Clinical, laboratory, and molecular characteristics of a cohort of children with hemoglobinopathy S/betathalassemia

ABSTRACT Introduction: Hemoglobinopathy Sβ-thalassemia (HbSβ-thal) has a wide range of clinical and laboratory severity. There is limited information on the natural history of HbSβ-thal and its modulating factors. We described the molecular, hematological, and clinical characteristics of a cohort of children with HbSβ-thal and estimated its incidence in Minas Gerais, Brazil. Methods: Laboratory and clinical data were retrieved from medical records. Molecular analysis was performed by HBB gene sequencing, PCR-RFLP, gap-PCR, and MLPA. Results: Eighty-nine children were included in the study. Fourteen alleles of β-thal mutations were identified. The incidence of HbSβ-thal in the state was 1 per 22,250 newborns. The most common βS-haplotypes were CAR and Benin. The most frequent βthal-haplotypes were V, II, and I. Coexistence of 3.7 kb HBA1/HBA2 deletion was present in 21.3 % of children. β-thalassemia mutations were associated with several clinical and laboratory features. In general, the incidence of clinical events per 100 patient-years was similar for children with HbSβ0-thal, IVS-I-5 G>A, and IVS-I-110 G>A. Children with HbSβ+-intermediate phenotypes had a more severe laboratory and clinical profile when compared with those with HbSβ+-mild ones. βS-haplotypes and α-thalassemia did not meaningfully influence the phenotype of children with HbSβ-thal. Conclusion: The early identification of b-thalassemia alleles may help the clinical management of these children. © 2023 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license

The impact of covid-19 on the epidemiological profile of fractures / O impacto da covid-19 sobre o perfil epidemiológico de fraturas

ABSTRACT Objective: To analyze the epidemiological transition of fractures in patients who were treated in a tertiary hospital which is reference in traumatology during the COVID-19 pandemic to assess the changes in trauma service. Methods: This is a retrospective and descriptive analysis of data on orthopedics lesions treated at Instituto Doutor Jose Frota between December 16, 2019 and June 16, 2020 (three months before and after the first case of COVID-19 in Ceará). Results: In total, we evaluated 913 patients, 28.5% of which were women and 71.5%, men. We found a significative reduction (p < 0.05) in the proportion of female patients operated in the analyzed time. We also observed an increase in patients' mean age, 35.4 years before the pandemic, and 38.48 (p = 0.04) during the consecutive period. Trauma mechanisms significantly changed (p < 0.05), with a proportional increase of high-energy traumas and reduction of instances of falling. We found a 11.9% reduction in orthopedic surgeries, from 655 to 577 at the time after the first case of COVID-19 (p = 0.071). Mean hospitalization length (p < 0.001) and time until surgeries decreased (p < 0.001). Conclusion: We observed the impact of lockdown in this hospital of trauma especially via the decreased number of operated cases and the change in patients' profile and trauma mechanism. Level of Evidence III, Retrospective Comparative Study.

RESUMO Objetivo: Analisar a transição do perfil epidemiológico de fraturas de pacientes atendidos em um hospital terciário referência em traumatologia durante a pandemia de COVID-19, a fim de verificar mudanças no atendimento traumatológico. Métodos: Análise retrospectiva e descritiva dos dados de lesões ortopédicas admitidas no Instituto Doutor José Frota entre 16 de dezembro de 2019 e 16 de junho de 2020 (três meses antes e depois do primeiro caso de COVID-19 no Ceará). Resultados: Dos 913 pacientes avaliados, 28,5% eram mulheres e 71,5% homens. Houve redução significativa (p < 0,05) nas proporções de mulheres operadas no tempo analisado. Houve aumento na média da idade, sendo 35,40 anos pré-pandemia, e 38,48 (p = 0,04) no período seguinte. Os mecanismos de trauma mudaram significativamente (p < 0,05), com aumento proporcional de fraturas por alta energia e redução no número daquelas por queda ao solo. A quantidade de cirurgias ortopédicas reduziu em 11,9%, de 655 antes do primeiro caso de COVID-19 para 577 posteriormente (p = 0,071). A média do número de dias diminuiu para duração do internamento (p < 0,001) e para o tempo até a realização da cirurgia (p < 0,001). Conclusão: O impacto do lockdown neste hospital de trauma se deu principalmente pela diminuição na quantidade de casos operados e pela mudança do perfil e mecanismo de trauma dos pacientes. Nível de Evidência III, Estudo Retrospectivo Comparativo.

Gee-logit model corrected biplots with harvest effects on coffee beans grading

In a granulometric analysis of coffee beans with different categories of defects, the data can be organized in contingency tables, and when considering the discrimination by harvest, they may have a structure that suggest a more complex model, by means of the counting of defective coffee beans compared to different crops interacting with the classification of defects and percentages of sieve grains, which characterizes a block design with multivariate responses. However, due to the techniques based on the analysis of variance, considering the uniform correlation structure for all plots, it becomes feasible to propose a model that allows contemplating different structures between the plots, associating the effects of the crops to the defects in the granulometric procedure applied to the coffee beans. Thus, the hypothesis of incorporating the effects of crops associated with defects arises using the biplot multivariate technique. This work aims to propose the use of corrected biplots by predictions obtained trhough the fit to the Generalized Linear Model in the coffee grain size classification, broken down by components of the effect of the harvests. In conclusion, the use of GEE models with the corrected biplot technique by the predictions is feasible for application to be applied to the granulometric analysis of defective coffee beans, presenting discrimination regarding the effects of harvests.

