Interstitial Growth Research Articles

Tuning tissue growth with scaffold degradation in enzyme-sensitive hydrogels: a mathematical model.

Despite tremendous advances in the field of tissue engineering, a number of obstacles remain that hinder its successful translation to the clinic. One challenge that relates to the use of cells encapsulated in a hydrogel is identifying a hydrogel design that can provide an appropriate environment for cells to successfully synthesize and deposit new matrix molecules while providing a mechanical support that can resist physiological loads at the early stage of implementation. A solution to this problem has been to balance tissue growth and hydrogel degradation. However, identifying this balance is difficult due to the complexity of coupling diffusion, deposition, and degradation mechanisms. Very little is known about the complex behavior of these mechanisms, emphasizing the need for a rigorous mathematical approach that can assist and guide experimental advances. To address this issue, this paper discusses a model for interstitial growth based on mixture theory, that can capture the coupling between cell-mediated hydrogel degradation (i.e., hydrogels containing enzyme-sensitive crosslinks) and the transport of extracellular matrix (ECM) molecules released by encapsulated cells within a hydrogel. Taking cartilage tissue engineering as an example, the model investigates the role of enzymatic degradation on ECM diffusion and its impact on two important outcomes: the extent of ECM transport (and deposition) and the evolution of the hydrogel's mechanical integrity. Numerical results based on finite element analysis show that if properly tuned, enzymatic degradation yields the appearance of a highly localized degradation front propagating away from the cell, which can be immediately followed by a front of growing neotissue. We show that this situation is key to maintaining mechanical properties (e.g., stiffness) while allowing for deposition of new ECM molecules. Overall, our study suggests a hydrogel design that could enable successful tissue engineering (e.g., of cartilage, bone, etc.) where mechanical integrity is important.

Are C-KIT, MMP-9 and Type II Collagen Positive Undifferentiated Cells Involved in Cartilage Growth? A Description of Unusual Interstitial Type of Cartilage Growth

Cartilages growth requires activation of perichondrial cells and chondrocyte multiplication. Activated perichondrial cells produce an outer cartilage matrix and in appositional growth and chondrocytes division produce new chondrogenic cells which participate in interstitial growth of cartilage. This study was performed to identify a third type of cartilage growth in skeletal elements of quail embryos at 6, 7, 8, 9, 10, 13, 16, 17 days of incubation. Paraffin sections of the whole embryos were stained using HE characterized by their small size, having multiple cell processes and staining positive for C-KIT. MMP-9 positive cells were detected in cartilage matrix. The mesenchymal cells further differentiated into chondrocytes which were positive for type II collagen immunostaining and secreted Safranin O positive cartilage matrix. In conclusion, our results suggest that C-KIT positive mesenchymal cells secrete MMP-9 to penetrate growing cartilage, produce type II collagen and proteoglycan and have a role in interstitial growth of embryonic cartilage templates in quail. (Graphical Abstract).

A mixture approach to investigate interstitial growth in engineering scaffolds

Controlling biological growth within a cell-laden polymeric scaffold is a critical challenge in the tissue engineering community. Indeed, construct growth must often be balanced with scaffold degradation and is often coupled to varying degrees of deformation that originate from swelling, external forces and the effects of confinement. These factors have been shown to affect growth in many ways, but to date, our understanding is mostly qualitative. While cell sensing, molecular transport and scaffold/tissue interactions are believed to be important players, it will be critical to quantify, predict and control these effects in order to eventually optimize tissue growth in the laboratory. The aim of this paper was thus to provide a theoretical framework to better understand how the scaffold-mediated mechanisms of transport, deposition (and possibly degradation) and elasticity affect the overall growth of a tissue subjected to finite deformations. We propose a formulation in which the macroscopic evolutions in tissue size, density as well as the appearance of residual stresses can be directly related to changes in internal composition by considering three fundamental principles: mechanical equilibrium, chemical equilibrium and molecular incompressibility. The resulting model allows us to pay particular attention to features that are critical to the interaction between growth and deformation: osmotic pressure and swelling, the strain mismatch between old and newly deposited material as well as the mechano-sensitive cell-mediated production. We show that all of these phenomena may indeed strongly affect the overall growth of a construct under finite deformations.

