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Several techniques have been advocated for knee arthrodesis, and there has been an increasing interest in modular intramedullary nails in the recent last years. We report a case of femoral and tibial fractures at each end of a modular nail in a solidly fused knee 8 months after an arthrodesis.
The presynaptic N type Ca channel (CaV2.2) is associated with the transmitter release site apparatus and plays a critical role in the gating of transmitter release. It has been suggested that a distinct CaV2.2 long C terminal splice variant is targeted to the nerve terminal and is anchored at the release face by calcium/calmodulin-dependent serine protein kinase (CASK) and Munc-18-interacting protein (MINT), two modular adaptor proteins. We used the isolated chick ciliary ganglion calyx terminal together with two new antibodies (L4569, L4570) selective for CaV2.2 long C terminal splice variant to test these hypotheses. CaV2.2 long C terminal splice variant was present at the presynaptic transmitter release sites, as identified by Rab3a-interacting molecule (RIM) co-staining and quantitative immunocytochemistry. CASK was also present at the terminal both in conjunction with, and independent of its binding partner, MINT. Immunoprecipitation of CaV2.2 long C terminal splice variant from brain lysate coprecipitated CASK, confirming that these two proteins can form a complex. However, CASK was not colocalized either with CaV2.2 long C terminal splice variant or the transmitter release site marker RIM at the calyx terminal release face. Neither was MINT colocalized with CaV2.2 long C terminal splice variant. Our results show that native CaV2.2 long C terminal splice variant is targeted to the transmitter release sites at an intact presynaptic terminal. However, the lack of enrichment of CASK at the release site combined with the failure of this protein or its partner MINT to colocalize with CaV2.2 argues against the idea that these modular adaptor proteins anchor CaV2.2 at presynaptic nerve terminals.
Norris et al. recently reported experimental evidence that listeners learn phoneme categories in response to lexical feedback. To reconcile these findings with their modular account of speech perception, the authors argue that top-down feedback can be used to support phoneme learning, but not to influence on-line phonemic processing. We suggest that these findings have broader implications than the authors assume, and we discuss potential challenges for integrating a modular theory with top-down learning.
Modular organisms are composed of iterated units of construction that vary in their spatial arrangement. This variation is expected to affect the fitness of modular organisms due to interactions among neighboring modules and the potential for such organisms to be genetically heterogeneous. We devise a spatially explicit model to investigate how spatial interactions among neighboring modules affect organism fitness. We show that fitness is strongly dependent on the spatial arrangement of modules in both genetically homogeneous and heterogeneous organisms, and that the magnitude of the variation is dependent on the strength of interactions among modules. Organism fitness is more variable with interactions among modules that are symmetrical (each affects each other in the same directions) than with asymmetrical interactions (neighbors affect each other in different directions). We conclude by discussing potential extension of the present framework to a general dynamic model of spatially structured organism development.
BACKGROUND: It is known that most adult patients with epilepsy often have poor knowledge of their disorder, treatment options, and social and vocational consequences, despite the huge amount of information available. Being pressed for time, health care professionals often are not able to provide the repetitive counseling and instruction necessary to address epilepsy care adequately. Therefore educational programs are considered extremely important in filling the gap. METHOD: For German-speaking countries, two educational programs called famoses, modulares Schulungsprogramm Epilepsie fur Familien [modular service package epilepsy for families], were developed by a multidisciplinary group of neuropediatricians, psychologists, social workers, and educators. The aims of the famoses programs are to improve children's and parents' knowledge about epilepsy and to help patients of childhood age and their parents achieve a better understanding of their disease, gain more self-confidence, and reduce specific fears regarding epilepsy. famoses comprises two different educational programs: famoses for kids with epilepsy within the developmental period of ages 7 to 13, and famoses for parents or caretakers. The programs are designed for interactive small-group education. RESULTS: The child-centered educational program is based on a fictional story: The children are sailors on a virtual cruise, sailing from island to island, accompanied by educated trainers. On each island there is something new to discover about epilepsy. The parent (and caretaker)-centered educational program covers different topics-overview and content of the program, basic knowledge, diagnostics, therapy, prognosis and development, and living with epilepsy-within six modules. The program was implemented in Germany and Switzerland in the spring of 2005 and is now operating in different epilepsy centers. CONCLUSION: Within comprehensive therapeutic management of epilepsy, educational programs for patients, and for parents (caretakers) of children with epilepsy, are considered to be extremely important. Such educational programs have two main goals: to increase knowledge about the disorder, and to strengthen the patients' responsibility for themselves, with the consequence of living with as few limitations as possible. famoses is an effective component of this comprehensive care. The program has been operating successfully in different epilepsy centers in Germany and Switzerland since the spring of 2005.