Tumor Fibro-histiocítico Plexiforme de Vulva: Relato de Caso / Vulva Plexiform Fibrohistiocytic Tumor: Case Report / Tumor Fibrohistiocítico Plexiforme de la Vulva: Reporte de Caso

Introdução: O tumor fibro-histiocítico plexiforme é uma condição clínica rara, com cerca de 150 casos descritos na literatura. Relato do caso: Paciente, 23 anos, sexo feminino, portadora de lesão nodular em região vulvar sem características de malignidade em exames de ultrassonografia. Realizou acompanhamento clínico, tendo apresentado aumento do tamanho da lesão inicial, sendo optado então por realização de ressecção cirúrgica da lesão. Em estudo histopatológico, evidenciou-se lesão compatível com tumor fibro-histiocítico plexiforme, com margens cirúrgicas livres. No seguimento, a paciente foi encaminhada para avaliação oncológica com a intenção de realizar exames complementares de rastreio e descartar diagnósticos morfologicamente semelhantes. Diante dos exames complementares confirmando o diagnóstico inicial e sem evidência de doença metastática após excisão cirúrgica completa com margens livres, foi iniciado seguimento clínico. Conclusão: Relatar o caso é de extrema importância para divulgar a apresentação clínica, etapas diagnósticas, tratamento proposto e compartilhar informações acerca de evolução clínica apresentada.

Introduction: Plexiform fibrohistiocytic tumor is a rare clinical condition, with about 150 cases described in the literature. Case report: 23-years-old, female patient with nodular lesion in vulva without malignancy characteristics on ultrasound image. She underwent clinical follow-up and after an increase in the size of the lesion, surgical resection was opted. Histopathological findings suggested plexiform fibrohistiocytic tumor, with free surgical margins. In follow up, she was referred to oncological evaluation for screening complementary exams and rule out morphologically similar diagnoses. After the complementary exams confirming the initial diagnosis of plexiform fibrohistiocytic tumor and without evidence of metastatic disease after complete surgical excision with free margins, the patient is in clinical follow-up. Conclusion: Reporting the case is extremely important to disseminate the clinical presentation, diagnostic steps, proposed treatment and share information about the clinical evolution presented.

Introducción: El tumor fibrohistiocítico plexiforme es una condición clínica poco frecuente, con unos 150 casos descritos en la literatura. Reporte del caso: Paciente de 23, sexo feminino, años con lesión nodular en una región vulvar sin características malignas en los exámenes de ultrasonido. Se sometió a un seguimiento clínico, habiendo presentado un aumento en el tamaño de la lesión inicial, y se decidió realizar la resección quirúrgica de la lesión. En un estudio histopatológico, se evidenció una lesión compatible con tumor fibrohistiocítico plexiforme con márgenes quirúrgicos libres. Fue referida para la evaluación oncológica, realizó pruebas complementarias para el cribado y para descartar diagnósticos morfológicamente similares. En vista de las pruebas complementarias que confirman el diagnóstico inicial y sin evidencia de enfermedad metastásica después de una escisión quirúrgica completa con márgenes libres, se inició el seguimiento clínico. Conclusión: Informar del caso es extremadamente importante para difundir la presentación clínica, etapas diagnósticas, tratamiento propuesto y compartir información sobre la evolución clínica presentada.

First report of bla GES-1 in Proteus mirabilis clinical isolates

Abstract Proteus mirabilis is one of the main pathogens causing urinary tract infections and sepsis. To our knowledge, this is the first report of a P. mirabilis hosting bla GES. The presence of these genes was determined using PCR and sequencing. We identified the presence of bla GES-1 in all three isolates. In addition, we identified the bla KPC-2 and bla NDM-1 genes in the two strains. These data emphasize the importance of monitoring and surveillance of all enterobacteria. The circulation of P. mirabilis strains carrying bla GES-1 constitutes a new scenario of resistance in this species and should be an epidemiological alert for global health.

High plasmid variability, and the presence of IncFIB, IncQ, IncA/C, IncHI1B, and IncL/M in clinical isolates of Klebsiella pneumoniae with bla KPC and bla NDM from patients at a public hospital in Brazil

Abstract INTRODUCTION Antibiotic resistance in carbapenemase-producing Klebsiella pneumoniae is acquired and disseminated mainly by plasmids. Therefore, we aimed to investigate the occurrence of carbapenemase genes, analyze the genetic diversity by ERIC-PCR, and examine the most common plasmid incompatibility groups (Incs) in clinical isolates of K. pneumoniae from colonization and infection in patients from a hospital in Brazil. METHODS Twenty-seven isolates of carbapenem-resistant K. pneumoniae were selected and screened for the presence of carbapenemase genes and Incs by PCR, followed by amplicon sequencing. RESULTS The bla KPC and bla NDM genes were detected in 24 (88.8 %) and 16 (59.2 %) of the isolates, respectively. Thirteen isolates (48.1 %) were positive for both genes. The IncFIB (92.6 %) and IncQ (88.8 %) were the most frequent plasmids, followed by IncA/C, IncHI1B, and IncL/M, indicating that plasmid variability existed in these isolates. To our knowledge, this is the first report of IncHI1B in Brazil. We found eight isolates with clonal relationship distributed in different sectors of the hospital. CONCLUSIONS The accumulation of resistance determinants, the variability of plasmid Incs, and the clonal dissemination detected in K. pneumoniae isolates demonstrate their potential for infection, colonization, and the dissemination of different resistance genes and plasmids.

Identification of plasmid IncQ1 and NTEKPC-IId harboring bla KPC-2 in isolates from Klebsiella pneumoniae infections in patients from Recife-PE, Brazil

Abstract INTRODUCTION: This study investigated the genetic environment of bla KPC-2 in Klebsiella pnemoniae multi-drug resistant clinical isolates. METHODS: Four carbapenemase gene isolates resistant to carbapenems, collected from infected patients from two hospitals in Brazil, were investigated using polymerase chain reaction and plasmid DNA sequencing. RESULTS: The bla KPC-2 gene was located between ISKpn6 and a resolvase tnpR in the non-Tn4401 element (NTEKPC-IId). It was detected on a plasmid belonging to the IncQ1 group. CONCLUSIONS To our knowledge, this is the first report of the presence of the bla KPC-2 gene in the NTEKPC-IId element carried by plasmid IncQ1 from infections in Brazil.

