RESUMO
The analysis of mammograms using artificial intelligence (AI) has shown great potential for assisting breast cancer screening. We use saliency maps to study the role of breast lesions in the decision-making process of AI systems for breast cancer detection in screening mammograms. We retrospectively collected mammograms from 191 women with screen-detected breast cancer and 191 healthy controls matched by age and mammographic system. Two radiologists manually segmented the breast lesions in the mammograms from CC and MLO views. We estimated the detection performance of four deep learning-based AI systems using the area under the ROC curve (AUC) with a 95% confidence interval (CI). We used automatic thresholding on saliency maps from the AI systems to identify the areas of interest on the mammograms. Finally, we measured the overlap between these areas of interest and the segmented breast lesions using Dice's similarity coefficient (DSC). The detection performance of the AI systems ranged from low to moderate (AUCs from 0.525 to 0.694). The overlap between the areas of interest and the breast lesions was low for all the studied methods (median DSC from 4.2% to 38.0%). The AI system with the highest cancer detection performance (AUC = 0.694, CI 0.662-0.726) showed the lowest overlap (DSC = 4.2%) with breast lesions. The areas of interest found by saliency analysis of the AI systems showed poor overlap with breast lesions. These results suggest that AI systems with the highest performance do not solely rely on localized breast lesions for their decision-making in cancer detection; rather, they incorporate information from large image regions. This work contributes to the understanding of the role of breast lesions in cancer detection using AI.
Assuntos
Inteligência Artificial , Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Estudos Retrospectivos , Mama/patologia , Mamografia/métodos , Detecção Precoce de Câncer/métodosRESUMO
Introduction. Rheumatoid arthritis patients under treatment with anti-TNF-α are at a high risk of developing active tuberculosis, and therefore, screening for latent tuberculosis infection is recommended before anti-TNF-α therapy. Objective. To compare the tuberculin test and IFNγ production induced by culture filtrate proteins(CFPs) and Mycobacterium tuberculosis-specific CFP-10 antigens in rheumatoid arthritis patients. Materials and methods. An analytic transversal study was conducted in rheumatoid arthritis patients treated at Hospital Universitario San Vicente Fundación between January and December 2007. IFNγ production in response to CFPs and CFP-10 was measured in the supernatants of whole blood cultures and evaluated for correlations with tuberculin reactivity. The degree of concordance between both tests was also established. Results. Forty-five patients were included, of which 14 (31.1%) had a tuberculin reaction of ≥10 mm of induration, 9 (20%) produced IFNγ in response to CFP-10, and 7 were positive for both tests. The correlation between tests was r=0.53 (IC 95%:0.28-0.72), and the global concordance between tests was80%, with a Kappa coefficient of 0.48 (IC95%:0.20-0.76). Conclusions. Only two tuberculin (-)/CFP-10+ "anergic" patients were observed. By contrast, six tuberculin +/CFP-10(-) "tuberculin false-positive" patients were observed. These data suggest that the tuberculin test is not an appropriate tool for determining the need for tuberculosis prophylaxis.
