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Management of autoimmune hepatitis:Focus on pharmacologic treatments beyond corticosteroids

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World Journal of Hepatology 2014年第6期6卷 410-418页

作者： Marta Casal Moura Rodrigo Liberal Hélder Cardoso ana maria horta e vale Guilherme Macedo Servico de Medicina Interna Centro Hospitalar de Sao JoaoE.P.E.Porto 4200-319Portugal Faculdade de Medicina da Universidade do Porto Hernani MonteiroPorto 4200-319Portugal Paediatric Liver Centre and Institute of Liver Studies King’s College London School of Medicine at King’s College HospitalLondon SE5 9RSUnited Kingdom Guilherme Macedo Servico de GastrenterologiaCentro Hospitalar de Sao JoaoE.P.E.Porto 4202-451Portugal

In autoimmune hepatitis, patients who are intolerant or with toxicity experience, non-responders, relapsers or refractory are challenging. Non-standard drugs are being tried to preemptively avoid corticosteroid-related side effects. Prognosis and quality of life of life rely on treatment optimization. Recently, emergence of powerful immunosuppressive agents, mainly from liver transplantation, challenged the supremacy of the corticosteroid regime and promise greater immunosuppression than conventional medications, offer site-specific actions and satisfactory patient tolerance. Successes in experimental models of related diseases have primed these molecular interventions. We performed a literature review on alternative treatments. Azatioprine intolerance is the principal indication for mycophenolate use butit can be used as a front-line therapy. Cyclosporine A and tacrolimus have been tested for non-responders or relapsers. Rituximab may be used as salvage therapy. Anti-tumor necrosis factor-alpha agents may be used for incomplete responses or non-responders. Methotrexate is possibly an alternative for induction of remission and maintenance in refractory patients. Cyclophosphamide has been included in the induction regimen with corticosteroids. Ursodeoxycholic acid action is mainly immunomodulatory. Non-standard treatments are coming slowly to the attention, but its use should be cautious performed by experienced centers.

关键词： Autoimmune hepatitis Pharmacologic nonstandard treatment Immunosuppression Azathioprine intolerance Difficult-to-treat patients Salvage therapy

Motivations for and barriers to innovation in non-profit organizations: The case of nursing homes in Northern Portugal

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International Journal of Innovation Studies 2024年第1期8卷 25-44页

作者： ana Rita Gonçalves Lopes Aldina Isabel de Azevedo Correia Alexandra maria da Silva Braga Center for Research and Innovation in Business Sciences and Information Systems School of Management and TechnologyPolitecnico do PortoRua do Curral-Margaride4610-156 FelgueirasPortugal

To contribute to the empirical literature on innovation in non-profit organizations,this study examines innovation in Private Social Solidarity Institutions with social responses for the elderly in Northern *** enriches the literature by clarifying the concept of innovation applied to non-profit organizations,which represents a perspective different from the business ***,it is important to support the innovation decisionmaking process in similar non-profit *** this study,the population was surveyed through questionnaires based on the PUBLIN research project,which has already been applied in different countries,and the targets were employees of organizations with social responses for the *** sample is small,with 28 respondent institutions and 51 employees,but it is representative,as it includes institutions from all districts in Northern *** study employed a quantitative approach,particularly factor analysis,multiple linear regression,and correlation analyses,using scales already applied in other dimensions of the social sector,to understand the effect of each innovation dimension/determinant on creativity and innovation in nonprofit *** results show that in these organizations with social responses for the elderly,learning orientation,risk-taking,and job satisfaction have a positive impact on innovation.

