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1.
Front Psychiatry ; 15: 1354762, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895036

RESUMO

Borderline Personality Disorder (BPD) symptoms include inappropriate control of anger and severe emotional dysregulation after rejection in daily life. Nevertheless, when using the Cyberball paradigm, a tossing game to simulate social exclusion, the seven basic emotions (happiness, sadness, anger, surprise, fear, disgust, and contempt) have not been exhaustively tracked out. It was hypothesized that these patients would show anger, contempt, and disgust during the condition of exclusion versus the condition of inclusion. When facial emotions are automatically detected by Artificial Intelligence, "blending", -or a mixture of at least two emotions- and "masking", -or showing happiness while expressing negative emotions- may be most easily traced expecting higher percentages during exclusion rather than inclusion. Therefore, face videos of fourteen patients diagnosed with BPD (26 ± 6 years old), recorded while playing the tossing game, were analyzed by the FaceReader software. The comparison of conditions highlighted an interaction for anger: it increased during inclusion and decreased during exclusion. During exclusion, the masking of surprise; i.e., displaying happiness while feeling surprised, was significantly more expressed. Furthermore, disgust and contempt were inversely correlated with greater difficulties in emotion regulation and symptomatology, respectively. Therefore, the automatic detection of emotional expressions during both conditions could be useful in rendering diagnostic guidelines in clinical scenarios.

2.
J Pediatr ; 266: 113878, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38135031

RESUMO

Current recommendations advise against blood transfusion in hemodynamically stable children with iron deficiency anemia. In an observational study of 125 children aged 6 through 36 months, hospitalized with iron deficiency anemia, we found that hemoglobin level predicted red blood cell transfusion (area under the curve 0.8862). A hemoglobin of 39 g/L had sensitivity 92% and specificity 72% for transfusion.


Assuntos
Anemia Ferropriva , Pré-Escolar , Humanos , Anemia Ferropriva/terapia , Transfusão de Sangue , Transfusão de Eritrócitos , Hemoglobinas/análise , Lactente
3.
Stat Methods Med Res ; 32(6): 1203-1216, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37077139

RESUMO

The discriminative and predictive power of a continuous-valued marker for survival outcomes can be summarized using the receiver operating characteristic and predictiveness curves, respectively. In this paper, fully parametric and semi-parametric copula-based constructions of the joint model of the marker and the survival time are developed for characterizing, plotting, and analyzing both curves along with other underlying performance measures. The formulations require a copula function, a parametric specification for the margin of the marker, and either a parametric distribution or a non-parametric estimator for the margin of the time to event, to respectively characterize the fully parametric and semi-parametric joint models. Estimation is carried out using maximum likelihood and a two-stage procedure for the parametric and semi-parametric models, respectively. Resampling-based methods are used for computing standard errors and confidence bounds for the various parameters, curves, and associated measures. Graphical inspection of residuals from each conditional distribution is employed as a guide for choosing a copula from a set of candidates. The performance of the estimators of various classification and predictiveness measures is assessed in simulation studies, assuming different copula and censoring scenarios. The methods are illustrated with the analysis of two markers using the familiar primary biliary cirrhosis data set.


Assuntos
Modelos Estatísticos , Simulação por Computador , Curva ROC
4.
J Clin Exp Hepatol ; 12(6): 1480-1491, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36340308

RESUMO

Hazardous alcohol consumption causes approximately 4% of deaths globally, constituting one of the leading risk factors for the burden of the disease worldwide. Alcohol has several health consequences, such as alcohol-associated liver disease, hepatocellular carcinoma, nonliver neoplasms, physical injury, cardiac disease, and psychiatric disorders. Alcohol misuse significantly affects workforce productivity, with elevated direct and indirect economic costs. Due to the high impact of alcohol consumption on the population, public health has led to the development of a range of strategies to reduce its harmful effects. Regulatory public health policies (PHP) for alcohol can exist at the global, regional, international, national, or subnational levels. Effective strategies incorporate a multilevel, multicomponent approach, targeting multiple determinants of drinking and alcohol-related harms. The World Health Organization categorizes the PHP into eight categories: national plan to fight the harmful consequences of alcohol, national license and production and selling control, taxes control and pricing policies, limiting drinking age, restrictions on alcohol access, driving-related alcohol policies, control over advertising and promotion, and government monitoring systems. These policies are supported by evidence from different populations, demonstrating that determinants of alcohol use depend on several factors such as socioeconomic level, age, sex, ethnicity, production, availability, marketing, and others. Although most policies have a significant individual effect, a higher number of PHP are associated with a lower burden of disease due to alcohol. The excessive consequences of alcohol constitute a call for action, and clinicians should advocate for developing and implementing a new PHP on alcohol consumption.

