Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis

IntroductionObesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification.MethodsWe performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003–02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype.ResultsMultivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype.ConclusionsSeverely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes

Insight from the draft genome of Dietzia cinnamea P4 reveals mechanisms of survival in complex tropical soil habitats and biotechnology potential

The draft genome of Dietzia cinnamea strain P4 was determined using pyrosequencing. In total, 428 supercontigs were obtained and analyzed. We here describe and interpret the main features of the draft genome. The genome contained a total of 3,555,295 bp, arranged in a single replicon with an average G+C percentage of 70.9%. It revealed the presence of complete pathways for basically all central metabolic routes. Also present were complete sets of genes for the glyoxalate and reductive carboxylate cycles. Autotrophic growth was suggested to occur by the presence of genes for aerobic CO oxidation, formate/formaldehyde oxidation, the reverse tricarboxylic acid cycle and the 3-hydropropionate cycle for CO2 fixation. Secondary metabolism was evidenced by the presence of genes for the biosynthesis of terpene compounds, frenolicin, nanaomycin and avilamycin A antibiotics. Furthermore, a probable role in azinomycin B synthesis, an important product with antitumor activity, was indicated. The complete alk operon for the degradation of n-alkanes was found to be present, as were clusters of genes for biphenyl ring dihydroxylation. This study brings new insights in the genetics and physiology of D. cinnamea P4, which is useful in biotechnology and bioremediation

New Insights into the Phylogeny and Molecular Classification of Nicotinamide Mononucleotide Deamidases

Nicotinamide mononucleotide (NMN) deamidase is one of the key enzymes of the bacterial pyridine nucleotide cycle (PNC). It catalyzes the conversion of NMN to nicotinic acid mononucleotide, which is later converted to NAD+ by entering the Preiss-Handler pathway. However, very few biochemical data are available regarding this enzyme. This paper represents the first complete molecular characterization of a novel NMN deamidase from the halotolerant and alkaliphilic bacterium Oceanobacillus iheyensis (OiPncC). The enzyme was active over a broad pH range, with an optimum at pH 7.4, whilst maintaining 90 % activity at pH 10.0. Surprisingly, the enzyme was quite stable at such basic pH, maintaining 61 % activity after 21 days. As regard temperature, it had an optimum at 65 °C but its stability was better below 50 °C. OiPncC was a Michaelian enzyme towards its only substrate NMN, with a Km value of 0.18 mM and a kcat/Km of 2.1 mM-1 s-1. To further our understanding of these enzymes, a complete phylogenetic and structural analysis was carried out taking into account the two Pfam domains usually associated with them (MocF and CinA). This analysis sheds light on the evolution of NMN deamidases, and enables the classification of NMN deamidases into 12 different subgroups, pointing to a novel domain architecture never before described. Using a Logo representation, conserved blocks were determined, providing new insights on the crucial residues involved in the binding and catalysis of both CinA and MocF domains. The analysis of these conserved blocks within new protein sequences could permit the more efficient data curation of incoming NMN deamidases

Avaliação do questionário de controle da asma validado para uso no Brasil Evaluation of the asthma control questionnaire validated for use in Brazil

OBJETIVO: Avaliar se a versão em língua portuguesa do Asthma Control Questionnaire (ACQ, Questionário de Controle da Asma) é um instrumento válido para medir o controle da asma em pacientes adultos ambulatoriais no Brasil. MÉTODOS: Foram avaliados 278 pacientes ambulatoriais com diagnóstico de asma. Todos os pacientes, durante a primeira visita, responderam ao questionário, foram submetidos à espirometria e avaliados clinicamente por um médico para a caracterização do controle da doença. Foram analisadas as versões do questionário com 5, 6 e 7 questões, utilizando dois escores distintos (0,75 e 1,50) como pontos de corte. RESULTADOS: Dos 278 pacientes, 77 (27,7%) tinham asma intermitente, 39 (14,0%) asma persistente leve, 40 (14,4%) asma persistente moderada e 122 (43,9%) asma persistente grave. A sensibilidade do questionário para identificar asma não-controlada variou de 77% a 99% e a especificidade variou de 36% a 84%. O valor preditivo positivo variou de 73% a 90%, e o valor preditivo negativo variou de 67% a 95%. A razão de verossimilhança positiva variou de 1,55 a 4,81, e a razão de verossimilhança negativa variou de 0,03 a 0,27. Nas versões do ACQ com 5 e 6 questões, o coeficiente de correlação intraclasse foi de 0,92, e estas versões foram responsivas a mudanças no quadro clínico dos pacientes. CONCLUSÕES: O ACQ, nas suas três versões, teve boa capacidade de discriminar indivíduos com asma não-controlada daqueles com asma controlada. As versões com 5 e 6 questões apresentaram também boa reprodutibilidade e responsividade. Trata-se, portanto, de um instrumento válido para avaliação do controle da asma em pacientes adultos ambulatoriais no Brasil.<br>OBJECTIVE: To evaluate whether the Portuguese version of the Asthma Control Questionnaire (ACQ) is a valid instrument to measure asthma control in adult outpatients in Brazil. METHODS: We selected 278 outpatients diagnosed with asthma. All of the patients completed the questionnaire, underwent spirometry and were clinically evaluated by a physician in order to characterize the control of the disease in the first visit. The questionnaire was evaluated in three versions, with 5, 6 and 7 questions, respectively, and scores of 0.75 and 1.50 were used as cut-off points. RESULTS: Of the 278 patients, 77 (27.7%) had intermittent asthma, 39 (14.0%) had mild persistent asthma, 40 (14.4%) had moderate persistent asthma and 122 (43.9%) had severe persistent asthma. The sensitivity of ACQ to identify uncontrolled asthma ranged from 77% to 99%, and the specificity ranged from 36% to 84%. The positive predictive value ranged from 73% to 90%, and the negative predictive value ranged from 67% to 95%. The positive likelihood ratio ranged from 1.55 to 4.81, and the negative likelihood ratio ranged from 0.03 to 0.27. In the 5- and 6-question versions of the ACQ, the intraclass correlation coefficient was 0.92. These two versions were both responsive to clinical changes in the patients. CONCLUSIONS: All three versions of the ACQ satisfactorily discriminated between patients with uncontrolled asthma and those with controlled asthma. The 5- and 6-question versions also presented good reliability and responsiveness. Therefore, the ACQ is a valid tool for evaluating asthma control in adult outpatients in Brazil

