bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFEITO AGUDO DO INDACATEROL EM DESFECHOS CLÍNICOS E FUNCIONAIS NOS PORTADORES DE DOENÇA PULMONAR OBSTRUTIVA CRÔNICA (DPOC): UM ENSAIO CLÍNICO RANDOMIZADO
Authors: Fróes Batista Ribeiro Thiago , Warken Rosa Fernanda , Blunck Resende Tiago Albertassi , Assunção Camelier Aquiles 
Published: August 2015

Introdução:Os broncodilatadores são fundamentais para o tratamento da doença pulmonar obstrutiva crônica (DPOC). O indacaterol é broncodilatador beta-2-agonista de longa ação recentemente aprovado para utilização na DPOC, que tem como principal característica referida pelos fabricantes um rápido início de ação. Objetivo: Avaliar o efeito agudo do indacaterol em portadores de DPOC. Métodos: Foi realizado um ensaio clínico randomizado, duplo cego, controlado com placebo utilizando indacaterol 150 mcg inalado em portadores de DPOC. Os desfechos avaliados foram o VEF1 e a CVF (obtidos da espirometria), frequência cardíaca e respiratória, pressão arterial, SpO2, sensação de dispneia e o teste do degrau. Resultados: Quarenta pacientes foram selecionados. Observou-se que não foi notada broncodilatação significante entre os grupos indacaterol e Placebo aos 5, 15 e 30 minutos seja em relação ao VEF1 ou a CVF. Diferenças estatísticas também não foram notadas para as variáveis secundárias como SpO2 ( p=0,89), FR (p=0,88), FC(p=0,31), pressão arterial (p=0,85), dispneia (p=0,60) e número de degraus subido ao final de 6 minutos (0,72). Conclusão: Em portadores de DPOC estáveis o indacaterol não produziu modificações nos desfechos avaliados em até 30 minutos após a sua utilização.
ARTROPLASTIA REVERSA DE OMBRO: RELATO DE CASO E PROPOSTA DE TRATAMENTO FISIOTERAPÊUTICO
Authors: Dias da Silva Garzedin Daniela , Cerqueira Luedir Cleriza Santos , Matos Marcos Almeida , Barros Rogério Meira 
Published: August 2015

Introdução: No cenário mundial, uma parcela significativa de pessoas sofre de doenças degenerativas do ombro. Esta enfermidade associada à lesão de manguito rotador constitui a principal indicação de artroplastia de ombro sendo a prótese reversa a principal opção nos casos de degeneração avançada da articulação gleno-umeral. Objetivo: esse estudo tem por objetivo apresentar um caso de paciente submetida à artroplastia reversa do ombro direito e seus resultados após aplicação de programa de tratamento fisioterapêutico. Metodologia: As informações foram colhidas através do relato da paciente durante a avaliação e nos prontuários do médico e da fisioterapeuta. Aplicou-se a University of California at Los Angeles (UCLA) no período pós operatório e após 6 meses de programa de fisioterapia. Resultados: O programa de reabiltação preconizou a utilização de ultra-som terapêutico, exercícios pendulares, exercícios isométricos e de fortalecimento. Os resultados da avaliação UCLA pré e pós-programa de reabilitação evoluíram de pobre (11 pontos) para bom (33 pontos). Conclusão: Em nossa paciente, a prótese reversa associada a um programa de reabilitação que priorizava adequado funcionamento da prótese, melhora da força muscular, ganho de amplitude de movimento e acima de tudo a funcionalidade, mostrou-se opção promissora de tratamento com retorno do paciente às atividades de vida diária e atividades laborativas, melhorando assim a sua qualidade de vida.
PERFIL FUNCIONAL DA PARALISIA FACIAL EM UM HOSPITAL
Authors: Konno Katia Mayumi , Zonta Marise Bueno , Teive Hélio Afonso Ghizoni , Corrêa Clynton Lourenço 
Published: August 2015