5.
Biomark Med ; 16(14): 1019-1028, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36052694

RESUMO

Introduction: The enzyme lactate dehydrogenase (LDH) is a good marker of general hyperinflammation correlated with mortality for COVID-19, and is therefore used in prognosis tools. In a current COVID-19 clinical randomized trial (CRT), the blood level of LDH was selected as an inclusion criterion. However, LDH decreased during the pandemic; hence, the impact of this decrease on the prognostic value of LDH for mortality was evaluated. Methods: Data on LDH levels in 843 patients were obtained and analyzed. Relative risk, standard error and receiver operating characteristic curves were calculated for two cutoff values. Results: Relative risk lost validity and the area under the curve narrowed by trimester during the pandemic. Conclusion: The progressive decrease in LDH impacted the capacity to predict mortality in COVID-19. More studies are needed to validate this finding and its implications.


Assuntos
COVID-19 , L-Lactato Desidrogenase , Humanos , COVID-19/enzimologia , COVID-19/epidemiologia , L-Lactato Desidrogenase/metabolismo , Pandemias , Prognóstico , Estudos Retrospectivos , Curva ROC
6.
Dose Response ; 20(3): 15593258221120485, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36158743

RESUMO

Phytochemicals (Pch) present in fruits, vegetables and other foods, are known to inhibit or induce drug metabolism and transport. An exhaustive search was performed in five databases covering from 2000 to 2021. Twenty-one compounds from plants were found to modulate CYP3A and/or P-gp activities and modified the pharmacokinetics and the therapeutic effect of 27 different drugs. Flavonols, flavanones, flavones, stilbenes, diferuloylmethanes, tannins, protoalkaloids, flavans, hyperforin and terpenes, reduce plasma concentration of cyclosporine, simvastatin, celiprolol, midazolam, saquinavir, buspirone, everolimus, nadolol, tamoxifen, alprazolam, verapamil, quazepam, digoxin, fexofenadine, theophylline, indinavir, clopidogrel. Anthocyanins, flavonols, flavones, flavanones, flavonoid glycosides, stilbenes, diferuloylmethanes, catechin, hyperforin, alkaloids, terpenes, tannins and protoalkaloids increase of plasma concentration of buspirone, losartan, diltiazem, felodipine, midazolam, cyclosporine, triazolam, verapamil, carbamazepine, diltiazem, aripiprazole, tamoxifen, doxorubicin, paclitaxel, nicardipine. Interactions between Pchs and drugs affect the gene expression and enzymatic activity of CYP3A and P-gp transporter, which has an impact on their bioavailability; such that co-administration of drugs with food, beverages and food supplements can cause a subtherapeutic effect or overdose. Therefore, it is important for the clinician to consider these interactions to obtain a better therapeutic effect.

7.
Eur J Radiol Open ; 9: 100400, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35198656

RESUMO

PURPOSE: This study aims to determine if the presence of specific clinical and computed tomography (CT) patterns are associated with epidermal growth factor receptor (EGFR) mutation in patients with non-small cell lung cancer. METHODS: A systematic literature review and meta-analysis was carried out in 6 databases between January 2002 and July 2021. The relationship between clinical and CT patterns to detect EGFR mutation was measured and pooled using odds ratios (OR). These results were used to build several mathematical models to predict EGFR mutation. RESULTS: 34 retrospective diagnostic accuracy studies met the inclusion and exclusion criteria. The results showed that ground-glass opacities (GGO) have an OR of 1.86 (95%CI 1.34 -2.57), air bronchogram OR 1.60 (95%CI 1.38 - 1.85), vascular convergence OR 1.39 (95%CI 1.12 - 1.74), pleural retraction OR 1.99 (95%CI 1.72 - 2.31), spiculation OR 1.42 (95%CI 1.19 - 1.70), cavitation OR 0.70 (95%CI 0.57 - 0.86), early disease stage OR 1.58 (95%CI 1.14 - 2.18), non-smoker status OR 2.79 (95%CI 2.34 - 3.31), female gender OR 2.33 (95%CI 1.97 - 2.75). A mathematical model was built, including all clinical and CT patterns assessed, showing an area under the curve (AUC) of 0.81. CONCLUSIONS: GGO, air bronchogram, vascular convergence, pleural retraction, spiculated margins, early disease stage, female gender, and non-smoking status are significant risk factors for EGFR mutation. At the same time, cavitation is a protective factor for EGFR mutation. The mathematical model built acts as a good predictor for EGFR mutation in patients with lung adenocarcinoma.

