bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining the Chemokine Basis for Leukocyte Recruitment during Viral Encephalitis
Authors: Michlmayr Daniela , McKimmie Clive S. , Pingen Marieke , Haxton Ben , Mansfield Karen , Johnson Nicholas , Fooks Anthony R. , Graham Gerard J. 
Published: June 2014

ABSTRACT
The encephalitic response to viral infection requires local chemokine production and the ensuing recruitment of immune and inflammatory leukocytes. Accordingly, chemokine receptors present themselves as plausible therapeutic targets for drugs aimed at limiting encephalitic responses. However, it remains unclear which chemokines are central to this process and whether leukocyte recruitment is important for limiting viral proliferation and survival in the brain or whether it is predominantly a driver of coincident inflammatory pathogenesis. Here we examine chemokine expression and leukocyte recruitment in the context of avirulent and virulent Semliki Forest virus (SFV) as well as West Nile virus infection and demonstrate rapid and robust expression of a variety of inflammatory CC and CXC chemokines in all models. On this basis, we define a chemokine axis involved in leukocyte recruitment to the encephalitic brain during SFV infection. CXCR3 is the most active; CCR2 is also active but less so, and CCR5 plays only a modest role in leukocyte recruitment. Importantly, inhibition of each of these receptors individually and the resulting suppression of leukocyte recruitment to the infected brain have no effect on viral titer or survival following infection with a virulent SFV strain. In contrast, simultaneous blockade of CXCR3 and CCR2 results in significantly reduced mortality in response to virulent SFV infection. In summary, therefore, our data provide an unprecedented level of insight into chemokine orchestration of leukocyte recruitment in viral encephalitis. Our data also highlight CXCR3 and CCR2 as possible therapeutic targets for limiting inflammatory damage in response to viral infection of the brain.

IMPORTANCE
Brain inflammation (encephalitis) in response to viral infection can lead to severe illness and even death. This therefore represents an important clinical problem and one that requires the development of new therapeutic approaches. Central to the pathogenesis of encephalitis is the recruitment of inflammatory leukocytes to the infected brain, a process driven by members of the chemokine family. Here we provide an in-depth analysis of the chemokines involved in leukocyte recruitment to the virally infected brain and demonstrate that simultaneous blockade of two of these receptors, namely, CXCR3 and CCR2, does not alter viral titers within the brain but markedly reduces inflammatory leukocyte recruitment and enhances survival in a murine model of lethal viral encephalitis. Our results therefore highlight chemokine receptors as plausible therapeutic targets in treating viral encephalitis.
Aggressive dentigerous cyst with ectopic central incisor
Authors: Jayam Cheranjeevi , Mitra Malay , Bandlapalli Anila , Jana Biswanath 
Published: June 2014

SummaryDentigerous cysts form from accumulation of fluid between reduced enamel epithelium and the crown of an unerupted tooth. They cause several difficulties such as swelling, non-eruption of the involved teeth, and displacement of adjacent teeth, and thus require early detection and prompt treatment. Treatment ranges from marsupialisation to enucleation. Enucleation is rarely used in children compared with marsupialisation. This paper discusses successful use of enucleation for treating a dentigerous cyst and explains the need for such a radical procedure.
Environments, risk and health harms: a qualitative investigation into the illicit use of anabolic steroids among people using harm reduction services in the UK
Authors: Kimergård Andreas , McVeigh Jim 
Published: June 2014