Qualidade de vida de famílias de filhos com deficiência intelectual moderada / Quality of life in families with children with moderate intellectual disability

RESUMO Objetivo Investigar a qualidade de vida familiar (QVF) entre famílias brasileiras que têm filhos com deficiência intelectual (DI) moderada. Métodos Estudo transversal, realizado com 50 famílias com filhos com DI moderada de São Carlos, São Paulo, Brasil. Os dados foram coletados por meio de formulários, com informações sociodemográficas, os índices de funcionalidade de Barthel e de Lawton & Brody e a Escala de Qualidade de Vida Familiar do Beach Center. Resultados Os domínios mais fortemente correlacionados com a QVF total foram "interação familiar" (r = 0,870; p < 0,001) e "cuidado dos pais com os filhos" (r = 0,845; p < 0,001). Não houve diferenças na distribuição da QVF em relação às variáveis sociodemográficas investigadas. Observou-se correlação moderada (r = 0,326) e significativa (p = 0,021) entre o índice de funcionalidade de Lawton & Brody e a QVF. O modelo de regressão linear ajustado explicou 10,6% da variabilidade encontrada na QVF (p = 0,021) e mostrou que o aumento de uma unidade no valor do índice de Lawton & Brody representou aumento de 0,092 na QVF. Conclusão A QVF das famílias investigadas encontra-se aquém de outras amostras internacionais. Ações clínicas que fortaleçam o diálogo e a coesão familiar e a construção de um plano terapêutico individualizado podem ser meios efetivos de ajuda a essas famílias.

ABSTRACT Objective To investigate the family quality of life (FQoL) among Brazilian families who have children with moderate intellectual disability (ID). Methods A cross-sectional study was carried out with 50 families who have children with moderate DI from São Carlos, São Paulo, Brazil. Data were collected by questionnaires including sociodemographic information, Barthel and Lawton & Brody functional indexes, and the Beach Center Family Quality of Life Scale. Results The domains "family interaction" (r = 0.870; p < 0.001) and "parenting" (r = 0.845; p < 0.001) were more strongly correlated with the total FQoL. There were no differences in the distribution of FQoL according to the sociodemographic variables investigated. A moderate (r = 0.326) and significant (p = 0.021) correlation was observed between the Lawton and Brody functional index and the FQoL. The adjusted linear regression model explained 10.6% of the variability found in the FQoL (p = 0.021) and showed that the increase of one point in the Lawton and Brody index represented an increase of 0.092 in the FQoL. Conclusion The FQoL of the families investigated is below other international samples. Clinical actions that strengthen dialogue and family cohesion, and the construction of an individualized therapeutic plan can be effective ways to help these families.

Strategies to minimize medication errors in emergency units: an integrative review / Estrategias para minimizar los errores de medicación en unidades de emergencia: una revisión integrativa / Estratégias para minimizar erros de medicação em unidades de emergência: revisão integrativa

ABSTRACT Objective: To assess the strategies used by the Nursing team to minimize medication errors in emergency units. Method: Integrative literature review in the PubMed, BDenf, Cochrane and LILACS databases. Timeless research, without language limitation, performed by peers. Articles published in full that answered the guiding question were included in research. Results: Educational strategies (conducting campaigns, elaborating explanatory manuals, creating a multidisciplinary committee involved in the prevention and reduction of adverse drug events); organizational (meetings, Deviance positive, creation of protocols and changes in the work process) and new technologies (implementation of prescription by computerized system, introduction of the unit doses and of the bar code in the administration of medicines) were evidenced in the studies with the purpose of minimizing medication errors in an emergency unit. Conclusion: The strategies identified were effective in minimizing medication errors in emergency units.

RESUMEN Objetivo: Evaluar las estrategias utilizadas por el equipo de Enfermería para minimizar los errores de medicación en las unidades de emergencia. Método: Revisión integrativa de la literatura realizada en las bases de datos PubMed, BDenf, Cochrane y LILACS. Búsqueda atemporal, sin limitación de idioma, realizada por pares. Se incluyeron en esta investigación artículos publicados en su totalidad que respondieran a la pregunta orientadora. Resultados: Las estrategias educativas (realización de campañas, elaboración de manuales explicativos, creación de una comisión multidisciplinaria involucrada con la prevención y la reducción de los eventos adversos a los medicamentos); organizacionales (reuniones, Deviance positive, creación de protocolos y cambios en el proceso de trabajo) y nuevas tecnologías (la aplicación de prescripciones por un sistema informatizado, la implantación de la dosis unitaria y el código de barras en la administración de medicamentos) fueron evidenciadas en los estudios con la finalidad de minimizar los errores de medicación en la unidad de emergencia. Conclusión: Las estrategias identificadas se mostraron eficaces para minimizar los errores de medicación en las unidades de emergencia.

RESUMO Objetivo: Avaliar as estratégias utilizadas pela equipe de Enfermagem para minimizar os erros de medicação nas unidades de emergência. Método: Revisão integrativa da literatura realizada nas bases de dados PubMed, BDenf, Cochrane e LILACS. Pesquisa atemporal, sem limitação de idioma, realizada por pares. Foram incluídos nesta pesquisa artigos publicados na íntegra que respondessem à pergunta norteadora. Resultados: As estratégias educacionais (realização de campanhas, elaboração de manuais explicativos, criação de comissão multidisciplinar envolvida com a prevenção e redução dos eventos adversos aos medicamentos); organizacionais (reuniões, Deviance positive, criação de protocolos e mudanças no processo de trabalho) e novas tecnologias (implementação de prescrição por sistema informatizado, implantação da dose unitária e do código de barras na administração de medicamentos) foram evidenciadas nos estudos com a finalidade de minimizar os erros de medicação em unidade de emergência. Conclusão: As estratégias identificadas mostraram-se eficazes para minimizar erros de medicação nas unidades de emergência.