关键词： Determinants of innovation non-profit organizations social responses for the elderly Northern Portugal

Long chikungunya?An overview to immunopathology of persistent arthralgia

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World Journal of Virology 2024年第2期13卷 48-57页

作者： Jayme euclydes Picasky Silveira-Freitas maria Luiza Campagnolo mariana dos Santos Cortez Fabrício Freire de Melo ana Carla Zarpelon-Schutz Kádima Nayara Teixeira Campus Toledo Universidade Federal do ParanáToledoParaná85919-899Brazil Instituto Multidisciplinar em Saúde Universidade Federal da BahiaCampus Anísio TeixeiraVitória da ConquistaBahia 45029-094Brazil Programa de Pós-graduação em Biotecnologia PalotinaUniversidade Federal do Paraná-Setor PalotinaParaná85950-000Brazil Programa Multicêntrico de Pós-graduação em Bioquímica e Biologia Molecular PalotinaUniversidade Federal do Paraná-Setor PalotinaParaná85950-000Brazil

Chikungunya fever(CF)is caused by an arbovirus whose manifestations are extremely diverse,and it has evolved with significant severity in recent *** clinical signs triggered by the Chikungunya virus are similar to those of other ***,fever starts abruptly and reaches high levels,followed by severe polyarthralgia and myalgia,as well as an erythematous or petechial maculopapular rash,varying in severity and *** 40%to 60%of affected individuals report persistent arthralgia,which can last from months to *** symptoms of CF mainly represent the tissue tropism of the virus rather than the immunopathogenesis triggered by the host's immune *** main mechanisms associated with arthralgia have been linked to an increase in T helper type 17 cells and a consequent increase in receptor activator of nuclear factor kappa-Βligand and bone *** review suggests that persistent arthralgia results from the presence of viral antigens post-infection and the constant activation of signaling lymphocytic activation molecule family member 7 in synovial macrophages,leading to local infiltration of CD4+T cells,which sustains the inflammatory process in the joints through the secretion of pro-inflammatory *** term"long chikungunya"was used in this review to refer to persistent arthralgia since,due to its manifestation over long periods after the end of the viral infection,this clinical condition seems to be characterized more as a sequel than as a symptom,given that there is no active infection involved.

关键词： Chikungunya Immunopathology Inflammation process Persistent arthralgia Signaling lymphocytic activation molecule family member 7

Synthesis, Characterization and Thermophysical Properties of Three Neoteric Solvents-Ionic Liquids Based on Choline Chloride

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Chemical Research in Chinese Universities 2014年第1期30卷 119-124页

作者： POPeSCU ana-maria CONSTANTIN Virgil Laboratory of Molten Salts llie Murgulescu Institute of Physical Chemistry of the Romanian Academy Bucharest 006021 Romania

The authors prepared,characterized and preliminary studied the properties of some neoteric solvents-ionic liquids based on choline chloride,i.e.,three ionic liquids based on the eutectics of choline chloride（2-hydroxyN,N,N-trimethylethanaminium chloride） with,respectively,urea,malonic acid and citric *** obtained mixtures were clear and colorless ionic liquids at room *** thermophysical properties,namely,density,viscosity,and electrical conductivity of these mixtures were investigated as a function of temperature within a range of 298-353 *** for the temperature dependence of the measured properties were generated and discussed in terms of Arrhenius *** the electrochemical windows of the eutectic liquids were determined.

关键词： Neoteric solvent Ionic liquid Choline chloride Malonic acid Citric acid Density Viscosity Conductivity

Current knowledge on esophageal atresia

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World Journal of Gastroenterology 2012年第28期18卷 3662-3672页

作者： Paulo Fernando Martins Pinheiro ana Cristina Simoes e Silva Regina maria Pereira Department of Pediatric Surgery Odilon Behrens HospitalAvenida JoséBonifácioSão CristovãoBelo Horizonte31210-690 Minas GeraisBrazil Department of Pediatrics Faculty of MedicineFederal University of Minas GeraisBelo Horizonte30130-100 Minas GeraisBrazil

esophageal atresia (eA) with or without tracheoesophageal fistula (TeF) is the most common congenital anomaly of the esophagus. The improvement of survival observed over the previous two decades is multifactorial and largely attributable to advances in neonatal intensive care, neonatal anesthesia, ventilatory and nutritional support, antibiotics, early surgical intervention, surgical materials and techniques. Indeed, mortality is currently limited to those cases with coexisting severe life-threatening anomalies. The diagnosis of eA is most commonly made during the first 24 h of life but may occur either antenatally or may be delayed. The primary surgical correction for eA and TeF is the best option in the absence of severe malformations. There is no ideal replacement for the esophagus and the optimal surgical treatment for patients with long-gap eA is still contro-versial. The primary complications during the postoperative period are leak and stenosis of the anastomosis, gastro-esophageal reflux, esophageal dysmotility, fistula recurrence, respiratory disorders and deformities of the thoracic wall. Data regarding long-term outcomes and follow-ups are limited for patients following eA/TeF repair. The determination of the risk factors for the complicated evolution following eA/TeF repair may positively impact long-term prognoses. Much remains to be studied regarding this condition. This manuscript provides a literature review of the current knowledge regarding eA.

