Osteosarcoma Pathogenesis Leads the Way to New Target Treatments

Osteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets.     

Extracellular Vesicles in CNS Developmental Disorders

The central nervous system (CNS) is the most complex structure in the body, consisting of multiple cell types with distinct morphology and function. Development of the neuronal circuit and its function rely on a continuous crosstalk between neurons and non-neural cells. It has been widely accepted that extracellular vesicles (EVs), mainly exosomes, are effective entities responsible for intercellular CNS communication. They contain membrane and cytoplasmic proteins, lipids, non-coding RNAs, microRNAs and mRNAs. Their cargo modulates gene and protein expression in recipient cells. Several lines of evidence indicate that EVs play a role in modifying signal transduction with subsequent physiological changes in neurogenesis, gliogenesis, synaptogenesis and network circuit formation and activity, as well as synaptic pruning and myelination. Several studies demonstrate that neural and non-neural EVs play an important role in physiological and pathological neurodevelopment. The present review discusses the role of EVs in various neurodevelopmental disorders and the prospects of using EVs as disease biomarkers and therapeutics.     

Alteration of Sertoli cell differentiation in the presence of carcinoma in situ in human testes

PURPOSE: We investigated Sertoli cells in testicular biopsies with carcinoma in situ (CIS) in respect to cytokeratin expression to elucidate the status of Sertoli cell differentiation adjacent to CIS in human testes. Cytokeratin 18 intermediate filaments indicate a state of undifferentiation usually observed in Sertoli cells of prepubertal testes. MATERIALS AND METHODS: 29 testicular biopsies presenting CIS were investigated by means of immunohistochemistry, using a polyclonal antibody against placental-alkaline phosphatase to detect CIS cells and a monoclonal antibody against human cytokeratin 18 to show expression of cytokeratin 18 intermediate filaments in Sertoli cells. RESULTS: All tubules bearing CIS showed positive cytokeratin expression of Sertoli cells if tubules were devoid of normal germ cells. However, a total of 13 specimen revealed CIS cells together with normal germ cells. In the presence of CIS cells together with round or elongated spermatids, adjacent Sertoli cells did not express cytokeratin immunoreactivity. In the case of combined presence of CIS and spermatogonia and primary spermatocytes, Sertoli cells could be found either immunopositive or immunonegative, and were positive in tubules with CIS and spermatogonia only. CONCLUSIONS: Sertoli cells associated with CIS cells undergo a process of dedifferentiation, seen by the re-expression of cytokeratin intermediate filaments. We suggest that this dedifferentiation results in a loss of Sertoli cell function and leads to a cessation of spermatogenic activity.     

An epidemic of roller-blade injuries in children

Roller blading is a new and increasingly popular leisure activity in many countries. We reviewed 110 consecutive patients with roller-blade injuries between 1 January and 30 June 1996. The patients ranged from 4 to 14 years in age (mean 6.5 years). Eighty-three (75.4%) sustained injuries to the upper limb and 27 (24.5%) injured the lower limb. Fifty-six patients, were girls and 54 were boys. Of the 110 patients, 79 (72.7%) sustained fractures, 28 (25.4%) soft tissue injuries and 3 (2.7%) dislocations. Eighty-three (75.4%) of the patients wore no protective equipment on the limbs. Four months following injury 103 (93.6%) patients were fully recovered. The mean duration of school absence was 3 days. Subsequently 101 children returned to using roller-blades following injury. Seventy-three (66.3%) of these now use protective equipment. We found that injuries were unrelated to age or duration of roller-blading experience or to the brand-name of roller blades used, and that most of our patients wore no protective equipment at the time of injury.     

Intralesional radiolabeled human monoclonal IgM in human tumor xenografts

Sensory-perceptual abnormalities in people with autism are discussed from two perspectives: published firsthand accounts and existing psychological research evidence. A range of abnormalities, including hyper- and hyposensitivity, sensory distortion and overload, and multichannel receptivity and processing difficulties, are described in firsthand accounts and frequently portrayed as central to the autistic experience. A number of dangers are inherent in uncritically accepting these accounts at face value and in any wider generalization to the autistic population as a whole. Evidence from clinical studies suggests that unusual sensory responses are present in a majority of autistic children, that they are manifested very early in development, and that they may be linked with other aspects of autistic behavior. In addition, experimental studies using a range of indices have found evidence of unusual responses to sensory stimuli in autistic subjects. However the clinical and experimental research to date suffers from serious methodological limitations and more systematic investigation is warranted. Key issues for future psychological research in the area are identified.     