ObjectivesThe illicit use of anabolic steroids among the gym population continues to rise, along with the number of steroid using clients attending harm reduction services in the UK. This presents serious challenges to public health. Study objectives were to account for the experiences of anabolic steroid users and investigate how ‘risk environments’ produce harm.MethodsQualitative face-to-face interviews with 24 users of anabolic steroids engaged with harm reduction services in the UK.ResultsBody satisfaction was an important factor when deciding to start the use of anabolic steroids. Many users were unaware of the potential dangers of using drugs from the illicit market, whereas some had adopted a range of strategies to negotiate the hazards relating to the use of adulterated products, including self-experimentation to gauge the perceived efficacy and unwanted effects of these drugs. Viewpoints, first-hand anecdotes, norms and practices among groups of steroid users created boundaries of ‘sensible’ drug use, but also promoted practices that may increase the chance of harms occurring. Established users encouraged young users to go to harm reduction services but, at the same time, promoted risky injecting practices in the belief that this would enhance the efficacy of anabolic steroids.ConclusionsCurrent steroid-related viewpoints and practices contribute to the risk environment surrounding the use of these drugs and may undermine the goal of current public health strategies including harm reduction interventions. The level of harms among anabolic steroid users are determined by multiple and intertwining factors, in addition to the harms caused by the pharmacological action or injury and illness associated with incorrect injecting techniques.
Do gastroenterologists monitor their patients taking 5-amino-salicylates following initiation of treatment
Authors: Siddique N , Farmer C , Muller A F 
Published: June 2014

Background5-Amino salicylate (5-ASA) medications may rarely be associated with a significant decline in renal function and interstitial nephritis. British Society of Gastroenterology guidelines advise regular renal function monitoring for patients taking these drugs.AimTo assess whether gastroenterologists in Kent were following best practice guidelines regarding the monitoring of their patients on 5-ASA therapy.MethodsUsing longitudinal community and regional pathology databases for the Kent population, our renal unit regularly screens a total population of 300 000 for evidence of renal disease. The data extracted are analysed using an automated computerised system to identify patients requiring intervention for kidney disease. All patients taking 5-ASA medication were identified from a population of 300 000. The pathology database was studied to identify the patients on 5-ASA treatment and whether they had had renal function tests.Results800 adult patients were identified taking 5-ASA therapy. 612 patients received 5-ASAs for 3 months or more, and these were included in the final analysis. 293 patients had no renal function checks while on treatment. 79 patients had renal function tests less than once every 4 years and 36 patients once every 2–4 years. 204 patients had renal function measurements in 50% or more of years of treatment, of whom 116 were checked every year. Some patients were started on treatment with abnormal results at baseline and some with identified kidney disease continued on their 5-ASAs.ConclusionsThe majority of patients receiving 5-ASA compounds do not have regular renal function monitoring. Clinicians are failing to follow best practice guidelines.
Next-Generation Sequencing of Translocation Renal Cell Carcinoma Reveals Novel RNA Splicing Partners and Frequent Mutations of Chromatin-Remodeling Genes
Authors: Malouf Gabriel G. , Su Xiaoping , Yao Hui , Gao Jianjun , Xiong Liangwen , He Qiuming , Compérat Eva , Couturier Jérôme , Molinié Vincent , Escudier Bernard , Camparo Philippe , Doss Denaha J. , Thompson Erika J. , Khayat David , Wood Christopher G. , Yu Willie , Teh Bin T. , Weinstein John , Tannir Nizar M. 
Published: June 2014

