Lentiviral-mediated delivery of mutant huntingtin in the striatum of rats induces a selective neuropathology modulated by polyglutamine repeat size, huntingtin expression levels, and protein length.

A new strategy based on lentiviral-mediated delivery of mutant huntingtin (htt) was used to create a genetic model of Huntington's disease (HD) in rats and to assess the relative contribution of polyglutamine (CAG) repeat size, htt expression levels, and protein length on the onset and specificity of the pathology. Lentiviral vectors coding for the first 171, 853, and 1520 amino acids of wild-type (19 CAG) or mutant htt (44, 66, and 82 CAG) driven by either the phosphoglycerate kinase 1 (PGK) or the cytomegalovirus (CMV) promoters were injected in rat striatum. A progressive pathology characterized by sequential appearance of ubiquitinated htt aggregates, loss of dopamine- and cAMP-regulated phosphoprotein of 32 kDa staining, and cell death was observed over 6 months with mutant htt. Earlier onset and more severe pathology occurred with shorter fragments, longer CAG repeats, and higher expression levels. Interestingly, the aggregates were predominantly located in the nucleus of PGK-htt171-injected rats, whereas they were present in both the nucleus and processes of CMV-htt171-injected animals expressing lower transgene levels. Finally, a selective sparing of interneurons was observed in animals injected with vectors expressing mutant htt. These data demonstrate that lentiviral-mediated expression of mutant htt provides a robust in vivo genetic model for selective neural degeneration that will facilitate future studies on the pathogenesis of cell death and experimental therapeutics for HD

Evidence based practice in radiology: the radiographer perspective

This study is included in the exploratory-descriptive type, since it aims to analyze the applicability of knowledge and evidence based radiology by radiographers during their daily work and their academic education

Balanced scorecard performance assessment in a medical imaging department

The authors present and discuss the development of a strategic management model based on the Balanced Scorecard by Kaplan and Norton to implement in an imaging ward and the relations with Performance Measurement System that allows for the monitoring of the service's evolution, the alignment of objectives, and the evaluation of individual employees within the strategy of the ward and the hospital

Silencing mutant ataxin-3 rescues motor deficits and neuropathology in machado-joseph disease transgenic mice.

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominantly-inherited neurodegenerative disorder caused by the over-repetition of a CAG codon in the MJD1 gene. This expansion translates into a polyglutamine tract that confers a toxic gain-of-function to the mutant protein - ataxin-3, leading to neurodegeneration in specific brain regions, with particular severity in the cerebellum. No treatment able to modify the disease progression is available. However, gene silencing by RNA interference has shown promising results. Therefore, in this study we investigated whether lentiviral-mediated allele-specific silencing of the mutant ataxin-3 gene, after disease onset, would rescue the motor behavior deficits and neuropathological features in a severely impaired transgenic mouse model of MJD. For this purpose, we injected lentiviral vectors encoding allele-specific silencing-sequences (shAtx3) into the cerebellum of diseased transgenic mice expressing the targeted C-variant of mutant ataxin-3 present in 70% of MJD patients. This variation permits to discriminate between the wild-type and mutant forms, maintaining the normal function of the wild-type allele and silencing only the mutant form. Quantitative analysis of rotarod performance, footprint and activity patterns revealed significant and robust alleviation of gait, balance (average 3-fold increase of rotarod test time), locomotor and exploratory activity impairments in shAtx3-injected mice, as compared to control ones injected with shGFP. An important improvement of neuropathology was also observed, regarding the number of intranuclear inclusions, calbindin and DARPP-32 immunoreactivity, fluorojade B and Golgi staining and molecular and granular layers thickness. These data demonstrate for the first time the efficacy of gene silencing in blocking the MJD-associated motor-behavior and neuropathological abnormalities after the onset of the disease, supporting the use of this strategy for therapy of MJD

Development and validation of a model of motor competence in children and adolescents

