Reactive oxygen species impair Na+ transport and renal components of the renin-angiotensin-aldosterone system after paraquat poisoning.

Paraquat (1,1'-dimethyl-4,4'-bipyridyl dichloride) is an herbicide widely used worldwide and officially banned in Brazil in 2020. Kidney lesions frequently occur, leading to acute kidney injury (AKI) due to exacerbated reactive O2 species (ROS) production. However, the consequences of ROS exposure on ionic transport and the regulator local renin-angiotensin-aldosterone system (RAAS) still need to be elucidated at a molecular level. This study evaluated how ROS acutely influences Na+-transporting ATPases and the renal RAAS. Adult male Wistar rats received paraquat (20 mg/kg; ip). After 24 h, we observed body weight loss and elevation of urinary flow and serum creatinine. In the renal cortex, paraquat increased ROS levels, NADPH oxidase and (Na++K+)ATPase activities, angiotensin II-type 1 receptors, tumor necrosis factor-α (TNF-α), and interleukin-6. In the medulla, paraquat increased ROS levels and NADPH oxidase activity but inhibited (Na++K+)ATPase. Paraquat induced opposite effects on the ouabain-resistant Na+-ATPase in the cortex (decrease) and medulla (increase). These alterations, except for increased serum creatinine and renal levels of TNF-α and interleukin-6, were prevented by 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (tempol; 1 mmol/L in drinking water), a stable antioxidant. In summary, after paraquat poisoning, ROS production culminated with impaired medullary function, urinary fluid loss, and disruption of Na+-transporting ATPases and angiotensin II signaling.

Demographic, social, and clinical aspects associated with access to COVID-19 health care in Pará province, Brazilian Amazon.

Internal social disparities in the Brazilian Amazon became more evident during the COVID-19 pandemic. The aim of this work was to examine the demographic, social and clinical factors associated with access to COVID-19 health care in Pará Province in the Brazilian Amazon. This was an observational, cross-sectional, analytical study using a quantitative method through an online survey conducted from May to August 2023. People were eligible to participate if they were current residents of Pará, 18-years-old or older, with self-reported diagnoses of COVID-19 through rapid or laboratory tests. Participants completed an electronic survey was developed using Research Electronic Data Capture (REDCap) software-The adapted questionnaire "COVID-19 Global Clinical Platform: Case Report Form for Post-COVID Condition". Questions focused on access to COVID-19 treatment, demographic characteristics, COVID-19 vaccine and clinical characteristics. Respondent-driven sampling was applied to recruit participants. Multiple logistic regression was utilized to identify the associated factors. Overall, a total of 638 participants were included. The average age was 31.1 years. Access to COVID-19 health care was 68.65% (438/638). The participants most likely to access health care were those with moderate or severe COVID-19 (p = 0.000; OR: 19.8) and females (p = 0.001; OR: 1.99). Moreover, participants who used homemade tea or herbal medicines were less likely to receive health care for COVID-19 in health services (p = 0.002; OR: 0.54). Ensuring access to healthcare is important in a pandemic scenario.

Association between the number of altered late potential criteria and increased arrhythmic risk in Brugada syndrome patients.

BACKGROUND: Brugada syndrome (BrS) is associated with abnormal electrophysiological properties at right ventricular epicardium, consisting of fragmented electrograms extending well beyond QRS termination. We aimed to evaluate the utility of signal-averaged electrocardiogram (SA-ECG) for the noninvasive assessment of late potentials (LP) and risk stratification of BrS patients. METHODS: A prospective, observational, single-center study of BrS patients is submitted to SA-ECG with the determination of the total filtered QRS duration (fQRS), root mean square voltage of the 40 ms terminal portion of the QRS (RMS40), and duration of the low-amplitude electric potential component of the terminal portion of the QRS (LAS40). LP were considered positive when above standard cut-offs: fQRS > 114 ms, RMS40 < 20 µV, and LAS40 > 38 ms. The rates of malignant arrhythmic events (MAEs), defined as sudden death or appropriate shocks, were compared in relation to clinical characteristics and SA-ECG findings. RESULTS: A total of 106 BrS patients (mean age, 48 ± 12 years, 67.9% male) were studied, 49% with type-1 spontaneous pattern and 81% asymptomatic. During a median follow up of 4.7 years, 10 patients (7.1%) suffered MAEs, including 4 sudden deaths. The presence of LP was significantly associated with the arrhythmic risk, which increased with the number of altered LP criteria. In comparison to the patients who had none or 1 altered LP criterium, MAE risk was 4.7 times higher in those with 2 altered criteria and 9.4 times higher in those with 3 altered LP criteria. CONCLUSIONS: SA-ECG may be a useful tool for risk stratification in BrS. The presence of 2 or 3 abnormal LP criteria could identify a subset of asymptomatic patients at high risk of arrhythmic events.