Abstract
Purpose: MITF/TFE translocation renal cell carcinoma (TRCC) is a rare subtype of kidney cancer. Its incidence and the genome-wide characterization of its genetic origin have not been fully elucidated.
Experimental Design: We performed RNA and exome sequencing on an exploratory set of TRCC (n = 7), and validated our findings using The Cancer Genome Atlas (TCGA) clear-cell RCC (ccRCC) dataset (n = 460).
Results: Using the TCGA dataset, we identified seven TRCC (1.5%) cases and determined their genomic profile. We discovered three novel partners of MITF/TFE (LUC7L3, KHSRP, and KHDRBS2) that are involved in RNA splicing. TRCC displayed a unique gene expression signature as compared with other RCC types, and showed activation of MITF, the transforming growth factor β1 and the PI3K complex targets. Genes differentially spliced between TRCC and other RCC types were enriched for MITF and ID2 targets. Exome sequencing of TRCC revealed a distinct mutational spectrum as compared with ccRCC, with frequent mutations in chromatin-remodeling genes (six of eight cases, three of which were from the TCGA). In two cases, we identified mutations in INO80D, an ATP-dependent chromatin-remodeling gene, previously shown to control the amplitude of the S phase. Knockdown of INO80D decreased cell proliferation in a novel cell line bearing LUC7L3–TFE3 translocation.
Conclusions: This genome-wide study defines the incidence of TRCC within a ccRCC-directed project and expands the genomic spectrum of TRCC by identifying novel MITF/TFE partners involved in RNA splicing and frequent mutations in chromatin-remodeling genes. Clin Cancer Res; 20(15); 4129–40. ©2014 AACR.
A Novel Small-Molecule Aurora Kinase Inhibitor Attenuates Breast Tumor–Initiating Cells and Overcomes Drug Resistance
Authors: Zheng Fei-Meng , Long Zi-Jie , Hou Zhi-Jie , Luo Yu , Xu Ling-Zhi , Xia Jiang-Long , Lai Xiao-Ju , Liu Ji-Wei , Wang Xi , Kamran Muhammad , Yan Min , Shao Shu-Juan , Lam Eric W.-F. , Wang Shao-Wu , Lu Gui , Liu Quentin 
Published: June 2014

Abstract
Chemoresistance is a major cause of cancer treatment failure. Tumor-initiating cells (TIC) have attracted a considerable amount of attention due to their role in chemoresistance and tumor recurrence. Here, we evaluated the small-molecule Aurora kinase inhibitor AKI603 as a novel agent against TICs in breast cancer. AKI603 significantly inhibited Aurora-A (AurA) kinase and induced cell-cycle arrest. In addition, the intragastric administration of AKI603 reduced xenograft tumor growth. Interestingly, we found that breast cancer cells that were resistant to epirubicin expressed a high level of activated AurA and also have a high CD24Low/CD44High TIC population. The inhibition of AurA kinase by AKI603 abolished the epirubicin-induced enrichment of TICs. Moreover, AKI603 suppressed the capacity of cells to form mammosphere and also suppressed the expression of self-renewal genes (β-catenin, c-Myc, Sox2, and Oct4). Thus, our work suggests the potential clinical use of the small-molecule Aurora kinase inhibitor AKI603 to overcome drug resistance induced by conventional chemotherapeutics in breast cancer. Mol Cancer Ther; 13(8); 1991–2003. ©2014 AACR.
Overexpression of DDX43 Mediates MEK Inhibitor Resistance through RAS Upregulation in Uveal Melanoma Cells
Authors: Ambrosini Grazia , Khanin Raya , Carvajal Richard D. , Schwartz Gary K. 
Published: June 2014

Abstract
The majority of uveal melanomas carry oncogenic mutations in the G proteins GNAQ and GNA11, with consequent activation of the MAPK pathway. Selective MEK inhibitors, such as selumetinib, have shown clinical benefit in uveal melanoma. However, mechanisms of drug resistance limit their efficacy in some patients. Analysis of MEK inhibitor–resistant uveal melanoma cell lines revealed the induction of RAS protein expression and activity. This effect was mediated by the RNA helicase DDX43, which was remarkably overexpressed in these cells. Depletion of DDX43 in MEK inhibitor–resistant cells decreased RAS proteins and inhibited ERK and AKT pathways. On the contrary, ectopic expression of DDX43 in parental uveal melanoma cells induced RAS protein levels and rendered cells resistant to MEK inhibition. Similar to DDX43 depletion, downregulation of KRAS, HRAS, and NRAS inhibited downstream pathways in the resistant cells, overcoming mutant GNAQ signaling. We also analyzed the expression of DDX43 in liver metastases of patients with uveal melanoma by RT-PCR, and found a significant overexpression of DDX43 in patients who did not benefit from selumetinib therapy. In conclusion, DDX43 induces RAS protein expression and signaling, mediating a novel mechanism of MEK inhibitor resistance. The detection of DDX43 in patients with uveal melanoma could lead to more targeted therapies for this disease. Mol Cancer Ther; 13(8); 2073–80. ©2014 AACR.
Avaliação da maturação do processo de raciocínio diagnóstico de estudantes de medicina
Authors: Sobral Dejano T. 
Published: June 2014

