Colorimetric Assessment of BCR-ABL1 Transcripts in Clinical Samples Via Gold Nanoprobes

Gold nanoparticles functionalized with thiolated oligonucleotides (Au-nanoprobes) have been used in a range of applications for the detection of bioanalytes of interest, from ions to proteins and DNA targets. These detection strategies are based on the unique optical properties of gold nanoparticles, in particular, the intense color that is subject to modulation by modification of the medium dieletric. Au-nanoprobes have been applied for the detection and characterization of specific DNA sequences of interest, namely pathogens and disease biomarkers. Nevertheless, despite its relevance, only a few reports exist on the detection of RNA targets. Among these strategies, the colorimetric detection of DNA has been proven to work for several different targets in controlled samples but demonstration in real clinical bioanalysis has been elusive. Here, we used a colorimetric method based on Au-nanoprobes for the direct detection of the e14a2 BCR-ABL fusion transcript in myeloid leukemia patient samples without the need for retro-transcription. Au-nanoprobes directly assessed total RNA from 38 clinical samples, and results were validated against reverse transcription-nested polymerase chain reaction (RT-nested PCR) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The colorimetric Au-nanoprobe assay is a simple yet reliable strategy to scrutinize myeloid leukemia patients at diagnosis and evaluate progression, with obvious advantages in terms of time and cost, particularly in low- to medium-income countries where molecular screening is not routinely feasible. Graphical abstract Gold nanoprobe for colorimetric detection of BCR-ABL1 fusion transcripts originating from the Philadelphia chromosome

Candidemia in Acute Leukemia Patients

Fungal infections are an important cause of morbidity and mortality in patients with acute leukemia (AL). Candidemia, once rare, is now a common nosocomial infection because of the intensity of chemotherapy, prolonged neutropenia, administration of broad-spectrum antibiotics and use of central venous catheters (CVC). We retrospectively identified patients treated for AL from 6/86 to 6/95 who also had candidemia. We describe 28 patients (incidence 6.3%) with a median age of 39 years, 24 of whom were on remission induction and 4 on postremission chemotherapy. All patients had CVC and empiric antimicrobial therapy, 4 had been given prophylactic antifungal drugs, and 2 had parenteral nutrition. Neutropenia was profound (median leukocyte nadir 200/microliters, median duration 19 days). Candida was isolated in blood cultures 10 days (median) after the start of neutropenia. The clinical presentation included fever (100%), respiratory symptoms (71.4%), skin lesions (39.2%) and septic shock (17.8%). Amphotericin B was given to 17 patients and liposomal amphotericin to 5 patients. Infection resolved in 18 patients (64.2%). 10 of whom were in complete remission. Mortality from candidemia was 17.8% (5/28). In conclusion, fungal infections are responsible for death in a significant number of patients. In our series treatment success was related to its rapid onset and to the recovery of neutropenia

A Double Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Patient, Co-Expressing P210 BCR-ABL1 and P195 BCR-ABL1 Isoforms

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A Novel BCR-ABL1 Mutation in a Patient with Philadelphia Chromosome-Positive B-Cell Acute Lymphoblastic Leukemia

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) represents the most common genetic subtype of adult ALL (20%-30%) and accounts for approximately 50% of all cases in the elderly. It has been considered the subgroup of ALL with the worst outcome. The introduction of tyrosine kinase inhibitors (TKIs) allows complete hematologic remission virtually in all patients, with improved disease-free survival and overall survival. Nevertheless, the emergence of resistant mutations in BCR-ABL1 may require different TKI strategies to overcome the patient's resistance and disease relapse. Here, we report a Ph+B-ALL case with persistent minimal residual disease (MRD) after treatment with dasatinib. The patient expressed the P190BCR-ABL1 isoform and a novel BCR-ABL1 mutation, p.Y440C. The latter is in the C-terminal lobe of the kinase domain, which likely induces deviations in the protein structure and activity and destabilizes its inactive conformation. The treatment was substituted by bosutinib, which binds to the active conformation of the protein, prior to allogeneic bone marrow transplant to overcome the lack of a complete response to dasatinib. These findings strengthen the importance of BCR-ABL1 mutational screening in Ph+ patients, particularly for those who do not achieve complete molecular remission.info:eu-repo/semantics/publishedVersio

