91 research outputs found
Systematic use of isolated pancreatic anastomosis after pancreatoduodenectomy: Five years of experience with zero mortality
No full textAbstractObjectiveThe aim of this study is to perform a comprehensive evaluation of 5 years of experience with the technique of isolated pancreatic anastomosis reconstruction after pancreatoduodenectomy from the perspective of safety and surgical efficacy using a prospective database.MethodsThe study included all consecutive patients undergoing pancreatoduodenectomy from April 2009 to April 2014 at a single referral center for hepato-pancreato-biliary diseases. The primary endpoint was the safety of the procedures, which was assessed as the occurrence of complications during hospitalization. Ninety-day mortality was also assessed. Postoperative pancreatic fistulas were classified as grade A, B, or C according to the International Study Group of Pancreatic Fistula classification.ResultsThe study group included 214 consecutive patients with a median age of 60 years who underwent pancreatoduodenectomy. Portal vein resection was performed on 41 patients. Indications for resection were 165 pancreatic head tumors, 33 ampullary tumors, 7 chronic pancreatitis, 3 distal bile duct tumors, and 6 duodenal tumors. There was no perioperative or 90-day mortality in this series. Complications occurred in 68 patients (32%), and 42 patients presented with pancreatic fistulas (19.6%). Grade A fistulas were present in 38 patients. Three patients presented persistent pancreatic fistula and were treated with percutaneous drainage. One patient developed combined pancreatic and biliary fistulas and was reoperated on for pancreatic abscess drainage.ConclusionsThe technique of isolated pancreatic anastomosis by diverting the pancreatic from biliary secretion may contribute to reducing the severity of pancreatic fistulas and therefore the severity of this complication
Increased transcript diversity: novel splicing variants of Machado-Joseph disease gene (ATXN3)
No full textMachado-Joseph disease (MJD) is a late-onset neurodegenerative disorder that presents clinical heterogeneity not completely explained by its causative mutation. MJD is caused by an expansion of a CAG tract at exon 10 of the ATXN3 gene (14q32.1), which encodes for ataxin-3. The main goal of this study was to analyze the occurrence of alternative splicing at the ATXN3 gene, by sequencing a total of 415 cDNAs clones (from 20 MJD patients and 14 controls). Two novel exons are described for the ATXN3 gene. Fifty-six alternative splicing variants, generated by four types of splicing events, were observed. From those variants, 50 were not previously described, and 26 were only found in MJD patients samples. Most of the variants (85.7%) present frameshift, which leads to the appearance of premature stop codons. Thirty-seven of the observed variants constitute good targets to nonsense-mediated decay, the remaining are likely to be translated into at least 20 different isoforms. The presence of ataxin-3 domains was assessed, and consequences of domain disruption are discussed. The present study demonstrates high variability in the ATXN3 gene transcripts, providing a basis for further investigation on the contribution of alternative splicing to the MJD pathogenic process, as well as to the larger group of the polyglutamine disorders.This work was supported by“Projecto RegionalIntegrado, DMJ (PRI-DMJ)”(funded by Regional Government of theAzores), and“Transcriptional variation of theATXN3gene asmodulator of the clinical heterogeneity in Machado–Joseph disease(MJD)”(PIC/IC/83074/2007, funded by“Fundação para a Ciência e aTecnologia”, FCT). C.B. (SFRH/BD/21875/2005) is a recipient of aPhD grant, and C.S. (SFRH/BPD/20944/2004) and M.C.C. (SFRH/BPD/28560/2006) are postdoctoral fellows from FC
Motion Cueing Algorithm for Simulators using MPC Strategy with Workspace Management
No full textIn research, training and entertainment industries, simulators are used to replicate human perception of vehicle motion in a safe and customizable environment. The perception of self- motion of the driver inside the simulator is improved by the presence of motion cues generated by a motion system. However, direct feedthrough of these vehicle cues require movements of the system that exceed the physical capabilities of its actuators. Therefore, a control process must be realized that translates these movements, this is typically the objective of a motion cueing algorithm. In this thesis a Model Predictive Control (MPC) based cueing algorithm is developed which transforms simulated vehicle cues into motions