This article examines four disorders of auditory processing that can result from selective brain damage (cortical deafness, pure word deafness, auditory agnosia and phonagnosia) in an effort to derive a plausible functional and neuroanatomical model of audition. The article begins by identifying three possible reasons why models of auditory processing have been slower to emerge than models of visual processing: neuroanatomical differences between the visual and auditory systems, terminological confusions relating to auditory processing disorders, and technical factors that have made auditory stimuli more difficult to study than visual stimuli. The four auditory disorders are then reviewed and current theories of auditory processing considered. Taken together, these disorders suggest a modular architecture analogous to models of visual processing that have been derived from studying neurological patients. Ideas for future research to test modular theory more fully are presented.
This biomechanical study was performed to evaluate a new modular, tibial testing system developed for analysis of tibial nails and their locking screws.A new testing system, consisting of five modules, was designed to simulate a tibia. For this study one module was removed to simulate a 55-mm distal tibial defect inducing maximum loading on the distal portion of the implant and locking bolts. The tibial load offsets were 23 mm proximally and 10 mm distally medial to the centreline of the tibial shaft to simulate the location of the expected resultant load during the peak loading and inversion torque on the ankle during the gait cycle. Four solid tibial nails (STN, Stryker-Howmedica-Osteonics, Kiel, Germany) were tested to static failure and 15 nails were tested dynamically. Our results showed that the solid tibial nails fractured in the testing device in the same manner and location as they do in clinical series. Evaluation of the results showed the mean fatigue limit of the STN to be 1.4 kN for 500,000 cycles with a standard deviation (S.D.) of 0.33 kN. This biomechanical study establishes a standard technique for the biomechanical testing of tibial nails, in a clinically relevant manner, avoiding the inconsistency of cadaver bone tests. As it is a standardised test set-up this new modular testing system could serve as a standard by which small diameter tibial nails and other devices could be evaluated and compared with other systems currently in use.
The stress distribution within the components and the micromotion of the interface significantly influence the long-term function of the taper lock joint in a modular segmental bone replacement prosthesis. Bending-induced gap opening between the cone and the sleeve can lead to an inflow of biological fluids, and thus accelerate implant corrosion. Local areas of high stress can also accelerate the corrosive processes and initiate local yielding, which may lead to a fracture in one of the components. In this study, a 3-D finite element (FE) model of a modular segmental bone replacement prosthesis was developed to study the interface micromotion and component stress distribution under the maximum loads applied during gait for a taper lock joint with multiple material combinations. Bending was the main cause of the local high stresses and interface separation within the taper joint. For Ti6A14V components, cortical bone bridging and ingrowth across the taper lock gap reduced the peak stress by 45% and reduced the contact interface separation by 55%. Such tissue formation around the taper lock joint could also form a closed capsule to restrict the migration of potential wear particles and thus prevent the biologic process of bone resorption induced by metal debris.
Nonconformity between the polyethylene liner and the metal shell may exist in modular acetabular components by design, due to manufacturing tolerances, or from locking mechanisms that attach the polyethylene liner to the metal shell. Relative motion at the liner/shell interface has been associated with backside wear, which may contribute to osteolysis which has been clinically observed near screw holes. The purpose of this study was to investigate the effect of nonconformity and locking restraints on the liner/shell relative motion and load transfer mechanisms in a commercially available, metal-backed acetabular component with a polar fenestration. The finite element method was used to explore the hypothesis that backside nonconformity and locking restraints play important roles in long-term surface damage mechanisms that are unique to modular components, such as backside wear and liner extrusion through screw holes. The three-body quasi-static contact problem was solved using a commercially available explicit finite element code, which modeled contact between the femoral head, polyethylene liner, and the metal shell. Four sets of liner boundary conditions were investigated: no restraints, rim restraints, equatorial restraints, and both rim and equatorial restraints. The finite element model with a conforming shell predicted between 8.5 and 12.8 microm of incremental extrusion of the polyethylene through the polar fenestration, consistent with in vitro experiments of the same design under identical loading conditions. Furthermore, idealized rim and/or equatorial liner restraints were found to share up to 71% of the load across the liner/shell interface. Consequently, the results of this study demonstrate that backside nonconformity and locking restraints substantially influence backside relative motion as well as load transfer at the liner/shell interface.
To determine the limits of cooperativity in a structurally modular protein, we characterized the structure and stability of glycine variants of the ankyrin repeat domain from the Drosophila melangaster Notch receptor. The substitutions are of analogous alanine residues to glycine in each repeat, and allow the same perturbation to be examined at different positions in the protein. The ankyrin domain is insensitive to substitution in repeat one, suggesting that the first repeat is not fully-folded. Glycine substitutions in repeat two through seven are strongly destabilizing, but the variants retain their overall secondary and tertiary structures. Spectroscopic and calorimetric data are consistent with two-state unfolding transitions for the repeat-two through repeat-five glycine variants, and for the wild-type protein. These data indicate that, despite its modular structure, the Notch ankyrin domain unfolds as a cooperative unit consisting of the six C-terminal repeats, and that this cooperativity is maintained in the presence of severely destabilizing substitutions in the N-terminal and central repeats. In contrast, glycine substitution in repeat six leads to a multi-state unfolding transition, suggesting that the coupling that gives rise to long-range cooperativity in the wild-type protein may have a weak link in the C-terminal region. Such behavior is captured by a simple statistical thermodynamic model in which an unstable C-terminal region is coupled to a stable N-terminal region through a strongly stabilizing interface.