Evaluación del vault en la adaptación de lentes de contacto esclerales con un biómetro óptico

[Extracto] Justificación y objetivos -   La tomografía de coherencia óptica (OCT) anterior es un método óptico que permite evaluar la separación entre la lente de contacto y la córnea – vault – en la adaptación de lentes de contacto esclerales (LCE). Sin embargo, el costo considerable de este tipo de equipo es un obstáculo a la aplicación en usuarios de LCE, especialmente en el ámbito de investigación. [...]info:eu-repo/semantics/publishedVersio

Polymerase Chain Reaction Screening for Fungemia and/or Invasive Fungal Infections in Patients with Hematologic Malignancies

INTRODUCTION: Invasive fungal infections (IFIs) are a life-threatening complication in patients with hematologic malignancies, mainly in acute leukemia patients, following chemotherapy. IFI incidence is increasing, and associated mortality remains high due to unreliable diagnosis. Antifungal drugs are often limited by inadequate antimicrobial spectrum and side effects. Thus, the detection of circulating fungal DNA has been advocated as a rapid, more sensitive diagnostic tool. PATIENTS AND METHODS: Between June 01 and January 03, weekly blood samples (1,311) were screened from 193 patients undergoing intensive myelosuppressive or immunosuppressive therapy. IFI cases were classified according to European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Fungal DNA was extracted from whole blood and amplified using polymerase chain reaction (PCR) published primers that bind to the conserved regions of the fungal 18S rRNA gene sequence. In our study, two or more consecutive positive samples were always associated with fungal disease. RESULTS: PCR screening predicted the development of IFI to be 17 days (median). This test had a specificity of 91.1% and a sensitivity of 75%. IFI incidence was 7.8%. DISCUSSION: Therefore, our results confirm the potential usefulness of PCR serial screening and the clinical applicability in everyday routine. PCR screening offers a noninvasive repeatable aid to the diagnosis of IFI

Efeito da densidade de plantio sobre a produção do primeiro ciclo da bananeira 'Pacovan'.

A banana é uma das frutas mais consumidas no mundo, sendo explorada na maioria dos países tropicais. O Brasil destaca-se como o segundo produtor mundial, ocupando a Índia a primeira colocação. Em nível nacional, a região Nordeste é a maior produtora de banana, destacando-se como principais produtores os estados da Bahia e Pernambuco (Agrianual..., 2001). No Piauí, a bananeira é cultivada sobretudo em pequenas propriedades, constituindo-se de grande importância social para a região, quer pelo seu amplo consumo em todas as camadas sociais, quer pelo fato do seu cultivo dar-se, principalmente, por pequenos produtores, gerando, dessa forma, uma quantidade significativa de emprego e renda no meio rural. Diversas densidades de plantio têm sido utilizadas, gerando grande controvérsia entre os produtores sobre qual a mais adequada e que otimize a produção de bananas. Vários autores relatam que as maiores produtividades por ciclo foram obtidas em maiores densidades (Gomes et al. 1984; Robinson & Nel, 1986; Lichtemberg et al. 1994, 1996), entretanto, Irizarry et al. (1978) não observaram efeitos significativos no primeiro ciclo de produção. Este trabalho teve por objetivo avaliar o comportamento produtivo da bananeira ?Pacovan? em diferentes densidades de plantio

A INCIDÊNCIA DO PROCESSO DE DESINDUSTRIALIZAÇÃO NOS ESTADOS BRASILEIROS

Os processos de desindustrialização têm sido objeto de intenso debate acadêmico nos últimos anos. Parte-se do ponto de vista de que há sinais inequívocos de um processo de desindustrialização na economia brasileira. Entretanto, em função do tamanho do país e de suas significativas desigualdades regionais, o processo de desindustrialização não se apresenta de modo uniforme em todas as regiões brasileiras. O objetivo central do artigo é apresentar as evidências do processo de desindustrialização por meio da ótica regional, apresentando dados recentes da produção e inserção externa. Por meio de indicadores de evolução do PIB industrial, emprego, produtividade, densidade industrial e inserção externa pode-se concluir que a incidência do processo de desindustrialização nos estados e regiões brasileiras não foi suficiente para alterar, de forma significativa, a forte concentração da indústria no Sul-Sudeste do país