A unified theoretical structure for modeling interstitial growth and muscle activation in soft tissues

The objective of this paper is to develop a new unified theoretical structure for modeling interstitial growth and muscle activation in soft tissues. The model assumes a simple continuum with a single velocity field. In contrast with many other formulations, evolution equations are proposed directly for a scalar measure of elastic dilatation and a tensorial measure of elastic distortional deformation. The evolution equation for elastic dilatation includes a rate of mass supply or removal that controls volumetric growth and causes the elastic dilatation to evolve towards its homeostatic value. Similarly, the evolution equation for elastic distortional deformation includes a rate of growth that causes the elastic distortional deformation tensor to evolve towards its homeostatic value. Specific forms for these inelastic rates of growth and the associated homeostatic values have been considered for volumetric, area and fiber growth processes, as well as for muscle activation. Since the rate of growth appears in the evolution equations and not a growth tensor it is possible to model the combined effects of multiple growth and muscle activation mechanisms simultaneously. Also, robust, strongly objective, numerical algorithms have been developed to integrate the evolution equations.

Computational modeling of chemical reactions and interstitial growth and remodeling involving charged solutes and solid-bound molecules.

Mechanobiological processes are rooted in mechanics and chemistry, and such processes may be modeled in a framework that couples their governing equations starting from fundamental principles. In many biological applications, the reactants and products of chemical reactions may be electrically charged, and these charge effects may produce driving forces and constraints that significantly influence outcomes. In this study, a novel formulation and computational implementation are presented for modeling chemical reactions in biological tissues that involve charged solutes and solid-bound molecules within a deformable porous hydrated solid matrix, coupling mechanics with chemistry while accounting for electric charges. The deposition or removal of solid-bound molecules contributes to the growth and remodeling of the solid matrix; in particular, volumetric growth may be driven by Donnan osmotic swelling, resulting from charged molecular species fixed to the solid matrix. This formulation incorporates the state of strain as a state variable in the production rate of chemical reactions, explicitly tying chemistry with mechanics for the purpose of modeling mechanobiology. To achieve these objectives, this treatment identifies the specific theoretical and computational challenges faced in modeling complex systems of interacting neutral and charged constituents while accommodating any number of simultaneous reactions where reactants and products may be modeled explicitly or implicitly. Several finite element verification problems are shown to agree with closed-form analytical solutions. An illustrative tissue engineering analysis demonstrates tissue growth and swelling resulting from the deposition of chondroitin sulfate, a charged solid-bound molecular species. This implementation is released in the open-source program FEBio ( www.febio.org ). The availability of this framework may be particularly beneficial to optimizing tissue engineering culture systems by examining the influence of nutrient availability on the evolution of inhomogeneous tissue composition and mechanical properties, the evolution of construct dimensions with growth, the influence of solute and solid matrix electric charge on the transport of cytokines, the influence of binding kinetics on transport, the influence of loading on binding kinetics, and the differential growth response to dynamically loaded versus free-swelling culture conditions.

Nutrigenomics and its role in male puberty of cattle: a mini review.