8.
Saudi Pharm J ; 29(9): 1061-1069, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34588851

RESUMO

The medicinal uses of Calotropis procera are diverse, yet some of them are based on effects that still lack scientific support. Control of diabetes is one of them. Recently, latex proteins from C. procera latex (LP) have been shown to promote in vivo glycemic control by the inhibition of hepatic glucose production via AMP-activated protein kinase (AMPK). Glycemic control has been attributed to an isolated fraction of LP (CpPII), which is composed of cysteine peptidases (95%) and osmotin (5%) isoforms. Those proteins are extensively characterized in terms of chemistry, biochemistry and structural aspects. Furthermore, we evaluated some aspects of the mitochondrial function and cellular mechanisms involved in CpPII activity. The effect of CpPII on glycemic control was evaluated in fasting mice by glycemic curve and glucose and pyruvate tolerance tests. HepG2 cells was treated with CpPII, and cell viability, oxygen consumption, PPAR activity, production of lactate and reactive oxygen species, mitochondrial density and protein and gene expression were analyzed. CpPII reduced fasting glycemia, improved glucose tolerance and inhibited hepatic glucose production in control animals. Additionally, CpPII increased the consumption of ATP-linked oxygen and mitochondrial uncoupling, reduced lactate concentration, increased protein expression of mitochondrial complexes I, III and V, and activity of peroxisome-proliferator-responsive elements (PPRE), reduced the presence of reactive oxygen species (ROS) and increased mitochondrial density in HepG2 cells by activation of AMPK/PPAR. Our findings strongly support the medicinal use of the plant and suggest that CpPII is a potential therapy for prevention and/or treatment of type-2 diabetes. A common epitope sequence shared among the proteases and osmotin is possibly the responsible for the beneficial effects of CpPII.

9.
Entropy (Basel) ; 22(3)2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33286116

RESUMO

MaxEnt is a popular maximum entropy-based algorithm originally developed for modelling species distribution, but increasingly used for land-cover classification. In this article, we used MaxEnt as a single-class land-cover classification and explored if recommended procedures for generating high-quality species distribution models also apply for generating high-accuracy land-cover classification. We used remote sensing imagery and randomly selected ground-true points for four types of land covers (built, grass, deciduous, evergreen) to generate 1980 classification maps using MaxEnt. We calculated different accuracy discrimination and quality model metrics to determine if these metrics were suitable proxies for estimating the accuracy of land-cover classification outcomes. Correlation analysis between model quality metrics showed consistent patterns for the relationships between metrics, but not for all land-covers. Relationship between model quality metrics and land-cover classification accuracy were land-cover-dependent. While for built cover there was no consistent patterns of correlations for any quality metrics; for grass, evergreen and deciduous, there was a consistent association between quality metrics and classification accuracy. We recommend evaluating the accuracy of land-cover classification results by using proper discrimination accuracy coefficients (e.g., Kappa, Overall Accuracy), and not placing all the confidence in model's quality metrics as a reliable indicator of land-cover classification results.

