Systematic Review and Meta-Analysis of Congenital Toxoplasmosis Diagnosis: Advances and Challenges.

Objective: To understand how congenital toxoplasmosis (CT) diagnosis has evolved over the years, we performed a systematic review and meta-analysis to summarize the kind of analysis that has been employed for CT diagnosis. Methods: PubMed and Lilacs databases were used in order to access the kind of analysis that has been employed for CT diagnosis in several samples. Our search combined the following combining terms: "congenital toxoplasmosis" or "gestational toxoplasmosis" and "diagnosis" and "blood," "serum," "amniotic fluid," "placenta," or "colostrum." We extracted data on true positive, true negative, false positive, and false negative to generate pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Random-effects models using MetaDTA were used for analysis. Results: Sixty-five articles were included in the study aiming for comparisons (75.4%), diagnosis performance (52.3%), diagnosis improvement (32.3%), or to distinguish acute/chronic infection phases (36.9%). Amniotic fluid (AF) and placenta were used in 36.9% and 10.8% of articles, respectively, targeting parasites and/or T. gondii DNA. Blood was used in 86% of articles for enzymatic assays. Colostrum was used in one article to search for antibodies. In meta-analysis, PCR in AF showed the best performance for CT diagnosis based on the highest summary sensitivity (85.1%) and specificity (99.7%) added to lower magnitude heterogeneity. Conclusion: Most of the assays being researched to diagnose CT are basically the same traditional approaches available for clinical purposes. The range in diagnostic performance and the challenges imposed by CT diagnosis indicate the need to better explore pregnancy samples in search of new possibilities for diagnostic tools. Exploring immunological markers and using bioinformatics tools and T. gondii recombinant antigens should address the research needed for a new generation of diagnostic tools to face these challenges.

Antifungal activity of liriodenine on clinical strains of Cryptococcus neoformans and Cryptococcus gattii species complexes.

Background: Cryptoccocal meningitis continues to present high incidence among AIDS patients. The treatment of choice is the synergistic combination of flucytosine (5-FC) with amphotericin B deoxycholate (AmBd) or its lipid formulations. However, 5-FC is unavailable in many countries and AmB demands hospitalization. The combination of AmB with the fungistatic fluconazole (FLC) or the use of high FLC daily doses alone became the choice. Nonetheless, sterilization of cerebrospinal fluid is delayed with FLC monotherapy, mainly with high fungal burden. These findings suggest the search for new antifungal compounds, such as liriodenine. Methods: Liriodenine antifungal activity was evaluated by three procedures: determining the minimum inhibitory concentration (MIC) on 30 strains of the Cryptococcus neoformans (C. neoformans) complex and 30 of the Cryptococcus gattii (C. gattii) complex, using EUCAST methodology and amphotericin B deoxycholate as control; performing the time-kill methodology in two strains of the C. neoformans complex and one of the C. gattii complex; and injury to cryptococcal cells, evaluated by transmission electron microscopy (TEM). Liriodenine absorption and safety at 0.75 and 1.50 mg.kg-1 doses were evaluated in BALB/c mice. Results: Liriodenine MICs ranged from 3.9 to 62.5 µg.mL-1 for both species complexes, with no differences between them. Time-kill methodology confirmed its concentration-dependent fungicidal effect, killing all the strains below the limit of detection (33 CFU.mL-1) at the highest liriodenine concentration (32-fold MIC), with predominant activity during the first 48 hours. Liriodenine induced severe Cryptococcus alterations - cytoplasm with intense rarefaction and/or degradation, injury of organelles, and presence of vacuoles. Liriodenine was better absorbed at lower doses, with no histopathological alterations on the digestive tract. Conclusion: The fungicidal activity confirmed by time-kill methodology, the intense Cryptococcus injury observed by TEM, the absorption after gavage administration, and the safety at the tested doses indicate that the liriodenine molecule is a promising drug lead for development of anticryptococcal agents.

Antifungal activity of liriodenine on agents of systemic mycoses, with emphasis on the genus Paracoccidioides.