关键词： esophageal atresia Tracheoesophageal fistula esophageal stenosis Long-gap Gastro-esophageal reflux

Subterranean termites （Isoptera： Rhinotermitidae）： exploitation of equivalent food resources with different forms of placement

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Insect Science 2012年第3期19卷 412-418页

作者： Juliana Toledo Lima ana maria Costa-Leonardo Departamento de Biologia Instituto de BiocienciasUNESP-Univ Estadual PaulistaRio Claro-SPBrazil

Coptotermes gestroi and Heterotermes tenuis have been described as important urban pests in Brazil. The establishment of control technologies using baits that consider the social behavior of termites requires a better knowledge of their foraging behavior. Thus, this study analyzed the feeding behavior of these species with three different forms of food placement： food on the surface of a substrate and food either partially or completely buried in the substrate. experimental arenas were composed of a central chamber connected to three food chambers. each central chamber contained 550 foragers of C. gestroi or 517 foragers of 11. tenuis. Blocks of Pinus elliottii were placed in the different food chambers. After 28 days, the consumption of each wood block and the percentage of foraging individuals recruited for food chambers were verified in relation to the total survival rate obtained for each one of the 20 replicates. Results showed that completely buried food was most consumed for H. tenuis and presented a higher recruitment rate of workers and soldiers for both species. Although the consumption had non-significant differences for C. gestroi, these termites exhibited a tendency to prefer completely buried food. In these conditions, it can be concluded that the forms of food placement used in the present research influenced the recruitment of individuals for both species. Data also suggests that when the foraging subterranean termites find food resources in the tunneling substrate, they tend to concentrate their efforts on it, a behavior regime that reduces exposure to external environment.

关键词： Coptotermes gestroi feeding behavior foraging behavior Heterotermes tenuis

Clinical features of AIDS patients with Hodgkin's lymphoma with isolated bone marrow involvement:report of 12 cases at a single institution

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Cancer Biology & Medicine 2015年第1期12卷 41-45页

作者： Marcelo Corti maria Villafa?e Gonzalo Minue ana Campitelli Marina Narbaitz Leonardo Gilardi HIV/AIDS Department F.J.Mu?iz Hospital Hematology Unit F.J.Mu?iz Hospital Histopathology Laboratory F.J.Mu?iz Hospital National Academy of Medicine Histopathology Laboratory Sociedad Iberoamericana de Informacion Cientifica Scientific Coordination

Objective： To study the main clinical and histopathological features of 12 patients with Hodgkin＇s lymphoma （HL） diagnosed primarily from bone marrow （BM） involvement. Methods： We included 12 acquired immunodeficiency syndrome （AIDS） patients with HL assisted in the F. J. Mufiiz Infectious Diseases Hospital since January 2002 to December 2013. The diagnosis of ilL with primary BM involvement in patients was confirmed by clinical, histopathological, and immunohistochemical findings. Results： All patients presented ＂B＂ symptoms and pancytopenia. All of them had stage IV neoplasm disease because of BM infiltration. The median of CD4＋ T-cell counts was 114 cells/μL, and mixed cellularity （MC） was the most frequent histopathological subtype of 92% cases. Conclusion： When other causes are excluded, BM biopsy should be performed in AIDS patients with ＂B＂ symptoms and pancytopenia to evaluate BM infiltration by atypical lymphocytes.