exerted on a motion system, while maintaining a realistic driving experience. It balances a trade-off between the perception fidelity of the generated cues and the usage of workspace, where models of the vestibular system are used to simulate the driver’s perceived motions. One of MPC’s benefits is the use of a receding horizon principle, which is characterized by a repeated optimization of control actions over a future prediction interval. The algorithm uses a Single DOF Excursion (SDE) analysis to be aware of the available size of the workspace and adapts its generated cues accordingly. Hence, adaptive weights and constraints are applied in order to manage the motions within the changing workspace, where an adaptive converging constraints method finally matched the research objectives. This method is verified with different case studies, the robustness to different input signals, the washout of the workspace and the influence of known future vehicle motions on the response are investigated. Furthermore, the method is compared to cueing algorithms from both literature and industry. It shows a workspace washout with minimized motion perception, an accurate reference tracking for different input signals and a full exploitation of the workspace. Moreover, knowledge about the future vehicle accelerations resulted in an improvement of the reference tracking, a reduction in false cues and it triggered the use of preposition techniques. Finally, comparisons with acknowledged cueing algorithms show a less smooth response with spurious jerks, however larger onsets, better reference tracking, longer sustained accelerations, and more efficient workspace exploitations are observed for the MPC based method.Delft Center for Systems and ControlMechanical, Maritime and Materials Engineerin
Citalopram reduces aggregation of ATXN3 in a YAC transgenic mouse model of Machado-Joseph disease
No full textMachado-Joseph disease, also known as spinocerebellar ataxia type 3, is a fatal polyglutamine disease with no disease-modifying treatment. The selective serotonin reuptake inhibitor citalopram was shown in nematode and mouse models to be a compelling repurposing candidate for Machado-Joseph disease therapeutics. We sought to confirm the efficacy of citalopram to decrease ATXN3 aggregation in an unrelated mouse model of Machado-Joseph disease. Four-week-old YACMJD84.2 mice and non-transgenic littermates were given citalopram 8 mg/kg in drinking water or water for 10 weeks. At the end of treatment, brains were collected for biochemical and pathological analyses. Brains of citalopram-treated YACMJD84.2 mice showed an approximate 50% decrease in the percentage of cells containing ATXN3-positive inclusions in the substantia nigra and three examined brainstem nuclei compared to controls. No differences in ATXN3 inclusion load were observed in deep cerebellar nuclei of mice. Citalopram effect on ATXN3 aggregate burden was corroborated by immunoblotting analysis. While lysates from the brainstem and cervical spinal cord of citalopram-treated mice showed a decrease in all soluble forms of ATXN3 and a trend toward reduction of insoluble ATXN3, no differences in ATXN3 levels were found between cerebella of citalopram-treated and vehicle-treated mice. Citalopram treatment altered levels of select components of the cellular protein homeostatic machinery that may be expected to enhance the capacity to refold and/or degrade mutant ATXN3. The results here obtained in a second independent mouse model of Machado-Joseph disease further support citalopram as a potential drug to be repurposed for this fatal disorder.This work was funded by Becky Babcox Research
Fund/pilot research award G015617, University of Michigan to M.C.C.
and NINDS/NIH R01NS038712 to H.L.P. The work performed at the
University of Minho was funded by the European Regional
Development Funds (FEDER), through the Competitiveness Factors
Operational Programme (COMPETE), and by National funds, through
the Foundation for Science and Technology (FCT), under the scope of the
project POCI-01-0145-FEDER-007038. This article was developed under the scope of the project NORTE-01-0145-FEDER-000013, supported
by the Northern Portugal Regional Operational Program (NORTE 2020),
under the Portugal 2020 Partnership Agreement, through the FEDER.
This work was also supported by FCT and COMPETE through the projects [PTDC/SAU-GMG/112617/2009] (to P.M.) and [EXPL/BIM-MEC/
0239/2012] (to A.T.C.); by FCT through the project [POCI-01-0145-
FEDER-016818 (PTDC/NEU-NMC/3648/2014)] (to P.M.); by National
Ataxia Foundation (to P.M. and to A.T.C.); and by Ataxia UK (to P.M.).