O propósito do estudo foi averiguar a utilidade do Inventário de Raciocínio Diagnóstico (IRD) na avaliação da maturação do processo de diagnóstico clínico, em conexão com percepções sobre o aprendizado na formação médica. O inventário foi aplicado entre 88 estudantes de Medicina, de ambos os sexos, em dois semestres consecutivos na fase de iniciação clínica. Foram, também, obtidos dados de percepções do aprendizado (valorização do aprendizado, autoconfiança do aprendiz e reflexão na aprendizagem) e de rendimento acadêmico. Os resultados revelaram diferenças significantes, porém pequenas, entre as duas medidas dos escores do IRD e correlações positivas e significantes desses escores com pontuações das três medidas de percepção do aprendizado. Observou-se uma relação significativa entre o tamanho do efeito e a percepção de autodeterminação do processo diagnóstico. Os dados indicam que o IRD reflete, além de conhecimento e habilidades específicas, a percepção de eficácia pessoal no processo de diagnóstico, que pode ser influenciada por diferentes fatores do contexto do aprendizado e de atitudes do aprendiz. Em conclusão, os achados apontam a sensibilidade discriminativa do instrumento e sugerem sua utilidade no acompanhamento da maturação do processo de diagnóstico clínico.
Transplante de fígado
Authors: França Alex V.C. , Martinelli Ana L.C. , Sankanrankutty Ajith K. , Rizzo Cláudia C. , Silva Junior Orlando Castro 
Published: June 2014

O transplante de fígado constitui o principal tratamento para os pacientes portadores de doença hepática crônica ou aguda, em situações em que outras opções terapêuticas clínicas e/ou cirúrgicas não tenham sido eficazes no controle da doença. Dentre as doenças do fígado, o carcinoma hepatocelular, quando de pequeno tamanho, constitui uma das indicações para a realização do transplante. Relatamos o caso do primeiro paciente submetido ao transplante de fígado no Hospital das Clínicas da Faculdade de Medicina de Ribeirão - USP. Ele era portador de cirrose hepática pelo vírus da hepatite C, associada à presença de carcinoma hepatocelular; enquanto em lista de espera pelo transplante, foi submetido à embolização arterial e alcoolização tumoral com o intuito de ser impedida a progressão da neoplasia. O transplante de fígado foi realizado sem intercorrências cirúrgicas, utilizando-se a técnica de piggyback com anastomose biliar colédoco-colédoco com permanência de dreno de Kher. O esquema imunossupressor utilizado foi o duplo, associando-se ciclosporina A e prednisona. No nono dia de pós-operatório, ocorreu episódio de rejeição celular, tratado com sucesso com metilprednisolona (1.0 g/dia, IV durante três dias). O paciente recebeu alta hospitalar no 13 o dia de pósoperatório. O caso evidencia a importância do diagnóstico precoce e a indicação do transplante de fígado em portadores de carcinoma hepatocelular, bem como, uma das possíveis complicações no pós-operatório. A concretização de mais um grupo especializado no tratamento das doenças crônicas do fígado e o desenvolvimento científico, tecnológico e de ensino da Região de Ribeirão Preto, no interior do Estado de São Paulo, possibilitaram a realização, com sucesso, do caso aqui relatado.
Análise quantitativa das células das ilhotas pancreáticas em ratos sob efeito de aloxana
Authors: Lima Marcus Aurelho , Lima Lilian Margareth Biagioni , Rita Danielle Patrícia Castanheira , Navarro Fábio Castilho , Tatsukawa Ranaia Santana , Pereira Gilberto Araújo , Reis Luiz Carlos , Abreu Marta Elena Araújo , Borges Maria de Fátima 
Published: June 2014