BACKGROUND: Endemic systemic mycoses remain a health challenge, since these opportunistic diseases are increasingly infecting immunosuppressed patients. The simultaneous use of antifungal compounds and other drugs to treat infectious or non-infectious diseases has led to several interactions and undesirable effects. Thus, new antifungal compounds should be investigated. The present study aimed to evaluate the activity of liriodenine extracted from Annona macroprophyllata on agents of systemic mycoses, with emphasis on the genus Paracoccidioides. METHODS: The minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) were determined by the microdilution method. The cellular alterations caused by liriodenine on a standard P. brasiliensis (Pb18) strain were evaluated by transmission and scanning electron microscopy. RESULTS: Liriodenine was effective only in 3 of the 8 strains of the genus Paracoccidioides and in the Histoplasma capsulatum strain, in a very low concentration (MIC of 1.95 µg.mL-1); on yeasts of Candida spp. (MIC of 125 to 250 µg.mL-1), including C. krusei (250 µg.mL-1), which has intrinsic resistance to fluconazole; and in Cryptococcus neoformans and Cryptococcus gattii (MIC of 62.5 µg.mL-1). However, liriodenine was not effective against Aspergillus fumigatus at the studied concentrations. Liriodenine exhibited fungicidal activity against all standard strains and clinical isolates that showed to be susceptible by in vitro tests. Electron microscopy revealed cytoplasmic alterations and damage to the cell wall of P. brasiliensis (Pb18). CONCLUSION: Our results indicate that liriodenine is a promising fungicidal compound that should undergo further investigation with some chemical modifications.

Macrophage migration inhibitory factor (MIF) and pregnancy may impact the balance of intestinal cytokines and the development of intestinal pathology caused by Toxoplasma gondii infection.

Toxoplasma gondii (T. gondii) is an intracellular parasite responsible for causing toxoplasmosis. When infection occurs during pregnancy, it can produce severe congenital infection with ocular and neurologic damage to the infant. From the oral infection parasite reaches the intestine, causing inflammatory response, damage in tissue architecture and systemic dissemination. Macrophage migration inhibition factor (MIF) is a cytokine secreted from both immune and non-immune cells, including gut epithelial cells. MIF is described to promote inflammatory responses, to be associated in colitis pathogenesis and also to play role in maintaining the intestinal barrier. The aim of the present study was to evaluate the influence of the pregnancy and MIF deficiency on T. gondii infection in the intestinal microenvironment and to address how these factors can impact on the intestinal architecture and local cytokine profile. For this purpose, small intestine of pregnant and non-pregnant C57BL/6 MIF deficient mice (MIF-/-) and Wild-type (WT) orally infected with 5 cysts of ME-49 strain of T. gondii were collected on day 8th of infection. Intestines were processed for morphological and morphometric analyses, parasite quantification and for cytokines mensuration. Our results showed that the absence of MIF and pregnancy caused an increase in T. gondii infection index. T. gondii immunolocalization demonstrated that segments preferentially infected with T. gondii were duodenum and ileum. The infection caused a reduction in the size of the intestinal villi, whereas, infection associated with pregnancy caused an increase in villi size due to edema caused by the infection. Also, the goblet cell number was increased in the ileum of MIF-/- mice, when compared to the corresponding WT group. Analyses of cytokine production in the small intestine showed that MIF was up regulated in the gut of pregnant WT mice due to infection. Also, infection provoked an intense Th1 response that was more exacerbated in pregnant MIF-/- mice. We also detected that the Th2/Treg response was more pronounced in MIF-/- mice. Altogether, our results demonstrated that pregnancy and MIF deficiency interferes in the balance of the intestinal cytokines and favors a Th1-immflamatory profile, which in turn, impact in the development of pathology caused by T. gondii infection in the intestinal microenvironment.

Erratum to "Macrophage migration inhibitory factor (MIF) and pregnancy may impact the balance of intestinal cytokines and the development of intestinal pathology caused by Toxoplasma gondii infection" [Cytokine: X 2 (2020) 100034].

[This corrects the article DOI: 10.1016/j.cytox.2020.100034.].