A paralisia do nervo facial pode ser central ou periférica, sendo a paralisia nervosa mais acometida do corpo humano. O objetivo deste estudo foi estabelecer o perfil funcional dos pacientes com paralisia facial internados no Setor de Neurologia do Hospital das Clínicas da UFPR. Por meio de estudo prospectivo, com amostragem por conveniência e aplicação de um questionário para coleta dos dados clínicos, foi realizada a identificação do paciente e avaliação do grau de comprometimento muscular que foi classificada de acordo com a escala de evolução motora de House-Brackmann pelo período de 12 meses. Participaram do estudo 50 pessoas que representaram 9% dos internados na unidade. A etiologia predominante da paralisia facial foi vascular, com 88% dos casos de origem central. Foi observado padrão sazonal para a paralisia facial central com maior prevalência nos meses de abril à julho e paralisia facial periférica entre os meses de maio à julho. Diferentemente de outros estudos, não foi relatada queixa em relação à aparência. Apesar de existir encaminhamento à fisioterapia foi observada a necessidade de estabelecer um fluxograma para reabilitação dos pacientes durante o internamento e no pós-alta.
Investigation of the relationship between virulence factors and genotype of Candida spp. isolated from blood cultures
Authors: Mutlu Sariguzel Fatma , Berk Elife , Koc Ayse Nedret , Sav Hafize , Demir Gonca 
Published: August 2015

Introduction: The aim of study was to investigate the virulence factors of phospholipase, proteinase, esterase production and biofilm formation in Candida species isolated from patients with candidemia, and to assess their relationship with Candida genotypes derived after repetitive sequence-based polymerase chain reaction (rep-PCR) fingerprinting. Methodology: Fifty-two strains were identified to species level according to conventional methods and sequencing. The DiversiLab system was used for the genotyping. Enzyme activities and biofilm formation were evaluated using microbiological methods. Results: The 52 strains were identified as follows: 29 C. parapsilosis, 19 C. albicans, 2 C. glabrata, and 2 C. tropicalis. Phospholipase and proteinase activities were observed to have statistically significant differences between C. albicans and non-albicans Candida (NAC) strains (p < 0.05), with C. albicans strains showing higher virulence. Rep-PCR revealed eight major genotypes (A-H).The 19 C. albicans and the 33 non-albicans Candida isolates yielded seven (A-G) and four (A, B, C, H) genotypes, respectively. C. albicans strains were not shown to have a predominant genotype and showed higher phospholipase and proteinase activitiy than did NAC, regardless of genotype. Genotype H (52%) was the predominant genotype for the NAC including 27 C. parapsilosis strains, but the majority of strains showed low virulence. Conclusions: NAC species were the most common causative agent for candidemia. Genotyping showed low transmission of C. albicans strains, but transmission of C. parapsilosis was high. In candidemia, several Candida virulence factors may be responsible at the same time. However, different genotypes of Candida strains showed different virulence activity.
Investigation of clonal relationships of K. pneumoniae isolates from neonatal intensive care units by PFGE and rep-PCR
Authors: Koroglu Mehmet , Ozbek Ahmet , Demiray Tayfur , Hafizoglu Taner , Guclu Ertugrul , Altindis Mustafa , Karabay Oguz , Durmaz Riza 
Published: August 2015

Introduction: Clonal relationships of Klebsiella pneumoniae strains obtained during an epidemic and after a one-year post-epidemic (non-epidemic) period in the same neonatal intensive care unit (NICU) using pulsed-field gel electrophoresis (PFGE) and repetitive polymerase chain reaction (rep-PCR) by the DiversiLab (DL) system were investigated, and the results of both molecular techniques were evaluated. Methodology: Fifteen K. pneumoniae strains were included in this study. All identified bacterial strains were confirmed by 16S rDNA sequencing and analyzed by PFGE and the DL system. Results: According to the PFGE results, 15 isolates showed 10 different band profiles. Nine of these 15 isolates were included in one of the formed clusters, and the remaining six isolates were not included in any of them. According to the DL system results, 15 isolates showed two different clusters, with three strains in one cluster and four strains in the other. The remaining strains could not be placed any one of the clusters. PFGE was used as the gold standard based on its strong genetic discriminatory power. The DL system results showed that PFGE missed the relationship of the two epidemic-related strains and demonstrated one epidemic-unrelated strain to be epidemic related. Conclusions: Both systems may easily be used for clonal relationships of K. pneumoniae strains. The DL system was clearly more rapid and convenient than PFGE, but its discriminatory power seemed to be inferior to that of PFGE based on 15 K. pneumoniae strains.
CD4+ T Cell Help Selectively Enhances High-Avidity Tumor Antigen-Specific CD8+ T Cells
Authors: Zhu Ziqiang , Cuss Steven M. , Singh Vinod , Gurusamy Devikala , Shoe Jennifer L. , Leighty Robert , Bronte Vincenzo , Hurwitz Arthur A. 
Published: August 2015