In the present study, we verified the influence of alloxan over the cells of pancreatic islet of rats, performing quantitative analysis of a, b and d cells through immunohistochemical study.
Twenty male rats (Rattus norvegiccus) were used of Wistar line, disposed in 2 groups of 10 rats on each, being a control group and an experimental one. After fasting of 36 hours, 40 ml/Kg of monohydrated of alloxan was administrated by intravenous via and about 30 minutes after, the animal was offered food. At the end of 10 days of observation, animals were sacrificed. Samples of different regions of pancreas were selected and undergone to a histological process and stained with hematoxilin-eosin. To the immunohistochemical study, anti-insulin, anti-glucagon and anti-somatostatin antibodies were used. Quantitative analysis was performed in eight most representative pancreatic islets of each animal. Results were considered significative when p<0.05. There was a significative reduction in the number of cells, destructing the islets and over the pancreatic-cells, which has already been observed in other studies. However, the action mechanism of alloxan over the pancreatic cells was not completely shown, therefore having necessity of more studies to its elucidation.
AVALIAÇÃO DE MÉTODOS INVASIVOS PARA DIAGNÓSTICO DA INFECÇÃO POR Helicobacter pylori EM CRIANÇAS E ADOLESCENTES COM SINTOMAS DISPÉPTICOS
Authors: Ogata Silvio K. , Kawakami Elisabete , Reis Francy P. S. 
Published: June 2014

Apesar do uso rotineiro de biópsias endoscópicas para o diagnóstico da infecção por Helicobacter pylori em nosso meio, há poucos estudos pediátricos, avaliando a acurácia dos métodos invasivos. Métodos: Foram avaliados prospectivamente 120 pacientes submetidos à endoscopia para investigação de sintomas dispépticos. Foram obtidos seis biópsias de região antral para detecção do Helicobacter pylori através do teste rápido da urease, histologia e cultura. Os pacientes foram considerados infectados, se a cultura ou a histologia e o teste rápido da urease resultaram positivos. Resultados: A idade variou de 3m a 17anos (média: 10a1m); 54% do sexo feminino e 46% masculino; 44% (53/120) estavam infectados. O exame endoscópico foi normal em 54% (65/120) e anormal em 46% (55/120). O diagnóstico foi gastrite - 69% (38/55), esofagite - 13% (13/55), úlcera duodenal - 13% (7/55) e duodenite - 5% (3/55). Os 3 métodos concordaram em 72,5% (87/120), foram todos negativos em 48% (58/120) e todos positivos em 24,5% (29/120). A melhor concordância ocorreu entre a histologia e o teste rápido da urease (91,7%), seguido pela cultura e histologia (78,3%) e, finalmente, a cultura e o teste rápido da urease (75%). A sensibilidade do teste rápido da urease foi 100%, seguido pela histologia (98,1%) e pela cultura (56,6%). A especificidade da histologia foi de 97%, seguida pelo teste rápido da urease (89,5%). Conclusão: A associação histologia e o teste rápido da urease mostraram maior acurácia na detecção da infecção por Helicobacter pylori devido a sua alta sensibilidade (teste rápido da urease) e alta especificidade (histologia), além do baixo custo e praticidade. A cultura isolada não deve ser utilizada como padrão-ouro devido à baixa sensibilidade.
Sonda nasogástrica/nasoentérica
Authors: Unamuno Maria do Rosário D. L. de , Marchini Julio S. 
Published: June 2014

Cada dia mais, a terapia nutricional é reconhecida como importante fator na recuperação de doentes. As sondas modernas possibilitam a oferta de nutrientes e a melhora do estado nutricional, por meio de métodos pouco invasivos, desde que o aparelho digestivo tenha conservado, pelo menos, parte de sua capacidade de absorção. O procedimento requer cuidados especializados, posto que não é isento de complicações. A equipe que assiste o paciente que recebe terapia nutricional através de sondas deve ter conhecimento da instalação das mesmas bem como da administração das dietas e treinamento para prevenir, reconhecer e tratar as complicações. Apresentamos, neste artigo, as técnicas de introdução das sondas, infusão das dietas e principais complicações, que podem advir dessa terapia.
Infecção de vias urinarias na comunidade de Ribeirão Preto – SP
Authors: Camargo Corina Bueno Siqueira de , Pedro Caroline Cássia , Lourenço Débora Silva , Gironi Rosa Helena A. Romaneilo , Martinez Roberto 
Published: June 2014