Introducción. Los pacientes con artritis reumatoide bajo tratamiento con anti-TNFα están en alto riesgo de desarrollar tuberculosis activa, por lo cual se recomienda hacer la tamización para infección latente de tuberculosis, antes de iniciar el tratamiento. Objetivo. Comparar la prueba de tuberculina y la producción de IFNγ inducida por antígenos CFP (Culture Filtrate Protein) y antígenos específicos de Mycobacterium tuberculosis (CFP-10) para el diagnóstico de infección latente de tuberculosis en pacientes con artritis reumatoide. Materiales y métodos. Se llevó a cabo un estudio transversal analítico en pacientes con artritis reumatoide atendidos en el Hospital Universitario San Vicente Fundación, entre enero y diciembre de 2007, a los cuales se les determinó la producción de IFNγ en respuesta a CFP y CFP-10 en sobrenadantes de cultivos de sangre total, y se correlacionó con la reacción en la prueba de tuberculina. Además, se estableció el grado de concordancia entre ambas pruebas. Resultados. Se incluyeron 45 pacientes, de los cuales, 14 (31,1 %) tuvieron un diámetro de induración ≥10 mm (tuberculina positiva), nueve (20 %) produjeron IFNγ en respuesta a CFP-10, y siete fueron positivos para ambas pruebas. La correlación entre las pruebas fue de r=0,53 (IC95%: 0,28-0,72) y la concordancia global entre pruebas fue de 80 %, con un coeficiente kappa de 0,48 (IC95%: 0,20-0,76). Conclusiones. Solo se observaron dos pacientes con tuberculina positiva y CFP-10 positivo "anérgicos" y se encontraron seis pacientes con tuberculina positiva y CFP-10 negativa "falsos positivos para tuberculina", lo cual sugiere que la prueba de la tuberculina no es la más adecuada para indicar profilaxis para tuberculosis.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos de Bactérias/farmacologia , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Teste Tuberculínico , Tuberculose/sangue , Tuberculose/diagnóstico , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Artrite Reumatoide/complicações , Células Cultivadas , Colômbia , Estudos Transversais , Tuberculose/complicaçõesRESUMO
Tuberculosis (TB) is one of the most important infectious diseases around the world. Several studies have focused on the identification of correlates of protection against TB. Most of them have concentrated on the study of IFN-γ due to its robust association with protection against TB. However, given the complexity of the immune response elicited after Mtb infection, other cytokines should also be considered. In the present study, we evaluated Th1 and Th17 responses and their association with the protection or development of active disease. Therefore, non infected individuals (nonTBi), latently infected individuals (LTBi) and patients with active TB (ATB) were studied. The evaluation of the number of cytokine producing cells by ELISPOT showed a higher number of IFN-γ-producing cells in ATB patients, but no differences were found regarding the number of IL-17 producing cells among studied groups. The evaluation of IFN-γ, IL-2, TNF-α and IL-17 producing CD4+ and CD8+ T cells at 1 day and 6 days of stimulation with mycobacterial antigens suggests the presence of functional signatures associated with latency or active TB. The results presented herein suggest the possible use of the evaluation of Th1-type cytokines, such as IFN-γ and/or TNF-α, as a correlate of protection against TB; however, these results need to be validated for other groups.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/biossíntese , Tuberculose/imunologia , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Humanos , Imunidade Celular , Interferon gama/biossíntese , Tuberculose Latente/imunologia , Mycobacterium tuberculosis/imunologia , Células Th1/imunologia , Células Th17/imunologia , Fatores de Tempo , Tuberculina/imunologia , Fator de Necrose Tumoral alfa/biossínteseRESUMO
INTRODUCTION: Rheumatoid arthritis patients under treatment with anti-TNF-α are at a high risk of developing active tuberculosis, and therefore, screening for latent tuberculosis infection is recommended before anti-TNF-α therapy. OBJECTIVE: To compare the tuberculin test and IFNγ production induced by culture filtrate proteins(CFPs) and Mycobacterium tuberculosis-specific CFP-10 antigens in rheumatoid arthritis patients. MATERIALS AND METHODS: An analytic transversal study was conducted in rheumatoid arthritis patients treated at Hospital Universitario San Vicente Fundación between January and December 2007. IFNγ production in response to CFPs and CFP-10 was measured in the supernatants of whole blood cultures and evaluated for correlations with tuberculin reactivity. The degree of concordance between both tests was also established. RESULTS: Forty-five patients were included, of which 14 (31.1%) had a tuberculin reaction of ≥10 mm of induration, 9 (20%) produced IFNγ in response to CFP-10, and 7 were positive for both tests. The correlation between tests was r=0.53 (IC 95%:0.28-0.72), and the global concordance between tests was80%, with a Kappa coefficient of 0.48 (IC95%:0.20-0.76). CONCLUSIONS: Only two tuberculin (-)/CFP-10+ "anergic" patients were observed. By contrast, six tuberculin +/CFP-10(-) "tuberculin false-positive" patients were observed. These data suggest that the tuberculin test is not an appropriate tool for determining the need for tuberculosis prophylaxis.