Comparação entre dois métodos de avaliação do controle da asma baseados na percepção individual Comparison between two methods of asthma control evaluation based on individual perception

OBJETIVO: Comparar a percepção subjetiva do controle da asma informada pelo paciente com aquela obtida por meio do escore do Asthma Control Questionnaire com seis questões (ACQ-6) em pacientes com asma grave e verificar se o controle da asma está associado ao número de visitas a salas de emergência no mês anterior. MÉTODOS: Estudo transversal de 528 pacientes acompanhados na Central de Referência do Programa para Controle da Asma e Rinite Alérgica na Bahia, entre agosto de 2008 e março de 2010, em Salvador (BA). Os pacientes responderam ao ACQ-6 e a uma questão adicional específica para avaliar sua percepção do controle da doença na semana prévia. RESULTADOS: Foram avaliados 423 pacientes, que preencheram os critérios de inclusão. A maioria era do gênero feminino (81,3%) e possuía renda familiar menor que dois salários mínimos (64,3%). A média de idade foi de 49,85 ± 13,71 anos, e a duração dos sintomas de asma foi de 32,11 ± 16,35 anos. Os pacientes eram regularmente tratados no programa há 36,65 ± 18,10 meses. Baseados na percepção subjetiva do controle, 8% dos pacientes consideraram a sua asma não controlada, enquanto 38,8% obtiveram escore do ACQ > 1,5, indicando falta de controle. O coeficiente kappa revelou fraca concordância entre os dois métodos. Houve uma associação direta entre falta de controle e número de visitas a emergência no mês anterior (p < 0,001). CONCLUSÕES: Nesta amostra de pacientes, a percepção subjetiva do paciente sobre o controle da asma diferiu da medida por meio do ACQ-6, e os pacientes superestimaram seu controle, trazendo risco de subtratamento.<br>OBJECTIVE: To compare the subjective perception of asthma control reported by the patient with that measured by the score obtained on the Asthma Control Questionnaire 6-item version (ACQ-6) in patients with severe asthma and to determine whether asthma control is associated with the number of emergency room visits in the previous month. METHODS: This was a cross-sectional study involving 528 patients treated at the Bahia State Asthma and Allergic Rhinitis Control Program Central Referral Clinic between August of 2008 and March of 2010, in the city of Salvador, Brazil. The patients completed the ACQ-6 and answered a specific additional question in order to evaluate their own perception of asthma control in the previous week. RESULTS: We evaluated 423 patients who met the inclusion criteria. The sample was predominantly female (81.3%), and 64.3% had an income lower than two times the national minimum wage. The mean age was 49.85 ± 13.71 years, and the duration of asthma symptoms was 32.11 ± 16.35 years. The patients had been regularly treated via the program for 36.65 ± 18.10 months. Based on the subjective perception of asthma control, only 8% of the patients considered their asthma to be uncontrolled, whereas 38.8% had an ACQ-6 score > 1.5, which indicates poor control. The kappa statistic revealed poor concordance between the two methods. There was a direct association between uncontrolled asthma and the number of emergency room visits in the previous month (p < 0.001). CONCLUSIONS: In this sample of patients, the subjective perception of asthma control differed from that measured by the ACQ-6 score, and the patients overestimated their own level of asthma control, which puts them at risk of being undertreated