Emergence of aph(3')-VI and accumulation of aminoglycoside modifying enzyme genes in KPC-2-possessing Enterobacter aerogenes isolates from infections and colonization in patients from Recife-PE, Brazil

Abstract INTRODUCTION: The objective of this study was to characterize genes of aminoglycoside modifying enzymes (AMEs) in colonizing and infecting isolates of E. aerogenes harboring bla KPC from patients at a public hospital in Recife-PE, Brazil. METHODS: We analyzed 29 E. aerogenes clinical isolates resistant to aminoglycosides. AMEs genes were investigated by PCR and sequencing. RESULTS: Colonizing and infecting isolates mainly presented the genetic profiles aac(3)-IIa/aph(3')-VI or ant(2")-IIa/aph(3')-VI. This is the first report of aph(3')-VI in E. aerogenes harboring bla KPC in Brazil. CONCLUSIONS: The results highlight the importance in establishing rigorous methods for the surveillance of resistance genes, especially in colonized patients.

Emergence of bla NDM-1 associated with the aac(6')-Ib-cr, acrB, cps, and mrkD genes in a clinical isolate of multi-drug resistant Klebsiella pneumoniae from Recife-PE, Brazil

Abstract INTRODUCTION: The emergence of New Delhi metallo-β-lactamase (NDM) is concernig because it reduces the antibiotic therapy options for bacterial infections. METHODS: Resistant and virulent genes from an isolate of Klebsiella pneumoniae derived from a patient with sepsis in a hospital in Recife-PE, Brazil, were investigated using PCR and DNA sequencing. RESULTS: bla NDM-1, aac(6')-Ib-cr and acrB resistance genes, and cps and mrkD virulence genes were detected. CONCLUSIONS To our knowledge, this is the first report on bla NDM-1 in Recife-PE. This detection alerts researchers to the need to control the spread of bla NDM-1 resistance gene by this bacterium in Brazil.

Impacto de uma capacitação para enfermeiros acerca da assistência no pós-operatório de cirurgia cardiáca / The impact of nurse training in cardiac surgery postoperative care / Impacto de una capacitación para enfermeros acerca de la asistencia en el postoperatorio de cirugía cardíaca

Objetivo: Avaliar o impacto de um programa de capacitação teórica para enfermeiros acerca dos cuidados ao paciente no pós-operatório de cirurgia cardíaca. Método: Estudo descritivo, quantitativo, realizado em um hospital filantrópico do interior do estado de São Paulo, dividido em três etapas: aplicação do instrumento de pré-teste, capacitação expositiva dialogada e aplicação do instrumento de pós-teste. Resultados: Participaram da pesquisa 47 enfermeiros, a maioria do sexo feminino, com experiência de 1 a 3 anos na enfermagem, e somente 4 enfermeiros com experiência em cirurgia cardíaca. Verificou-se aumento significativo no número de acertos na avaliação após a capacitação, no pós-teste em relação ao pré-teste. Conclusão: Foi evidenciada a necessidade de formação continuada para os enfermeiros atuantes no pós-operatório de cirurgias cardíacas. O programa de capacitação teórica para os enfermeiros se mostrou significante, porém limitado, no que tange ao processo ensino aprendizagem.

Objective: To evaluate the impact of a theoretical training program for nurses in care for postoperative cardiac surgery patients. Method: Descriptive, quantitative study, conducted at a philanthropic hospital in the countryside of the state of São Paulo, and divided into three stages: application of a pre-test, training with active participation, and application of a post-test. Results: A total of 47 nurses participated in the study, most of them females, with 1 to 3 years of experience in nursing, and only 4 of them had experience in cardiac surgery. We observed a significant increase in the number of right answers on the test after the training program, in comparison with the pre-test. Conclusion: The study demonstrated the need for continuing education for nurses working in postoperative of cardiac surgeries. The theoretical training program for nurses proved to be significant but limited in terms of teaching-learning process.

Objetivo: Evaluar el impacto de un programa de capacitación teórica para enfermeros acerca de los cuidados al paciente en el postoperatorio de cirugía cardiaca. Método: Estudio descriptivo, cuantitativo, cumplido en un hospital filantrópico del interior del estado de São Paulo, dividido en tres etapas: aplicación del instrumento de pre-prueba, capacitación expositiva dialogada y aplicación del instrumento de post-prueba. Resultados: Participaron de la investigación 47 enfermeros, la mayoría del sexo femenino, con experiencia de 1 a 3 años en la enfermería, y solamente 4 enfermeros con experiencia en cirugía cardiaca. Se encontró un aumento significativo en el número de aciertos en la evaluación después de la capacitación, en el post-prueba en relación a la pre-prueba. Conclusión: Se ha evidenciado la necesidad de formación continuada para los enfermeros actuante en el postoperatorio de cirugías cardíacas. El programa de capacitación teórica para los enfermeros se mostró significante, pero limitado, en lo que se refiere al proceso enseñanza-aprendizaje.

Functional investigation of bone implant viability using radiotracers in a new model of osteonecrosis

OBJECTIVES: Conventional imaging methods are excellent for the morphological characterization of the consequences of osteonecrosis; however, only specialized techniques have been considered useful for obtaining functional information. To explore the affinity of radiotracers for severely devascularized bone, a new mouse model of isolated femur implanted in a subcutaneous abdominal pocket was devised. To maintain animal mobility and longevity, the femur was harvested from syngeneic donors. Two technetium-99m-labeled tracers targeting angiogenesis and bone matrix were selected. METHODS: Medronic acid and a homodimer peptide conjugated with RGDfK were radiolabeled with technetium-99m, and biodistribution was evaluated in Swiss mice. The grafted and control femurs were evaluated after 15, 30 and 60 days, including computed tomography (CT) and histological analysis. RESULTS: Radiolabeling achieved high (>95%) radiochemical purity. The biodistribution confirmed good blood clearance 1 hour after administration. For 99mTc-hydrazinonicotinic acid (HYNIC)-E-[c(RGDfK)2, remarkable renal excretion was observed compared to 99mTc-methylene diphosphonate (MDP), but the latter, as expected, revealed higher bone uptake. The results obtained in the control femur were equal at all time points. In the implanted femur, 99mTc-HYNIC-E-[c(RGDfK)2 uptake was highest after 15 days, consistent with early angiogenesis. Regarding 99mTc-MDP in the implant, similar uptake was documented at all time points, consistent with sustained bone viability; however, the uptake was lower than that detected in the control femur, as confirmed by histology. CONCLUSIONS: 1) Graft viability was successfully diagnosed using radiotracers in severely ischemic bone at all time points. 2) Analogously, indirect information about angiogenesis could be gathered using 999mTc-HYNIC-E-[c(RGDfK)2. 3) These techniques appear promising and warrant further studies to determine their potential clinical applications.