Assuntos
Antígenos de Bactérias/farmacologia , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Teste Tuberculínico , Tuberculose/sangue , Tuberculose/diagnóstico , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Adulto , Artrite Reumatoide/complicações , Células Cultivadas , Colômbia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tuberculose/complicaçõesRESUMO
Phenotypic and functional alterations in Mycobacterium tuberculosis T cell subsets have been reported in patients with active tuberculosis. A better understanding of these alterations will increase the knowledge about immunopathogenesis and also may contribute to the development of new diagnostics and prophylactic strategies. Here, the ex vivo phenotype of CD4(+) and CD8(+) T cells and the frequency and phenotype of gamma interferon (IFN-γ)- and interleukin 17 (IL-17)-producing cells elicited in short-term and long-term cultures following CFP-10 and purified protein derivative (PPD) stimulation were determined in noninfected persons (non-TBi), latently infected persons (LTBi), and patients with active tuberculosis (ATB). Phenotypic characterization of T cells was done based on the expression of CD45RO and CD27. Results show that ATB had a reduced frequency of circulating CD4(+) CD45RO(+) CD27(+) T cells and an increased frequency of CD4(+) CD45RO(-) CD27(+) T cells. ATB also had a higher frequency of circulating IL-17-producing CD4(+) T cells than did LTBi after PPD stimulation, whereas LTBi had more IFN-γ-producing CD4(+) T cells than did non-TBi. The phenotype of IFN-γ-producing cells at 24 h differs from the phenotype of IL-17-producing cells with no differences between LTBi and ATB. At 144 h, IFN-γ- and IL-17-producing cells were mainly CD45RO(+) CD27(+) T cells and they were more frequent in ATB. These results suggest that M. tuberculosis infection induces alterations in T cells which interfere with an adequate specific immune response.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Memória Imunológica , Interferon gama/metabolismo , Interleucina-17/metabolismo , Células Th17/imunologia , Tuberculose/imunologia , Adulto , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Cultivadas , Feminino , Humanos , Antígenos Comuns de Leucócito/análise , Masculino , Mycobacterium tuberculosis/imunologia , Subpopulações de Linfócitos T/imunologia , Tuberculina/imunologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/análiseRESUMO
Mycobacterium tuberculosis DosR regulon-encoded proteins elicit strong immune T-cell responses in individuals with latent tuberculosis (LTBI). Also, resuscitation (Rpf) proteins can induce such responses. However, variations in the immunogenicity of the DosR and Rpf proteins have been observed in European and African populations, and no data are published from other geographic areas. In Colombian LTBI and patients with recently diagnosed PTB, we therefore studied the immune response to DosR, Rpf, stress, and nominal antigens from Mtb, in 7-day stimulated cultures. Three DosR (Rv1737c, Rv2029c, Rv2628c) and 2 Rpf (Rv0867 and Rv2389c) antigens were recognized most prominently on the basis of the net IFNγ production (DosR) or the percentage of responding individuals (Rpf). Results show that the selected DosR antigens induced a higher proportion of CD4-T cells producing IFNγ from LTBI, compared to pulmonary TB patients (PTB), while there were no differences in the proportion of CD8-T cells. An increased frequency of CD4, but not CD8 T-cells with a CD45RO(+)CD27(+) phenotype was observed in LTBI in response to Rv2029c, Rv0867c, and Rv2389c, compared to PTB. The levels of cytokines and chemokines in the supernatants of stimulated cells, showed that the DosR and Rpf antigens induced higher levels of IFNγ in cultures from LTBI compared to PTB, although the induced pattern of cytokines and chemokines was also antigen dependent. In summary, our results are consistent with the significant immunogenicity of Mtb DosR and Rpf antigens in LTBI individuals, and confirm and extend previously reported data from other TB affected human populations.