Objectives: This study was aimed at developing a quantitative model to evaluate motor competence (MC) in children and adolescents, to be applicable in research, education, and clinical contexts. Design: Cross-sectional. Methods: A total of 584 children (boys n = 300) with ages between 6 and 14 years were assessed using nine well known quantitative motor tasks, divided into three major components (stability, locomotor and manipulative). Structural equation modelling through EQS 6.1 was used to find the best model for representing the structural and measurement validity of MC. Results: The final MC model was composed by three latent factors closely related with each other. Each factor was best represented by two of the initial three motor tasks chosen. The model was shown to give a very good overall fit (!2 = 12.04, p = .061; NFI = .982; CFI = .991; RMSEA = .059). Conclusions: MC can be parsimoniously represented by six quantitative motor tasks, grouped into three interrelated factors. The developed model was shown to be robust when applied to different samples, demonstrating a good structural and measurement reliability. The use of a quantitative protocol with few, simple to administer and well known, motor tasks, is an important advantage of this model, since it can be used in several contexts with different objectives. We find it especially beneficial for physical educations teachers who have to regularly assess their students

Determination of thresholds for storm impacts

Storms are responsible for important erosion, coastal retreat and damage when infrastructures are placed within their acting area. The characterisation of storm parameters and associated thresholds for erosion and damage are therefore of fundamental importance for coastal management purposes. This work presents ways of determining thresholds for important morphological changes (including erosion), overwash occurrence and damage associate to storm occurrence. These methods were tested and applied to Ancão Peninsula (South Portugal) and the results shown. The use of these approaches will enable coastal managers to have a quantitative knowledge of consequences associated to each particular storm and to act accordingly, for instance defining set-back lines, designing nourishments or implementing evacuation plans.info:eu-repo/semantics/publishedVersio