Nutrigenomics a novel era in genomics research is based on puzzling issue on how nutrition and genes re-interacts. Perusal of literature reveals that very few information are available in this field and especially when it is associated with puberty in cattle which is a multigenic trait of great economic importance. Thus it opens a new area of research interest. Various markers like-gonadotropin releasing hormone/GNRH (responsible for sexual differentiation and reproduction), interstitial growth regulating factor/IGF1 (having signal controlling reproduction function linked to somatic growth); circulating metabolic hormones viz., leptin apart from GnRH and IGF1 (having impact on testicular development in peripubertal bull) are proved to be associated with male puberty in cattle. Various minerals (copper, selenium, manganese, zinc, chromium, iron and molybdenum) and vitamins (Vit. A, D, E and C) are directly or indirectly linked to male puberty. But no research till today initiated how the nutrients effect on the transcriptome/proteome/metabolome level of marker genes associated with male puberty in cattle. Application of nanotechnology to make food safer for promotion of good health has created much excitement and nanoparticles has been developed against infectious diseases (e.g., Campylobacteriosis) affecting puberty along with certain nanocarriers that can facilitate the uptake of essential nutrients associated with puberty. Much of nutrigenomics research is however in infancy and hence the present mini-review will allow building the concept among researchers and scientists to initiate research in this interesting area.

Interstitial growth and remodeling of biological tissues: Tissue composition as state variables

Growth and remodeling of biological tissues involves mass exchanges between soluble building blocks in the tissue's interstitial fluid and the various constituents of cells and the extracellular matrix. As the content of these various constituents evolves with growth, associated material properties, such as the elastic modulus of the extracellular matrix, may similarly evolve. Therefore, growth theories may be formulated by accounting for the evolution of tissue composition over time in response to various biological and mechanical triggers. This approach has been the foundation of classical bone remodeling theories that successfully describe Wolff's law by establishing a dependence between Young's modulus and bone apparent density and by formulating a constitutive relation between bone mass supply and the state of strain. The goal of this study is to demonstrate that adding tissue composition as state variables in the constitutive relations governing the stress–strain response and the mass supply represents a very general and straightforward method to model interstitial growth and remodeling in a wide variety of biological tissues. The foundation for this approach is rooted in the framework of mixture theory, which models the tissue as a mixture of multiple solid and fluid constituents. A further generalization is to allow each solid constituent in a constrained solid mixture to have its own reference (stress-free) configuration. Several illustrations are provided, ranging from bone remodeling to cartilage tissue engineering and cervical remodeling during pregnancy.

Effects of bevacizumab and hyperthermia in a rodent model of hyperthermic intraperitoneal chemotherapy (HIPEC)

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is more and more used in the treatment of patients with peritoneal carcinomatosis (PC) of different primary tumours. However, survival of patients with PC is still poor. The aim of this study was to evaluate the effects of preoperatively administered bevacizumab and temperature of the perfusion in an experimental model of HIPEC.Materials and methods: A model for peritoneal carcinomatosis of colorectal origin was created by implantation of tumour fragments (HT29) in the abdomen of athymic nude rats. All animals were treated with oxaliplatin-based HIPEC. Animals were randomised into different treatment groups: hyperthermic treatment was compared to normothermic treatment and in both groups there were animals with and without preoperative administration of bevacizumab. Interstitial fluid pressure (IFP), bio-availability (concentrations of the drug in blood and tumour) and tumour growth delay (TGD) were evaluated.Results: In this study, preoperative bevacizumab lowered IFP but there was no effect on the bio-availability. The effect on the size of the tumour was ambivalent with no statistically significant effect on TGD. The area under the curve (AUC) of platinum was higher in animals treated with hyperthermic perfusion as compared to normothermic perfusion. In the TGD-study a post-operative mortality of 100% was observed in the hyperthermic group, compared to 1 out of 16 rats in the normothermic group.Conclusions: The results of this study suggest that bevacizumab is not promising for clinical implementation in the setting of HIPEC: the effects on tumour size were ambivalent and there was no statistically significant benefit in TGD. The effects of hyperthermic perfusion in this study were negative: a higher blood concentration of oxaliplatin as compared to normothermic perfusion, without a higher intra-tumoural concentration. There was a higher mortality rate after hyperthermic perfusion as compared to normothermic perfusion (p < 0.001).