10.
J Tradit Complement Med ; 9(3): 184-191, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31193893

RESUMO

Epidemiological studies indicate an inverse association of coffee consumption with risk of type 2 diabetes mellitus. However, studies to determine the clinical effects of coffee consumption on the glucose metabolism biomarkers remain uncertain. The aim of this systematic review was to evaluate the effects of coffee consumption on glucose metabolism. A search of electronic databases (PubMed and Web of Science) was performed identifying studies published until September 2017. Eight clinical trials (n = 247 subjects) were identified for analyses. Participants and studies characteristics, main findings, and study quality (Jadad Score) were reported. Short-term (1-3 h) and long-term (2-16 weeks) studies were summarized separately. Short-term studies showed that consumption of caffeinated coffee may increase the area under the curve for glucose response, while for long-term studies, caffeinated coffee may improve the glycaemic metabolism by reducing the glucose curve and increasing the insulin response. The findings suggest that consumption of caffeinated coffee may lead to unfavourable acute effects; however, an improvement on glucose metabolism was found on long-term follow-up.

11.
São Paulo; s.n; 2019. 175 p
Tese em Português | LILACS, BDENF - Enfermagem | ID: biblio-1397629

RESUMO

Introdução: os índices de trauma são ferramentas metodológicas essenciais para estratificação da gravidade e previsão de desfechos de vítimas de trauma. Analisar o desempenho dos índices na predição de complicações e mortalidade hospitalar é fundamental para auxiliar no alcance e manutenção da qualidade da assistência. Objetivo: avaliar o desempenho de índices de gravidade na predição de complicações e mortalidade de vítimas de trauma durante a internação hospitalar. Método: estudo de coorte retrospectivo, realizado por meio da análise de prontuários de vítimas de trauma, com idade 16 anos, atendidas entre 2017 e 2018 em um hospital privado da cidade de São Paulo, Brasil. As variáveis analisadas contemplaram dados sociodemográficos, informações relacionadas ao evento traumático, ao atendimento hospitalar e à ocorrência de complicações (gerais, infecciosas e não infecciosas) e mortalidade, além dos índices de gravidade Injury Severity Score (ISS), New Injury Severity Score (NISS), Revised Trauma Score (RTS), modified Rapid Emergency Medicine (mREMS), Trauma and Injury Severity Score (TRISS), New Trauma and Injury Severity Score (NTRISS), TRISS-like, NTRISS-like, TRISS SpO2 e NTRISS-like SpO2. Os testes Exato de Fisher e Qui- Quadrado de Pearson, além de Receiver Operating Characteristic Curves e análise da área sob a curva (AUC), foram realizados, com nível de significância de 5%. Resultados: a casuística foi composta por 837 pacientes (62,0% homens; idade média 51,3 anos). As quedas (44,7%) prevaleceram na amostra. As médias dos índices RTS, mREMS, ISS e NISS foram: 7,7 (±0,7), 2,3 (±2,4), 7,9 (±6,7) e 10,7 (±9,2), respectivamente. Com exceção do TRISS SpO2 (87,3±16,0), a média de probabilidade de sobrevida prevista em todos os demais índices mistos foi superior a 96,0%. Aproximadamente 17,0% das vítimas tiveram complicação, com destaque às não infecciosas (n=128), especialmente delirium (n=41) e lesão renal aguda (n=34). A taxa de mortalidade hospitalar foi de 2,9%. Houve diferença significativa entre o desfecho clínico dos pacientes e a ocorrência de complicações em geral (p<0,001) e não infecciosas (p<0,001). Na análise do desempenho dos índices para cada tipo de complicação infecciosa e não infecciosa avaliada individualmente, observou-se que os valores preditivos positivos (VPP) foram sempre muito baixos, contraindicando a sua aplicação na prática clínica. Na predição de complicações em geral (n=141) e não infecciosas (n=128), o TRISS (AUC 0,793 e 0,787, respectivamente) e o NTRISS (AUC 0,792 e 0,783, respectivamente) apresentaram os melhores desempenhos, com aumento importante dos VPP. Para os desfechos complicações infecciosas e mortalidade, nenhum dos índices apresentou boa capacidade preditiva nessa amostra, dados os VPP baixos. Conclusão: O TRISS e o NTRISS apresentaram melhor desempenho na predição de complicações em geral e não infecciosas dos pacientes da amostra. Considerando que o TRISS é um índice reconhecido e aplicado mundialmente, sugere-se seu uso na predição desses desfechos em vítimas de trauma atendidas em instituição privada, cujos resultados podem auxiliar em estratégias de programas de prevenção, pautados no melhor custo-benefício e na segurança do doente.


