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Clinical experience with a modular noncemented femoral component in revision total hip arthroplasty: 4- to 7-year results.

A series of 163 revision total hip arthroplasties performed using a modular proximally porous-coated device was reviewed. Twenty patients died before achieving minimum follow-up, and 13 hips with Paprosky type IV femora were excluded. One patient was lost to follow-up. Minimum 4-year clinical data on the remaining 129 hips showed an improvement in modified Harris hip scores, from an average of 47.7 to 87.5. Spot welds at the sleeve-bone interface were found in 83 of the 102 hips with minimum radiographic follow-up. The aseptic failure rate was 2.9%; these hips showed progressive subsidence, with 1 resulting in the only repeat revision in the series. Three hips had osteolytic lesions of <5 mm; none threatened implant stability. There were no complications related to modularity.

Adult↗

The long-term success of modular proximal fixation stems in revision total hip arthroplasty.

A prospective study was carried out on the use of a proximally modular, proximal ingrowth noncemented stem in hip revision surgery. There were 109 short stems and 211 long stems. The mean follow-up was 7 years (range, 2-12 years). No revisions were required in the short-stem group for aseptic loosening; 3 (1.4%) revisions were required in the long-stem group. Lucency was absent in 91.7% of short-stem cases, was low grade in 7.2%, and was high grade in 1.1%. In the long-stem group, lucency was absent in 72.9% of cases, was low grade in 24.5%, and was high grade in 2.6%. No measurable subsidence occurred in the short-stem group, and 5 mm of subsidence occurred early in 2 of the long-stem group. This subsidence stabilized subsequently. Osteolysis distal to the sleeve was not observed. A proximal ingrowth, proximally modular stem can be used in revision hip surgery.

Adult↗

Serum levels of cobalt and chromium in a complex modular total hip arthroplasty system.

There is concern that modularity in a total hip arthroplasty system increases serum cobalt and chromium ion levels. This study measures the serum cobalt and chromium levels in patients with an Oxford Universal Hip (Corin, Cirencester, United Kingdom), which has a modular sliding mechanism; patients with a similarly manufactured hip with no sliding mechanism; and a control group. Loosening was excluded clinically and radiologically. Arthroplasty patients had statistically higher levels of serum cobalt and chromium than controls, but there was no significant difference in levels between the implanted groups.

Arthroplasty, Replacement, Hip↗

Computerized detection of clustered microcalcifications: a modular approach with non-linear filters.

The ideal computerized mammogram processing system still needs to be developed. In order to achieve maximum flexibility we suggest a modular scheme, dividing the processing sequence into functionally autonomous modules. This paper provides a general scheme for detection and/or automated recognition of microcalcifications. Some modules that perform ROI selection are introduced, using special non-linear filters designed for microcalcification detection. A first type of filter selects pixels with specific statistical local features, as compared to the local mean. Among these, only pixels satisfying particular constraints on the local standard deviation are kept. Another type of filter then checks the local mean values of gradient components, so that sharp variations, unrelated to small close objects, can be eliminated. The scheme thus applies different non-linear filters in combination, making precise identification of clustered microcalcifications possible. This modular approach seems greatly to simplify system maintenance and consistency, as well as affording a comparison of different processing techniques and parameters.

Algorithms↗

[Late outcome after implantation of the PFC modular knee system].

AIM: The objective of the current, prospective study was the evaluation of long-term results after total knee arthroplasty with the PFC-Modular-knee system. METHOD: A total of 514 total knee arthroplasties were implanted between 1991 and 1994 in 248 female and 55 male patients. Their average age amounted to 62.4 years and 449 of them (87.4%) were re-investigated within the first half-year of 2000. Clinical and radiological data were evaluated according the recommendations of the American Knee Society. RESULTS: Late complications were observed in 6.5% of the cases. They consisted of prosthetic loosening (13 knees), patella problems (11 knees), instability (2 knees), periprosthetic fractures (2 knees), and one prosthesis fracture, 18 patients complained about a therapy-resistant, chronic pain syndrome. These findings lead to revision arthroplasty in 15 cases (3.3%). Preoperative American Knee Society Score values were on average 33, 35 an 17 points and improved to mean values of about 85, 79 and 5 points. Radiological signs of prosthetic loosening were observed in 12 cases (2.7%). CONCLUSION: Long-term results after total knee arthroplasty with the PFC-Modular-knee system showed a significant improvement in the patients' complaints and clinical findings at an average of 7.8 years postoperatively. Complication and revision rates of 6.5% and 3.3%, respectively, were low when compared with the international literature and--apart from this--decreased in the course of the observation time.

