High production MBL2 polymorphisms protect against COVID-19 complications in critically ill patients: A retrospective cohort study.

Mannose-binding lectin (MBL) binds to SARS-CoV-2, inhibits infection of susceptible cells, and activates the complement system via the lectin pathway. In this study, we investigated the association of MBL2 polymorphisms with the risk of hospitalization and clinical worsening in patients with COVID-19. A total of 550 patients with COVID-19 were included (94 non-hospitalized and 456 hospitalized). Polymorphisms in MBL2 exon 1 (codons 52, 54 and 57) and promoter region (-550, -221, and +4) were determined by real-time PCR. MBL and complement proteins were measured by Luminex. A higher frequency of the H/H genotype and the HYPA haplotype was observed in non-hospitalized patients when compared to hospitalized. In addition, critically ill patients carrying haplotypes associated with high MBL levels (HYPA/HYPA + HYPA/LYPA + HYPA/LYQA + LYPA/LYQA + LYPA/LYPA + LYQA/LYQA + LXPA/HYPA + LXPA/LYQA + LXPA/LYPA) were protected against lower oxygen saturation levels (P = 0.02), use of invasive ventilation use (P = 0.02, OR 0.38), and shock (P = 0.01, OR 0.40), independent of other potential confounders adjusted by multivariate analysis. Our results suggest that variants in MBL2 associated with high MBL levels may play a protective role in the clinical course of COVID-19.

Association of PTX3 gene polymorphisms and PTX3 plasma levels with leprosy susceptibility.

BACKGROUND: Pentraxin 3 (PTX3) is a soluble pattern recognition receptor that plays a crucial role in modulating the inflammatory response and activating the complement system. Additionally, plasma PTX3 has emerged as a potential biomarker for various infectious diseases. The aim of this study was to evaluate the association of PTX3 gene polymorphisms and PTX3 plasma levels with susceptibility to leprosy and clinical characteristics. METHODS: Patients with leprosy from a hyperendemic area in the Northeast Region of Brazil were included. Healthy household contacts and healthy blood donors from the same geographical area were recruited as a control group. The rs1840680 and rs2305619 polymorphisms of PTX3 were determined by real-time PCR. Plasma levels of PTX3 were determined by ELISA. RESULTS: A total of 512 individuals were included. Of these, 273 were patients diagnosed with leprosy; 53 were household contacts, and 186 were healthy blood donors. No association was observed between PTX3 polymorphisms and susceptibility to leprosy or development of leprosy reaction or physical disability. On the other hand, plasma levels of PTX3 were significantly higher in patients with leprosy when compared to household contacts (p = 0.003) or blood donors (p = 0.04). It was also observed that PTX3 levels drop significantly after multidrug therapy (p < 0.0001). CONCLUSIONS: Our results suggest that PTX3 may play an important role in the pathogenesis of leprosy and point to the potential use of this molecule as an infection marker.

Identification of Potential Multitarget Compounds against Alzheimer's Disease through Pharmacophore-Based Virtual Screening.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive loss of cognitive functions, and it is the most prevalent type of dementia worldwide, accounting for 60 to 70% of cases. The pathogenesis of AD seems to involve three main factors: deficiency in cholinergic transmission, formation of extracellular deposits of ß-amyloid peptide, and accumulation of deposits of a phosphorylated form of the TAU protein. The currently available drugs are prescribed for symptomatic treatment and present adverse effects such as hepatotoxicity, hypertension, and weight loss. There is urgency in finding new drugs capable of preventing the progress of the disease, controlling the symptoms, and increasing the survival of patients with AD. This study aims to present new multipurpose compounds capable of simultaneously inhibiting acetylcholinesterase (AChE), butyrylcholinesterase (BChE)-responsible for recycling acetylcholine in the synaptic cleft-and beta-secretase 1 (BACE-1)-responsible for the generation of amyloid-ß plaques. AChE, BChE, and BACE-1 are currently considered the best targets for the treatment of patients with AD. Virtual hierarchical screening based on a pharmacophoric model for BACE-1 inhibitors and a dual pharmacophoric model for AChE and BChE inhibitors were used to filter 214,446 molecules by QFITBACE > 0 and QFITDUAL > 56.34. The molecules selected in this first round were subjected to molecular docking studies with the three targets and further evaluated for their physicochemical and toxicological properties. Three structures: ZINC45068352, ZINC03873986, and ZINC71787288 were selected as good fits for the pharmacophore models, with ZINC03873986 being ultimately prioritized for validation through activity testing and synthesis of derivatives for SAR studies.

[Body image is associated with anthropometric status in adolescents, but not with lifestyle]. / Imagem corporal está associada com estado antropométrico em adolescentes, mas não com estilo de vida.