Assuntos
Proteínas de Bactérias/imunologia , Citocinas/imunologia , Tuberculose Latente/imunologia , Proteínas Quinases/imunologia , Subpopulações de Linfócitos T/imunologia , Tuberculose Pulmonar/imunologia , Adolescente , Adulto , Idoso , Antígenos de Bactérias/imunologia , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Células Cultivadas , Quimiocinas/biossíntese , Colômbia , Citocinas/biossíntese , Proteínas de Ligação a DNA , Feminino , Humanos , Memória Imunológica , Imunofenotipagem , Interferon gama/biossíntese , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Adulto JovemRESUMO
There is lack of age-specific seroprevalence surveys and identification of factors associated with herpes simplex virus type-2 seropositivity (HSV-2) in rural populations in Colombia. A random sample of 869 women was interviewed about socio-demographic aspects, sexual and reproductive history. Antibodies to HSV-2 were determined by a specific type immunoenzymatic technique (ELISA). Participants had a mean age of 38±16.1 years, 67% were married, 60% monogamous and 47% reported use of condoms. HSV-2 seroprevalence was 19.1% (95% CI: 16.6-21.9) and it was strongly associated with increasing age (Ptrend<0.001). In the logistic regression analysis, women who reported between two or three lifetime sexual partners (OR=2.4; 95% CI: 1.5-3.7), >31 years of sexual activity with regular or occasional sexual partners (OR=4.3; 95% CI: 1.2-15.7) and not using condoms with regular sexual partners (OR=2.1; 95% CI: 1.4-3.3) were more likely to be HSV-2 seropositive. The overall seroprevalence rate of women of Pueblorrico, Colombia, is lower than that reported in other Latin American countries especially in women>45 years. The difference may be explained by higher prevalence of condom use in this population or lower exposure to herpes infection in male as well as females in the past.
Assuntos
Anticorpos Antivirais/sangue , Herpes Genital/imunologia , Herpesvirus Humano 2/imunologia , Adulto , Colômbia/epidemiologia , Feminino , Herpes Genital/epidemiologia , Herpes Genital/transmissão , Humanos , Entrevistas como Assunto , Exame Físico , Prevalência , Qualidade de Vida/psicologia , Fatores de Risco , Saúde da População Rural , Estudos Soroepidemiológicos , Parceiros Sexuais/psicologiaRESUMO
Regulatory T cells (Tregs) play an essential role in immune homeostasis. In infectious diseases Tregs may inhibit protective responses facilitating pathogen multiplication and dissemination, but they may also limit the inflammatory response diminishing tissue damage. Although there is experimental and clinical evidence that Tregs are induced during Mycobacterium tuberculosis infection, their role in the immunopathogenesis of tuberculosis is still not completely understood. In this study, the phenotype, frequency and activity of circulating Tregs in active and latent tuberculosis were evaluated. Phenotypic analysis showed that Tregs were CD4(+)CD25(high)FOXP3(+)CD45RO(+)CD127(-). High levels of circulating Tregs were found in patients with active pulmonary tuberculosis, compared to individuals with latent infection. Treg activity was evaluated by ELISPOT by determining the effect of CD25(+) cell depletion on the frequency of IFN-gamma and IL-17 producing cells after in vitro stimulation with ESAT-6, CFP-10 and PPD. Treg depletion increased the frequency of IFN-gamma producing cells, without affecting the frequency of IL-17 producing cells, in both active and latent tuberculosis, irrespective of the antigen used. Neutralization of IL-10 did not have any effect on the frequency of IFN-gamma and IL-17 producing cells. Altogether, these results suggest that during active tuberculosis Tregs inhibit protective Th1 responses, but not the proinflammatory Th17 responses, facilitating mycobacterial replication and tissue damage.