A utilização da progesterona natural micronizada em gestações gemelares na prevenção do trabalho de parto prematuro / Use of natural micronized progesterone in the prevention of preterm labor in twin pregnancies

Com o objetivo de determinar a eficácia da progesterona natural micronizada em gestações gemelares para a profilaxia do trabalho de parto prematuro, foi avaliada uma coorte histórica de 43 mulheres com gestações gemelares. As gestantes foram divididas em dois grupos: usuárias da progesterona (Grupo 1) e não usuárias da progesterona (Grupo 2). O medicamento foi administrado na dosagem de 200 mcg por via vaginal, a partir de 20 semanas de gestação. Das 43 gestações estudadas, 20 foram tratadas com a progesterona. Não houve associação entre uso da progesterona e época do parto, de forma que o uso da progesterona natural micronizada não impediu o parto prematuro (p = 0,87). Portanto, a progesterona natural micronizada não reduziu a frequência do trabalho de parto prematuro em gestações gemelares...

A historical cohort of 43 women with twin pregnancies were assessed to determine the effectiveness of natural micronized progesterone in twin pregnancies for the prophylaxis of preterm labor. The women were divided into two groups: progesterone users (Group 1) and non-users of progesterone (Group 2). The drug was administered at a dose of 200 mcg vaginally, from 20 weeks of gestation. Of the 43 pregnancies studied, 20 were treated with progesterone. There was no association between use of progesterone and delivery time, so that the use of natural micronized progesterone did not prevent preterm birth (p = 0.87). Therefore, natural micronized progesterone did not reduce the frequency of preterm birth in twin pregnancies...

Relação entre o nível de atividade física e a incidência da síndrome pré-menstrual / Relationship between the level of physical activity and premenstrual syndrome incidence

OBJETIVO: Verificar a relação entre o nível de atividade física e a incidência da síndrome pré-menstrual. MÉTODOS: Trata-se de um estudo transversal realizado com 71 universitárias aparentemente saudáveis (24,4±4,8 anos; 61,5±8,7 kg; 1,63±0,06 m). O nível de atividade física foi mensurado através de questionário, e a síndrome pré-menstrual foi verificada através de um diário de sintomas respondido durante dois ciclos menstruais consecutivos. No diário são considerados 17 sintomas, os quais deveriam ser pontuados em uma escala de 5 pontos (0 a 4) de acordo com sua ocorrência, possibilitando assim o cálculo de um escore em cada ciclo. Foi considerada a ocorrência da síndrome pré-menstrual se três ou mais sintomas fossem relatados até seis dias antes da menstruação (fase pré-menstrual) e ausentes até seis dias após (fase pós-menstrual). RESULTADOS: A correlação de Spearman demonstrou uma relação significativa e negativa entre o nível de atividade física e o escore da síndrome pré-menstrual (r=-0,506; IC95% -0,335 a -0,678; p<0,001). Quando a amostra foi dividida em um grupo com diagnóstico positivo para síndrome pré-menstrual (n=31) e um grupo saudável (n=40), o teste de Mann-Whitney demonstrou que o grupo saudável possui um nível de atividade física habitual significativamente maior do que o grupo com síndrome pré-menstrual (7,96±1,17; 6,63±1,20 respectivamente) (p<0,001). CONCLUSÕES: Existe uma relação negativa entre o nível de atividade física habitual e a incidência da síndrome pré-menstrual, sendo que as mulheres com diagnóstico positivo para síndrome pré-menstrual possuem um nível de atividade física menor que as mulheres saudáveis.

PURPOSE: To determine the relationship between the level of physical activity and the incidence of premenstrual syndrome. METHODS: A cross-sectional design was conducted on 71 apparently healthy university students (24.4±4.8 yrs; 61.5±8.7 kg; 1.63±0.06 m). The level of physical activity was determined with a questionnaire and the presence of premenstrual syndrome was verified based on daily symptoms self-reported in a diary during two consecutive menstrual cycles. 17 premenstrual symptoms are considered in the diary, which should be scored on a 5-point scale (0-4) according to their occurrence, so that a score can be calculated in each cycle. The occurrence of premenstrual syndrome was considered if three or more symptoms were reported up to six days before menstruation (premenstrual period) and were absent up to six days after menstruation (postmenstrual period). RESULTS: The Spearman correlation coefficient showed a significant and negative relationship between the level of physical activity and premenstrual syndrome score (r=-0.506; 95%CI -0.335 to -0.678; p<0.001). When the participants were divided into a group with a positive diagnosis of premenstrual syndrome (n=31) and a healthy group (n=40), the Mann-Whitney test showed higher habitual physical activity in the healthy group than in the premenstrual syndrome group (7.96±1.17 and 6.63±1.20, respectively) (p<0.001). CONCLUSIONS: There is a negative relationship between the level of physical activity and the incidence of premenstrual syndrome, with women with a positive diagnosis of premenstrual syndrome having a lower level of physical activity than healthy women.