Body image is a construct of the multifaceted representation of body identity that involves self-perception, beliefs, attitudes about the body itself, which can be influenced by several factors. This study evaluated the association of body image with anthropometric and lifestyle indicators among adolescents. The sample comprised 465 adolescents aged 10 to 17 years from public schools in the city of Salvador-Bahia. The Silhouettes Scale assessed the body image. The anthropometric data (body mass index and waist circumference), the lifestyle (Physical Activity Questionnaire for Adolescents and television time), economic and demographic data were evaluated. Polytomous logistic regression assessed associations of interest by STATA, version 16.0. Overweight (OR:9,7; CI95%:5,4-17,5) and abdominal obesity (OR:14,0; CI95%: 5,0-39,3) were positively associated with body dissatisfaction. However, there was no association with lifestyle variables (physical activity: OR: 1,7, CI: 0,9-2,9, and TV time: OR:1,2; CI:0,8-1,9). The conclusion reached is that anthropometric status is an essential indicator of adverse body image outcomes in adolescents.

A imagem corporal é um constructo da representação multifacetada da identidade corporal, envolve autopercepção, crenças e atitudes sobre o próprio corpo, podendo ser influenciada por diversos fatores. Este estudo avaliou a associação da imagem corporal com indicadores antropométricos e do estilo de vida em adolescentes. Constituíram a amostra 465 adolescentes de 10 a 17 anos de escolas públicas da cidade de Salvador, na Bahia. A imagem corporal foi avaliada pela Escala de Silhuetas. Os dados antropométricos (índice de massa corporal e a circunferência da cintura), de estilo de vida (Physical Activity Questionnaire for Adolescents e o tempo de televisão), econômicos e demográficos foram avaliados. Regressão logística politômica avaliou as associações de interesse. Os dados foram analisados pelo software STATA, versão 16.0. O sobrepeso/obesidade (OR: 9,7; IC95%: 5,4-17,5) e a obesidade abdominal (OR: 14,0; IC95%: 5,0-39,3) se mostraram positivamente associados à insatisfação corporal, mas não foi observada associação com as variáveis de estilo de vida (atividade física: OR: 1,7; IC95%: 0,9-2,9; e tempo de TV: OR: 1,2; IC95%: 0,8-1,9). Conclui-se que o estado antropométrico é um importante indicador dos desfechos negativos da imagem corporal em adolescentes.

Imagem corporal está associada com estado antropométrico em adolescentes, mas não com estilo de vida / Body image is associated with anthropometric status in adolescents, but not with lifestyle

Resumo A imagem corporal é um constructo da representação multifacetada da identidade corporal, envolve autopercepção, crenças e atitudes sobre o próprio corpo, podendo ser influenciada por diversos fatores. Este estudo avaliou a associação da imagem corporal com indicadores antropométricos e do estilo de vida em adolescentes. Constituíram a amostra 465 adolescentes de 10 a 17 anos de escolas públicas da cidade de Salvador, na Bahia. A imagem corporal foi avaliada pela Escala de Silhuetas. Os dados antropométricos (índice de massa corporal e a circunferência da cintura), de estilo de vida (Physical Activity Questionnaire for Adolescents e o tempo de televisão), econômicos e demográficos foram avaliados. Regressão logística politômica avaliou as associações de interesse. Os dados foram analisados pelo software STATA, versão 16.0. O sobrepeso/obesidade (OR: 9,7; IC95%: 5,4-17,5) e a obesidade abdominal (OR: 14,0; IC95%: 5,0-39,3) se mostraram positivamente associados à insatisfação corporal, mas não foi observada associação com as variáveis de estilo de vida (atividade física: OR: 1,7; IC95%: 0,9-2,9; e tempo de TV: OR: 1,2; IC95%: 0,8-1,9). Conclui-se que o estado antropométrico é um importante indicador dos desfechos negativos da imagem corporal em adolescentes.

Abstract Body image is a construct of the multifaceted representation of body identity that involves self-perception, beliefs, attitudes about the body itself, which can be influenced by several factors. This study evaluated the association of body image with anthropometric and lifestyle indicators among adolescents. The sample comprised 465 adolescents aged 10 to 17 years from public schools in the city of Salvador-Bahia. The Silhouettes Scale assessed the body image. The anthropometric data (body mass index and waist circumference), the lifestyle (Physical Activity Questionnaire for Adolescents and television time), economic and demographic data were evaluated. Polytomous logistic regression assessed associations of interest by STATA, version 16.0. Overweight (OR:9,7; CI95%:5,4-17,5) and abdominal obesity (OR:14,0; CI95%: 5,0-39,3) were positively associated with body dissatisfaction. However, there was no association with lifestyle variables (physical activity: OR: 1,7, CI: 0,9-2,9, and TV time: OR:1,2; CI:0,8-1,9). The conclusion reached is that anthropometric status is an essential indicator of adverse body image outcomes in adolescents.

Clinical characteristics and laboratory parameters associated with the risk of severe COVID-19 in patients from two hospitals in Northeast Brazil.