Growth patterns of lung metastases from sarcoma: prognostic and surgical implications from histology

Pulmonary metastasectomy is firmly established in the multidisciplinary management of patients with advanced sarcomas. While the number of metastases, completeness of resection, disease-free interval and grading of the primary sarcoma are well established prognostic factors in metastatic surgery, histological parameters are not widely evaluated. The objective of the present study was to evaluate the prognostic impact of intrapulmonary growth patterns of sarcoma metastases. We retrospectively analysed the clinicopathological characteristics of 52 sarcoma patients who underwent surgical resection of lung metastases at our centre from January 2006 to January 2009. The histological growth characteristics of all 261 metastases have been categorized and published previously. 'Interstitial growth' was defined as a diffuse spread of the sarcoma cells into the alveolar septae at the transition of the metastasis to the normal lung tissue and was found to be prognostic. 'Pleural penetration' was defined as the infiltration and destruction of all visceral pleural layers by the tumour and was found to be a risk factor for local recurrence. The median post-metastasectomy overall survival was 50.3 months, and the corresponding 5-year survival rate was 44.7%. Age >55 years at metastasectomy (P = 0.02), the presence of interstitial growth (P = 0.008), size of the largest metastasis >35 mm (P = 0.023) and the presence of tumour recurrence at any site after metastasectomy (P < 0.001) were identified as risk factors for death. Pleural penetration (P = 0.007) and size of the metastasis >5 mm were found to be risk factors for local intrapulmonary recurrence. Interstitial tumour growth, which is easily detected by light microscopy, can serve as a strong predictor of survival following pulmonary metastasectomy in sarcoma patients. Obvious pleural infiltration indicates the need for larger margins.

Germline deletion of FAK-related non-kinase delays post-natal cardiomyocyte mitotic arrest

The cardiomyocyte phenotypic switch from a proliferative to terminally differentiated state impacts normal heart development and pathologic myocardial remodeling, yet the signaling mechanisms that regulate this vital process are incompletely understood. Studies from our lab and others indicate that focal adhesion kinase (FAK) is a critical regulator of cardiac growth and remodeling and we found that expression of the endogenous FAK inhibitor, FAK-related non kinase (FRNK) coincided with postnatal cardiomyocyte arrest. Mis-expression of FRNK in the embryonic heart led to pre-term lethality associated with reduced cardiomyocyte proliferation and led us to speculate that the postnatal FRNK surge might be required to promote quiescence in this growth promoting environment. Herein, we provide strong evidence that endogenous FRNK contributes to post-mitotic arrest. Depletion of FRNK promoted DNA synthesis in post-natal day (P) 10 hearts accompanied by a transient increase in DNA content and multi-nucleation by P14, indicative of DNA replication without cell division. Interestingly, a reduction in tri- and tetra-nucleated cardiomyocytes, concomitant with an increase in bi-nucleated cells by P21, indicated the possibility that FRNK-depleted cardiomyocytes underwent eventual cytokinesis. In support of this conclusion, Aurora B-labeled central spindles (a hallmark of cytokinesis) were observed in tetra-nucleated P20 FRNK(-/-) but not wt cardiomyocytes, while no evidence of apoptosis was observed. Moreover, hearts from FRNK null mice developed ventricular enlargement that persisted until young adulthood which resulted from myocyte expansion rather than myocyte hypertrophy or interstitial growth. These data indicate that endogenous FRNK serves an important role in limiting DNA synthesis and regulating the un-coupling between DNA synthesis and cytokinesis in the post-natal myocardium.

Coastal salina evaporites of the Triassic-Liassic boundary in the Iberian Peninsula: the Alacón borehole