S.D.S. and A.T.C. were supported by fellowships from FCT, SFRH/BD/
78388/2011 and SFRH/BPD/102317/2014, respectively. FCT fellowships are co-financed by POPH, QREN, Governo da República
Portuguesa and EU/FSE
Occupational Accidents And Health-related Quality Of Life: A Study In Three Hospitals [accidentes De Trabajo Y Calidad De Vida: Un Estudio En Tres Hospitales]
No full textThis study analyzed the occurrence of occupational accidents among hospital workers between 2000 and 2005 and health-related quality of life of a sample of injured workers in 2005. Data obtained through occupational accident reports indicated 286 injured workers. In typical accidents (91.6%), accidents with piercing-cutting instruments affected 68.5% of workers. The results related to health-related quality of life obtained from 61 injured workers in 2005, through the SF-36 Medical Outcomes Study 36 - item short form health survey, evidenced high average values in most of the analyzed domains, while the lowest score observed was Vitality and Bodily Pain. No significant differences in health-related quality of life were found among injured workers from the three studied hospitals.171101107Benatti, M.C.C., (1997) Acidentes do trabalho em um hospital universitário: Um estudo sobre a ocorrência e os fatores de risco entre trabalhadores de enfermagem, , [Tese]. São Paulo (SP): Escola de Enfermagem/USPThe development of the world health organization quality of life assessment instrument (the WHOQOL) (1994) Quality of Life Assessment: International Perspectives, , Whoqol Group, In: Orley J, Kuyken W, editors, Heigelberg: Springer VerlagAuquier, P., Simeoni, M.C., Mendizabal, H., Approaches théoriques et méthodologiques de la qualité de vie a la santé (1997) Rev Prevenir, 33, pp. 77-86Ware, J.E., Sherbourne, C.D., The MOS 36- Item Short-Form Health Survey (SF-36) (1992) Med Care, 30 (6), pp. 473-83Ciconelli, R.M., Ferraz, M.B., Santos, W., Meinão, I., Quaresma, M.R., Tradução para a língua portuguesa e validação do questionário genérico de avaliação de qualidade de vida SF-36 (1999) Rev Bras Reumatol, 39 (3), pp. 143-50Nunnally, J.C., (1978) Psychometric Theory, , New York: McGraw-HillBalsamo, A.C., (2002) Estudo sobre os acidentes do trabalho com exposição aos líquidos corporais humanos em trabalhadores da saúde, , [Dissertação]. São Paulo (SP): Escola de Enfermagem/USPMarziale, M.H.P., Rodrigues, C.M., A produção científica sobre acidentes de trabalho com material perfurocortante entre trabalhadores de enfermagem (2002) Rev Latino-am Enfermagem, 10 (4), pp. 571-7. , julhoSouza, M., (1999) Acidentes ocupacionais e situações de risco para a equipe de enfermagem: Um estudo em cinco hospitais do município de São Paulo, , [Tese]. São Paulo (SP): Escola Paulista de Medicina/UNIFESPSilva, V.E.F., (1988) Estudo sobre acidentes de trabalho ocorridos com trabalhadores de enfermagem de um hospital de ensino, , São Paulo (SP): Escola de Enfermagem/USPCanini, S.R.M.S., Gir, E., Hayahida, M., Machado, A.A., Acidentes perfurocortantes entre trabalhadores de enfermagem de um hospital universitário do interior paulista (2002) Rev Latino-am Enfermagem, 10 (2), pp. 172-8. , março/abrilGurgueira, G.P., (2005) Contribuições ao estudo de qualidade de vida e restrições de trabalho em uma instituição hospitalar, , [Dissertação-Mestrado]. Campinas: Faculdade de Ciências Médicas, Universidade Estadual de CampinasOliveira, A.P.B.M., (2004) Qualidade de vida e sintomas osteomusculares em médicos de um hospital universitário, , [Dissertação-Mestrado]. Campinas: Faculdade de Ciências Médicas, Universidade Estadual de Campina
Potencialidades e limitações das práticas de saúde desenvolvidas por apoiadores institucionais da política nacional de humanização
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Saúde Coletiva, Florianópolis, 2013This research investigates the potential and limitations of the devices and actions developed from a process of training intervention of institutional supporters of the HNP, to change health practices, from their plans. The analysis revealed three categories: "Devices and actions of PNH" Pointing Method Wheel as potential for discussion on health services and co-management that stands out while device HNP; " Difficulties faced ", which are described weaknesses relating to the management and labor relations, and finally, "Intervention for Transformation", which shows the formation of networks, links, personal change, inclusion and valuation of all such transformations occurred. We conclude that the PNH achieved through the course of supporters in Santa Catarina, create spaces of the building and the exchange of knowledge, ways of investing in teamwork
Functional genomics and biochemical characterization of the C. elegans orthologue of the Machado-Joseph disease protein ataxin-3