BACKGROUND: Although most coronavirus disease 2019 (COVID-19) infections are mild, some patients have severe clinical conditions requiring hospitalization. Data on the severity of COVID-19 in Brazil are scarce and are limited to public databases. This study aimed to investigate the clinical and laboratory factors associated with the severity of COVID-19 in a cohort of hospitalized adults from two hospitals in Northeast Brazil. METHODS: Patients over 18 years of age who were hospitalized between August 2020 and July 2021 with a confirmed diagnosis of COVID-19 were included. The patients were classified into two groups: moderate and severe. Clinical, laboratory and imaging parameters were collected and compared between the groups. A multivariate logistic regression model was used to determine the predictors of COVID-19 severity. RESULTS: This study included 495 patients (253 moderate and 242 severe). A total of 372 patients (75.2%) were between 18 and 65 years of age, and the majority were male (60.6%; n = 300). Patients with severe disease had higher levels of leukocytes, neutrophils, platelets, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, blood glucose, C-reactive protein, ferritin, D-dimer, aspartate aminotransferase, creatinine, and urea (p < 0.05). In multivariate logistic regression, the following variables were significant predictors of COVID-19 severity: leukocytes (odds ratio [OR] 3.27; 95% confidence interval [CI] 2.12-5.06), international normalized ratio (INR) (OR 0.22, 95% CI 0.14-0.33), and urea (OR 4.03; 95% CI 2.21-7.35). CONCLUSIONS: The present study identified the clinical and laboratory factors associated with the severity of COVID-19 in hospitalized Brazilian individuals.

Risk factors for breast cancer and their association with molecular subtypes in a population of Northeast Brazil.

BACKGROUND: The risk factors for breast cancer (BC) among women in Brazilian populations are poorly understood. To date, few Brazilian studies have addressed the potential association between risk factors and molecular BC subtypes. This case-control study aimed to identify risk factors for BC in a population of Northeast Brazil. METHODS: Data from 313 patients with invasive BC and 321 healthy controls were obtained from medical records from two cancer treatment centres and personal interviews. Of the 313 BC patients, 224 (71.6%) had reached menopause. The following distribution of subtypes was found among 301 patients: (1) Luminal A: 54 (17.9%); (2) Luminal B: 175 (58.1%); (3) HER2/neu: 29 (9.7%); and (4) triple-negative breast cancer (TNBC): 43 (14.3%). Odds ratios (ORs) and confidence intervals (CIs) were determined using regression analysis. RESULTS: Regression modelling indicated that family history, obesity (≥ 30.0 kg/m2), alcohol consumption and contraceptive use increased the overall risk of BC 1.78 (95% CI: 1.22-2.59), 1.69 (95% CI: 1.08-2.63), 2.21 (95% CI: 1.44-3.39) and 2.99 (95% CI: 2.09-4.28) times, respectively. After stratification for menopausal status, alcohol consumption increased the risk of BC 4.15 (95% CI: 2.13-8.11) times, and obesity, as a single variable, increased the risk of BC 2.02 (95% CI: 1.22-3.37) times, only among postmenopausal women. In a case-control analysis, the risk of TNBC and Luminal B breast cancer were 4.06 (95% CI: 1.58-10.42) and 1.87 times (95% CI: 1.13-3.11) higher, respectively, in obese women than in non-obese women. Furthermore, alcohol consumption increased the risk of Luminal A and B subtypes 7.08 (3.40-14.73) and 1.77 (1.07-2.92) times, respectively. CONCLUSION: Family history, contraceptive use, obesity and alcohol consumption increased the risk of BC. Obesity and alcohol consumption differentially increased risk of TNBC and Luminal molecular subtypes.

Cox model and decision trees: an application to breast cancer data.

Objective: To evaluate, using semiparametric methodologies of survival analysis, the relationship between covariates and time to death of patients with breast cancer, as well as the determination discriminatory power in the conditional inference tree of patients who had cancer. Methods: A retrospective cohort study was conducted using data collected from medical records of women who had breast cancer and underwent treatment between 2005 and 2015 at the Hospital da Fundação de Assistencial da Paraíba in Campina Grande, State of Paraiba, Brazil. Survival curves were estimated using the Kaplan-Meier method, Cox regression, and conditional decision tree. Results: Women with triple-negative molecular subtypes had a shorter survival time compared to women with positive hormone receptors. The addition of hormone therapy reduced the risk of a patient dying by 5.5%, and the risk of a HER2-positive patient dying was 34.5% lower compared to those who were negative for this gene. Patients undergoing hormone therapy had a median survival time of 4 753 days. Conclusions: This paper shows a favorable scenario for the use of immunotherapy for patients with HER2 overexpression. Further studies could assess the effectiveness of immunotherapy in patients with other conditions, to favor the prognosis and better quality of life for the patient.

Cox model and decision trees: an application to breast cancer data

[ABSTRACT]. Objective. To evaluate, using semiparametric methodologies of survival analysis, the relationship between covariates and time to death of patients with breast cancer, as well as the determination discriminatory power in the conditional inference tree of patients who had cancer. Methods. A retrospective cohort study was conducted using data collected from medical records of women who had breast cancer and underwent treatment between 2005 and 2015 at the Hospital da Fundação de Assistencial da Paraíba in Campina Grande, State of Paraiba, Brazil. Survival curves were estimated using the Kaplan–Meier method, Cox regression, and conditional decision tree. Results. Women with triple-negative molecular subtypes had a shorter survival time compared to women with positive hormone receptors. The addition of hormone therapy reduced the risk of a patient dying by 5.5%, and the risk of a HER2-positive patient dying was 34.5% lower compared to those who were negative for this gene. Patients undergoing hormone therapy had a median survival time of 4 753 days. Conclusions. This paper shows a favorable scenario for the use of immunotherapy for patients with HER2 overexpression. Further studies could assess the effectiveness of immunotherapy in patients with other conditions, to favor the prognosis and better quality of life for the patient.