Assuntos
Interferon gama/biossíntese , Interleucina-17/biossíntese , Linfócitos T Reguladores/imunologia , Tuberculose/imunologia , Adolescente , Adulto , Idoso , Antígenos de Bactérias/imunologia , ELISPOT/métodos , Feminino , Seguimentos , Humanos , Tolerância Imunológica/imunologia , Imunofenotipagem , Interleucina-10/imunologia , Tuberculose Latente/imunologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia , Adulto JovemRESUMO
OBJECTIVES: Household contacts (HHCs) of pulmonary tuberculosis patients are at high risk of Mycobacterium tuberculosis infection and early disease development. Identification of individuals at risk of tuberculosis disease is a desirable goal for tuberculosis control. Interferon-gamma release assays (IGRAs) using specific M. tuberculosis antigens provide an alternative to tuberculin skin testing (TST) for infection detection. Additionally, the levels of IFNgamma produced in response to these antigens may have prognostic value. We estimated the prevalence of M. tuberculosis infection by IGRA and TST in HHCs and their source population (SP), and assessed whether IFNgamma levels in HHCs correlate with tuberculosis development. METHODS: A cohort of 2060 HHCs was followed for 2-3 years after exposure to a tuberculosis case. Besides TST, IFNgamma responses to mycobacterial antigens: CFP, CFP-10, HspX and Ag85A were assessed in 7-days whole blood cultures and compared to 766 individuals from the SP in Medellín, Colombia. Isoniazid prophylaxis was not offered to child contacts because Colombian tuberculosis regulations consider it only in children under 5 years, TST positive without BCG vaccination. RESULTS: Using TST 65.9% of HHCs and 42.7% subjects from the SP were positive (OR 2.60, p<0.0001). IFNgamma response to CFP-10, a biomarker of M. tuberculosis infection, tested positive in 66.3% HHCs and 24.3% from the SP (OR = 6.07, p<0.0001). Tuberculosis incidence rate was 7.0/1000 person years. Children <5 years accounted for 21.6% of incident cases. No significant difference was found between positive and negative IFNgamma responders to CFP-10 (HR 1.82 95% CI 0.79-4.20 p = 0.16). However, a significant trend for tuberculosis development amongst high HHC IFNgamma producers was observed (trend Log rank p = 0.007). DISCUSSION: CFP-10-induced IFNgamma production is useful to establish tuberculosis infection prevalence amongst HHC and identify those at highest risk of disease. The high tuberculosis incidence amongst children supports administration of chemoprophylaxis to child contacts regardless of BCG vaccination.
Assuntos
Características da Família , Interferon gama/biossíntese , Mycobacterium tuberculosis/fisiologia , Tuberculose/imunologia , Tuberculose/microbiologia , Adolescente , Adulto , Envelhecimento/patologia , Antígenos de Bactérias/imunologia , Colômbia/epidemiologia , Demografia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Valor Preditivo dos Testes , Fatores de Risco , Teste Tuberculínico , Tuberculose/epidemiologia , Adulto JovemRESUMO
El artículo presenta reflexiones académicas fruto del trabajo docente de las autoras con estudiantes de la Carrera de Psicología de la Pontifica Universidad Javeriana. Se señala cómo, a partir de la realidad sociopolítica de América Latina, son necesarias miradas complejas sobre la ciudadanía, que, desde los escenarios educativos, permitan hacerle frente a las crisis de la región en general, y de Colombia en particular. Se presentan algunas implicaciones formativas que tiene dicha mirada para el trabajo profesional de psicólogas y psicólogos, proponiendo al sujeto y a la subjetividad como el corazón de las prácticas formativas. Finalmente, se esbozan algunos retos significativos para el quehacer psicológico en el campo de la formación ciudadana en contextos educativos.
The article presents academic reflections resulting from the teaching work of the authors with students of the Psychology career at the Javeriana University. Beginning from Latinamericas sociopolitical reality, it is pointed out that complex views of citizenship are needed that permit the confrontation of the regions crises, particularly in Colombia, from the educational scenarios. Formative implications of that view for the professional work of Psychologists are reviewed, proposing subject and subjectivity as the heart of formative practices. Finally, some significant challenges to the Psychologists task in the field of civic formation in educational contexts are outlined.