Monocytes subpopulations pattern in the acute respiratory syndrome coronavirus 2 virus infection and after long COVID-19.

INTRODUTION AND OBJECTIVE: The present study sought to characterize the pattern of monocyte subpopulations in patients during the course of the infections caused by SARS-CoV-2 virus or who presented long COVID-19 syndrome compared to monocytes from patients with zika virus (Zika) or chikungunya virus (CHIKV). CASUISTRY: Study with 89 peripheral blood samples from patients, who underwent hemogram and serology (IgG and IgM) for detection of Zika (Control Group 1, n = 18) or CHIKV (Control Group 2, n = 9), and from patients who underwent hemogram and reverse transcription polymerase chain reaction for detection of SARS-CoV-2 at the acute phase of the disease (Group 3, n = 19); and of patients who presented long COVID-19 syndrome (Group 4, n = 43). The monocyte and subpopulations counts were performed by flow cytometry. RESULTS: No significant difference was observed in the total number of monocytes between the groups. The classical (CD14++CD16-) and intermediate (CD14+CD16+) monocytes counts were increased in patients with acute infection or with long COVID-19 syndrome. The monocytes subpopulations counts were lower in patients with infection Zika or CHIKV. CONCLUSION: Increase in the monocyte subpopulations in patients with acute infection or with long COVID-19 syndrome may be an important finding of differentiated from the infection Zika or CHIKV.

Análise dos Critérios Imunofenotípicos por Citometria de Fluxo para Definição das Doenças Linfoproliferativas Crônicas de Células B / Analysis of Immunophenotypic Criteria by Flow Cytometry to Define B-Cell Chronic Lymphoproliferative Diseases / Análisis de Criterios Inmunofenotípicos por Citometría de Flujo para Definir Enfermedades Linfoproliferativas Crónicas de Células B

Introdução: A citometria de fluxo é uma metodologia importante para o diagnóstico das doenças linfoproliferativas crônicas de células B (DLPCB), contudo, por vezes, o citometrista não encontra subsídios suficientes para a definição exata da entidade patológica envolvida. Objetivo: Analisar os laudos emitidos a pacientes com doenças linfoproliferativas crônicas (DLPC) atendidos em um laboratório particular de Belém-PA, segundo os critérios de classificação estabelecidos pelos estudos de Matutes et al. e Craig e Foon. Método: Estudo retrospectivo com laudos de pacientes que realizaram imunofenotipagem por citometria de fluxo para diagnóstico de DLPCB no período entre setembro de 2015 a dezembro de 2019. Resultados: Depois de aplicados os critérios de Matutes et al. e Craig e Foon para os laudos analisados, observou-se concordância em: 45,24% casos de leucemia linfoide crônica de células B/linfoma linfocítico de pequenas células B; 14,29% casos de linfoma folicular; 4,76% casos de leucemia de células pilosas; e 21,43% de casos definidos como "outras DLPCB não classificáveis por citometria de fluxo". Entretanto, o teste de hipóteses de Hotelling (p=0,0409) mostrou haver diferença estatística para a definição das DLPCB segundo os critérios aplicados. Conclusão: Os resultados ressaltam que, mesmo sendo a citometria de fluxo importante para a caracterização das DLPCB, por vezes, o citometrista necessita incluir no laudo a categoria "outras doenças linfoproliferativas crônicas de células B não classificadas por citometria de fluxo" para induzir o prescritor a solicitar mais exames complementares.