Preparation and characterization of chitosan‐based dispersions

Complexation of chitosan in aqueous solutions by low molecular weight electrolytes is one of the simplest methods for the preparation of aqueous chitosan dispersions. In this work, the influence of storage time, sulfate concentration, method of preparation and surfactant content on some properties of the resultant chitosan dispersions (turbidity, viscosity and zeta potential) was analyzed. Turbidimetry was adequate to monitor the formation of particles, while viscometry was suitable to monitor changes in the dispersing phase. An analysis of the properties of these systems, mainly in terms of particle–particle and macromolecule–macromolecule interactions was carried out. Copyright © 2004 Society of Chemical Industry     

Self-adjusting the intensity of assortative mating in genetic algorithms

Mate selection plays a crucial role in both natural and artificial systems. While traditional Evolutionary Algorithms (EA) usually engage in random mating strategies, that is, mating chance is independent of genotypic or phenotypic distance between individuals, in natural systems non-random mating is common, which means that somehow this mechanism has been favored during the evolutionary process. In non-random mating, the individuals mate according to their parenthood or likeness. Previous studies indicate that negative assortative mating (AM)—also known as dissortative mating—, which is a specific type of non-random mating, may improve EAs performance by maintaining the genetic diversity of the population at a higher level during the search process. In this paper we present the Variable Dissortative Mating Genetic Algorithm (VDMGA). The algorithm holds a mechanism that varies the GA’s mating restrictions during the run by means of simple rule based on the number of chromosomes created in each generation and indirectly influenced by the genetic diversity of the population. We compare VDMGA not only with traditional Genetic Algorithms (GA) but also with two preceding non-random mating EAs: the CHC algorithm and the negative Assortative Mating Genetic Algorithm (nAMGA). We intend to study the effects of the different methods in the performance of GAs and verify the reliability of the proposed algorithm when facing an heterogeneous set of landscapes. In addition, we include the positive Assortative Mating Genetic Algorithm (pAMGA) in the experiments in order test both negative and positive AM mechanisms, and try to understand if and when negative AM (or DM) speeds up the search process or enables the GAs to escape local optima traps. For these purposes, an extensive set of optimization test problems was chosen to cover a variety of search landscapes with different characteristics. Our results confirm that negative AM is effective in leading EAs out of local optima traps, and show that the proposed VDMGA is at least as efficient as nAMGA when applied to the range of our problems, being more efficient in very hard functions were traditional GAs usually fail to escape local optima. Also, scalability tests have been made that show VDMGA ability to decrease optimal population size, thus reducing the amount of evaluations needed to attain global optima. We like to stress that only two parameters need to be hand-tuned in VDMGA, thus reducing the tuning effort present in traditional GAs and nAMGA.     

The Simulation of Impact Loads on Beam-type Structures using a Pseudo-dynamic Procedure

Abstract:  This study proposes an alternate method for the analysis of beams with solid cross-section or built as a framed structure and subjected to transverse impact loads from an external striker. The procedure used in the analysis is a combination of two essential tools using pseudo-dynamic techniques. The method reported here involves only one degree of freedom for the structure modelling and assumes an elastic contact between an external striker and the beam structure, which in reality does not happen. As only one degree of freedom is considered in the analysis, some important limitations are inherent to the method proposed here. Essentially, there is the difficulty of modelling the displacement field associated with the transient structure behaviour accurately, as a consequence of fast-rate impact loads. Another difficulty faced by the method refers to a local structure behaviour associated with contact loads. The present method can deal with large displacements in transversely loaded beams associated to a collapse mechanism having a simple geometry and defined with precision from a single parameter. This ensures reasonable accuracy in the evaluation of the strain energy absorbing capacity of transversely impacted beam structures using a single degree of freedom model in a pseudo-dynamic procedure.