Este estudo teve como objetivo avaliar a etiologia da infecção do trato urinário e a susceptibilidade das bactérias mais freqüentemente isoladas da urina de pacientes atendidos em Unidades Básicas de Saúde de Ribeirão Preto, SP. A urina foi coletada entre outubro de 1996 e maio de 2000. A identificação bacteriana e o teste de sensibilidade a antimicrobianos foram realizados pelo sistema automatizado Microscan (Dade — Behring ), menos nos seis meses iniciais do período acima citado, quando se recorreu à identificação bacteriológica convencional e ao método de difusão de disco.
Os agentes causais distribuíram-se em enterobactérias (87,6%), bacilos Gram-negativos não fermentadores (1,5%) e cocos Gram-positivos (11,9%). De um total de 1.638 bactérias, as espécies mais prevalentes foram Escherichia coli (1108 - 67,6% ), Klebsiella pneumoniae (107-6,5% ), Proteus mirabillis (67 - 4,1% ), Staphylococcus saprophyticus ( 63 - 3,8% ), Citrobacter koseri ( 26 — 1,6% ) e Enterococcus faecalis ( 25 — 1,5% ). A sensibilidade de E. coli foi baixa para ampicilina ( 45%) e cefalotina ( 54%), mediana para sulfametoxazol e trimetoprim (63%) e alta para amoxicilina e clavulanato, cefuroxima, ceftriaxona, ceftazidima, gentamicina, amicacina, nitrofurantoína, norfloxacina, ácidos pipemídico e nalidíxico e ciprofloxacina (92% - 100%). A sensibilidade geral dos uropatógenos sugere que norfloxacina e outras quinolonas, nitrofurantoina, cefuroxima e gentamicina são opções terapéuticas adequadas para as infecções de vias urinárias na comunidade.
AFECÇÕES OCULARES EM CRIANÇAS DE 2 A 8 ANOS DA REDE PÚBLICA MUNICIPAL DE PIRACICABA – SP
Authors: Gaiotto Paulo Cesar , Passos Júnior Walberto , Schellini Silvana Artioli , Shiratori Cláudia Akemi , Padovani Carlos Roberto 
Published: June 2014

Modelo do Estudo: observacional. Objetivo: determinar a freqüência de ametropias e outros distúrbios oculares em uma população de crianças de 2 a 8 anos de idade, das escolas públicas municipais de Piracicaba - SP. Pacientes e Método: durante o ano letivo de 2000, foram encaminhadas para exame oftalmológico, completo 1001 crianças com idade entre 2 e 8 anos, matriculadas nas escolas públicas municipais de Piracicaba-SP. A medida de acuidade visual (tabela E de Snellen) foi previamente avaliada por professoras treinadas. As crianças que apresentaram acuidade visual menor ou igual a 0,8, bem como queixas ou sinais oftalmológicos, foram selecionadas para exame. Resultados: dentre 1001 crianças selecionadas, 5,09% não compareceram ao exame, foram submetidas a exame oftalmológico completo 950 crianças. Detectaram-se ametropias em 70,84%, sendo o astigmatismo hipermetrópico composto e a hipermetropia, simples os erros refracionais prevalentes (49,62% e 32,98%, respectivamente). Anisometropia foi observada em 1,78% dos examinados. Outras afecções oculares foram constatadas em 10,21% das crianças; estrabismo (3,36%), alterações palpebrais, conjuntivite alérgica, dacrioestenose congênita, atrofia óptica, coriorretinite e glaucoma congênito. Conclusão: a freqüência dos problemas oculares, observados indica quão importante é a realização de campanhas do tipo da apresentada para a redução dos índices de cegueira prevenível , no Brasil.