Introduction: Flow cytometry is an important methodology for the diagnosis of chronic B-cell lymphoproliferative diseases (CBCLPD), however, sometimes the cytometrist does not find sufficient elements for the exact definition of the pathological entity involved. Objective: To analyze the reports issued to patients with chronic lymphoproliferative diseases (CLPD) tested at a private laboratory in Belém-PA, according to the classification criteria established by the studies by Matutes et al. and Craig and Foon. Method: Retrospective study with reports of patients who underwent immunophenotyping by flow cytometry for the diagnosis of CBCLPD from September 2015 to December 2019. Results: After applying the criteria by Matutes et al. and Craig and Foon to the reports analyzed, agreement was reached for 45.24% of the cases of chronic b-cell lymphocytic leukemia/small B-cell lymphocytic lymphoma, 14.29% of the cases of follicular lymphoma, 4.76% of the cases of hairy cell leukemia and 21.43% of the cases defined as "other CBCLPDs not classifiable by flow cytometry". However, Hotelling's hypothesis test (p=0.0409) showed a statistical difference for the definition of CBCLPD according to the criteria adopted. Conclusion: The results emphasize that even though flow cytometry is important for the characterization of CBCLPD, sometimes the cytometrist needs to include the category "other chronic B-cell lymphoproliferative diseases not classified by flow cytometry" in the report to induce the prescriber to request additional complementary exams.

Introducción. La citometría de flujo es una metodología importante para el diagnóstico de enfermedades linfoproliferativas crónicas de células B (ELPCB), sin embargo, en ocasiones el citometrista no encuentra suficientes subsidios para la definición exacta de la entidad patológica involucrada. Objetivo: Analizar los informes emitidos a pacientes con enfermedades linfoproliferativas crónicas (ELPC) tratados en un laboratorio privado en Belém-PA, de acuerdo con los criterios de clasificación establecidos por los estudios de Matutes et al. y Craig y Foon. Método: Retrospectivo con relatos de pacientes que se sometieron a inmunofenotipificación por citometría de flujo para el diagnóstico de ELPC de septiembre de 2015 a diciembre de 2019. Resultados: Tras aplicar los criterios de Matutes et al. y Craig y Foon a los informes analizados, se observó concordancia en: 45,24% de los casos de leucemia linfocítica crónica de células B/linfoma linfocítico de células B pequeñas; 14,29% casos de linfoma folicular; 4,76% casos de leucemia de células peludas; y 21,43% de los casos definidos como "otros ELPCB no clasificables por citometría de flujo". Sin embargo, la prueba de hipótesis de Hotelling (p=0,0409) mostró diferencia estadística para la definición de ELPCB según los criterios aplicados. Conclusión: Nuestros resultados enfatizan que si bien la citometría de flujo es importante para la caracterización de ELPCB, en ocasiones el citometrista necesita incluir en el informe la categoría "otras enfermedades linfoproliferativas crónicas de células B no clasificadas por citometría de flujo" para inducir al prescriptor a solicitar más exámenes complementarios.

The discourse change in drugs users or addicts care: critical discourse analysis of a federal Act. / A mudança discursiva na assistência ao usuário ou dependente de drogas: análise de discurso crítica de uma lei federal.

Brazilian drug policies have undergone changes over time, bearing marks for each historical period and experienced sanitary-political interests. Nowadays, an anti-reformist character was perceived in changes concentrated on Law no. 13,840, of June 5, 2019. The aim of this study is to analyze the key elements of a normative document on drugs based on the Critical Discourse Analysis. We analyzed the Law no. 13,840 using Fairclough's method for three-dimensional analysis and then discussed it with Foucault's notions of Biopower and Biopolitics. We consider that the emphasis on involuntary hospitalization, therapeutic communities and abstinence opposes the Brazilian psychiatric reform movement. The development of oppressive care practices are hidden by the so-called ideological neutrality and scientific evidence.