Head And Heck Mucoepidermoid Carcinoma: Clinicopathologic Study Of 173 Cases

Introduction: Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor, however few studies have been reported in Brazilian populations. Aim: To report clinical and pathologic data from 173 head and neck MEC treated in the Treatment and Research Center at Hospital do Câncer A. C. Camargo in São Paulo. Study design: Clinical randomized. Material and Method: From 1953 to 1997, 173 cases of MEC were found in the medical files of the center. Data were obtained from the patients' records and histological review of all cases. Results: The mean age of the patients was 44 years and 93 (53.8%) were men; parotid glands were affected in 61 cases (35.2%) and intraoral minor salivary glands in 75 (43.4%). TNM revealed 50.3% of the cases in stages I and II, and histological grading revealed 45.2%, 18.5% and 36.3% low-grade, intermediate-grade and high-grade tumors, respectively. Surgical treatment was employed in 80.3% of the cases, with neck dissection in 52 cases (30.1%), and radiotherapy in 73 (42.2%). Local recurrence, regional and distant metastases were found in 12.7%, 9.8% and 9.2% of the patients, respectively; 5-year and 10-year overall survival rates were 70% and 60%, respectively. Conclusions: MEC affected mainly the parotid gland and the palate of adults, without gender preference. Half of the cases were diagnosed at initial clinical stages and 64% of the tumors were low or intermediate-grade lesions. Surgery was the treatment of choice and prognosis was good.685679684Ellis, G.L., Auclair, P.L., Gnepp, D.R., Surgical Pathology of the salivary glands (1991) Major Problems in Pathology Series, 25. , Philadelphia: WB Saunders CompanyEllis, G.L., Auclair, P.L., Tumors of the Salivary Glands (1996) Armed Forces Institute of Pathology. Atlas of Tumor Pathology. 3 rd Series, , Fascicle 17. WashingtonAuclair, P.L., Goode, R.K., Ellis, G.L., Mucoepidermoid carcinoma of intraoral salivary glands (1992) Cancer, 69, pp. 2021-2030Cardoso, W.P., Denardin, O.V., Rapoport, A., Araujo, V.C., Carvalho, M.B., Proliferating cell nuclear antigen expression in mucoepidermoid carcinoma of salivary glands (2000) São Paulo Med J, 118, pp. 69-74Goode, R.K., Auclair, P.L., Ellis, G.L., Mucoepidermoid carcinoma of the major salivary glands: Clinical and histopathologic analysis of 234 cases with evaluation of grading criteria (1998) Cancer, 82, pp. 1217-1224Brandwein, M.S., Ivanov, K., Wallace, D.I., Hille, J.J., Wang, B., Fahmy, A., Bodian, C., Mills, S.E., Mucoepidermoid carcinoma: A clinicopathologic study of 80 patients with special reference to histological grading (2001) Am J Surg Pathol, 25, pp. 835-845Evans, H.L., Mucoepidermoid carcinoma of salivary glands: A study of 69 cases with special attention to histologic grading (1984) Am J Clin Pathol, 81, pp. 696-701Nascimento, A.G., Amaral, A.L.P., Prado, L.A.F., Kligerman, J., Silveira, T.R.P., Mucoepidermoid carcinoma of salivary glands: A clinicopathologic study of 46 cases (1986) Head Neck Surg, 8, pp. 409-417Plambeck, K., Friedrich, R.E., Bahlo, M., Bartel-Friedrich, S., Klapdor, R., TNM staging, histopathological grading, and tumor-associated antigens in patients with a history of mucoepidermoid carcinoma of the salivary glands (1999) Anticancer Res, 19, pp. 2397-2404Spiro, R.H., Huvos, A.G., Berk, R., Strong, E.W., Mucoepidermoid carcinoma of salivary gland origin: A clinicopathologic study of 367 cases (1978) Am J Surg, 136, pp. 461-468Chinellato, L.E.M., Marquez, I.M., Fleury, R.N., Quevedo, F.C., Estudos da prevalência dos tumores de origem epitelial de glândulas salivares em Serviços de Anatomia Patológica das cidades de Bauru e Jaú (Estado de São Paulo, Brasil) (1994) Rev Fac Odontol Bauru, 2, pp. 45-51Franzi, A.S., Carvalho, M.B., Carcinoma mucoepidermóide avançado das glândulas salivares (1997) Rev Bras Cancerol, 43, pp. 273-280Kusama, K., Iwanari, S., Aisaki, K., Wada, M., Ohtani, J., Itoi, K., Hanai, K., Moro, I., Intraoral minor salivary gland tumors: A retrospective study of 129 cases (1997) J Nihon Univ Sch Dent, 39, pp. 128-132Lopes, M.A., Kowalski, L.P., Santos, G.C., Almeida, O.P., A clinicopathologic study of 196 intraoral minor salivary gland tumors (1999) J Oral Pathol Med, 28, pp. 264-267Loyola, A.M., De Araujo, V.C., De Sousa, S.O.M., De Araujo, N.S., Minor salivary gland tumours: A retrospective study of 164 cases in a Brazilian population (1995) Oral Oncol Eur J Cancer, 31 B, pp. 197-201Rapoport, A., De Andrade Sobrinho, J., Brasilino De Carvalho, M., Magrin, J., Fava, A.S., Cancer of the parotid gland (1981) Int Surg, 66, pp. 243-246Rapoport, A., Carvalho, M.B., Fava, A.S., Góis Filho, J.F., Chagas, J.F.S., Kowalski, L.P., Kanda, J.L., Cheuhen, J.A., Diagnóstico e tratamento das neoplasias das glândulas salivares menores: Estudo de 55 casos (1988) Rev Col Bras Cirur, 15, pp. 289-293Regis De Brito Santos, I., Kowalski, L.P., Cavalcante De Araujo, V., Flavia Logullo, A., Magrin, J., Multivariate analysis of risk factors for neck metastasis in surgically treated parotid carcinomas (2001) Arch Otolaryngol Head Neck Surg, 127, pp. 56-60Spiro, R.H., Thaler, H.T., Hicks, W.F., Kher, U.A., Huvos, A.H., Strong, E.W., The importance of clinical staging of minor salivary gland carcinoma (1991) Am J Surg, 162, pp. 330-336Hicks, M.J., El-Naggar, A.K., Flaitz, C.M., Luna, M.A., Batsakis, J.G., Histocytologic grading of mucoepidermoid carcinoma of major salivary glands in prognosis and survival: A clinicopathologic and flow cytometric investigation (1995) Head Neck, 17, pp. 89-95Hicks, J., Flaitz, C., Mucoepidermoid carcinoma of salivary glands in children and adolescents: Assessment of proliferation markers (2000) Oral Oncol, 36, pp. 454-460Ma'aita, J.K., Al-Kalsi, N., Al-Tamimi, S., Wraikat, A., Salivary gland tumors in Jordan: A retrospective study of 221 patients (1999) Croat Med J, 40, pp. 539-54