Modular polyketide synthases (PKSs) are large multi-enzymatic, multi-domain megasynthases, which are involved in the biosynthesis of a class of pharmaceutically important natural products, namely polyketides. These enzymes harbor a set of repetitive active sites termed modules and the domains present in each module dictate the chemical moiety that would add to a growing polyketide chain. This modular logic of biosynthesis has been exploited with reasonable success to produce several novel compounds by genetic manipulation. However, for harnessing their vast potential of combinatorial biosynthesis, it is essential to develop knowledge based in silico approaches for correlating the sequence and domain organization of PKSs to their polyketide products. In this work, we have carried out extensive sequence analysis of experimentally characterized PKS clusters to develop an automated computational protocol for unambiguous identification of various PKS domains in a polypeptide sequence. A structure based approach has been used to identify the putative active site residues of acyltransferase (AT) domains, which control the specificities for various starter and extender units during polyketide biosynthesis. On the basis of the analysis of the active site residues and molecular modelling of substrates in the active site of representative AT domains, we have identified a crucial residue that is likely to play a major role in discriminating between malonate and methylmalonate during selection of extender groups by this domain. Structural modelling has also explained the experimentally observed chiral preference of AT domain in substrate selection. This computational protocol has been used to predict the domain organization and substrate specificity for PKS clusters from various microbial genomes. The results of our analysis as well as the computational tools for prediction of domain organization and substrate specificity have been organized in the form of a searchable computerized database (PKSDB). PKSDB would serve as a valuable tool for identification of polyketide products biosynthesized by uncharacterized PKS clusters. This database can also provide guidelines for rational design of experiments to engineer novel polyketides.
Modular Formula is a dietary preparation for use in treating infants with complex malabsorptive disorders and for weaning infants from total parenteral nutrition. With this formula the physician can alter the quality of the various nutrients normally fed to infants as well as concentrations of those nutrients. Infants who cannot tolerate existing proprietary formulas will often thrive with the judicious use of this flexible formula. Modular Formula provides the clinician with a useful aid in the diagnosis and treatment of chronic diarrhea of infancy.
PURPOSE: In 1998 the first ICI was held in Monaco, sponsored by WHO and organized by the International Continence Society and International Consultation on Urological Diseases. The Scientific Committee recognized the need to develop a universally applicable questionnaire for wide application across international populations in clinical practice and research to assess urinary incontinence, facilitating the comparison of findings from different settings and studies, in a manner similar to the International Prostate Symptom Score. MATERIALS AND METHODS: An Advisory Board was formed to steer the development of the ICIQ and a decision was made to extend the concept further, developing the ICIQ Modular Questionnaire. RESULTS: The first module developed was the ICIQ Short Form Questionnaire for urinary incontinence. ICIQ modules have been developed or adapted for urinary tract symptoms and they are being developed for vaginal and lower bowel symptoms. Additional sexual matters and quality of life modules will become available for each condition area. Modules to assess patient satisfaction are expected to be of particular use for assessing treatment effectiveness. The ICIQ Advisory Board recently proposed the development of the ICIQ website, which is anticipated to be crucial for informing potential users of the phase of development of all ICIQ modules. CONCLUSION: The ICIQ can offer a full range of urinary tract symptom questionnaires. The website will aim to attract collaborators committed to the concept of this internationally accepted modular questionnaire who are willing to help with its development.
Project 2000 has given nurse educators an opportunity to consider and plan educational programmes that will endure until the year 2000 and beyond. The United Kingdom Central Council for Nursing, Midwifery and Health Visiting (1986) highlighted the need for preparing practitioners for uncertainty by developing structures that adapt to rapid change. This includes planning smaller units of study, that are accessible and allow for credit transfers. This article describes the development of a semester based, modular programme of study, for Project 2000. The idea of modularity, both from the higher education and nurse education perspective is examined. An outline of the course is offered and for the benefit of colleagues who may be considering embarking on a similar remit, areas of difficulty encountered on implementation are highlighted with some resolutions.