Introduction: trauma scores are essential methodological tools to stratify the severity and to predict the outcomes of trauma victims. Analyzing the score performance in predicting complications and hospital mortality is fundamental to aid in achieving and maintaining the quality of care. Objective: to evaluate the performance of the severity scores in predicting the complications and mortality of trauma victims during hospitalization. Method: retrospective cohort study conducted by analysis of records of trauma victims, aging 16 years old, attended between 2017 and 2018 in a private hospital at São Paulo city, Brazil. The analyzed variables included sociodemographic data; information related to the trauma event, the hospital attendance, and the occurrence of complications (general, infectious, and noninfectious); and mortality; besides the severity scores Injury Severity Score (ISS), New Injury Severity Score (NISS), Revised Trauma Score (RTS), modified Rapid Emergency Medicine (mREMS), Trauma and Injury Severity Score (TRISS), New Trauma and Injury Severity Score (NTRISS), TRISS-like, NTRISS-like, TRISS SpO2, and NTRISS-like SpO2. Fisher's Exact Test and Pearson's Chi-Square Test, besides Receiver Operating Characteristic Curves and area the under curve analysis (AUC), were performed, with a 5% significance level. Results: the sample was composed by 837 patients (62.0% males; mean age of 51.3 years old). Falls (44.7%) prevailed in the sample. The mean RTS, mREMS, ISS, and NISS scores were: 7.7 (±0.7), 2.3 (±2.4), 7.9 (±6.7), and 10.7 (±9.2), respectively. Except for TRISS SpO2 (87.3±16.0), the mean survival probability predicted in all other mixed scores was higher than 96.0%. Approximately 17.0% of the victims presented a complication, highlighting the non-infectious ones (n=128), especially delirium (n=41) and acute kidney injury (n=34). The hospital mortality score was 2.9%. There was a significant difference between the clinical outcome of the patients and occurrence of general (p <0.001) and non-infectious (p <0.001) complications. In the score performance analysis individually assessed for each infectious and non-infectious complication, it was verified that the positive predictive values (PPV) were always very low, contraindicating their application in the clinical practice. In the prediction of general (n=141) and non-infectious (n=128) complications, TRISS (AUC of 0.793 and 0.787, respectively) and NTRISS (AUC of 0.792 and 0.783, respectively) presented the best performances, with a significant increase in PPV. For the outcomes infectious complications and mortality, no score presented good predictive capability in this sample, considering the low PPV. Conclusion: TRISS and NTRISS presented better performance in predicting general and non-infectious complications in the patients in the sample. Considering that TRISS is a recognized score that is applied worldwide, its use is suggested to predict such outcomes in trauma victims in private institutions, which results might aid in prevention program strategies, guided by the best costbenefit and the patient safety.


Assuntos
Ferimentos e Lesões , Enfermagem , Avaliação de Resultados em Cuidados de Saúde , Mortalidade
12.
Stat Med ; 37(11): 1859-1873, 2018 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-29508421

RESUMO

Discrimination surfaces are here introduced as a diagnostic tool for localizing brain regions where discrimination between diseased and nondiseased participants is higher. To estimate discrimination surfaces, we introduce a Mann-Whitney type of statistic for random fields and present large-sample results characterizing its asymptotic behavior. Simulation results demonstrate that our estimator accurately recovers the true surface and corresponding interval of maximal discrimination. The empirical analysis suggests that in the anterior region of the brain, schizophrenic patients tend to present lower local asymmetry scores in comparison with participants in the control group.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Modelos Estatísticos , Área Sob a Curva , Bioestatística , Encefalopatias/diagnóstico por imagem , Encefalopatias/patologia , Simulação por Computador , Humanos , Interpretação de Imagem Assistida por Computador/estatística & dados numéricos , Imageamento Tridimensional/estatística & dados numéricos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Método de Monte Carlo , Curva ROC , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia
13.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;51(6): e6801, 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-889107