[RESUMEN]. Objetivo. Evaluar, mediante métodos semiparamétricos del análisis de supervivencia, la relación entre las covariables y el tiempo hasta la muerte de las pacientes con cáncer de mama, así como la determinación del poder discriminatorio en el árbol de inferencia condicional de las pacientes con cáncer. Métodos. Se llevó a cabo un estudio retrospectivo de cohortes con datos recogidos de los expedientes médicos de mujeres con cáncer de mama que recibieron tratamiento entre los años 2005 y 2015 en el Hospital da Fundação de Assistencial da Paraíba en Campina Grande, en el estado de Paraíba (Brasil). Se calcularon las curvas de supervivencia mediante el método Kaplan–Meier, el modelo de regresión de Cox y un árbol de decisiones condicionales. Resultados. Las mujeres con subtipos moleculares triple negativos tuvieron un período de supervivencia más corto en comparación con las mujeres con receptores hormonales positivos. La adición del tratamiento hormonal redujo en 5,5 % el riesgo de muerte de la paciente y en un 34,5% el riesgo de muerte de pacientes con cáncer HER2-positivo en comparación con las pacientes negativas para este gen. Las pacientes en tratamiento hormonal tuvieron un tiempo medio de supervivencia de 4 753 días. Conclusiones. Este estudio muestra un escenario favorable para el uso de la inmunoterapia en las pacientes con sobreexpresión del HER2. En futuros estudios se podría evaluar la eficacia de la inmunoterapia en pacientes con otras enfermedades, con el fin de favorecer el pronóstico y mejorar la calidad de vida de la paciente.

[RESUMO]. Objetivo. Avaliar, por meio de métodos semiparamétricos de análise de sobrevida, a relação entre covariáveis e tempo até a morte em pacientes com câncer de mama e determinar o poder discriminatório na árvore de inferência condicional em pacientes que tiveram câncer. Métodos. Estudo de coorte retrospectivo realizado a partir de dados coletados de prontuários médicos de mulheres com câncer de mama, tratadas entre 2005 e 2015 no Hospital da Fundação Assistencial da Paraíba em Campina Grande, no estado da Paraíba, Brasil. As curvas de sobrevida foram estimadas pelo método de Kaplan-Meier, regressão de Cox e árvore de decisão condicional. Resultados. As pacientes com subtipos moleculares de tumor triplo-negativo tiveram uma sobrevida menor em comparação com as que apresentavam tumor com receptores hormonais. O acréscimo de hormonioterapia reduziu o risco de morte em 5,5%. O risco de morte foi 34,5% menor em pacientes com HER2+ quando comparadas às que tinham tumores sem a expressão desse gene. A mediana de sobrevida das pacientes tratadas com hormonioterapia foi de 4 753 dias. Conclusões. A presente análise revela um cenário favorável para o uso de imunoterapia em pacientes com superexpressão de HER2. Outros estudos devem ser realizados para avaliar a eficácia da imunoterapia em outras doenças e os fatores que favorecem o prognóstico e melhoram a qualidade de vida dessas pessoas.

Clinical characteristics and laboratory parameters associated with the risk of severe COVID-19 in patients from two hospitals in Northeast Brazil

ABSTRACT Background: Although most coronavirus disease 2019 (COVID-19) infections are mild, some patients have severe clinical conditions requiring hospitalization. Data on the severity of COVID-19 in Brazil are scarce and are limited to public databases. This study aimed to investigate the clinical and laboratory factors associated with the severity of COVID-19 in a cohort of hospitalized adults from two hospitals in Northeast Brazil. Methods: Patients over 18 years of age who were hospitalized between August 2020 and July 2021 with a confirmed diagnosis of COVID-19 were included. The patients were classified into two groups: moderate and severe. Clinical, laboratory and imaging parameters were collected and compared between the groups. A multivariate logistic regression model was used to determine the predictors of COVID-19 severity. Results: This study included 495 patients (253 moderate and 242 severe). A total of 372 patients (75.2%) were between 18 and 65 years of age, and the majority were male (60.6%; n = 300). Patients with severe disease had higher levels of leukocytes, neutrophils, platelets, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, blood glucose, C-reactive protein, ferritin, D-dimer, aspartate aminotransferase, creatinine, and urea (p < 0.05). In multivariate logistic regression, the following variables were significant predictors of COVID-19 severity: leukocytes (odds ratio [OR] 3.27; 95% confidence interval [CI] 2.12-5.06), international normalized ratio (INR) (OR 0.22, 95% CI 0.14-0.33), and urea (OR 4.03; 95% CI 2.21-7.35). Conclusions: The present study identified the clinical and laboratory factors associated with the severity of COVID-19 in hospitalized Brazilian individuals.

