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Infections in the bionic man.
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Insulin replacement: bionic or natural.
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Biologic versus bionic heart substitutes. Will xenotransplantation play a role?
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[Bionic cast sprue design for fixed dentures in cast model preparations (branch-casting or delta-casting technology)].
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Bionics in spare parts medicine: management and clinical issues.
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Genetics of major depressive disorder in a homogeneous population with uniform phenotyping.
Harmonized phenotyping and diverse population-specific studies are crucial for advancing gene discovery in psychiatric genetics. We conducted a genome-wide association (GWAS) mega-analysis of DSM-defined lifetime major depressive disorder (MDD) in 64 941 participants (25.7% cases) from the Dutch BIObanks Netherlands Internet Collaboration (BIONIC) consortium. Liability-scale SNP-based heritability was 12.0% (SE = 1.4%) as estimated by LDSC (assuming a lifetime prevalence of 15%) and 26.6% (SE = 1.1%) when estimated by LDAK-REML on individual-level genotype data, indicating substantial common-variant signal in this clinically harmonized sample. The genetic correlation with the latest major depression GWAS from the Psychiatric Genomics Consortium (PGC-MD) was high (rG = 0.89, SE = 0.048). Polygenic scores (PGSs) based on BIONIC predicted depression in UK Biobank, and PGSs derived from PGC-MD predicted MDD in BIONIC, supporting transferability of depression polygenic signal across cohorts and phenotype definitions. Within-family PGS analyses in twins suggested that the observed prediction was not primarily driven by detectable family-level confounding, and twin concordance for MDD increased with polygenic burden. We identified one genome-wide significant locus, indexed by rs3818852 in PALMD, but this finding currently lacks independent replication and should be interpreted cautiously. Finally, genetic correlation and latent causal variable analyses identified multiple traits showing shared or directionally consistent genetic associations with MDD. Together, these findings underscore the value of clinically harmonized phenotyping in regional biobank collaborations for studying the genetic architecture of MDD.
Electrophysiologic effects of placing cochlear implant electrodes in a perimodiolar position in young children.
OBJECTIVE: The purpose of this study was to intraoperatively record the electrically evoked auditory brainstem response (EABR) before and after placement of the electrode positioning system (EPS) (CII Bionic Ear with HiFocus I cochlear implant electrode array) as well as before and after stylet removal (Nucleus Contour cochlear implant electrode array). It was hypothesized that physiologic changes would occur after perimodiolar positioning of the electrode array and these changes would be evident from the EABR recordings. STUDY DESIGN: Consecutive young (11-36 month old) pediatric cochlear implant recipients (n = 17) had intraoperative EABRs recorded from three intracochlear electrodes that represented apical, medial, and basal locations. Wave V amplitudes and thresholds were studied relative to electrode location and pre- versus postperimodiolar positioning. These evoked potential measures were analyzed for statistical significance. SETTING: Tertiary referral children's hospital/medical college. RESULTS: Wave V thresholds of the EABR were lower, and amplitudes were larger after perimodiolar positioning, although the changes were dependent on electrode location and implant design. Statistically significant decreases in EABR wave V threshold and increases in suprathreshold wave V amplitude were found for the basal electrode for the CII Bionic Ear HiFocus I and for the apical electrode for the Nucleus Contour. CONCLUSIONS: Placement of either the CII Bionic Ear HiFocus I or Nucleus Contour cochlear implant electrode array in the perimodiolar position in young children resulted in less electrical current necessary to stimulate the auditory system. Changes in electrophysiologic thresholds and amplitudes, measured with EABR, indicate that the electrode array is placed closer to the modiolus with both electrode designs.
[Medical nanodevices].
Development of implantable medical nanodevices enables us continuous automatic treatment of patients from inside of their body. Bionic devices, interfacing with neural systems and substituting native functions, such as bionic pacemaker, bionic pressure controller are candidates to miniaturize. For such miniaturization, efforts to reduce size of power supply (e.g., biological fuel cell) and to establish reliable high-throughput, low power telecommunication (e.g., spread spectrum telecommunication) are required. Simple devices such as pacemakers would benefit from miniaturization by lowering invasion and by developing a new usage such as ventricular resynchronization.
Economic aspects of amino acids production.