No full textMachado-Joseph disease (MJD) is the most common dominant spinocerebellar ataxia. MJD is caused by a CAG trinucleotide expansion in the ATXN3 gene, which encodes a protein named ataxin-3. Ataxin-3 has been proposed to act as a deubiquitinating enzyme in the ubiquitin-proteasome pathway and to be involved in transcriptional repression; nevertheless, its precise biological function(s) remains unknown. To gain further insight into the function of ataxin-3, we have identified the Caenorhabditis elegans orthologue of the ATXN3 gene and characterized its pattern of expression, developmental regulation, and subcellular localization. We demonstrate that, analogous to its human orthologue, C. elegans ataxin-3 has deubiquitinating activity in vitro against polyubiquitin chains with four or more ubiquitins, the minimum ubiquitin length for proteasomal targeting. To further evaluate C. elegans ataxin-3, we characterized the first known knockout animal models both phenotypically and biochemically, and found that the two C. elegans strains were viable and displayed no gross phenotype. To identify a molecular phenotype, we performed a large-scale microarray analysis of gene expression in both knockout strains. The data revealed a significant deregulation of core sets of genes involved in the ubiquitin-proteasome pathway, structure/motility, and signal transduction. This gene identification provides important clues that can help elucidate the specific biological role of ataxin-3 and unveil some of the physiological effects caused by its absence or diminished function.This research was supported by the National Ataxia Foundation(Minneapolis, MN, USA), by the Portuguese-American Foundation for Development (FLAD) (Project 582–99), by Fundação Calouste Gulbenkian, and by FEDER/FCT (POCTI/SAU-MGI/34759/99 and POCTI/SAU-MMO/60412/2004). A.J.R., C.S.,and M.C.C. received scholarships from FCT
Genomic structure, promoter activity, and developmental expression of the mouse homologue of the Machado–Joseph disease (MJD) gene
No full textMachado–Joseph disease (MJD) is a neurodegenerative disorder, caused by the expansion of the (CAG)n tract in the MJD gene. This
encodes the protein ataxin-3, of unknown function. The mouse Mjd gene has a structure similar to that of its human counterpart and it also
contains a TATA-less promoter. Its 5V flanking region contains conserved putative binding regions for transcription factors Sp1, USF, Arnt,
Max, E47, and MyoD. Upon differentiation of P19 cells, the Mjd gene promoter is preferentially activated in endodermal and mesodermal
derivatives, including cardiac and skeletal myocytes; and less so in neuronal precursors. Mouse ataxin-3 is ubiquitously expressed during
embryonic development and in the adult, with strong expression in regions of the CNS affected in MJD. It is particularly abundant in all types
of muscle and in ciliated epithelial cells, suggesting that it may be associated with the cytoskeleton and may have an important function in
cell structure and/or motility.We thank Mark Tessaro, Laura Montermini, Margarida Duarte, João Sousa, and Teresa Summavielle for their cooperation in this study and Sandra Macedo Ribeiro for critical review of the manuscript. We also thank Henry Paulson for providing of the anti-human ataxin-3 antiserum. This work was supported by the FSE/FEDER and the Fundação para a Ciência e Tecnologia (FCT) (Project POCTI/MGI 33759/99) and the Fundação Luso-Americana para o Desenvolvimento (Proc. 3.L./A.II/P.582/99) and by a grant from the Canadian Institutes of Health Research (CIHR, Grant MOP44045) to M.M.S. M.M.S. is the recipient of a CIHR New Investigator award. M.C.C. is the recipient of a Ph.D. scholarship from FCT, (BD/9759/2003). Printing of color figures was supported by Bioportugal, Bonsai Technologies, and Vidrolab
Occupational Exposure Of Health Care Workers To Organic Fluids And Adhesion To Chemoprophylaxis [exposições Ocupacionais Por Fluidos Corpóreos Entre Trabalhadores Da Saúde E Sua Ades-tiao à Qulmioprofilaxia]
No full textThis study was aimed at investigating the characteristics of occupational accidents and of the workers that suffered them, and at evaluating the adhesion to chemoprophylaxis and to control and follow up tests after occupational accidents with risk of contamination by the human immunodeficiency virus and of the hepatitis B and C virus. This is a descriptive epidemiological study whose data was collected from the notifications of one of the administrative regions of the State of São Paulo's Secretary of Health between 2000 and 2001. It was observed 7.3% of refusals for chemoprophylaxis against human immunodeficiency virus by antiretrovirals, and that 40.6% of the care workers who accepted the chemoprophylaxis did not complete the treatment in the four weeks estimated for it. This diagnosis highlights the need for the institutions involved to establish strategies that make possible an increase in the adherence of health workers to these care