Cox model and decision trees: an application to breast cancer data / El modelo de regresión de Cox y los árboles de decisiones: su aplicación a los datos sobre cáncer de mama / Modelo de Cox e árvores de decisão: utilização com dados de câncer de mama

ABSTRACT Objective. To evaluate, using semiparametric methodologies of survival analysis, the relationship between covariates and time to death of patients with breast cancer, as well as the determination discriminatory power in the conditional inference tree of patients who had cancer. Methods. A retrospective cohort study was conducted using data collected from medical records of women who had breast cancer and underwent treatment between 2005 and 2015 at the Hospital da Fundação de Assistencial da Paraíba in Campina Grande, State of Paraiba, Brazil. Survival curves were estimated using the Kaplan-Meier method, Cox regression, and conditional decision tree. Results. Women with triple-negative molecular subtypes had a shorter survival time compared to women with positive hormone receptors. The addition of hormone therapy reduced the risk of a patient dying by 5.5%, and the risk of a HER2-positive patient dying was 34.5% lower compared to those who were negative for this gene. Patients undergoing hormone therapy had a median survival time of 4 753 days. Conclusions. This paper shows a favorable scenario for the use of immunotherapy for patients with HER2 overexpression. Further studies could assess the effectiveness of immunotherapy in patients with other conditions, to favor the prognosis and better quality of life for the patient.

RESUMEN Objetivo. Evaluar, mediante métodos semiparamétricos del análisis de supervivencia, la relación entre las covariables y el tiempo hasta la muerte de las pacientes con cáncer de mama, así como la determinación del poder discriminatorio en el árbol de inferencia condicional de las pacientes con cáncer. Métodos. Se llevó a cabo un estudio retrospectivo de cohortes con datos recogidos de los expedientes médicos de mujeres con cáncer de mama que recibieron tratamiento entre los años 2005 y 2015 en el Hospital da Fundação de Assistencial da Paraíba en Campina Grande, en el estado de Paraíba (Brasil). Se calcularon las curvas de supervivencia mediante el método Kaplan-Meier, el modelo de regresión de Cox y un árbol de decisiones condicionales. Resultados. Las mujeres con subtipos moleculares triple negativos tuvieron un período de supervivencia más corto en comparación con las mujeres con receptores hormonales positivos. La adición del tratamiento hormonal redujo en 5,5 % el riesgo de muerte de la paciente y en un 34,5% el riesgo de muerte de pacientes con cáncer HER2-positivo en comparación con las pacientes negativas para este gen. Las pacientes en tratamiento hormonal tuvieron un tiempo medio de supervivencia de 4 753 días. Conclusiones. Este estudio muestra un escenario favorable para el uso de la inmunoterapia en las pacientes con sobreexpresión del HER2. En futuros estudios se podría evaluar la eficacia de la inmunoterapia en pacientes con otras enfermedades, con el fin de favorecer el pronóstico y mejorar la calidad de vida de la paciente.

RESUMO Objetivo. Avaliar, por meio de métodos semiparamétricos de análise de sobrevida, a relação entre covariáveis e tempo até a morte em pacientes com câncer de mama e determinar o poder discriminatório na árvore de inferência condicional em pacientes que tiveram câncer. Métodos. Estudo de coorte retrospectivo realizado a partir de dados coletados de prontuários médicos de mulheres com câncer de mama, tratadas entre 2005 e 2015 no Hospital da Fundação Assistencial da Paraíba em Campina Grande, no estado da Paraíba, Brasil. As curvas de sobrevida foram estimadas pelo método de Kaplan-Meier, regressão de Cox e árvore de decisão condicional. Resultados. As pacientes com subtipos moleculares de tumor triplo-negativo tiveram uma sobrevida menor em comparação com as que apresentavam tumor com receptores hormonais. O acréscimo de hormonioterapia reduziu o risco de morte em 5,5%. O risco de morte foi 34,5% menor em pacientes com HER2+ quando comparadas às que tinham tumores sem a expressão desse gene. A mediana de sobrevida das pacientes tratadas com hormonioterapia foi de 4 753 dias. Conclusões. A presente análise revela um cenário favorável para o uso de imunoterapia em pacientes com superexpressão de HER2. Outros estudos devem ser realizados para avaliar a eficácia da imunoterapia em outras doenças e os fatores que favorecem o prognóstico e melhoram a qualidade de vida dessas pessoas.

Shorter delay to treatment by integrated diagnostic services and NGO-provided support among breast cancer patients in two Brazilian referral centres.