Aged↗

[The cement-free modular revision prosthesis MRP-hip revision stem prosthesis in clinical follow-up].

INTRODUCTION: We present prospective medium-term results of the modular revision prostheses "MRP-TITANIUM". MATERIAL AND METHODS: 45 patients (n = 48 prostheses) were evaluated. The mean follow-up was 4.7 years (min.-max.: 1.0-9.0 years). Pre- and postoperatively the Harris hip score (differentiated to Paprosky I-III) was examined. 66.67 % of the cases had extensive bony defects (> or = Paprosky II b). By means of X-ray examinations, the stability of the prostheses, periprosthetic bone remodelling, the presence of radiolucent lines as well as bone defect regeneration were assessed postoperatively. RESULTS: The mean Harris hip score improved from 25.6 preoperative to 71.4 postoperative (p < or = 0.05). In 44 cases the X-ray showed stable fixation without secondary migration. In one case the stem (stand time 2.36 years) was revised due to secondary migration (> or = 5 mm). The survival rate (Kaplan-Meier) was 97 %. Bone transplantation with consecutive defect regeneration was (n = 30) complete in all cases. In six cases (12.5 %) a postoperative dislocation occurred with subsequent successful closed reposition four times (8.3 %). In two cases (4.2 %) an open reposition was done with correction of the antetorsion angle of the prostheses. CONCLUSION: The "MRP-TITANIUM modular revision prostheses" has proved to be reliable in cases of revision surgery with extensive bony defects. The failure rate was 2.1 % for 48 prospectively examined prostheses.

Aged↗

[Residual particle free surfaces after shot peening in modular hip arthroplasty are feasible].

INTRODUCTION: Shot peening with steel balls is used for introduction of compressive stress in the production of morse taper junctions of modular hip endoprostheses. After this procedure, significant contamination with residual particles can be detected, which may lead to increased corrosion and third body wear. Additionally, the European norm EN 12010 requires surfaces free of residual particles. The aim of this study is to evaluate the effects of several cleaning procedures with regard to complying with EN 12010. MATERIAL AND METHOD: The surfaces of 12 Ti6Al7Nb rods with a diameter of 15 mm was shot peened with steel balls (GS VERA, Fa. Würth, Bad Friedrichshall, Germany). A field emission scanning electron microscopy (SEM, LEO 1525) was used for the detection of residual particles on the surface of the rods with a backscattered electron detector. After SEM examination, one sample each was cleaned using shot peening with sugar or dry ice and 10 rods using a pH dependent cleaning procedure. After these cleaning procedures, the samples were again analysed with the SEM for residual particle contamination. RESULTS: The surface of all rods showed a considerable contamination with steel particles after shot-peening with steel balls. After the cleaning procedure with dry ice or sugar steel contamination was lower, however, only the pH dependent cleaning procedure was able to achieve surfaces free of residual particles. DISCUSSION: For smooth shot-peened surfaces in modular hip arthroplasty Euro Norm EN 12010 can be fulfilled using shot peening with steel balls followed by a pH dependent cleaning procedure.

Hip Prosthesis↗

[Modular education in diabetes and pregnancy: analysis of results of 58 pregnancies in diabetic patients with functional insulin treatment].