procedures.411120126Gerberding, J.L., Management of occupational exposures to blood-borne viruses (1995) N Engl J Med, 332 (7), pp. 444-451Needlestick transmission of HTLV-III from a patient infected in Africa (1984) Lancet, 2 (8416), p. 1376Cardo, D.M., Bell, D.M., Bloodborne pathogen transmission in health care workers. Risks and prevention strategies (1997) Infect Dis Clin North Am, 11 (2), pp. 331-346Case control study of HIV serocon-version in health-care workers after percutaneous exposure to HIV-infected blood. France, United Kingdom, and United States, January 1988 - August 1994 (1995) MMWR Morb Mortal Wkly Rep, 44 (50), pp. 929-933. , Centers for Disease Control CDCConnor, E.M., Sperling, R.S., Gelber, R., Kiselev, P., Scott, G., O'Sullivan, M.J., Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment (1994) N Engl J Med, 331 (12), pp. 1173-1180(1996) New drugs for HIV infection. Med Lett Drugs Ther, 38 (972), pp. 35-37Update: Provisional Public Health Service recommendations for chemoprophylaxis after occupational exposure to HIV (1996) MMWR Morb Mortal Wkly Rep, 45 (22), pp. 468-480. , Centers for Disease Control and Prevention CDCNemes MIB, Souza MFM, Kalichman AO, Grangeiro A, Souza RA, Lopes JF. Aderência ao tratamento por anti-retrovirais em serviços públicos de saúde no Estado de São Paulo [monografia na Internet]. Brasília: Ministério da Saúde2000 [citado 2003 fev. 1]. Disponível em http://www.aids.gov.br/final/ biblioteca./avalia1/home.htmAlexandre, N.M.C., Nordim, M., Hiebert, R., Campello, M., Predictors of compliance with short-term treatment among patients with back pain (2002) Rev Panam Salud Publica, 12 (2), pp. 86-94Cramer, J.A., Microelectronic systems for monitoring and enchancing patient compliance with medication regimens (1995) Drugs, 49 (3), pp. 321-327Sollitto, S., Mehlman, M., Youngner, S., Lederman, M.M., Should physicians withhold highly active antiretroviral therapies from HIV-AIDS patients who are thought to be poorly adherent to treatment? (2001) AIDS, 15 (2), pp. 153-159Chesney, M.A., Ickovics, J.R., Chambers, D.B., Gifford, A.L., Neidig, J., Zwickl, B., Self-reported adherence to antiretroviral medications among participants in HIV clinical trial: The AACTG Adherence Instruments (2000) AIDS Care, 12 (3), pp. 255-266Paulo, S., Secretaria de Estado da Saúde. 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São Paulo: Escola de Enfermagem, Universidade de São Paulo1988Benatti, M.C.C., Acidente do trabalho em um hospital universitário: Um estudo sobre a ocorrência e os fatores de risco entre trabalhadores de enfermagem [tese] (1997) São Paulo: Escola de Enfermagem, , Universidade de São Paulo;Stanford, M.P., Black, T.R., March, L.M., Holt, D.A., Campbell, D.H., Hepatitis B vaccination rates among staff at a District General Hospital (1995) Med J Austral, 162 (20), pp. 304-306Thiengo, M.A., Oliveira, D.C., Rodrigues, B.M.R.D., Representações sociais do HIV/AIDS entre adolescentes: Implicações para os cuidados de enfermagem. 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Motor uncoordination and neuropathology in a transgenic mouse model of Machado-Joseph disease lacking intranuclear inclusions and ataxin-3 cleavage products
No full textMachado-Joseph disease (MJD) is a late-onset neurodegenerative disorder caused by a polyglutamine (polyQ) expansion in the ataxin-3 protein. We generated two transgenic mouse lineages expressing the expanded human ataxin-3 under the control of the CMV promoter: CMVMJD83 and CMVMJD94, carrying Q83 and Q94 stretches, respectively. Behavioral analysis revealed that the CMVMJD94 transgenic mice developed motor uncoordination, intergenerational instability of the CAG repeat and a tissue-specific increase in the somatic mosaicism of the repeat with aging. Histopathological analysis of MJD mice at early and late stages of the disease revealed neuronal atrophy and astrogliosis in several brain regions; however, we found no signs of microglial activation or neuroinflammatory response prior to the appearance of an overt phenotype. In our model, the appearance of MJD-like symptoms was also not associated with the presence of ataxin-3 cleavage products or intranuclear aggregates. We propose the transgenic CMVMJD94 mice as a useful model to study the early stages in the pathogenesis of MJD and to explore the molecular mechanisms involved in CAG repeat instability.We would like to thank to Dr. Henry Paulson for providing the anti-ataxin-3 serum, Dr. Monica Sousa for the pCMV vector and to Eng. Lucilia Goreti Pinto for technical assistance. AS-F., M.C.C., S.S. and C.B. received FCT fellowships (SFRH/BD/15910/2005; SFRH/BPD/28560/2006; PTDC/SAU-GMG/64076/2006; SFRH/BPD/20987/2004). This research was funded by Fundacao para a Ciencia e Tecnologia through projects FEDER/FCT, POCI/SAU-MMO/60412/2004, PTDC/SAU-GMG/64076/2006; and Ataxia MJD Research Project
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