No Brasil, as políticas sobre drogas passaram por modificações ao longo do tempo, carregando marcas de cada período histórico e interesse sanitário-político. Na atual conjuntura, por exemplo, há uma tendência de oposição aos ideais do movimento de reforma psiquiátrica. Nesse contexto, este artigo objetiva analisar os elementos-chave evidenciados a partir do estudo de um documento normativo sobre drogas, na perspectiva da análise de discurso crítica. Realizou-se a análise da Lei no 13.840, de 2019, conforme o modelo tridimensional de Fairclough, com discussão a partir dos conceitos de biopoder e biopolítica de Foucault. A ênfase no tratamento pautado pela internação involuntária, comunidade terapêutica e abstinência reproduz uma perspectiva asilar de tratamento. Observa-se, assim, a reprodução de concepções asilar, proibicionista e autoritária, justificadas sob um véu de neutralidade ideológica e evidências científicas, que corroboram a existência de um movimento antirreformista.

A mudança discursiva na assistência ao usuário ou dependente de drogas: análise de discurso crítica de uma lei federal / The discourse change in drugs users or addicts care: critical discourse analysis of a federal Act

Resumo No Brasil, as políticas sobre drogas passaram por modificações ao longo do tempo, carregando marcas de cada período histórico e interesse sanitário-político. Na atual conjuntura, por exemplo, há uma tendência de oposição aos ideais do movimento de reforma psiquiátrica. Nesse contexto, este artigo objetiva analisar os elementos-chave evidenciados a partir do estudo de um documento normativo sobre drogas, na perspectiva da análise de discurso crítica. Realizou-se a análise da Lei no 13.840, de 2019, conforme o modelo tridimensional de Fairclough, com discussão a partir dos conceitos de biopoder e biopolítica de Foucault. A ênfase no tratamento pautado pela internação involuntária, comunidade terapêutica e abstinência reproduz uma perspectiva asilar de tratamento. Observa-se, assim, a reprodução de concepções asilar, proibicionista e autoritária, justificadas sob um véu de neutralidade ideológica e evidências científicas, que corroboram a existência de um movimento antirreformista.

Abstract Brazilian drug policies have undergone changes over time, bearing marks for each historical period and experienced sanitary-political interests. Nowadays, an anti-reformist character was perceived in changes concentrated on Law no. 13,840, of June 5, 2019. The aim of this study is to analyze the key elements of a normative document on drugs based on the Critical Discourse Analysis. We analyzed the Law no. 13,840 using Fairclough's method for three-dimensional analysis and then discussed it with Foucault's notions of Biopower and Biopolitics. We consider that the emphasis on involuntary hospitalization, therapeutic communities and abstinence opposes the Brazilian psychiatric reform movement. The development of oppressive care practices are hidden by the so-called ideological neutrality and scientific evidence.

Morphological changes in leukocytes of acute SARS-CoV-2 infection patients, Amazon, Brazil / Alterações morfológicas em leucócitos de pacientes com infecção aguda por SARS-CoV-2, Amazônia, Brasil

Introduction: The pandemic for the new coronavirus (SARS-CoV-2) brought many uncertainties about which laboratory parameters would be most suitable during the evolution of COVID 19. Objectives: Correlate the results of the blood count (BC), the neutrophil/lymphocyte ratio (N/LR), the C-reactive protein (CRP) and morphological findings of individuals diagnosed with SARS-CoV-2 infection through Polymerase Chain Reaction in Real Time (RT-PCR) in a private laboratory in Belém, Pará, from March to September 2020. Materials and Methods: Retrospective study with 30 individuals, of both sexes, any age and clinical complaint, of home or hospital origin who underwent BC, CRP and RT-PCR for COVID 19 until the 8th day of infection. Morphological changes were analyzed after selecting the slides for these patients. Results: Sample composed of 15 men and 15 women, aged between 7 and 92 years. Of these 12/30 individuals were at home and 18/30 were hospitalized. The main complaints were fever, malaise, diarrhea and respiratory distress. The statistical study showed a direct dependency relationship between increases in N/LR, CRP and the need for hospitalization (p = 0.0005). Morphological analysis showed hyposegmented neutrophils with toxic granulations, vacuolated monocytes, and reactive lymphocytes with basophilic cytoplasm. Conclusion: Our results associate intermediate and elevated levels of N/LR with increased CRP and disease severity, however, unrelated to the morphological findings in neutrophils, lymphocytes and monocytes that were common to all patients diagnosed up to the 8th day of infection (AU)