Abstract
Maintaining antitumor immunity remains a persistent impediment to cancer immunotherapy. We and others have previously reported that high-avidity CD8+ T cells are more susceptible to tolerance induction in the tumor microenvironment. In the present study, we used a novel model where T cells derived from two independent TCR transgenic mouse lines recognize the same melanoma antigenic epitope but differ in their avidity. We tested whether providing CD4+ T cell help would improve T cell responsiveness as a function of effector T cell avidity. Interestingly, delivery of CD4+ T cell help during in vitro priming of CD8+ T cells improved cytokine secretion and lytic capacity of high-avidity T cells, but not low-avidity T cells. Consistent with this observation, copriming with CD4+ T cells improved antitumor immunity mediated by higher avidity, melanoma-specific CD8+ T cells, but not T cells with similar specificity but lower avidity. Enhanced tumor immunity was associated with improved CD8+ T cell expansion and reduced tolerization, and it was dependent on presentation of both CD4+ and CD8+ T cell epitopes by the same dendritic cell population. Our findings demonstrate that CD4+ T cell help preferentially augments high-avidity CD8+ T cells and provide important insight for understanding the requirements to elicit and maintain durable tumor immunity.
Negative Regulation of Memory Phenotype CD8 T Cell Conversion by Adhesion and Degranulation–Promoting Adapter Protein
Authors: Fiege Jessica K. , Burbach Brandon J. , Shimizu Yoji 
Published: August 2015

Abstract
The maintenance of T cell repertoire diversity involves the entry of newly developed T cells, as well as the maintenance of memory T cells generated from previous infections. This balance depends on competition for a limited amount of homeostatic cytokines and interaction with self-peptide MHC class I. In the absence of prior infection, memory-like or memory phenotype (MP) CD8 T cells can arise from homeostatic cytokine exposure during neonatal lymphopenia. Aside from downstream cytokine signaling, little is known about the regulation of the conversion of naive CD8 T cells to MP CD8 T cells during acute lymphopenia. We have identified a novel negative regulatory role for adhesion and degranulation–promoting adapter protein (ADAP) in CD8 T cell function. We show that in the absence of ADAP, naive CD8 T cells exhibit a diminished response to stimulatory Ag, but an enhanced response to weak agonist-altered peptide ligands. ADAP-deficient mice exhibit more MP CD8 T cells that occur following thymic emigration and are largely T cell intrinsic. Naive ADAP-deficient CD8 T cells are hyperresponsive to lymphopenia in vivo and exhibit enhanced activation of STAT5 and homeostatic Ag-independent proliferation in response to IL-15. Our results indicate that ADAP dampens naive CD8 T cell responses to lymphopenia and IL-15, and they demonstrate a novel Ag-independent function for ADAP in the suppression of MP CD8 T cell generation.
Intrinsic Differences in Donor CD4 T Cell IL-2 Production Influence Severity of Parent-into-F1 Murine Lupus by Skewing the Immune Response Either toward Help for B Cells and a Sustained Autoantibody Response or toward Help for CD8 T Cells and a Downregulatory Th1 Response
Authors: Soloviova Kateryna , Puliaiev Maksym , Haas Mark , Dalgard Clifton L. , Schaefer Brian C. , Via Charles S. 
Published: August 2015

Abstract
Using the parent-into-F1 model of induced lupus and (C57BL/6 × DBA2) F1 mice as hosts, we compared the inherent lupus-inducing properties of the two parental strain CD4 T cells. To control for donor CD4 recognition of alloantigen, we used H-2d identical DBA/2 and B10.D2 donor T cells. We demonstrate that these two normal, nonlupus-prone parental strains exhibit two different T cell activation pathways in vivo. B10.D2 CD4 T cells induce a strong Th1/CMI pathway that is characterized by IL-2/IFN-γ expression, help for CD8 CTLs, and skewing of dendritic cell (DC) subsets toward CD8a DCs, coupled with reduced CD4 T follicular helper cells and transient B cell help. In contrast, DBA/2 CD4 T cells exhibit a reciprocal, lupus-inducing pathway that is characterized by poor IL-2/IFN-γ expression, poor help for CD8 CTLs, and skewing of DC subsets toward plasmacytoid DCs, coupled with greater CD4 T follicular helper cells, prolonged B cell activation, autoantibody formation, and lupus-like renal disease. Additionally, two distinct in vivo splenic gene-expression signatures were induced. In vitro analysis of TCR signaling revealed defective DBA CD4 T cell induction of NF-κB, reduced degradation of IκBα, and increased expression of the NF-κB regulator A20. Thus, attenuated NF-κB signaling may lead to diminished IL-2 production by DBA CD4 T cells. These results indicate that intrinsic differences in donor CD4 IL-2 production and subsequent immune skewing could contribute to lupus susceptibility in humans. Therapeutic efforts to skew immune function away from excessive help for B cells and toward help for CTLs may be beneficial.
Endocannabinoid System Contributes to Liver Injury and Inflammation by Activation of Bone Marrow–Derived Monocytes/Macrophages in a CB1-Dependent Manner
Authors: Mai Ping , Yang Le , Tian Lei , Wang Lin , Jia Shuangshuang , Zhang Yuanyuan , Liu Xin , Yang Lin , Li Liying 
Published: August 2015