Antifungal activity of liriodenine on agents of systemic mycoses, with emphasis on the genus Paracoccidioides

Endemic systemic mycoses remain a health challenge, since these opportunistic diseases are increasingly infecting immunosuppressed patients. The simultaneous use of antifungal compounds and other drugs to treat infectious or non-infectious diseases has led to several interactions and undesirable effects. Thus, new antifungal compounds should be investigated. The present study aimed to evaluate the activity of liriodenine extracted from Annona macroprophyllata on agents of systemic mycoses, with emphasis on the genus Paracoccidioides. Methods: The minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) were determined by the microdilution method. The cellular alterations caused by liriodenine on a standard P. brasiliensis (Pb18) strain were evaluated by transmission and scanning electron microscopy. Results: Liriodenine was effective only in 3 of the 8 strains of the genus Paracoccidioides and in the Histoplasma capsulatum strain, in a very low concentration (MIC of 1.95 µg.mL-1); on yeasts of Candida spp. (MIC of 125 to 250 µg.mL-1), including C. krusei (250 µg.mL-1), which has intrinsic resistance to fluconazole; and in Cryptococcus neoformans and Cryptococcus gattii (MIC of 62.5 µg.mL-1). However, liriodenine was not effective against Aspergillus fumigatus at the studied concentrations. Liriodenine exhibited fungicidal activity against all standard strains and clinical isolates that showed to be susceptible by in vitro tests. Electron microscopy revealed cytoplasmic alterations and damage to the cell wall of P. brasiliensis (Pb18). Conclusion: Our results indicate that liriodenine is a promising fungicidal compound that should undergo further investigation with some chemical modifications.(AU)

Dor torácica aguda: enfermeiro desafiando uma patologia tempo dependente nas portas de entrada hospitalares / Dolor torácico agudo: enfermero desafiando una patología dependiente del tiempo en las puertas de entrada hospitalarias / Acute chest pain: nurses challenging a time-dependent pathology at the hospital entrance doors

Objetivo: avaliar a percepção dos enfermeiros diante do paciente com dor torácica nas portas de entrada do Serviço de Urgência e Emergência de um hospital geral. Método: estudo exploratório, descritivo, com abordagem qualitativa, realizado com 10 enfermeiros em um hospital geral de grande porte do Rio Grande do Sul, em 2018. A coleta de dados ocorreu através de entrevistas semiestruturadas, estudadas conforme análise de conteúdo. Resultados: constataram-se dificuldades no entendimento da Classificação de Risco, questões estruturais e organizacionais e a falta de profissionais qualificados. Como potencialidades, atendimento de maneira ágil, buscando a mais correta identificação dos sinais apresentados pelo paciente e a realização do eletrocardiograma no tempo adequado. Conclusão: evidenciou-se que o enfermeiro percebe estar apto para tomar decisões rápidas e precisas por meio do conhecimento de protocolos assistenciais. Porém, verifica-se a interferência de processos como o subdimensionamento de pessoal e a demanda excessiva dos serviços de porta de entrada.

Objective: to assess the perception of nurses in the face of patients with chest pain at the entrance doors of the Urgent and Emergency Service in a general hospital. Method: exploratory and descriptive study, with a qualitative approach, carried out with 10 nurses in a large general hospital in Rio Grande do Sul, in 2018. Data collection occurred through semi-structured interviews, studied according to content analysis. Results: there were difficulties in understanding the Risk Classification, structural and organizational issues, besides the lack of qualified professionals. As for potentialities, care in a quick way, seeking the most correct identification of the signs presented by the patient and the accomplishment of the electrocardiogram in the appropriate time. Conclusion: it was evidenced that the nurse perceives to be able to make quick and accurate decisions through the knowledge of care protocols. Nevertheless, there is interference from processes such as undersizing of personnel and the excessive demand for entrance door services.

Objetivo: evaluar la percepción de los enfermeros ante los pacientes con dolor torácico en las puertas de entrada del Servicio de Urgencia y Emergencia de un hospital general. Método: estudio exploratorio, descriptivo, con enfoque cualitativo, realizado con 10 enfermeros en un gran hospital general en Rio Grande do Sul, en 2018. La recolección de datos ocurrió mediante entrevistas semiestructuradas, estudiadas según el análisis de contenido. Resultados: se encontraron dificultades para comprender la Clasificación de Riesgos, las cuestiones estructurales y organizacionales y la falta de profesionales calificados. Como potenciales, atención desarrollada rápidamente, buscando la identificación más correcta de los signos presentados por el paciente y la realización del electrocardiograma a tiempo. Conclusión: se evidenció que el enfermero percibe la capacidad de tomar decisiones rápidas y precisas mediante el conocimiento de protocolos asistenciales. Sin embargo, hay interferencia de procesos como el subdimensionamiento de personal y la excesiva demanda de servicios de admisión.