Introdução: A pandemia pelo novo coronavírus (SARS-CoV-2) trouxe muitas incertezas sobre quais parâmetros laboratoriais seriam mais adequados durante a evolução da COVID 19. Objetivos: Correlacionar os resultados do hemograma (HGM), da relação neutrófilos/linfócitos (R N/L), da proteína C reativa (PCR) e dos achados morfológicos de indivíduos diagnosticados com infecção por SARS-CoV-2 através de Reação em Cadeia da Polimerase em Tempo Real (RT-PCR) em um laboratório particular de Belém, Pará, no período de março a setembro de 2020. Materiais e Métodos: Estudo retrospectivo com 30 indivíduos, de ambos os sexos, qualquer idade e queixa clínica, de origem domiciliar ou hospitalar que realizaram HGM, PCR e RT-PCR para COVID 19 até o 8o dia de infecção. As alterações morfológicas foram analisadas após a seleção das lâminas desses pacientes. Resultados:Amostra composta por 15 homens e 15 mulheres, com idades entre 7 e 92 anos. Desses, 12/30 indivíduos estavam em domicílio e 18/30 internados. As principais queixas foram febre, mal-estar geral, diarreia e desconforto respiratório. O estudo estatístico mostrou a existência de relação de dependência direta entre os aumentos da R N/L, PCR e necessidade de internação (p=0,0005). A análise morfológica mostrou neutrófilos hipossegmentados com granulações tóxicas, monócitos vacuolizados e linfócitos reativos com citoplasma basofílico. Conclusão: Nossos resultados associam os níveis intermediários e elevados da R N/L com o aumento de PCR e a gravidade da doença, porém, sem relação com os achados morfológicos em neutrófilos, linfócitos e monócitos que foram comuns a todos os pacientes diagnosticados até o 8o dia de infecção

The Impact of an Intensivist-Led Critical Care Transition Program.

OBJECTIVE: Evaluate the impact of a post-discharge critical care transition program (CTP) on intensive care unit (ICU) readmission, in-hospital mortality, and six-month survival. METHODS: This was a prospective observational, single-center study, with a before-after design, in a critical care department in a tertiary hospital in Northern Portugal. Critically ill patients with ICU stay > 48 h or intermediate care stay >72 h or tracheostomized patients were included in the program. Historic controls included critically ill patients admitted in the six months prior to program implementation. The follow-up visit included a medical evaluation by an intensivist and a meeting with the attending physician. The primary outcome was critical care department readmission. Secondary outcomes were mortality at hospital discharge, 28-day, and six-month mortality. The readmission rate was compared between groups. Multivariate analysis and Kaplan-Meyer survival analysis were used to evaluate survival benefits. RESULTS:  Between September 2020 and March 2021, 132 patients were included in the CTP. The Control group included 196 patients. The intensivist's assessment led to management change in 15.1% of patients. The CTP group had a non-significant lower readmission rate (0.8% vs. 4.1%; p=0.09). Multivariate analysis showed a benefit for the CTP regarding in-hospital, 28-day, and six-month mortality. Kaplan-Meyer survival analysis showed improved survival in the CTP group. CONCLUSIONS:  The CTP reduced, non-significantly, the readmission rate, and significantly improved in-hospital and six-month mortality. Further analyses are needed to improve inclusion criteria and better allocate human resources.

Morphological changes in leukocytes of acute SARS-CoV-2 infection patients, Amazon, Brazil / Alterações morfológicas em leucócitos de pacientes com infecção aguda por SARS-CoV-2, Amazônia, Brasil