RESUMO

Gene networks have been broadly used to predict gene functions based on guilt by association (GBA) principle. Thus, in order to better understand the molecular mechanisms of esophageal squamous cell carcinoma (ESCC), our study was designed to use a network-based GBA method to identify the optimal gene functions for ESCC. To identify genomic bio-signatures for ESCC, microarray data of GSE20347 were first downloaded from a public functional genomics data repository of Gene Expression Omnibus database. Then, differentially expressed genes (DEGs) between ESCC patients and controls were identified using the LIMMA method. Afterwards, construction of differential co-expression network (DCN) was performed relying on DEGs, followed by gene ontology (GO) enrichment analysis based on a known confirmed database and DEGs. Eventually, the optimal gene functions were predicted using GBA algorithm based on the area under the curve (AUC) for each GO term. Overall, 43 DEGs and 67 GO terms were gained for subsequent analysis. GBA predictions demonstrated that 13 GO functions with AUC>0.7 had a good classification ability. Significantly, 6 out of 13 GO terms yielded AUC>0.8, which were determined as the optimal gene functions. Interestingly, there were two GO categories with AUC>0.9, which included cell cycle checkpoint (AUC=0.91648), and mitotic sister chromatid segregation (AUC=0.91597). Our findings highlight the clinical implications of cell cycle checkpoint and mitotic sister chromatid segregation in ESCC progression and provide the molecular foundation for developing therapeutic targets.


Assuntos
Humanos , Carcinoma de Células Escamosas/genética , Biologia Computacional/métodos , Neoplasias Esofágicas/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Área Sob a Curva
14.
J Clin Exp Hepatol ; 7(2): 135-143, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28663678

RESUMO

BACKGROUND/OBJECTIVES: to compare the prognostic accuracy for 28 and 90-day transplant-free mortality of a modified CLIF-SOFA score (including a dynamic definition of acute kidney injury) with that of the classic CLIF-SOFA score and KDIGO score for acute kidney injury in patients with acute decompensation of cirrhosis. METHODS: A retrospective analysis of all admissions of acutely decompensated patients with cirrhosis was carried out from January 2012 to December 2014. Classic and modified CLIF-SOFA scores were analyzed, as well as acute kidney injury diagnosis using the KDIGO score regarding their accuracy for 28- and 90-day transplant free mortality prediction. RESULTS: 108 admissions were analyzed. Acute kidney injury diagnosis was met in 37 (34%) patients. Acute-on-chronic liver failure was diagnosed in 59 (55%) patients using the classic CLIF-SOFA score; and in 64 (59%) patients using the modified CLIF-SOFA score. Both CLIF-SOFA scores were highly effective in predicting 28-day transplant-free mortality (AUCROC 0.93 and 0.92, p = 0.34) as well as 90-day transplant-free mortality (AUCROC 0.79 and 0.78, p = 0.78). Acute kidney injury diagnosis had significantly lower accuracy in mortality assessment (28 and 90-day transplant free mortality AUCROC 0.67 [p = 0.002] and 0.63 [p = 0.02]). CONCLUSIONS: To our knowledge, this is the first evidence of the limited impact of modifying the fixed kidney injury definition currently used for acute-on-chronic liver failure.

15.
J Cheminform ; 9: 7, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28203291

RESUMO

A new metric for the evaluation of model performance in the field of virtual screening and quantitative structure-activity relationship applications is described. This metric has been termed the power metric and is defined as the fraction of the true positive rate divided by the sum of the true positive and false positive rates, for a given cutoff threshold. The performance of this metric is compared with alternative metrics such as the enrichment factor, the relative enrichment factor, the receiver operating curve enrichment factor, the correct classification rate, Matthews correlation coefficient and Cohen's kappa coefficient. The performance of this new metric is found to be quite robust with respect to variations in the applied cutoff threshold and ratio of the number of active compounds to the total number of compounds, and at the same time being sensitive to variations in model quality. It possesses the correct characteristics for its application in early-recognition virtual screening problems.