BACKGROUND: The diagnosis of breast cancer requires a complicated series of diagnostic exams. The present study addressed the delay of patients who used publicly and privately financed diagnostic services. Non-governmental organizations (NGOs) donated diagnostic mammograms and biopsies. DESIGN AND METHODS: Data from 304 patients were obtained from two Brazilian referral centres. In one referral centre (FAP), diagnostic mammography, clinic-histopathological exam and immunohistochemistry were outsourced, whereas in the other centre (HNL), these services were integrated. Cox regression, Kaplan-Meier analysis and non-parametric tests were used to compare variables and time intervals. RESULTS: If diagnostic mammography was financed privately and covered by private health insurance, the likelihood of a delay of >90 days between the first medical visit and the initiation of treatment decreased 2.15-fold (95%CI: 1.06- 4.36; p=0.033) and 4.44-fold (95%CI: 1.58-12.46; p=0.004), respectively. If the clinic-histopathological exam was outsourced (FAP) and publicly or privately financed, the median time between diagnostic mammography and the diagnostic result was 53 and 65 days in the integrated (HNL) and outsourced public system, compared to 29 days in the outsourced private system (p<0.050). The median time between the first medical visit and the diagnostic results of patients who were supported by NGOs, who financed their diagnostic services privately, and who used exclusively public diagnostic services was, respectively, 28.0, 48.5 and 77.5 days (p<0.050). CONCLUSION: Patients who used privately financed health services had shorter delays. Compared to outsourcing, the integration of the publicly financed clinic- histopathological exam diminished the delay. The support of patients by NGOs accelerated patient flow.

Availability of Diagnostic Services and their Impact on Patient Flow in Two Brazilian Referral Centres of Breast Cancer Treatment.

BACKGROUND: System delay (SD) is a leading cause of advanced stage of disease and poor prognosis among Brazilian breast cancer patients. METHODS: Cox regression and Kaplan-Meier analysis were used to identify variables that contributed to SD among 128 breast cancer patients. Time intervals between first medical consultation and treatment initiation were compared among patients of two referral centres: Patients of a referral centre with outsourced (FAP), respectively, integrated (HNL) diagnostic services. RESULTS: Women who used a specialized private clinic at the beginning of patient flow had an 2.32 fold increased chance (95% CI: 1.17 - 4.60; p = 0.016) of hospital admission within 90 days after first medical consultation, compared to women who used a public health care provider (HCP). Of 73 and 34 patients of the FAP hospital and the HNL, respectively, 10 (13.7%) and 11 (32.5%) used one HCP prior to hospital admission (p = 0.000). The median time between first medical consultation and treatment initiation was 150 days. The median time between first medical consultation and hospital admission was 136.0 and 52.0 days for patients of the FAP hospital, respectively the HNL (p < 0.050). The median time between first medical consultation and diagnostic mammography was 36.5 and 23.0 days for patients from the FAP hospital and the HNL (p < 0.050). CONCLUSIONS: Usage of public diagnostic services was associated with increased SD, whereas the usage of private diagnostic services diminished it. The usage of a lower number of HCPs accelerated patient flow.

Comparación de Panc3 con Apache II como escalas predictoras de severidad en pancreatitis aguda en Hospital de Especialidades Carlos Andrade Marín / Comparison between Panc3 score and Apache II score to predict severity in acute pancreatitis in Carlos Andrade Marin Speciality Hospital

INTRODUCCIÓN. La pancreatitis aguda es una patología que conlleva importante morbilidad, la adecuada estratificación de su severidad determina su manejo oportu-no. OBJETIVO. Comparar la escala Panc3 con el Apache II como predictora de seve-ridad en pacientes con pancreatitis aguda. MATERIALES Y MÉTODOS. Se realizó un estudio analítico observacional, con universo y muestra conocida de 148 pacientes con pancreatitis aguda atendidos en el Hospital de Especialidades Carlos Andrade Marín entre agosto 2018 a junio 2019. Los criterios de inclusión fueron: pacientes adultos jóvenes, mayores de 18 años con pancreatitis aguda, como criterios de ex-clusión: pacientes con antecedente de pancreatitis crónica. Se obtuvo los datos con medidas de asociación y análisis bivariado con pruebas de hipótesis de Chi cuadra-do, un nivel de confianza de 95,0% y con una p menor de 0,05, y con error de 5,0%. RESULTADOS. Las escalas Apache II y Panc3 mostraron resultados estadísticamen-te significativos para predecir severidad de pancreatitis aguda, no existió asociación significativa entre la severidad y los factores de riesgo o antecedentes estudiados DISCUSIÓN. La asociación de las escalas con la severidad fue similar a estudios disponibles. CONCLUSIONES. La escala Panc3 fue tan eficaz como la escala Apa-che II para predecir la severidad en los pacientes con pancreatitis aguda, no existió asociación entre los factores de riesgo, los antecedentes estudiados y la severidad, además la escala Apache II fue útil para predecir severidad.

INTRODUCTION. Acute pancreatitis is a pathology that carries important morbidity, the adequate stratification determines its timely management. OBJECTIVE. Com-pare the Panc3 scale with Apache II as a predictor of severity in patients with acute pancreatitis. MATERIALS AND METHODS. An observational analytical study was conducted, with universe and known sample of 148 patients with acute pancreati-tis treated at the Carlos Andrade Marín Specialities Hospital between august 2018 and june 2019. The inclusion criteria were: young adult patients, over 18 years old with acute pancreatitis, as exclusion criteria: patients with chronic pancreatitis history. Data was obtained with bivariate association measures and analysis with Chi square hypothesis tests, a confidence level of 95,0% and with a p less than 0,05, and with error of 5,0%. RESULTS. The Apache II and Panc3 scales showed statistically signifi-cant results in predicting severity of acute pancreatitis, there was no significant asso-ciation between severity and risk factors or background studied. DISCUSSION. The association of scales with severity was similar to available studies. CONCLUSIONS. The Panc3 scale was as effective as the Apache II scale in predicting severity in pa-tients with acute pancreatitis, there was no association between risk factors, the back-ground studied and severity, and the Apache II scale was useful in predicting severity.