RESUMO: Introdução: A pandemia pelo novo coronavírus (SARS-CoV-2) trouxe muitas incertezas sobre quais parâmetros laboratoriais seriam mais adequados durante a evolução da COVID 19. Objetivos: Correlacionar os resultados do hemograma (HGM), da relação neutrófilos/linfócitos (R N/L), da proteína C reativa (PCR) e dos achados morfológicos de indivíduos diagnosticados com infecção por SARS-CoV-2 através de Reação em Cadeia da Polimerase em Tempo Real (RT-PCR) em um laboratório particular de Belém, Pará, no período de março a setembro de 2020. Materiais e Métodos: Estudo retrospectivo com 30 indivíduos, de ambos os sexos, qualquer idade e queixa clínica, de origem domiciliar ou hospitalar que realizaram HGM, PCR e RT-PCR para COVID 19 até o 8o dia de infecção. As alterações morfológicas foram analisadas após a seleção das lâminas desses pacientes. Resultados:Amostra composta por 15 homens e 15 mulheres, com idades entre 7 e 92 anos. Desses, 12/30 indivíduos estavam em domicílio e 18/30 internados. As principais queixas foram febre, mal-estar geral, diarreia e desconforto respiratório. O estudo estatístico mostrou a existência de relação de dependência direta entre os aumentos da R N/L, PCR e necessidade de internação (p=0,0005). A análise morfológica mostrou neutrófilos hipossegmentados com granulações tóxicas, monócitos vacuolizados e linfócitos reativos com citoplasma basofílico. Conclusão: Nossos resultados associam os níveis intermediários e elevados da R N/L com o aumento de PCR e a gravidade da doença, porém, sem relação com os achados morfológicos em neutrófilos, linfócitos e monócitos que foram comuns a todos os pacientes diagnosticados até o 8o dia de infecção. (AU)

ABSTRACT: Morphological changes in leukocytes of acute SARS-CoV-2 infection patients, Amazon, BrazilORIGINAL ARTICLEIntroduction: The pandemic for the new coronavirus (SARS-CoV-2) brought many uncertainties about which laboratory parameters would be most suitable during the evolution of COVID 19. Objectives: Correlate the results of the blood count (BC), the neutrophil/lymphocyte ratio (N/LR), the C-reactive protein (CRP) and morphological findings of individuals diagnosed with SARS-CoV-2 infection through Polymerase Chain Reaction in Real Time (RT-PCR) in a private laboratory in Belém, Pará, from March to September 2020. Materials and Methods: Retrospective study with 30 individuals, of both sexes, any age and clinical complaint, of home or hospital origin who underwent BC, CRP and RT-PCR for COVID 19 until the 8th day of infection. Morphological changes were analyzed after selecting the slides for these patients. Results: Sample composed of 15 men and 15 women, aged between 7 and 92 years. Of these 12/30 individuals were at home and 18/30 were hospitalized. The main complaints were fever, malaise, diarrhea and respiratory distress. The statistical study showed a direct dependency relationship between increases in N/LR, CRP and the need for hospitalization (p = 0.0005). Morphological analysis showed hyposegmented neutrophils with toxic granulations, vacuolated monocytes, and reactive lymphocytes with basophilic cytoplasm. Conclusion: Our results associate intermediate and elevated levels of N/LR with increased CRP and disease severity, however, unrelated to the morphological findings in neutrophils, lymphocytes and monocytes that were common to all patients diagnosed up to the 8th day of infection. (AU)

The PALliative MUlticenter Study in Intensive Care (PalMuSIC). Results From a Multicenter Study Addressing Frailty and Palliative Care Interventions in Intensive Care Units in Portugal.

Objective: Frailty is a clinically recognizable state of increased vulnerability common in critical medicine. When underrecognized, it may lead to invasive treatments that do not serve the patients' best interest. Our aim was to evaluate the use of both palliative care consultation and invasive interventions in frail patients admitted to Intensive Care Units in Portugal. Methods: This was a prospective, observational study. All consecutive adult patients admitted for more than 24 h, over a 15-day period were enrolled. Twenty-three Portuguese Intensive Care Units were included. Informed consent was obtained from all patients or their surrogate. The doctor and nurse in charge calculated the Clinical Frailty Score as well as the reference family member Results: A total of 335 patients were included in the study (66% male). Mean age was 63.2 ± 16.8 and SAPS II score was 41.8 ± 17.4. Mean Clinical Frailty Score value was 3.5 ± 1.7. Frailty prevalence (mean score ≥ 5) was 20.9%. Frail patients were offered organ support therapy (64,3% invasive mechanical ventilation; 24,3% renal replacement therapy; 67,1% vasopressors) more often than non-frail patients. Nevertheless, limitation of therapeutic effort or a do not resuscitate order (p < 0.001) were more common in frail patients. Mortality rate by 6 months was higher among frail patients (50% vs. 32.3%, p < 0.001). Palliative Care was offered to only 15% of frail patients (3.9% overall). Conclusions: The authors suggest that palliative care should be universally consulted once frailty is identified in critical patients.