In vertebrates, growth hormone (GH) gene expression requires the pituitary-specific transcription factor Pit-1/GHF1 but is differently regulated by a variety of factors in different vertebrate species. Here, we have studied the transcriptional activity of the trout GH (tGH) promoter, which is synergistically stimulated by cAMP and glucocorticoid. Gel shift assays indicated that Pit-1 binds as a dimer to three high affinity sites in the -226/+24 tGH region, and that recombinant cAMP response element (CRE)-binding protein (CREB) binds to a CRE situated between the two distal Pit-1 sites. Deletional and mutational transfection experiments, performed in pituitary Pit-1-expressing GC cells, showed that the different Pit-1 sites play distinct roles and are obligatory elements in the mechanisms mediating cAMP and glucocorticoid responses. Remarkably, the results suggest a hierarchical modular model of regulation of the tGH promoter, according to which a critical module, triggered by Pit-1 bound to the proximal Pit-1 site, is necessary and sufficient to turn on and drive basal levels of transcription. The latter may be stimulated synergistically by two Pit-1-dependent reciprocally non-cooperative auxiliary modules, activated by cAMP and glucocorticoid, respectively. Such modularity explains, in evolutionary terms, the crucial role played by Pit-1 in transcriptional activation and the emergence of the wide variety of mechanisms regulating transcriptional levels of GH, prolactin and other Pit-1-target genes in vertebrates.
PURPOSE: The study evaluated the deployment and healing of a novel self-expanding modular bifurcation endovascular prosthesis in a canine abdominal aortic aneurysm model. The endoluminal prosthesis consists of self-expanding nitinol stents lined by a synthetic prosthesis. One component of the device is a bifurcated body with a 12- to 14-mm diameter aortic segment and an integral 7- to 8-mm diameter iliac limb. The bifurcated body also has a stent-reinforced opening (pant-leg) for subsequent insertion of a contralateral 7- to 8-mm diameter iliac limb component. METHODS: Seventeen bifurcated prosthesis were placed; 7 were inserted through the left common carotid artery and 10 from the femoral arteries. With either route of access the 16F or 17F aortoiliac limb and the 13F iliac limb delivery catheters enabled easy passage and secure positioning of the bifurcated prostheses. Predeployment and postdeployment inspection of the dimensions and continuity of the aortoiliac prosthetic components were evaluated by cinefluoroscopy and intravascular ultrasonography (IVUS). RESULTS: After deployment was done, interval patency was assessed with angiography, IVUS, and contrast-enhanced computed tomography with the prostheses removed for analysis at 1 week (n = 4), 1 month (n = 3), 3 months (n = 4), and 6 months (n = 6). Five of the first seven implanted prostheses had occlusion of segments of the device. In two dogs the bifurcated body and both legs were occluded. In the other three the nonoccluded leg and bifurcation body were fully patent. In the first seven animals IVUS at implantation showed compression of an iliac leg by the orifice of the contralateral iliac component. After concentric fixation of the flow divider was performed, only one additional iliac limb occlusion occurred in the next 10 animals. Cinefluoroscopy, computed tomography, IVUS imaging, and histologic analysis of retrieved specimens demonstrated healing of the aortoiliac prostheses without evidence of perigraft leaks. CONCLUSIONS: This feasibility study demonstrates the ability to deploy and maintain acceptable patency of a self-expanding endoluminal, modular bifurcation prosthesis in a canine aortic model. Clinical evaluation of the device is planned for the near future.
Eighty primary total hip arthroplasties were performed using a first-generation modular femoral stem inserted without cement. Modular distal sleeves made of methacrylate were used in 33% of the hips. Dorr type B or C femoral geometry was present in 80% of the cases. The mean follow-up period was 81 months with a minimum of 48 months. Satisfactory clinical results were observed in 74% of the hips at the final follow-up visit. Revision of the stem had been performed in 14% of the hips, all for aseptic loosening. The overall mechanical failure rate was 48%. Canal fill by the stem was not any better with the sleeves than without. The incidence of failure, however, was less in those hips in which sleeves were used. Femoral osteolysis was present in 19% of the hips. The experience with this particular stem design has been disappointing.
One of the primary reasons for utilizing modular tibial polyethylene inserts (MTPI) at the time of total knee arthroplasty is to have the ability to simply exchange the polyethylene at the time of revision surgery when polyethylene failure has occurred. During a 2-year period from January 1993 to December 1994, 62 revision total knee arthroplasties were reviewed from five different institutions in North America, which were performed secondary to modular tibial insert failure. In 55 cases (88.7%), significant scoring and/or damage to the femoral and/or tibial components occurred necessitating revision of one or both components. This series does not support the premise that polyethylene exchange is common at the time of revision surgery for MTPI failure. Of the patients 88.7% had MTPI failure resulted in femoral and/or tibial component revision secondary to surface damage to the femoral component and/or tibial component baseplate. In order to avoid femoral and tibial component wear secondary to MTPI failure, early recognition is necessary to allow the much simpler operation consisting of polyethylene liner exchange only.