16.
Cancer Biol Ther ; 16(6): 958-64, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26024008

RESUMO

It is known that antidiabetic drug metformin, which is used worldwide, has anti-cancer effects and can be used to prevent cancer growth. We tested the hypothesis that tumor cell growth can be inhibited by early treatment with metformin. For this purpose, adult rats chronically treated with metformin in adolescence or in adulthood were inoculated with Walker 256 carcinoma cells. Adult rats that were treated with metformin during adolescence presented inhibition of tumor growth, and animals that were treated during adult life did not demonstrate any changes in tumor growth. Although we do not have data to disclose a molecular mechanism to the preventive metformin effect, we present, for the first time, results showing that cancer growth in adult life is dependent on early life intervention, thus supporting a new therapeutic prevention for cancer.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Metformina/farmacologia , Neoplasias/patologia , Animais , Antineoplásicos/administração & dosagem , Modelos Animais de Doenças , Feminino , Xenoenxertos , Masculino , Metformina/administração & dosagem , Neoplasias/tratamento farmacológico , Ratos
17.
Metabolism ; 63(2): 226-32, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24290838

RESUMO

OBJECTIVE: Higher insulin levels during an oral glucose test (OGTT) have been shown in South Asians. We aimed to investigate if this increased insulin response causes reactive hypoglycemia later on, and if an increased glucagon-like-peptide-1 (GLP-1) response, which could contribute to the hyperinsulinemia, is present in this ethnic group. METHODS: A prolonged, 6-h, 75-g OGTT was performed in healthy, young Caucasian (n=10) and South Asian (n=8) men. The glucose, insulin and GLP-1 response was measured and indices of insulin sensitivity and beta-cell activity were calculated. RESULTS: Age (Caucasians (CAU) 21.5±0.7 years vs South Asians (SA) 21.4±0.7 years (mean±SEM)) and body mass index (CAU 22.7±0.7 kg/m(2) vs SA 22.1±0.8 kg/m(2)) were comparable between the two groups. South Asian men were more insulin resistant, as indicated by a comparable glucose but significantly higher insulin response, and a significantly lower Matsuda index (CAU 8.7(8.6) vs SA 3.2(19.2), median(IQR)). South Asians showed a higher GLP-1 response, as reflected by a higher area under the curve for GLP-1 (CAU 851±99.8 mmol/l vs SA 1235±155.0 mmol/L). During the whole 6-h period, no reactive hypoglycemia was observed. CONCLUSION: Healthy, young South Asian men have higher insulin levels during an OGTT as compared to Caucasians. This does not, however, lead to reactive hypoglycemia. The hyperinsulinemia is accompanied by increased levels of GLP-1. Whether this is an adaptive response to facilitate hyperinsulinemia to overcome insulin resistance or reflects a GLP-1 resistant state has yet to be elucidated.


Assuntos
Povo Asiático , Peptídeo 1 Semelhante ao Glucagon/sangue , Insulina/sangue , População Branca , Adulto , Área Sob a Curva , Glicemia/metabolismo , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina , Masculino , Valores de Referência , Suriname
18.
J Am Coll Cardiol ; 63(2): 170-80, 2014 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-24076282

RESUMO

OBJECTIVES: The objective of this study was to determine whether measuring post-operative B-type natriuretic peptides (NPs) (i.e., B-type natriuretic peptide [BNP] and N-terminal fragment of proBNP [NT-proBNP]) enhances risk stratification in adult patients undergoing noncardiac surgery, in whom a pre-operative NP has been measured. BACKGROUND: Pre-operative NP concentrations are powerful independent predictors of perioperative cardiovascular complications, but recent studies have reported that elevated post-operative NP concentrations are independently associated with these complications. It is not clear whether there is value in measuring post-operative NP when a pre-operative measurement has been done. METHODS: We conducted a systematic review and individual patient data meta-analysis to determine whether the addition of post-operative NP levels enhanced the prediction of the composite of death and nonfatal myocardial infarction at 30 and ≥180 days after surgery. RESULTS: Eighteen eligible studies provided individual patient data (n = 2,179). Adding post-operative NP to a risk prediction model containing pre-operative NP improved model fit and risk classification at both 30 days (corrected quasi-likelihood under the independence model criterion: 1,280 to 1,204; net reclassification index: 20%; p < 0.001) and ≥180 days (corrected quasi-likelihood under the independence model criterion: 1,320 to 1,300; net reclassification index: 11%; p = 0.003). Elevated post-operative NP was the strongest independent predictor of the primary outcome at 30 days (odds ratio: 3.7; 95% confidence interval: 2.2 to 6.2; p < 0.001) and ≥180 days (odds ratio: 2.2; 95% confidence interval: 1.9 to 2.7; p < 0.001) after surgery. CONCLUSIONS: Additional post-operative NP measurement enhanced risk stratification for the composite outcomes of death or nonfatal myocardial infarction at 30 days and ≥180 days after noncardiac surgery compared with a pre-operative NP measurement alone.