Vision based referee sign language recognition system for the RoboCup MSL league

In RoboCup Middle Size league (MSL) the main referee uses assisting technology, controlled by a second referee, to support him, in particular for conveying referee decisions for robot players with the help of a wireless communication system. In this paper a vision-based system is introduced, able to interpret dynamic and static gestures of the referee, thus eliminating the need for a second one. The referee's gestures are interpreted by the system and sent directly to the Referee Box, which sends the proper commands to the robots. The system is divided into four modules: a real time hand tracking and feature extraction, a SVM (Support Vector Machine) for static hand posture identification, an HMM (Hidden Markov Model) for dynamic unistroke hand gesture recognition, and a FSM (Finite State Machine) to control the various system states transitions. The experimental results showed that the system works very reliably, being able to recognize the combination of gestures and hand postures in real-time. For the hand posture recognition, with the SVM model trained with the selected features, an accuracy of 98,2% was achieved. Also, the system has many advantages over the current implemented one, like avoiding the necessity of a second referee, working on noisy environments, working on wireless jammed situations. This system is easy to implement and train and may be an inexpensive solution

Activity-regulated cytoskeleton-associated protein controls AMPAR endocytosis through a direct interaction with clathrin-adaptor protein 2

The activity-regulated cytoskeleton-associated (Arc) protein controls synaptic strength by facilitating AMPA receptor (AMPAR) endocytosis. Here we demonstrate that Arc targets AMPAR to be internalized through a direct interaction with the clathrin-adaptor protein 2 (AP-2). We show that Arc overexpression in dissociated hippocampal neurons obtained from C57BL/6 mouse reduces the density of AMPAR GluA1 subunits at the cell surface and reduces the amplitude and rectification of AMPAR-mediated miniature-EPSCs (mEPSCs). Mutations of Arc, that prevent the AP-2 interaction reduce Arc-mediated endocytosis of GluA1 and abolish the reduction in AMPAR-mediated mEPSC amplitude and rectification. Depletion of the AP-2 subunit µ2 blocks the Arc-mediated reduction in mEPSC amplitude, an effect that is restored by reintroducing µ2. The Arc-AP-2 interaction plays an important role in homeostatic synaptic scaling as the Arc-dependent decrease in mEPSC amplitude, induced by a chronic increase in neuronal activity, is inhibited by AP-2 depletion. These data provide a mechanism to explain how activity-dependent expression of Arc decisively controls the fate of AMPAR at the cell surface and modulates synaptic strength, via the direct interaction with the endocytic clathrin adaptor AP-2

Travelling waves for the Gross-Pitaevskii equation II

The purpose of this paper is to provide a rigorous mathematical proof of the existence of travelling wave solutions to the Gross-Pitaevskii equation in dimensions two and three. Our arguments, based on minimization under constraints, yield a full branch of solutions, and extend earlier results, where only a part of the branch was built. In dimension three, we also show that there are no travelling wave solutions of small energy.Comment: Final version accepted for publication in Communications in Mathematical Physics with a few minor corrections and added remark