Functional insulin treatment based on the patient's education for selective use of insulin for fasting, eating or correction of hyperglycaemia was used between 1985 and 1994 prospectively in 58 pregnancies (in 18 cases after conception) in 47 pregnant diabetic patients. We hypothesised that near-normalisation of glycaemia is possible throughout pregnancy by modular outpatient group education, individual counselling and functional insulin treatment. We wanted to investigate to which degree it might eliminate classical diabetes-associated neonatal complications. To avoid hospitalisation if possible and premature induction of labour, patients were taught both the primary adjustment (immediate correction of hyperglycaemia) and the secondary adjustment of the insulin dosages: correction of individual algorithms for insulin use according to daily insulin consumption and mean blood glucose MBG. A target metabolic control (HbA1c levels in the normal range, MBG < 100 and < 90 mg/dl after the 28th week of gestation respectively) was achieved in the majority of the 58 pregnancies. Severe hypoglycaemia occurred in 12 patients (21%). The gestational age at delivery was 39.0 +/- 1.6 (34-41; in 3 cases only [5%] < 37) weeks with an average birth weight of 3335 +/- 521 (1950-4450) g. The birth weight of only 5 newborn (9%) was above the 90th percentile and no one below the 10th percentile for weight of a comparable population. No cases of respiratory distress were observed. Hypoglycaemia was recorded in only 4 newborn (7%) and was comparable also to that of offsprings in non-diabetic women. Malformations were found in two offsprings whose mothers had presented first for diabetes education after conception, pregnancy being terminated in one case of meningomyelocele. Caesarean section (n = 15; 26%) was primarily due to maternal reasons. Functional insulin treatment prior to conception, modular diabetes group education, specific patient motivation for a near-normal glycaemia throughout pregnancy as well as interdisciplinary care allow pregnancy outcome in diabetic patients similar to that in non-diabetic women and thus the realisation of the 5-year targets of the WHO Declaration of St. Vincent 1989.

Adolescent↗

The modular architecture of protein-protein binding interfaces.

Protein-protein interactions are essential for life. Yet, our understanding of the general principles governing binding is not complete. In the present study, we show that the interface between proteins is built in a modular fashion; each module is comprised of a number of closely interacting residues, with few interactions between the modules. The boundaries between modules are defined by clustering the contact map of the interface. We show that mutations in one module do not affect residues located in a neighboring module. As a result, the structural and energetic consequences of the deletion of entire modules are surprisingly small. To the contrary, within their module, mutations cause complex energetic and structural consequences. Experimentally, this phenomenon is shown on the interaction between TEM1-beta-lactamase and beta-lactamase inhibitor protein (BLIP) by using multiple-mutant analysis and x-ray crystallography. Replacing an entire module of five interface residues with Ala created a large cavity in the interface, with no effect on the detailed structure of the remaining interface. The modular architecture of binding sites, which resembles human engineering design, greatly simplifies the design of new protein interactions and provides a feasible view of how these interactions evolved.

Bacterial Proteins↗

Vertex operator algebras, the Verlinde conjecture, and modular tensor categories.

Let V be a simple vertex operator algebra satisfying the following conditions: (i) V(n)) = 0 for n < 0, V(0)=C1, and the contragredient module V' is isomorphic to V as a V-module; (ii) every N-gradable weak V-module is completely reducible; (iii) V is C(2)-cofinite. We announce a proof of the Verlinde conjecture for V, that is, of the statement that the matrices formed by the fusion rules among irreducible V-modules are diagonalized by the matrix given by the action of the modular transformation tau |--> -1/tau on the space of characters of irreducible V-modules. We discuss some consequences of the Verlinde conjecture, including the Verlinde formula for the fusion rules, a formula for the matrix given by the action of tau |--> -1/tau, and the symmetry of this matrix. We also announce a proof of the rigidity and nondegeneracy property of the braided tensor category structure on the category of V-modules when V satisfies in addition the condition that irreducible V-modules not equivalent to V have no nonzero elements of weight 0. In particular, the category of V-modules has a natural structure of modular tensor category.

Journal Article↗

Simple fold composition and modular architecture of the nuclear pore complex.

The nuclear pore complex (NPC) consists of multiple copies of approximately 30 different proteins [nucleoporins (nups)], forming a channel in the nuclear envelope that mediates macromolecular transport between the cytosol and the nucleus. With <5% of the nup residues currently available in experimentally determined structures, little is known about the detailed structure of the NPC. Here, we use a combined computational and biochemical approach to assign folds for approximately 95% of the residues in the yeast and vertebrate nups. These fold assignments suggest an underlying simplicity in the composition and modularity in the architecture of all eukaryotic NPCs. The simplicity in NPC composition is reflected in the presence of only eight fold types, with the three most frequent folds accounting for approximately 85% of the residues. The modularity in NPC architecture is reflected in its hierarchical and symmetrical organization that partitions the predicted nup folds into three groups: the transmembrane group containing transmembrane helices and a cadherin fold, the central scaffold group containing beta-propeller and alpha-solenoid folds, and the peripheral FG group containing predominantly the FG repeats and the coiled-coil fold. Moreover, similarities between structures in coated vesicles and those in the NPC support our prior hypothesis for their common evolutionary origin in a progenitor protocoatomer. The small number of predicted fold types in the NPC and their internal symmetries suggest that the bulk of the NPC structure has evolved through extensive motif and gene duplication from a simple precursor set of only a few proteins.