Structural and immunological characterization of a new nucleotidyltransferase-like antigen from Paracoccidioides brasiliensis.

Pb27 antigen is an interesting alternative to immunological diagnosis of Paracoccidioidomycosis (PCM) and has demonstrated to be protective in experimental PCM. Its tertiary structure and possible function remained unknown till now. To study Pb27 at the atomic level, the recombinant protein was expressed in Escherichia coli BL21(DE3), purified, and its three-dimensional structure was solved by X-ray crystallography. Based on this structure, we performed a residue correlation analysis and in silico ligand search assays to address a possible biological function to Pb27. We identified Pb27 as a member of the extensive nucleotidyltransferase superfamily. The protein has an αßαßαß topology with two domains (N- and C-terminal domains) and adopts a monomeric form as its biological unit in solution. Structural comparisons with similar members of the superfamily clearly indicate Pb27 C-terminal domain is singular and may play an important role in its biological function. Bioinformatics analysis suggested that Pb27 might bind to ATP and CTP. This suggestion is corroborated by the fact that a magnesium cation is coordinated by two aspartic acid residues present at the active site (between N- and C-terminal domains), as evidenced by X-ray diffraction data. Besides, NMR assays (1H-15N HSQC spectra) confirmed the binding of CTP to Pb27, demonstrating for the first time an interaction between a nucleotide and this protein. Moreover, we evaluated the reactivity of sera from patients with Paracoccidioides brasiliensis infection against the recombinant form of Pb27 and showed that it was recognized by sera from infected and treated patients. Predicted B and T cell epitopes were synthesized and further evaluated against sera of PCM patients, providing information of the most reactive peptides in Pb27 primary structure which interact with specific Pb27 antibodies.

Immune response markers in sera of children infected with Giardia duodenalis AI and AII subassemblages.

In this study, we evaluated serum markers of immune responses in children infected with G. duodenalis and compared them with the characterized parasite isolates. The reactivity indexes (RI) of IgG (1.503 ± 0.819) and IgA (2.308 ± 1.935) antibodies were significantly higher (P < 0.001) in infected children than in non-infected children. There were also statistically significantly higher serum levels (P < 0.05) of IFN-γ (393.10 ± 983.90 pg/mL) as well as serum (30.03 ± 10.92 µmol/L) and saliva nitric oxid derivatives (NOx) (192.4 ± 151.2 µmol/L) in children infected with G. duodenalis compared to the group of non-parasitized children (127.4 ± 274.30 pg/mL; 25.82 ± 7.74 µmol/L and 122.5 ± 105.90 µmol/L, respectively). Regarding the characterized genetic variants of G. duodenalis and the immune response profiles, no differences were observed in terms of antibody reactivity or levels of serum cytokine and NOx among children infected with AI or AII subassemblages. The elevated levels of IFN-γ and NOx indicate that G. duodenalis intestinal infection in humans induces a cellular immune response detectable at the systemic level. Moreover, no significant differences in the antibody reactivity profile or the cytokine and NOx production in the sera of children infected with AI or AII G. duodenalis variants were observed, suggesting that subtypes of the parasite do not influence the immune response profile.

Impaired immunoregulatory network of the CD4 T lymphocytes in refractory asthma.

BACKGROUND: The immunopathogenesis of severe asthma has been associated with an inefficient regulatory response. There are a few studies about the CD4 T cells profile among individuals with severe asthma refractory to treatment. OBJECTIVE: To evaluate the CD4 T lymphocyte profile from individuals with severe asthma according to their response to treatment, relating to their atopy status and age of asthma onset. METHODS: We evaluated nineteen individuals with severe asthma refractory to treatment (SAR), 21 with well-controlled or partly controlled severe asthma (CSA) and 23 with mild-to-moderate asthma (MMA). Lymphocytes were obtained from PBMC, and the frequency of expression of different molecules in this population was assessed using the flow cytometry. RESULTS: We observed the frequency of CD4+ IFN-γ+ T cells was higher in atopic individuals with SAR than with CSA. In addition, among the atopic and early-onset asthma (EOA), the frequency of CD4+ CTLA-4+ T cells was lower in the SAR group than the CSA group. In relation to non-atopic and late-onset asthma (LOA) phenotypes, we noted the frequency of CD4+ FoxP3+ T cells was lower in individuals with SAR than with CSA. We also observed among the LOA patients, the frequency of CD4+ TGF-ß+ T cells was decreased in SAR group than the in CSA group. CONCLUSION AND CLINICAL RELEVANCE: Our data suggest that refractoriness to treatment in asthma is associated with a lower expression of distinct regulatory molecules by CD4 T cells between those who are atopic and have EOA and those who are non-atopic and have LOA. Thus, these results may contribute to the identification of new regulatory strategies to treat asthma according to their phenotypes.