Diagnósticos de enfermagem de pacientes em tratamento radioterápico / Nursing diagnoses of patients undergoing radiation therapy

Objetivo: identificar a incidência dos diagnósticos de enfermagem, bem como características definidoras, fatores relacionados e fatores de risco, com base na taxonomia NANDA-I de pacientes em tratamento radioterápico. Método: trata-se de estudo quantitativo, transversal, exploratório-descritivo, realizado com 60 pacientes em um ambulatório. Resultados: identificou-se 23 Diagnósticos de Enfermagem, sendo os mais incidentes: risco de integridade da pele prejudicada (35%), mobilidade física prejudicada (15%) e eliminação urinária prejudicada (7%). As características definidoras evidenciadas foram amplitude limitada de movimentos (15,3%), incontinência e dificuldade para deglutir (7,2%). Dentre os fatores relacionados, estão dor (18,3%), desconforto (10,7%) e radiação (6%) e os fatores de risco radiação (56%), mudanças na pigmentação da pele/mudanças no turgor da pele (26,3%) e estado nutricional desequilibrado (6,3%). Conclusão: os resultados do estudo contribuem para atender às necessidades de saúde dos pacientes em tratamento radioterápico e na tomada de decisão clínica pelo enfermeiro.(AU)

Caracterização de pacientes em tratamento radioterápico a partir da consulta de enfermagem / Characterization of patients in radiotherapical treatment from the nursing consultation / Caracterización de los pacientes en tratamiento radioterapéutico a partir de la consulta de enfermería

Objetivo: caracterizar o perfil sociodemográfico e clínico de pacientes em tratamento radioterápico, a partir da consulta de enfermagem. Método: estudo quantitativo, do tipo exploratório descritivo realizado em um ambulatório de radioterapia, com 60 pacientes em tratamento radioterápico, com idade igual ou superior a 18 anos. A coleta de dados ocorreu nos meses de junho e julho de 2015 e foram analisados por estatística descrita. Resultados: a maioria dos pacientes foi do sexo feminino, com idade entre 50 e 79 anos, com ensino fundamental completo, casados e com 1 a 3 filhos, sendo o câncer de mama em mulheres e o de próstata em homens, os mais incidentes. Considerações finais: a consulta de enfermagem mostrou-se uma estratégia de trabalho eficiente. O estudo pode contribuir para a elaboração de protocolos assistenciais que possibilitam qualificar o cuidado prestado.

Aim: to characterize the sociodemographic and clinical profile of patients in radiotherapical treatment from the nursing consultation. Method: this is a quantitative,descriptive exploratory study carried out in a radiotherapy outpatient clinic, with 60 patients undergoing radiotherapy treatment aged 18 years or older. The data analysis was made through descriptive statistics and its collection occurred during June and July 2015. Results: the majority of the patients were female, aged between 50 and 79 years old, with complete primary education, married and with 1 to 3 children. The most incidental outcomes were breast cancer in women and prostate cancer in men. Final considerations: nursing consultation proved to be an efficient work strategy. The study can contribute to the elaboration of assistance protocols that allows qualifying the care provided.

Objetivo: caracterizar el perfil sociodemográfico y clínico de los pacientes en tratamiento radioterapéutico a partir de la consulta de enfermería. Método: estudio cuantitativo, exploratorio, descriptivo realizado en un ambulatorio de radioterapia, con 60 pacientes en tratamiento radioterapéutico, con edades iguales o mayores que 18 años. La recolección de datos ocorrió durante los meses de junio y julio de 2015 y fueron analizados por estadística descrita. Resultados: la mayoría de los pacientes eran mujeres, con edades entre 50 y 79 años, con la escuela primaria completa, casados y con 1 a 3 hijos, el mayor número de incidencia es el cáncer de mama entre las mujeres y próstata entre los hombres. Consideraciones finales: la consulta de enfermería demostró ser una estrategia de trabajo eficiente. El estudio puede contribuir para el desarrollo de protocolos asistenciales, que pueden calificar el cuidado ofrecido