Computational Biology↗

Vascularized organoid engineered by modular assembly enables blood perfusion.

Tissue engineering is one approach to address the donor-organ shortage, but to attain clinically significant viable cell densities in thick tissues, laboratory-constructed tissues must have an internal vascular supply. We have adopted a biomimetic approach and assembled microscale modular components, consisting of submillimeter-sized collagen gel rods seeded with endothelial cells (ECs) into a (micro)vascularized tissue; in some prototypes the gel contained HepG2 cells to illustrate the possibilities. The EC-covered modules then were assembled into a larger tube and perfused with medium or whole blood. The interstitial spaces among the modules formed interconnected channels that enabled this perfusion. Viable cell densities were high, within an order of magnitude of cell densities within tissues, and the percolating nature of the flow through the construct was evident in microcomputed tomography and Doppler ultrasound measurements. Most importantly, the ECs retained their nonthrombogenic phenotype and delayed clotting times and inhibited the loss of platelets associated with perfusion of whole blood through the construct. Unlike the conventional scaffold and cell-seeding paradigm of other tissue-engineering approaches, this modular construct has the potential to be scalable, uniform, and perfusable with whole blood, circumventing the limitations of other approaches.

Animals↗

Stress promotes maleness in hermaphroditic modular animals.

Sex-allocation theory developed for hermaphroditic plants predicts that impaired phenotype or reduced parental survivorship caused by environmental stress should induce relatively greater allocation to the male function. We provide experimental evidence of stress-induced maleness, already well documented in flowering plants, in a modular animal. By using cloned copies of replicate genotypes, we show that the marine bryozoan Celleporella hyalina increases the ratio of male to female modules in response to diverse environmental stressors. Mating trials confirmed that paternity is determined by fair-raffle sperm competition, which should obviate local mate competition at characteristic population density and promote the advantage of increased male allocation. The demonstrated similarity to plants transcends specific physiological pathways and suggests that stress-induced bias toward male function is a general response of hermaphroditic modular organisms to impaired prospects for parental productivity or survival.

Animals↗

Modular mutagenesis of human placental ribonuclease inhibitor, a protein with leucine-rich repeats.

Human placental ribonuclease inhibitor (PRI) is a potent protein inhibitor of pancreatic ribonucleases and the homologous blood vessel-inducing protein angiogenin. Although inhibition by PRI occurs with a 1:1 stoichiometry, its primary structure is composed predominantly of seven internal leucine-rich repeats. These internal repeats were systematically deleted either singly or in combination by "modular" mutagenesis. Deletion of repeat units 3 plus 4 or repeat unit 6 results in mutants that both bind to and inhibit ribonuclease A. Therefore, the angiogenin/ribonuclease binding site in PRI must reside primarily or entirely in repeats 1, 2, 5, or 7, the short N- or C-terminal segments, or a combination of these. Deletion of repeat units 3-5, 5-6, or 5 alone results in mutants that exhibit only binding activity. Hence, the binding site cannot reside exclusively in repeat 5. Other internal deletions or N- or C-terminal deletions of 6-86% of the protein all abolish activity. These results suggest that PRI has a modular structure, with one primary structural repeat constituting one module. The approach taken may be applicable to other proteins with repeat structures.

Amino Acid Sequence↗

Modular cis-regulatory organization of developmentally expressed genes: two genes transcribed territorially in the sea urchin embryo, and additional examples.