Amino acids represent basic elements of proteins, which as a main source of nutrition themselves serve as a major reserve for maintaining essential functions of humans as well as animals. Taking the recent state of scientific knowledge into account, the industrial sector of amino acids is a priori "suitable" to a specific kind of an ecologically sound way of production, which is based on biotechnology. The following article may point out characteristics of this particular industrial sector and illustrates the applicability of the latest economic methods, founded on development of the discipline of bionics in order to describe economic aspects of amino acids markets. The several biochemical and technological fields of application of amino acids lead to specific market structures in high developed and permanently evolving systems. The Harvard tradition of industrial economics explains how market structures mould the behaviour of the participants and influences market results beyond that. A global increase in intensity of competition confirms the notion that the supply-side is characterised by asymmetric information in contrast to Kantzenbachs concept of "narrow oligopoly" with symmetrical shared knowledge about market information. Departing from this point, certain strategies of companies in this market form shall be derived. The importance of Research and Development increases rapidly and leads to innovative manufacturing methods which replace more polluting manufacturing processes like acid hydrolysis. In addition to these modifications within the production processes the article deals furthermore with the pricing based on product life cycle concept and introduces specific applications of tools like activity based costing and target costing to the field of amino acid production. The authors come to the conclusion that based on a good transferability of latest findings in bionics and ecological compatibility competitors in amino acids manufacturing are well advised to exercise concepts of the management of complex systems in order to choose the right strategy towards gaining market leadership.
Neural remodeling in retinal degeneration.
Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, Müller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in phase 1 or 2 in some animal models, but depletion of all neuronal classes is evident in phase 3. As remodeling progresses over months and years, more neurons are lost and patches of the ganglion cell layer can become depleted. Some survivor neurons of all classes elaborate new neurites, many of which form fascicles that travel hundreds of microns through the retina, often beneath the distal glial seal. These and other processes form new synaptic microneuromas in the remnant inner nuclear layer as well as cryptic connections throughout the retina. Remodeling activity peaks at mid-phase 3, where neuronal somas actively migrate on glial surfaces. Some amacrine and bipolar cells move into the former ganglion cell layer while other amacrine cells are everted through the inner nuclear layer to the glial seal. Remodeled retinas engage in anomalous self-signaling via rewired circuits that might not support vision even if they could be driven anew by cellular or bionic agents. We propose that survivor neurons actively seek excitation as sources of homeostatic Ca(2+) fluxes. In late phase 3, neuron loss continues and the retina becomes increasingly glial in composition. Retinal remodeling is not plasticity, but represents the invocation of mechanisms resembling developmental and CNS plasticities. Together, neuronal remodeling and the formation of the glial seal may abrogate many cellular and bionic rescue strategies. However, survivor neurons appear to be stable, healthy, active cells and given the evidence of their reactivity to deafferentation, it may be possible to influence their emergent rewiring and migration habits.
Regenerative biology and engineering: strategies for tissue restoration.
Over the past 50 years, we have made remarkable advances in the use of bionic devices and solid organ transplants as replacement parts for failing tissues and organs. These approaches to tissue restoration, however, have a number of drawbacks. Thus, a new approach, regenerative biology and engineering, has been developed, consisting of the strategies of cell transplantation, bioartificial tissue constructs, and stimulation of regeneration in vivo. Cell transplants have been successfully used to restore articular cartilage and to treat Parkinson's disease in humans. In rats, transplanted fetal and embryonic stem cell line-derived cardiomyocytes have been shown to differentiate and integrate well with the ventricular myocardium, suggesting the feasibility of using such transplants to restore damaged cardiac muscle. Diabetic symptoms in humans have been alleviated by implanting a bioartificial pancreas consisting of islet cells microencapsulated in alginate. Hydroxyapatite matrixes can stimulate the regeneration of bone across large gaps. Collagenous artificial matrixes can stimulate the regeneration of dermis, and peripheral nerve grafts embedded in a fibrin clot containing fibroblast growth factor-1 stimulate some regeneration of spinal cord axons in adult rats. Future research in regenerative biology will focus on several issues: (1) providing adequate sources of cells for transplantation and bioartificial tissue construction and determining ways to prevent these cells from coming under attack by the immune system, (2) developing new and better materials to build better bionic devices and bioartificial constructs and to stimulate regeneration in vivo, (3) determining how many tissues of the body might contain reserve cells for regeneration in vivo, (4) analyzing the molecular differences between cells and environments of regenerating versus nonregenerating tissues, and (5) understanding the factors and mechanisms involved in the proliferation and patterning of regenerating tissues.