The evaporite unit (the Lecera Formation), which was formed at the Triassic–Liassic boundary in the Aragonian Branch of the Iberian Chain, was studied at the 01 Alacon borehole (Alacon village, Teruel province), where it is mainly constituted by a thick (>300 m) succession of predominant sulphates (anhydrite, secondary gypsum and carbonate) overlain by brecciated carbonates. In the evaporite succession, a number of lithofacies were recognized, which can be grouped into an “ideal cycle”, from base to top: (C1) massive to banded carbonate mudstone, (C2) alternation of carbonate and anhydrite laminae, (A1) alternation of anhydrite and carbonate bands, (A2) clastic intercalations in the alternation of anhydrite and carbonate bands, (A3) laminated to banded anhydrite, (A4) bedded pseudomorphs, (A5) interstitial pseudomorphs, and (A6) massive to nodular anhydrite. Fine-grained gypsum (anhydrite laminae and bands), bedded selenitic gypsum (bedded pseudomorphs), interstitial selenitic gypsum (interstitial pseudomorphs), and graded-nodular anhydrite (a particular fabric of nodular anhydrite) were the most outstanding depositional lithofacies. The evaporite succession exhibits a marked cyclicity: in the lower part the individual cycles are more similar to the ideal cycle and reflect deeper water settings, whereas in the upper part they correspond to shallower water settings. The evaporite sedimentation mainly occurred in a subsiding coastal basin of the salina or lagoon type. In this setting, the subaqueous precipitation of the carbonate and gypsum lithofacies was followed, in each cycle, by the interstitial growth of anhydrite in exposed conditions. As a whole, the evaporite succession reflects an infilling process. The conversion into anhydrite of the selenitic gypsum -probably also of the rest of depositional gypsum lithofaciesstarted under synsedimentary conditions and followed during shallow to moderate burial diagenesis.

Multi-Scale Modeling of Interstitial Dislocation Loop Growth in Irradiated Materials

ABSTRACTIn order to reduce the inherent uncertainty in kinetic theory models and promote their transition to become predictive methodologies, a multi-scale modeling approach is proposed and demonstrated in this work. KiValues of key materials properties such as point defect (vacancy and interstitial) migration enthalpies, as well as kinetic factors, such as dimer formation and defect recombination coefficients and self-interstitial atom – interstitial loop reaction rates, were obtained by ab initio/molecular dynamics calculations. A rate theory model was used to interpret the evolution of dislocation loops in irradiated molybdenum. Calculations of the dose dependence of average loop diameter were performed and compared to experimental measurements obtained from irradiations with high-energy electrons. The comparison demonstrates reasonable agreement between model-predicted and experiment-measured data.

Mixture theory-based poroelasticity as a model of interstitial tissue growth

This contribution presents an alternative approach to mixture theory-based poroelasticity by transferring some poroelastic concepts developed by Maurice Biot to mixture theory. These concepts are a larger RVE and the subRVE-RVE velocity average tensor, which Biot called the micro–macro velocity average tensor. This velocity average tensor is assumed here to depend upon the pore structure fabric. The formulation of mixture theory presented is directed toward the modeling of interstitial growth, that is to say changing mass and changing density of an organism. Traditional mixture theory considers constituents to be open systems, but the entire mixture is a closed system. In this development the mixture is also considered to be an open system as an alternative method of modeling growth. Growth is slow and accelerations are neglected in the applications. The velocity of a solid constituent is employed as the main reference velocity in preference to the mean velocity concept from the original formulation of mixture theory. The standard development of statements of the conservation principles and entropy inequality employed in mixture theory are modified to account for these kinematic changes and to allow for supplies of mass, momentum and energy to each constituent and to the mixture as a whole. The objective is to establish a basis for the development of constitutive equations for growth of tissues.