Diferenciação de células-tronco em hepatócitos e desenvolvimento de modelo pré-clínico de fibrose hepática para ensaios de terapia celular / Mesenchymal stem cell differentiation in hepatocytes and development of pre-clinic model of hepatic fibrosis for cellular therapy assays

Este trabalho teve como objetivo desenvolver um protocolo para a diferenciação in vitro de células-tronco mesenquimais (CTM) em hepatócitos e a padronização de um modelo animal de fibrose hepática induzida por dimetilnitrosamina (DMN) para ensaios pré-clínicos de transplante de CTM. CTM isoladas de fontes variadas apresentaram morfologia fibroblastóide e aderência ao plástico e o padrão de marcadores de superfície celular esperado na análise por citometria de fluxo. A capacidade de diferenciação osteogênica e adipogênica dessas células foi comprovada pelas colorações de vermelho de alizarina, oil red e azul de toluidina, respectivamente, confirmando, que as células isoladas para este estudo se comportaram como CTM conforme proposto pela Sociedade Internacional de Pesquisa em Células-tronco. A diferenciação hepática foi avaliada quanto à morfologia e capacidade das células diferenciadas de estocar glicogênio confirmada por PAS (ácido periódico-Schiff), de sintetizar albumina confirmada por imunofluorescência, além da capacidade de expressar genes hepato-específicos verificada por ensaios de PCR em tempo real. Com base na literatura para diferenciação hepática, diferentes protocolos de um, dois e três passos foram testados. CTM humanas mostraram capacidade de produzir e estocar glicogênio e de sintetizar albumina, apenas quando diferenciadas com protocolos de três etapas, porém sem uma expressão aumentada dos genes hepato-específicos albumina, α-fetoproteína e c-Met. Uma etapa de diferenciação endodérmica, previamente aplicada à diferenciação hepática, aumentou a capacidade de produzir e estocar glicogênio das CTM diferenciadas. Para a padronização do modelo de fibrose hepática induzida por DMN, foram realizados experimentos de dose-resposta e foi verificado o efeito da hepatectomia em modelos mistos DMN/hepatectomia. A injúria hepática e o efeito do transplante de CTM foram avaliados por análise macroscópica dos fígados, histologia das biópsias de fígados corados com HE e tricromo de Masson e parâmetros bioquímicos séricos. Alterações macroscópicas, histológicas e nos níveis séricos de fosfatase alcalina indicam a indução da fibrose hepática nos ratos Wistar tratados com DMN na dose de 10 µg/g de peso animal por três dias consecutivos durante quatro semanas, mas não observamos nenhum efeito induzido pela hepatectomia. Porém, este modelo com DMN se mostra semelhante a estágios iniciais de uma fibrose hepática. O transplante de 1 x 107 CTM de veia de cordão umbilical humano (VCUH) no modelo de injúria hepática induzida por DMN não resultou em melhora da fibrose, diminuição dos níveis séricos de fosfatase alcalina e nem em ganho de peso dos animais quando comparados aos animais tratados com PBSA após a injúria hepática (grupo placebo). Em conjunto, esses resultados sugerem que CTM humanas se diferenciam após tratamentos mais complexos, onde os indutores hepatogênicos são sequencialmente adicionados ao meio de modo a mimetizar a sinalização durante o desenvolvimento embrionário. O transplante de CTM de VCUH parece não ter efeito positivo em um modelo pré-clínico de injúria hepática similar a estágios iniciais de fibrose. Financiado por CNPq (573578/2008-7) e FAPESP (2007/54260-2)

This study aimed to develop an in vitro differentiation protocol of mesenchymal (MSC) stem cells to hepatocytes and to standardize an animal model for hepatic fibrosis induced by dimethylnitrosamine (DMN) for preclinical transplant assays of MSC. MSC isolated from various sources presented fibroblastoid morphology, plastic adherence, and the expected pattern of cell surface markers by flow cytometry analysis. The capacity of osteogenic, adipogenic and chondrogenic differentiation of these cells was confirmed by alizarin red, oil red and toluidine blue staining, respectively, confirming that the cells isolated for this study behave as MSC, as proposed by the International Society for Stem Cell Research. Hepatogenic differentiation was evaluated by analysis of cell morphology, capacity to store glycogen confirmed by PAS (periodic acid-Schiff), albumin synthesis confirmed by immunofluorescence, as well as hepatic-specific gene expression verified by real time PCR assays. Based on the published literature on hepatic differentiation, several protocols of one, two, and three steps were tested. Human MSC differentiated solely when treated in a three step-protocol, showing the ability to produce and store glycogen and synthesize albumin; however the expression of hepatic-specific genes such as albumin, α-fetoprotein and c-Met was not increased. An endoderm differentiation stage, added to the hepatic differentiation protocol, increased the capacity to produce and store glycogen of differentiated MSC. In order to standardize the model of liver fibrosis induced by DMN, dose-response experiments were performed and the effect of hepatectomy in mixed models DMN/hepatectomy was observed. Severity of liver injury and the effect of cell transplantation were evaluated by macroscopic analysis of the livers, histology of liver biopsies stained with HE and Masson's trichrome, and evaluation of serum biochemical parameters. The macroscopic and histological observations, and altered alkaline phosphatase serum levels indicated the success in inducing liver fibrosis in DMN-treated rats at a dose of 10 µg/g of animal weight for three consecutive days, during four weeks, without any additional effect upon hepatectomy. Transplanting 1 x 107 umbilical cord MSC in the model of liver injury induced by DMN did not result in improvement of the fibrosis, decrease of alkaline phosphatase serum levels, or in weight gain of the treated animals compared to animals treated with PBSA after liver injury (placebo group). Together, these results suggest that human MSC are capable of differentiating to hepatocyte-like cells after more complex protocols, where hepatogenic inducers are sequentially added to the medium in order to mimic signaling that occurs during fetal development. Transplantation of undifferentiated umbilical cord MSC did not have any positive effect in a preclinical liver injury model characterized by an early stage of fibrosis. Supported by CNPq (573578/2008-7) and FAPESP (2007/54260-2)