Abnormal neuronal ionic flux activity: learning paradigms of schizophrenic thought disorders.
New developments in biological psychiatry have prompted the development of our pathophysiological theory of the etiology of schizophrenic thought disorders. We suggest that the presence of brain bionic lesions may produce microneuropathies in certain neuronal electrical pathways, leading to abnormal biological communication. These blockages force the rerouting of incoming electric signals through bypass pathways which divert the message from target to non-target neurons for decoding and integration. Using this model, we were able to link specific schizophrenic disturbances to different types of brain bionic lesion effects. This model should be further investigated to facilitate the understanding of the nature and origin of schizophrenic disorders and to stimulate further interest in this fascinating field.
Artificial organs as a bridge to transplantation.
Current organ shortage is estimated to keep outpacing demand for years to come. Among the advocated strategies, artificial and bioartificial devices may prove beneficial to a wide category of patients on transplant waiting lists. Bionic organ science allows to reproduce organ architecture and function through a complex interplay of cellular and mechanical elements. Some bioartificial organs may well be used to replace anatomical defects, while others allow to compensate for failing organ functions and to bridge patients to transplantation. Among these latter, bioartificial liver (BAL) systems bear the highest potential for clinical application, even if their use is raising several controversial issues. These latter regard the identification and stratification of patients fit for transplantation, timing and type of transplantation after recovery, appropriateness of double-blind, randomized clinical trials and safety of animal and/or human cell lines. Nonetheless, bionic organ science needs to be regarded as a useful adjunct in the armamentarium of organ replacement therapies for the third millennium.
Contact dermatitis to silicone after cochlear implantation.
Complications, although rare, do occur with cochlear implantation. We present a 2-year old with persistent erythema and pruritus over the implantation site with serous discharge from the implanted ear. Patch testing revealed contact dermatitis to silicone LSR-30 encasing the Nuclear Contour-24 device. Hypersensitivity was also noted to silicone LSR-30 in the Med-el device but not to silicone LSR-70 in the Advance Bionics device. Device explantation resulted in complete resolution of symptoms. The patient was then successfully reimplanted with the Advance Bionics device. Erythema and irritation at the implantation site, without leukocytosis, should prompt evaluation for silicone contact dermatitis.
Cation permeability of a cloned rat epithelial amiloride-sensitive Na+ channel.
1. Conductance of heterotrimeric rat epithelial Na+ channels (alpha, beta, gamma-rENaCs) for Li+ and Na+ in planar lipid bilayers was a non-linear function of ion concentration, with a maximum of 30.4 +/- 2.9 pS and 18.5 +/- 1.9 pS at 1 M Li+ and Na+, respectively. 2. The alpha, beta, gamma-rENaC conductance measured in symmetrical mixtures of Na(+)-Li+ (1 M) exhibited an anomalous mole fraction dependence, with a minimum at 4:1 Li+ to Na+ molar ratio. 3. Permeability ratios PK/PNa and PLi/PNa of the channel calculated from the bionic reversal potentials were dependent on ion concentration: PK/PNa was 0.11 +/- 0.01, and PLi/PNa was 1.6 +/- 0.3 at 50 mM; PK/PNa was 0.04 +/- 0.01 and PLi/PNa was 2.5 +/- 0.4 at 3 M, but differed from the ratios of single-channel conductances in symmetrical Li+, Na+ or K+ solutions. The permeability sequence determined by either method was Li+ > Na+ > K+ >> Rb+ Cs+. 4. Predictions of a model featuring two binding sites and three energy barriers (2S3B), and allowing double occupancy, developed on the basis of single ion current-voltage relationships, are in agreement with the observed conductance maximum in single ion experiments, conductance minimum in the mole fraction experiments, non-linearity of the current-voltage curves in bionic experiments, and the concentration dependence of permeability ratios. 5. Computer simulations using the 2S3B model recreate the ion concentration dependencies of single-channel conductance observed for the immunopurified bovine renal amiloride-sensitive Na+ channel, and short-circuit current in frog skin, thus supporting the hypothesis that ENaCs form a core conduction unit of epithelial Na+ channels.
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.