The cis-regulatory systems that control developmental expression of two sea urchin genes have been subjected to detailed functional analysis. Both systems are modular in organization: specific, separable fragments of the cis-regulatory DNA each containing multiple transcription factor target sites execute particular regulatory subfunctions when associated with reporter genes and introduced into the embryo. The studies summarized here were carried out on the CyIIIa gene, expressed in the embryonic aboral ectoderm and on the Endo16 gene, expressed in the embryonic vegetal plate, archenteron, and then midgut. The regulatory systems of both genes include modules that control particular aspects of temporal and spatial expression, and in both the territorial boundaries of expression depend on a combination of negative and positive functions. In both genes different regulatory modules control early and late embryonic expression. Modular cis-regulatory organization is widespread in developmentally regulated genes, and we present a tabular summary that includes many examples from mouse and Drosophila. We regard cis-regulatory modules as units of developmental transcription control, and also of evolution, in the assembly of transcription control systems.

Actins↗

SMART, a simple modular architecture research tool: identification of signaling domains.

Accurate multiple alignments of 86 domains that occur in signaling proteins have been constructed and used to provide a Web-based tool (SMART: simple modular architecture research tool) that allows rapid identification and annotation of signaling domain sequences. The majority of signaling proteins are multidomain in character with a considerable variety of domain combinations known. Comparison with established databases showed that 25% of our domain set could not be deduced from SwissProt and 41% could not be annotated by Pfam. SMART is able to determine the modular architectures of single sequences or genomes; application to the entire yeast genome revealed that at least 6.7% of its genes contain one or more signaling domains, approximately 350 greater than previously annotated. The process of constructing SMART predicted (i) novel domain homologues in unexpected locations such as band 4.1-homologous domains in focal adhesion kinases; (ii) previously unknown domain families, including a citron-homology domain; (iii) putative functions of domain families after identification of additional family members, for example, a ubiquitin-binding role for ubiquitin-associated domains (UBA); (iv) cellular roles for proteins, such predicted DEATH domains in netrin receptors further implicating these molecules in axonal guidance; (v) signaling domains in known disease genes such as SPRY domains in both marenostrin/pyrin and Midline 1; (vi) domains in unexpected phylogenetic contexts such as diacylglycerol kinase homologues in yeast and bacteria; and (vii) likely protein misclassifications exemplified by a predicted pleckstrin homology domain in a Candida albicans protein, previously described as an integrin.

Amino Acid Sequence↗

Compact stellarators with modular coils.

Compact stellarator designs with modular coils and only two or three field periods are now available; these designs have both good stability and quasiaxial symmetry providing adequate transport for a magnetic fusion reactor. If the bootstrap current assumes theoretically predicted values a three field period configuration is optimal, but if that net current turns out to be lower, a device with two periods and just 12 modular coils might be better. There are also attractive designs with quasihelical symmetry and four or five periods whose properties depend less on the bootstrap current. Good performance requires that there be a satisfactory magnetic well in the vacuum field, which is a property lacking in a stellarator-tokamak hybrid that has been proposed for a proof of principle experiment. In this paper, we present an analysis of stability for these configurations that is based on a mountain pass theorem asserting that, if two solutions of the problem of magnetohydrodynamic equilibrium can be found, then there has to be an unstable solution. We compare results of our theory of equilibrium, stability, and transport with recently announced measurements from the large LHD experiment in Japan.

Journal Article↗

Modularity of serpins. A bifunctional chimera possessing alpha1-proteinase inhibitor and thyroxine-binding globulin properties.

An exciting application of protein engineering is the creation of proteins with novel functions by the retrofitting of native proteins. Such attempts might be facilitated by the idea of a mosaic architecture of proteins out of structural units. Even though numerous theoretical concepts deal with the delineation of structural "modules," their potential in the design of proteins has not yet been sufficiently exploited. To address this question we used a gain of function approach by designing modular chimeric molecules out of two structurally homologous but functionally diverse members of the superfamily of serine-proteinase inhibitors, alpha1-proteinase inhibitor and thyroxine-binding globulin. Substitution of two of four alpha1-proteinase inhibitor modules (Lys222 to Leu288 and Pro362 to Lys394, respectively), identified by alpha-backbone distance analysis, with their thyroxine-binding globulin homologues resulted in a bifunctional chimera with inhibition of human leukocyte elastase and high affinity thyroxine binding. To our knowledge, this is the first report on a bifunctional chimera engineered from modules of homologous globular proteins. Our results demonstrate how a modular concept can facilitate the design of new functional proteins by swapping structural units chosen from members of a protein superfamily.

Humans↗