关键词： Acquired immunodeficiency syndrome (AIDS) Hodgkin's lymphoma (HL) bone marrow (BM)

Composition of Fractional Orlicz Maximal Operators and A1-weights on Spaces of Homogeneous Type

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Acta Mathematica Sinica,english Series 2010年第8期26卷 1509-1518页

作者： ana L. BeRNARDIS Gladis PRADOLINI maria LOReNTe maria Silvina RIVeROS IMAL ( CONICeT)-FIQ (UNL) Guemes 3450 (3000) Santa Fe Argentina Departamento de analisis Matemdtico Facultad de CienciasUniversidad de Malaga 29071-Malaga Spain FaMAF Universidad Nacional de Cordoba CIeM ( CONICeT) 5000 Cordoba Argentina

For a Young function θ with 0 ≤α 〈 1, let Mα,θ be the fractional Orlicz maximal operator defined in the context of the spaces of homogeneous type （X, d, μ） by Mα,θf（x） = supx∈（B）α ｜｜f｜｜θ,B, where ｜｜f｜｜θ,B is the mean Luxemburg norm of f on a ball B. When α= 0 we simply denote it by Me. In this paper we prove that if Ф and ψare two Young functions, there exists a third Young function θ such that the composition Mα,ψ o MФ is pointwise equivalent to Mα,θ. As a consequence we prove that for some Young functions θ, if Mα,θf 〈∞a.e. and δ ∈（0,1） then （Mα,θf）δ is an A1-weight.

关键词： Orlicz maximal function spaces of homogeneous type weights

Development of a Ready-to-Use PSMA-11 Kit Formulation and Biological evaluation of Binding Affinity

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Advances in Molecular Imaging 2024年第2期13卷 7-22页

作者： maria Renata valente Brandão Freire Natália Marchesan Bexiga Marco Antonio Stephano João ezequiel Oliveira Carlos Roberto Jorge Soares ana Cláudia Camargo Miranda Anna Carolina de Alcântara Barbosa Marycel Figols de Barboza Laura Fernanda Garcia Luiz Felipe S. Teixeira maria Helena Marumo Bellini Natanael Gomes da Silva Luiza Mascarenhas Balieiro Joel Mendes elaine Bortoleti de Araújo Centro de Radiofarmcia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil Departamento de Tecnologia Farmacutica Faculdade de Cincias Farmacuticas (USP) Cidade Universitria So Paulo Brasil Centro de Biotecnologia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil Departamento de Medicina Nuclear do Hospital Israelita Albert einstein So Paulo/SP Brasil

Introduction: 68Ga-PSMA-11 is considered the gold standard in detection of micro and oligometastases in advanced prostate cancer, being used for therapeutic planning, as well as, potentially, for evaluating response to treatment. The development of ready-to-use lyophilized kit of PSMA-11 adds quality and safety to the routine use of this radiopharmaceutical and represents a pharmacotechnical challenge as it must preserve the integrity and specificity of the ligand. Methods: PSMA-11 kit formulation was proposed, considering radiolabeling parameters and the preservation of the peptide during the lyophilization process, using mannitol as an excipient. Critical temperature characterization studies were carried out using DSC equipment and the freeze-drying process was developed. The direct radiolabeling conditions were evaluated and standardized using 68Ge/68Ga generator eluate from two different manufacturers (ITG and eckert & Ziegler). The radiochemical purity was evaluated by TLC and HPLC. Biological evaluation was carried out with lyophilized PSMA-11 to demonstrate the integrity of the peptide and preservation of biological activity after the lyophilization process. Results: Based on critical temperature characterization studies, the freeze-drying cycle was designed to reach a freezing temperature of around −40˚C and primary drying at 2˚C. Using 20 mg of mannitol, an intact and elegant lyophilized cake was obtained. PSMA-11 lyophilized kit was directly labeled with 68Ga eluate from 68Ge/68Ga GMP generators (ITG and eckert & Ziegler) resulting in % RP > 95% at pH 4.0 to 4.5. The results obtained from in vitro and in vivo biological competition studies confirmed the preservation of PSMA-11 affinity for the receptor after lyophilization. Conclusion: A lyophilized formulation (Kit) of PSMA-11 was successfully obtained, which preserved the integrity and biological activity of the peptide and guaranteed radiolabeling efficiency.

关键词： 68Ga-PSMA-11 Prostate-Specific Membrane Antigen (PSMA) Ready-to-Use Kit GMP-Grade Generators Metastatic Prostate Cancer PeT Imaging