Assuntos
Doenças Cardiovasculares , Peptídeo Natriurético Encefálico/sangue , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Operatórios , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Saúde Global , Humanos , Incidência , Fragmentos de Peptídeos/sangue , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Período Pré-Operatório , Prognóstico
19.
Thromb Res ; 133(2): 177-81, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24342535

RESUMO

INTRODUCTION: The role of the Wells score for patients who develop signs and symptoms of pulmonary embolism (PE) during hospitalization has not been sufficiently validated. The aim of this study is to evaluate the performance of the Wells score for inpatients with suspected PE and to evaluate the prevalence of pulmonary embolism. MATERIALS AND METHODS: We conducted a cross sectional study nested in the prospective Institutional Registry of Thromboembolic Disease at Hospital Italiano de Buenos Aires from June 2006 to March 2011. We included patients who developed symptoms of pulmonary embolism during hospitalization. Patients were stratified based on the Wells score as PE likely (>4 points) or PE unlikely (≤4 points). The presence of pulmonary embolism was defined by pre-specified criteria. RESULTS: Six hundred and thirteen patients met the inclusion criteria, with an overall prevalence of PE of 36%. Two hundred and nineteen (34%) were classified as PE likely and 394 (66%) as PE unlikely with a prevalence of PE of 66% and 20%, respectively. The Wells score showed a sensitivity of 65 (95% CI 59-72), specificity 81 (95% CI 77-85), positive predictive value 66 (95% CI 60-72) and negative predictive value 80 (95% CI 77-84). CONCLUSIONS: The Wells Score is accurate to predict the probability of PE in hospitalized patients and this population had a higher prevalence of PE than other cohorts. However, the score is not sufficiently predictive to rule out a potentially fatal disorder.


Assuntos
Embolia Pulmonar/diagnóstico , Embolia Pulmonar/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Estudos Transversais , Feminino , Hospitalização , Hospitais Comunitários , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Prevalência
20.
J Pediatr ; 163(5): 1432-6, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23968741

RESUMO

OBJECTIVES: Little is known about the relation of pubertal development on endothelial function and arterial elasticity in children and adolescents; therefore, we compared brachial artery flow-mediated dilation and carotid artery elasticity across Tanner (pubertal) stages in children and adolescents. STUDY DESIGN: Blood pressure, fasting lipids, glucose and insulin, body fat, insulin sensitivity adjusted for lean body mass, brachial flow-mediated dilation (percent dilation and area under the curve), endothelium-independent dilation (peak dilation and area under the curve), and carotid artery elasticity were evaluated across pubertal stages (Tanner I vs Tanner II-IV vs Tanner V) in 344 children and adolescents (184 males, 160 females; ages 6 to 21 years). RESULTS: One hundred twenty-four subjects (mean age 8.23 ± 0.15 years; 52 females) were Tanner stage I; 105 subjects (mean age 13.19 ± 0.17 years; 47 females) were Tanner stages II-IV; and 115 subjects (mean age 17.19 ± 0.16 years; 61 females) were Tanner stage V. There were no significant differences for any of the measures of vascular structure and function across pubertal stages. CONCLUSION: Results of the current study indicate that smooth-muscle and endothelial function, as well as carotid artery elasticity, do not differ throughout pubertal development and that accounting for pubertal stage when reporting vascular data in children and adolescents may be unnecessary.


Assuntos
Velocidade do Fluxo Sanguíneo , Artéria Braquial/fisiologia , Artéria Carótida Primitiva/fisiologia , Endotélio Vascular/fisiologia , Puberdade , Tecido Adiposo , Adolescente , Área Sob a Curva , Glicemia/metabolismo , Pressão Sanguínea , Composição Corporal/fisiologia , Criança , Estudos Transversais , Elasticidade , Feminino , Humanos , Insulina/sangue , Lipídeos/sangue , Masculino , Adulto Jovem
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