Comparison of two peptide radiotracers for prostate carcinoma targeting

OBJECTIVES: Scintigraphy is generally not the first choice treatment for prostate cancer, although successful studies using bombesin analog radiopeptides have been performed. Recently, a novel peptide obtained using a phage display library demonstrated an affinity for prostate tumor cells. The aim of this study was to compare the use of a bombesin analog to that of a phage display library peptide (DUP-1) radiolabeled with technetium-99m for the treatment of prostate carcinoma. The peptides were first conjugated to S-acetyl-MAG3 with a 6-carbon spacer, namely aminohexanoic acid. METHODS: The technetium-99m labeling required a sodium tartrate buffer. Radiochemical evaluation was performed using ITLC and was confirmed by high-performance liquid chromatography. The coefficient partition was determined, and in vitro studies were performed using human prostate tumor cells. Biodistribution was evaluated in healthy animals at various time points and also in mice bearing tumors. RESULTS: The radiochemical purity of both radiotracers was greater than 95 percent. The DUP-1 tracer was more hydrophilic (log P = -2.41) than the bombesin tracer (log P = -0.39). The biodistribution evaluation confirmed this hydrophilicity by revealing the greater kidney uptake of DUP-1. The bombesin concentration in the pancreas was greater than that of DUP-1 due to specific gastrin-releasing peptide receptors. Bombesin internalization occurred for 78.32 percent of the total binding in tumor cells. The DUP-1 tracer showed very low binding to tumor cells during the in vitro evaluation, although tumor uptake for both tracers was similar. The tumors were primarily blocked by DUP1 and the bombesin radiotracer primarily targeted the pancreas. CONCLUSION: Further studies with the radiolabeled DUP-1 peptide are recommended. With further structural changes, this molecule could become an efficient alternative tracer for prostate tumor diagnosis.

Weight-adjusted neonatal 17OH-progesterone cutoff levels improve the efficiency of newborn screening for congenital adrenal hyperplasia / Determinação de pontos de corte para 17OH-progesterona de acordo com o peso ao nascimento melhora a eficiência da triagem neonatal da hiperplasia adrenal congênita

OBJECTIVE: To evaluate weight-adjusted strategy for levels of neonatal-17OHP in order to improve newborn screening (NBS) efficiency. SUBJECTS AND METHODS: Blood samples collected between 2-7 days of age from 67,640 newborns were evaluated. When N17OHP levels were > 20 ng/mL, and a second sample was requested. We retrospectively analyzed neonatal-17OHP levels measured by Auto DELFIA- B024-112 assay, grouped according to birth-weight: G1: < 1,500 g, G2: 1,501-2,000 g, G3: 2,000-2,500 g and G4: > 2,500 g. 17OHP cutoff values were determined for each group using the 97.5th, 99th, 99.5th and 99.8th percentiles. RESULTS: 0.5 percent of newborns presented false-positive results using the cutoff level > 20 ng/mL for all groups. Neonates of low birthweight made up 69 percent of this group. Seven full-term newborns presented congenital adrenal hyperplasia (CAH) and, except for one of them, 17OHP levels were > 120 ng/mL. Only the 99.8th percentile presented higher predictive positive value (2 percent), and lower rate of false-positives in all groups. CONCLUSIONS: We suggest the use of 99.8th percentile obtained by weight-adjusted N17OHP values of healthy newborns to reduce the rate of false-positive results in NBS.

OBJETIVO: Avaliamos retrospectivamente os valores da 17OHP ajustados para o peso ao nascimento para melhorar a eficiência da triagem neonatal. SUJEITOS E MÉTODOS: 67.640 recém-nascidos com amostras coletadas entre 2-7 dias de vida. Uma segunda amostra foi solicitada na presença de testes com valores da 17OHP > 20 ng/mL. 17OHP dosada pelo método DELFIA- B024-112 e correlacionada com o peso ao nascimento: G1 < 1.500 g, G2 1.501-2.000 g, G3 2.000-2.500 g e G4 > 2.500 g. Pontos de corte da 17OHP foram determinados para cada grupo usando os percentis 97,5th, 99th, 99,5th e 99,8th. RESULTADOS: Falso-positivos ocorreram em 5 por cento dos resultados com o ponto de corte > 20 ng/mL, dos quais 69 por cento eram prematuros. Sete recém-nascidos apresentaram deficiência da 21-hidroxilase e, exceto em um, os valores da 17OHP foram > 120 ng/mL. Somente o valor da 17OHP do 99,8th apresentou maior valor preditivo positivo (2 por cento) e menor índice de falso-positivos. CONCLUSÕES: Sugerimos o valor da 17OHP do 99,8th ajustado para o peso ao nascimento para se reduzir a taxa de resultados falso-positivos da triagem neonatal.

Neovascularization after ischemic injury: evaluation with 99mTc-HYNIC-RGD / Neovascularização após lesão isquêmica: avaliação com 99mTc-HYNIC-RGD

Purpose: Angiogenesis involves many mediators including integrins, and the tripeptide RGD is a target amino acid recognition sequence for many of them. Hindlimb ischemia is a simple and convenient animal model however standardization of the injection procedures in the devascularized and control limb is lacking, thus rendering difficult the interpretation of results. The aim of this investigations was to evaluate neovascularization in a hindlimb murine model by means of 99mTc-HYNIC-ß-Ala-RGD. Methods: 99mTc-HYNIC-RGD analog was prepared using coligands. Ischemia was induced in Wistar rats by double- ligation of the common femoral artery. Radiolabeled RGD was injected after 2h, as well as 1, 3, 5, 7, 10 and 14 days. Uptake was evaluated by planar imaging and biodistribution studies. Results: The highest ratio between ischemia and control was achieved at the 7th day (2.62 ± 0.95), with substantial decrease by the 14th day. For pertechnetate the 7th day ratio was 0.87 ± 0.23. Scintigraphic image confirmed different uptakes. Conclusion: 99mTc-HYNIC-RGD analog concentrated in ischemic tissue by the time of widespread angiogenesis and pertechnetate confirmed reduction in blood flow. In this sense, the protocol can be recommended for ischemic models.