Growth patterns of lung metastases from sarcomas

Complete resection of pulmonary metastases from sarcomas is an established method of treatment. While resection margins are well described for primary sarcoma lesions, minimal knowledge is available about margins and factors influencing local tumour control in the lung. The objective of the present study was to describe intrapulmonary patterns of growth for sarcoma metastases as a basis for planning resections. From January 2006 to January 2009, we retrospectively analysed 261 resected pulmonary sarcoma metastases from 52 patients. All metastases were reviewed for histological characteristics and resection margins. Metastases characterised by a solid, well-defined tumour mass were found in 127 of 261 metastases (48.7%). Interstitial spread (39.8%), vascular infiltration (20.7%), satellite nodules (16.1%) and lymphangitic spread (10.7%) were identified as aggressive histological growth characteristics. Forty-five of 52 patients (86.5%) had metastases with a mitotic index of 10 or more per 10 HPF, underlining their high-grade malignant potential. The following characteristics of aggressive intrapulmonary growth were highly correlated with each other: interstitial growth and lymphangitic spread (p = 0.002), interstitial growth and vascular infiltration (p < 0.001), vascular infiltration and satellite nodules (p = 0.009), interstitial growth and pleural invasion (p = 0.004); by contrast, the presence of a fibrous pseudocapsule (17.2%) was not associated with aggressive growth patterns. Almost half of all pulmonary sarcoma metastases could be identified with aggressive patterns of local growth, and only 17.2% are surrounded by a pseudocapsule which might allow safe resection margins.

A Review of the Actual Knowledge of the Processes Governing Growth and Development of Long Bones

Autoptic samples of human bones (from 8 weeks of gestation to 12 years of age) and a second group of serial, skeletal x-rays (required for pathologies not related to bone dysplasia in children from 4 months to 17 years of age) provided the material for the analysis of the physes normal growth mechanism presented in this review. Before the appearance of the ossification centers epiphyseal growth rests exclusively on chondrocytes proliferation (interstitial growth), without any detectable differentiated cellular organization. When endochondral ossification starts a defined spatial disposition of chondrocytes and a corresponding organization of the intercellular matrix is set up, so that it is possible to identify a growth vector corresponding to the columns of piled chondrocytes with direction from hypertrophic toward the proliferative cell layers. The complexity of the tubular bones growth process is well represented by the spatial arrangement of the growth vectors. In the late epiphyseal growth another mechanism is active in addition to endochondral ossification, namely, articular cartilage interstitial growth and subchondral remodelling. The knowledge of the normal mode of organization of the physis and its temporal sequence can help to better understand of the deviaton from the normal development of metaphyseal and epiphyseal dysplasias.

Effect of surface nucleation on isothermal crystallization kinetics: Theory, simulation and experiment

Surface nucleation of poly( l/ d-lactide) at the interface with aluminum was studied by performing isothermal DSC analysis of amorphous samples of varying thickness between 100 °C and 130 °C. To ensure complete wetting of the aluminum surface, a hot melt laminating process was used to prepare the samples. Theoretical aspects of surface crystallization kinetics were explored and the resulting model was compared with the results of Monte-Carlo simulations. Three stages of surface crystallization were identified depending on the growth geometry: (1) impingement-free growth, (2) increasingly laterally-constrained transverse growth, and (3) interstitial growth. By fitting the Monte-Carlo simulation to the experimental half-times of crystallization the surface nucleation concentration and the bulk nucleation rate was estimated at 4 different temperatures. It was found that both surface nucleation concentration and the bulk nucleation concentration decrease with increasing crystallization temperature.

β-Cell Growth and Regeneration: Replication Is Only Part of the Story

> “I am accordingly of the opinion that the normal regulation of islet content in the pancreas is by interstitial growth of pre-existing islets and by the formation of new islets from the duct epithelium, and not at all by the formation of new islets out of acini.” > > R.R. Bensley Am J Anatomy 1911;12:297–388 For almost a century (for historical review, see 1) both β-cell replication and neogenesis (the differentiation of new islet cells from progenitors or stem cells) have been thought to be responsible for postnatal growth of the endocrine pancreas. Even though doubts have been raised in recent years about the existence and importance of neogenesis, this skepticism may be subsiding. Replication and neogenesis are not mutually exclusive. Both processes often occur simultaneously, as seen during the regeneration that follows pancreatic injury. However, there are important differences in the balance of these two pathways that depend upon species and age. Replication of β-cells is an important mechanism particularly in adult rodents, but there are compelling data that after-birth progenitors also have a role in renewal and growth of islets. Eventually one or both of these pathways may be manipulated for therapeutic treatment of diabetes. Since we and others have extensively reviewed the regulation of β-cell mass (2,3), this Perspective will specifically address the contributions of the neogeneic pathway to new β-cell formation, considering whether postnatal neogenesis occurs, to what extent; possible differences between mammalian species; and whether it might be exploited therapeutically. ### β-Cell expansion in normal growth. The concept that β-cell mass is dynamic and increases and decreases both in function and mass to maintain the glycemic level within a very narrow physiological range (4) is now generally accepted. In both normal and pathophysiological states, the mechanisms responsible are changes in replication and neogenesis, changes in individual cell volume, and changes in cell loss or death rates. In …