Abstract
Hepatic injury undergoes significant increases in endocannabinoidsand infiltrations of macrophages, yet the concrete mechanisms of changes in endocannabinoids and the functions of macrophage-expressed cannabinoid receptors (CBs) are unclear. Biosynthetic and degradative enzymes of endocannabinoids revealed a significant change in human fibrotic liver. Meanwhile, we showed dynamic changes of these enzymes and CBs (CB1 and CB2) from 1 to 56 d in carbon tetrachloride–induced murine liver injury. Biosynthetic enzymes (N-acylphosphatidyl-ethanolamine selective phospholipase D and diacylglycerol lipase-α) and CBs were markedly increased, whereas degradative enzymes (fatty acid amidohydrolase and monoacylglycerol lipase) were downregulated. Moreover, these enzymes intimately correlated with the fibrosis parameter [procollagen α1(III)]. Bone marrow–derived monocytes/macrophages (BMM) expressed CBs. Interestingly, CB1 but not CB2 mediated BMM migration through a Boyden chambers assay, and the effect depended on the G(α)i/o/RhoA/ROCK signaling pathway. ICR mice were lethally irradiated and received BM transplants from enhanced GFP transgenic mice. Four weeks later, mice of BM reconstruction were subjected to carbon tetrachloride–induced liver injury. In the chimeric murine model, we found that blockade of CB1 by administration of a CB1 antagonist inhibited the recruitment of BMM into injured liver using immunofluorescence staining and FACS, but it did not have effects on migration of T cells and dendritic cells without CB1 expression. Furthermore, activation of CB1 enhanced cytokine expression of BMM. In vivo, inhibition of CB1 attenuated the inflammatory cytokine level through real-time RT-PCR and cytometric bead array, ameliorating hepatic inflammation and fibrosis. In this study, we identify inactivation of BMM-expressed CB1 as a therapeutic strategy for reducing hepatic inflammation and fibrosis.
Microchip-Based Single-Cell Imaging Reveals That CD56dimCD57−KIR−NKG2A+ NK Cells Have More Dynamic Migration Associated with Increased Target Cell Conjugation and Probability of Killing Compared to CD56dimCD57−KIR−NKG2A− NK Cells
Authors: Forslund Elin , Sohlberg Ebba , Enqvist Monika , Olofsson Per E. , Malmberg Karl-Johan , Önfelt Björn 
Published: August 2015

Abstract
NK cells are functionally educated by self-MHC specific receptors, including the inhibitory killer cell Ig-like receptors (KIRs) and the lectin-like CD94/NKG2A heterodimer. Little is known about how NK cell education influences qualitative aspects of cytotoxicity such as migration behavior and efficacy of activation and killing at the single-cell level. In this study, we have compared the behavior of FACS-sorted CD56dimCD57−KIR−NKG2A+ (NKG2A+) and CD56dimCD57−KIR−NKG2A− (lacking inhibitory receptors; IR−) human NK cells by quantifying migration, cytotoxicity, and contact dynamics using microchip-based live cell imaging. NKG2A+ NK cells displayed a more dynamic migration behavior and made more contacts with target cells than IR− NK cells. NKG2A+ NK cells also more frequently killed the target cells once a conjugate had been formed. NK cells with serial killing capacity were primarily found among NKG2A+ NK cells. Conjugates involving IR− NK cells were generally more short-lived and IR− NK cells did not become activated to the same extent as NKG2A+ NK cells when in contact with target cells, as evident by their reduced spreading response. In contrast, NKG2A+ and IR− NK cells showed similar dynamics in terms of duration of conjugation periods and NK cell spreading response in conjugates that led to killing. Taken together, these observations suggest that the high killing capacity of NKG2A+ NK cells is linked to processes regulating events in the recognition phase of NK–target cell contact rather than events after cytotoxicity has been triggered.
B Cell–Intrinsic Expression of the HuR RNA-Binding Protein Is Required for the T Cell–Dependent Immune Response In Vivo
Authors: DeMicco Amy , Naradikian Martin S. , Sindhava Vishal J. , Yoon Je-Hyun , Gorospe Myriam , Wertheim Gerald B. , Cancro Michael P. , Bassing Craig H. 
Published: August 2015