Preparo dental com pontas ultrassônicas e cimentação com resina termomodificada / Clinical sequence of ceramic laminates ­ dental preparation with ultrasonic tips and thermically modified resin cementation

Paciente apresentava dentes 12 e 22 com formatos conoides e restaurações insatisfatórias, os demais dentes eram hígidos e apresentavam formato natural. Assim, o tratamento adotado foi a remoção das restaurações insatisfatórias associada a preparos minimamente invasivo e laminados confeccionados com cerâmica feldspática nos dentes 12 e 22. As restaurações em resina composta apresentavam proporções e anatomias adequadas, adotando-as como guia para os preparos dentais. Inicialmente, foram utilizadas brocas diamantadas em alta rotação para o preparo inicial e, em seguida, pontas ultrassônicas para remoção da resina composta e finalização dos preparos. Realizou-se a moldagem com silicone de adição e os laminados cerâmicos foram confeccionados pela técnica da aplicação sobre troquel refratário. Clinicamente, realizou-se a prova das cerâmicas e a cimentação após aprovação da paciente. A fase da cimentação seguiu o seguinte protocolo: isolamento absoluto, profilaxia dos preparos dentais, condicionamento ácido e aplicação de sistema adesivo. As superfícies internas dos laminados foram condicionadas e então aplicados silano e sistema adesivo. A resina composta foi aquecida e inserida na superfície dos laminados, que foram posicionados sobre os preparos dentais com o auxílio do instrumento ultrassônico até a sua posição final. Após a remoção dos excessos, realizou-se a fotopolimerização do conjunto, polimento da interface adesiva, ajustes oclusais e polimentos finais. O caso foi realizado com acompanhamento clínico e radiográfico de 12 meses, e favorável prognóstico. (AU)

This patient had conoid teeth at the 12 and 22 positions with unsatisfactory restorations. The remaining teeth were healthy. Thus, the treatment adopted was the removal of the restorations associated with minimally invasive preparations and feldspathic ceramics on tooth numbers 12 and 22. The restorations in composite resin had adequate proportions and anatomy, adopting them as a guide for dental preparations. Initially, diamond burs were used in high-rotation speed for the initial preparation, and then ultrasonic tips for removal of the composite resin and finalization. An impression was carried out with addition silicone and the ceramic laminates made using the refractory die technique. Clinically, the ceramics were tried-in and cemented after patient approval. The cementation phase was made as the following: rubber dam isolation, prophylaxis, acid etching and adhesive application. The inner laminate surfaces were conditioned, silanated, and received the adhesive system. The composite resin was heated and inserted into the laminates, which were placed on the dental preparations with the the ultrasonic instrument to their final position. After excess removal, photactivation was made and the adhesive interface was polished, followed by occlusal adjustments and fi nal polishing. After clinical and radiographic follow-up of 12 months, a favorable prognosis was observed. (AU)

From Live Cells to Caenorhabditis elegans: Selective Staining and Quantification of Lipid Structures Using a Fluorescent Hybrid Benzothiadiazole Derivative.

The current article describes the synthesis, characterization, and application of a designed hybrid fluorescent BTD-coumarin (2,1,3-benzothiadiazole-coumarin) derivative (named BTD-Lip). The use of BTD-Lip for live-cells staining showed excellent results, and lipid droplets (LDs) could be selectively stained. When compared with the commercially available dye (BODIPY) for LD staining, it was noted that the designed hybrid fluorescence was capable of staining a considerable larger number of LDs in both live and fixed cells (ca. 40% more). The new dye was also tested on live Caenorhabditis elegans (complex model) and showed an impressive selectivity inside the worm, whereas the commercial dye showed no selectivity in the complex model.

Rhamnolipids production from sucrose by engineered Saccharomyces cerevisiae.

Biosurfactants are biological tensioactive agents that can be used in the cosmetic and food industries. Rhamnolipids are glycolipid biosurfactants naturally produced by Pseudomonas aeruginosa and are composed of one or two rhamnose molecules linked to beta-hydroxy fatty acid chains. These compounds are green alternatives to petrochemical surfactants, but their large-scale production is still in its infancy, hindered due to pathogenicity of natural producer, high substrate and purification costs and low yields and productivities. This study, for the first time, aimed at producing mono-rhamnolipids from sucrose by recombinant GRAS Saccharomyces cerevisiae strains. Six enzymes from P. aeruginosa involved in mono-rhamnolipid biosynthesis were functionally expressed in the yeast. Furthermore, its SUC2 invertase gene was disrupted and a sucrose phosphorylase gene from Pelomonas saccharophila was also expressed to reduce the pathway's overall energy requirement. Two strains were constructed aiming to produce mono-rhamnolipids and the pathway's intermediate dTDP-L-rhamnose. Production of both molecules was analyzed by confocal microscopy and mass spectrometry, respectively. These strains displayed, for the first time as a proof of concept, the potential of production of these molecules by a GRAS eukaryotic microorganism from an inexpensive substrate. These constructs show the potential to further improve rhamnolipids production in a yeast-based industrial bioprocess.