foot (KAF) system during gait initiation, steady-state walking (i.e. constant speed gait), and gait termination. The KAF roll-over shapes were characterized by transforming COP data of 10 able-bodied subjects from a laboratory-based coordinate system into a leg-based coordinate system. The resulting roll-over shapes (effective rockers) were characterized using a circular arc model. The KAF roll-over shapes exhibit an overall "flexed" orientation during the first step of gait initiation and an "extended" orientation during the last step of gait termination. Understanding the behavior of the anatomical KAF system during gait initiation and termination may aid in the design of prosthetic components, i.e. mechanical devices that replace complete anatomical structures. Prostheses that intend to mimic the overall behavior of physiological KAF systems (biomimetic designs) could be manufactured using approaches that are much simpler than attempting to reconstruct the complexity of the lower limb.

A uniaxial bioMEMS device for quantitative force-displacement measurements.

There is a need for experimental techniques that allow the simultaneous imaging of cellular cystoskeletal components with quantitative force measurements on single cells. A bioMEMS device has been developed for the application of strain to a single cell while simultaneously quantifying its force response. The prototype device presented here allows the mechanical study of a single, adherent cell in vitro. The device works in a fashion similar to a displacement-controlled uniaxial tensile machine. The device is calibrated using an AFM cantilever and shows excellent agreement with the calculated spring constant. The device is demonstrated on a single fibroblast. The force response of the cell is seen to be linear until the onset of de-adhesion with the de-adhesion from the cell platform occurring at a force of approximately 1500 nN.

The effects of prosthetic foot roll-over shape arc length on the gait of trans-tibial prosthesis users.

The Shape&Roll prosthetic foot was used to examine the effect of roll-over shape arc length on the gait of 14 unilateral trans-tibial prosthesis users. Simple modifications to the prosthetic foot were used to alter the effective forefoot rocker length, leaving factors such as alignment, limb length, and heel and mid-foot characteristics unchanged. Shortening the roll-over shape arc length caused a significant reduction in the maximum external dorsiflexion moment on the prosthetic side at all walking speeds (p < 0.001 for main effect of arc length), due to a reduction in forefoot leverage (moment arm) about the ankle. Roll-over shape arc length significantly affected the initial loading on the sound limb at normal and fast speeds (p = 0.001 for the main effect of arc length), with participants experiencing larger first peaks of vertical ground reaction forces on their sound limbs when using the foot with the shortest effective forefoot rocker arc length. Additionally, the difference between step lengths on the sound and prosthetic limbs was larger with the shortest arc length condition, although this difference was not statistically significant (p = 0.06 for main effect). It appears that prosthesis users may experience a drop-off effect at the end of single limb stance on prosthetic feet with short roll-over shape arc lengths, leading to increased loading and/or a shortened step on the contralateral limb.

Toward a self-deploying shape memory polymer neuronal electrode.

The widespread application of neuronal probes for chronic recording of brain activity and functional stimulation has been slow to develop partially due to long-term biocompatibility problems with existing metallic and ceramic probes and the tissue damage caused during probe insertion. Stiff probes are easily inserted into soft brain tissue but cause astrocytic scars that become insulating sheaths between electrodes and neurons. In this communication, we explore the feasibility of a new approach to the composition and implantation of chronic electrode arrays. We demonstrate that softer polymer-based probes can be inserted into the olfactory bulb of a mouse and that slow insertion of the probes reduces astrocytic scarring. We further present the development of a micromachined shape memory polymer probe, which provides a vehicle to self-deploy an electrode at suitably slow rates and which can provide sufficient force to penetrate the brain. The deployment rate and composition of shape memory polymer probes can be tailored by polymer chemistry and actuator design. We conclude that it is feasible to fabricate shape memory polymer-based electrodes that would slowly self-implant compliant conductors into the brain, and both decrease initial trauma resulting from implantation and enhance long-term biocompatibility for long-term neuronal measurement and stimulation.

The effects of static friction and backlash on extended physiological proprioception control of a powered prosthesis.

In general, externally powered prostheses do not provide proprioceptive feedback and thus require the user to rely on cognitively expensive visual feedback to effectively control the prosthesis. Applying the concept of extended physiological proprioception (EPP) to externally powered prostheses provides direct feedback to the user's proprioceptive system regarding the position, velocity, and forces applied to the prosthesis. However, electric elbows with EPP controllers developed at the Northwestern University Prosthetics Research Laboratory have exhibited unexplained "jerky" behavior in both clinical fittings and bench-top operation. In addition, the development of limit cycles, a specific type of constant-amplitude oscillation, had been observed in bench-top use of these elbows. Backlash and static friction within the EPP system were found to be primarily responsible for the development of limit cycles. Reducing static friction and backlash improved the system's performance. These results suggest that to most effectively implement EPP, prosthesis manufacturers should design prosthetic components that minimize static friction and backlash.

Effects of adding weight to the torso on roll-over characteristics of walking.

Ten participants without physical impairment walked with 0 kg, 11.5 kg, and 23.0 kg of added weight equally distributed about the torso in a harness. At each weight level, the participants walked at slow, normal, and fast self-selected walking speeds. We examined the roll-over characteristics by determining the ankle-foot and knee-ankle-foot roll-over shapes. These shapes, which are the effective rockers created by the respective lower-limb systems between heel contact and opposite heel contact of walking, are found if one transforms the center of pressure of ground reaction force into body coordinate systems. The roll-over shapes of the ankle-foot and knee-ankle-foot systems did not change appreciably with added weight at any of the three walking speeds. The invariance of these biologic systems to added weight should be considered when prostheses and orthoses are designed that intend to replace and augment their function in walking.