Objetivo: A angiogênese em resposta a fenômenos isquêmicos envolve vários mediadores como as integrinas, sendo que o tripeptídeo RGD possui uma seqüência de aminoácidos com reconhecimento para este alvo. O modelo animal de isquemia de pata traseira é simples e conveniente, porém não há uma padronização do procedimento de injeção e controle radioisotópico em membro desvascularizado, dificultando, portanto a interpretação de resultados. O objetivo deste estudo foi avaliar a neovascularização em modelo murino de isquemia de pata traseira através do radiotraçador 99mTc-HYNIC-ß-Ala-RGD. Métodos: O análogo 99mTc-HYNIC-RGD foi preparado usando coligantes. A isquemia foi induzida em ratos Wistar por dupla-ligação da artéria femoral comum na prega inguinal. Peptídeo RGD radiomarcado foi injetado após 2h, assim como 1, 3, 5, 7, 10 e 14 dias. A captação foi avaliada por imagem planar e estudos de biodistribuição. Resultados: A maior diferença de captação entre isquemia e pata controle foi obtida no 7º dia (2,62 ± 0,95), com decréscimo acentuado no 14º dia. Para o pertecnetato a razão no 7º dia foi 0,87 ± 0,23. A imagem cintilográfica confirmou as diferentes captações. Conclusões: O análogo 99mTc-HYNIC-RGD concentrou-se no tecido isquêmico na etapa em que a angiogênese é mais acentuada, e o estudo do pertecnetato confirmou a redução no fluxo sanguíneo. Desta maneira, este protocolo diagnóstico pode ser recomendado para modelos isquêmicos.

Pré-eclâmpsia precoce e tardia: uma classificação mais adequada para o prognóstico materno e perinatal? / Early-onset preeclampsia: is it a better classification for maternal and perinatal outcomes?

OBJETIVO: avaliar as diferenças entre o resultado materno e perinatal de gestações complicadas pela pré-eclâmpsia, segundo classificação em sua forma grave/leve e de início precoce/tardio. MÉTODOS: estudo retrospectivo envolvendo 211 gestações complicadas pela pré-eclâmpsia, avaliadas em centro universitário de referência, no período de 2000 a 2010. O diagnóstico e a gravidade da doença foram baseados nos valores da pressão arterial, proteinúria e nos achados clínicos e laboratoriais. A idade da gestante, cor da pele, paridade, pressão arterial, valores de proteinúria semiquantitativa, presença de incisura bilateral em artérias uterinas à doplervelocimetria e as condições de nascimento foram comparados entre os casos de forma leve/grave, assim como entre aqueles de surgimento precoce/tardio. A doença foi considerada precoce quando diagnosticada antes da 34ª semana. RESULTADOS: a maioria das gestantes apresentava a forma grave da pré-eclâmpsia (82,8 por cento) e 50,7 por cento, de início precoce. Os valores da pressão arterial (133,6±14,8 versus 115,4 mmHg, p=0,0004, e 132,2±16,5 versus 125,7 mmHg, p=0,0004) e proteinúria semiquantitativa (p=0,0003 e p=0,0005) foram mais elevados nas formas grave e precoce em relação às formas leve e tardia. O peso ao nascimento (1.435,4±521,6 versus 2.710±605,0 g, 1.923,7±807,9 versus 2.415,0±925,0 g, p<0,0001 para ambos) e o índice de Apgar (p=0,01 para ambos) foram menores nas formas grave e precoce da pré-eclâmpsia, em relação às formas leve e tardia. Por outro lado, a presença de incisura bilateral em artérias uterinas se associou às formas de início precoce (69,2 versus 47,9 por cento, p=0,02), enquanto a restrição de crescimento fetal foi mais frequente nas formas graves da pré-eclâmpsia (30 versus 4,4 por cento, p=0,008). CONCLUSÃO: a classificação da pré-eclâmpsia baseada em parâmetros clínicos maternos refletiu melhor as condições de nutrição fetal, enquanto o seu surgimento precoce se associou melhor à vasculopatia placentária detectada à doplervelocimetria.

PURPOSE: to evaluate the differences between the maternal and perinatal outcomes of pregnancies complicated by preeclampsia, according to the classification as the severe/mild form, and the early/late onset form. METHODS: a retrospective study with 211 pregnancies complicated by preeclampsia, assessed at a university reference center from 2000 to 2010. The diagnosis and disease severity were based on the values of blood pressure, proteinuria, and clinical and laboratory findings. The pregnant's age, skin color, parity, blood pressure, urine protein semiquantitative values, presence of bilateral notch in the uterine artery dopplervelocimetry and birth conditions were compared between patients with mild and severe disease, as well as between those of early/late onset. The disease was considered to be of early onset when diagnosed at less than 34 weeks of gestational age. RESULTS: most patients had the severe form of preeclampsia (82.8 percent), and the onset of the condition was early in 50.7 percent. Blood pressure values (133.6±14.8 versus 115.4 mmHg, p=0.0004 and 132.2±16.5 versus 125.7 mmHg, p=0.0004) and semiquantitative proteinuria (p=0.0003 and p=0.0005) were higher in the early and severe forms compared to mild and late forms. Infant birth weight (1,435.4±521.6 versus 2,710±605.0 g, 1,923.7±807.9 versus 2,415.0±925.0 g, p<0.0001 for both) and Apgar score (p=0.01 for both) were smaller for severe and early preeclampsia compared to mild and late preeclampsia. On the other hand, the presence of a bilateral notch in the uterine arteries was linked to the forms of early onset (69.2 versus 47.9 percent, p=0.02), whereas fetal growth restriction was more frequent in the severe forms of preeclampsia (30 versus 4.4 percent, p=0.008). CONCLUSION: the preeclampsia classification based on maternal clinical parameters better reflected the conditions of fetal nutrition, while the early onset of the condition was associated with placental vasculopathy detected by dopplervelocimetry.