Multigenerational interstitial growth of biological tissues

This study formulates a theory for multigenerational interstitial growth of biological tissues whereby each generation has a distinct reference configuration determined at the time of its deposition. In this model, the solid matrix of a growing tissue consists of a multiplicity of intermingled porous permeable bodies, each of which represents a generation, all of which are constrained to move together in the current configuration. Each generation's reference configuration has a one-to-one mapping with the master reference configuration, which is typically that of the first generation. This mapping is postulated based on a constitutive assumption with regard to that generations' state of stress at the time of its deposition. For example, the newly deposited generation may be assumed to be in a stress-free state, even though the underlying tissue is in a loaded configuration. The mass content of each generation may vary over time as a result of growth or degradation, thereby altering the material properties of the tissue. A finite element implementation of this framework is used to provide several illustrative examples, including interstitial growth by cell division followed by matrix turnover.

Juvenile Xanthogranuloma Presenting as a Testicular Mass in Infancy: A Clinical and Pathologic Study of Three Cases

Juvenile xanthogranulomas (JXG) is a histiocytic disorder whose most common clinical presentation is a solitary cutaneous nodule in a child under 5 years of age, but it has come to be recognized that solitary extracutaneous lesions may present in a number of sites, including the soft tissues and various organs. Involvement of the genitourinary tract has been documented in children with multifocal or systemic JXG. The current report describes our experience with 3 cases of JXG presenting as a solitary mass in the testicle of infants between 2.5 and 13 months without manifestations of JXG elsewhere. The masses were intratesticular and had an infiltrative pattern of interstitial growth by mononuclear, histiocyte-like cells with replacement of seminiferous tubules and involvement of the epididymis whose pattern resembled leukemic and lymphomatous involvement of the testis. Because extracutaneous lesions of JXG may have few or no Touton giant cells, immunohistochemistry is an important adjunct to the histopathologic diagnosis. One of the previous 2 cases in the literature of JXG of the testis recurred after partial resection without an orchiectomy. Neither of the 2 youngest patients has experienced a local recurrence of JXG elsewhere in excess of 1 year since the original orchiectomy. The oldest patient, who was treated with partial orchiectomy, remains free of recurrence after 3 months of follow-up. Though uncommon, JXG joins several other distinctive neoplasms presenting in the infantile testis.

Integrated atomistic modelling of interstitial defect growth in silicon

A new theoretical approach that combines Metropolis Monte Carlo, tight-binding molecular dynamics, and density functional theory calculations is introduced as an efficient technique to determine the structure and stability of native defects in crystalline silicon. Based on this combined approach, the growth behaviour of self-interstitial defects in crystalline Si is presented. New stable structures for small interstitial clusters (I n , 5 ≤ n ≤ 16) are determined and show that the compact geometry appears favoured when the cluster size is smaller than 10 atoms (n < 10). The fourfold-coordinated dodeca-interstitial (I12) structure with C 2h symmetry is identified as an effective nucleation centre for larger extended defects. This work provides the first theoretical support for earlier experiments that suggest a shape transition from compact to elongated structures around n = 10. We also provide some theoretical evidence that suggests that {3 1 1} extended defects grow slowly along ⟨2 3 3⟩ and relatively faster along ⟨1 1 0⟩, which is consistent with typical defect aspect ratios observed through transmission electron microscopy.