Abstract
The HuR RNA-binding protein posttranscriptionally controls expression of genes involved in cellular survival, proliferation, and differentiation. To determine roles of HuR in B cell development and function, we analyzed mice with B lineage–specific deletion of the HuR gene. These HuRΔ/Δ mice have reduced numbers of immature bone marrow and mature splenic B cells, with only the former rescued by p53 inactivation, indicating that HuR supports B lineage cells through developmental stage-specific mechanisms. Upon in vitro activation, HuRΔ/Δ B cells have a mild proliferation defect and impaired ability to produce mRNAs that encode IgH chains of secreted Abs, but no deficiencies in survival, isotype switching, or expression of germinal center (GC) markers. In contrast, HuRΔ/Δ mice have minimal serum titers of all Ab isotypes, decreased numbers of GC and plasma B cells, and few peritoneal B-1 B cells. Moreover, HuRΔ/Δ mice have severely decreased GCs, T follicular helper cells, and high-affinity Abs after immunization with a T cell–dependent Ag. This failure of HuRΔ/Δ mice to mount a T cell–dependent Ab response contrasts with the ability of HuRΔ/Δ B cells to become GC-like in vitro, indicating that HuR is essential for aspects of B cell activation unique to the in vivo environment. Consistent with this notion, we find in vitro stimulated HuRΔ/Δ B cells exhibit modestly reduced surface expression of costimulatory molecules whose expression is similarly decreased in humans with common variable immunodeficiency. HuRΔ/Δ mice provide a model to identify B cell–intrinsic factors that promote T cell–dependent immune responses in vivo.
Single-Cell Analysis of B Cell/Antibody Cross-Reactivity Using a Novel Multicolor FluoroSpot Assay
Authors: Hadjilaou Alexandros , Green Angela M. , Coloma Josefina , Harris Eva 
Published: August 2015

Abstract
Dengue is a major public health problem globally. It is caused by four antigenically distinct serotypes of dengue virus (DENV1–4), and although serotype-specific and strongly neutralizing cross-reactive immune responses against the four DENV serotypes are thought to be protective, subneutralizing Abs can contribute to increased disease severity upon secondary infection with a different DENV serotype. Understanding the breadth of the immune response in natural DENV infections and in vaccinees is crucial for determining the correlates of protection or disease severity. Transformation of B cell populations to generate mAbs and ELISPOT assays have been used to determine B cell and Ab specificity to DENV; however, both methods have technical limitations. We therefore modified the conventional ELISPOT to develop a Quad-Color FluoroSpot to provide a means of examining B cell/Ab serotype specificity and cross-reactivity on a single-cell basis. Abs secreted by B cells are captured by an Fc-specific Ab on a filter plate. Subsequently, standardized concentrations of all four DENV serotypes are added to allow equal stoichiometry for Ag binding. After washing, the spots, representing individual B cells, are visualized using four fluorescently labeled DENV serotype-specific detection mAbs. This method can be used to better understand the breadth and magnitude of B cell responses following primary and secondary DENV infection or vaccination and their role as immune correlates of protection from subsequent DENV infections. Furthermore, the Quad-Color FluoroSpot assay can be applied to other diseases caused by multiple pathogen serotypes in which determining the serotype or subtype-specific B cell response is important.
Cathepsin G in Experimental Tuberculosis: Relevance for Antibacterial Protection and Potential for Immunotherapy
Authors: Walter Kerstin , Steinwede Kathrin , Aly Sahar , Reinheckel Thomas , Bohling Jennifer , Maus Ulrich A. , Ehlers Stefan 
Published: August 2015

Abstract
Neutrophil serine proteases, such as cathepsin G (CG) and neutrophil elastase (NE), have been implicated in the protective response against infections, including experimental mycobacterial infections. The goal of this study was to explore the role of CG in immunocompetent mice challenged aerogenically with Mycobacterium tuberculosis. We used genetically CG- or CG/NE-deficient mice to define the importance of these neutrophil serine proteases for antibacterial protection, granulomatous response, and survival. In addition, we explored the effect of intratracheally delivered liposomally encapsulated CG/NE as a therapeutic approach early during M. tuberculosis infection. Our data show that the presence of CG or CG/NE prolongs survival in M. tuberculosis–infected mice. However, CG is not directly involved in antibacterial defenses, and exogenous intratracheal administration of CG combined with NE does not reduce bacterial loads in the lungs of M. tuberculosis–infected mice.