Validation of the mindray BC6000 hematology analyzer for erythroblast counting in peripheral blood / Validação do analisador hematológico Mindray BC6000 para a contagem de eritroblastos em sangue periférico

ABSTRACT Introduction Differential counting of erythroblasts in blood samples by hematology analyzers still has limitations. Technological advances in blood count equipment have proposed the fully automated counting of these cells, however, not without its validation. Objective Validate the automated count of erythroblasts in peripheral blood in the Mindray BC6000 hematology analyzer and verify the existence of correlation of the maturation stages of erythroblasts with the equipment's graphics. Material and Methods Prospective study with peripheral blood samples from the Clinical Pathology Laboratory Dr Paulo C. Azevedo, regardless of age and gender, to validate the erythroblast count in the Mindray BC6000 hematology analyzer compared to the manual method (gold standard), in the period of June 2019 to December 2020. Results Seventeen peripheral blood samples were analyzed from newborns (09/17 - 52.3%) and from patients older than 2 years (08/17 - 47.7%) who had more than 18% of erythroblasts after morphological analysis of the sample. Statistical analysis of erythroblast counts by the two methodologies showed that the Mindray BC6000 hematological counter has good reproducibility, precision and linearity. There was no correlation between the maturation stages of erythroblasts and the equipment graphics. Conclusion The proposed validation showed that the Mindray BC6000 hematological counter has good analytical performance for counting erythroblasts in peripheral blood. However, there is no correlation between the maturation stages of erythroblasts with the graphics generated by the equipment.

RESUMO Introdução A contagem diferencial de eritroblastos em amostras de sangue por analisadores de hematologia ainda apresenta limitações. Os avanços tecnológicos nos equipamentos de hemograma têm proposto a contagem totalmente automatizada dessas células, porém, não sem sua validação. Objetivo Validar a contagem automatizada de eritroblastos no sangue periférico no analisador hematológico Mindray BC6000 e verificar a existência de correlação dos estágios de maturação dos eritroblastos com os gráficos do equipamento. Material e Métodos Estudo prospectivo com amostras de sangue periférico do Laboratório de Patologia Clínica Dr. Paulo C. Azevedo, independente de idade e sexo, para validação da contagem de eritroblastos no analisador hematológico Mindray BC6000 em comparação ao método manual (padrão ouro), no período de junho de 2019 a dezembro de 2020. Resultados Foram analisadas 17 amostras de sangue periférico de recém-nascidos (17/09 - 52,3%) e de pacientes maiores de 2 anos (17/08 - 47,7%) que apresentavam mais de 18% de eritroblastos após análise morfológica da amostra. A análise estatística das contagens de eritroblastos pelas duas metodologias mostrou que o contador hematológico Mindray BC6000 tem boa reprodutibilidade, precisão e linearidade. Não houve correlação entre os estágios de maturação dos eritroblastos e os gráficos do equipamento. Conclusão A validação proposta mostrou que o contador hematológico Mindray BC6000 apresenta bom desempenho analítico para contagem de eritroblastos em sangue periférico. Porém, não há correlação entre os estágios de maturação dos eritroblastos com os gráficos gerados pelo equipamento.

NPCdc, a synthetic natriuretic peptide, is a substrate to neprilysin and enhances blood pressure-lowering induced by enalapril in 5/6 nephrectomized rats.

NPCdc is a natriuretic peptide synthesized from the amino acid sequence of the Crotalus durissus cascavella snake venom peptide, NP2Casca. NPCdc presents hypotensive and antioxidants effects. This study aimed to investigate in vivo whether angiotensin I-converting enzyme (ACE) inhibition would influence the impact of NPCdc in arterial pressure of rats submitted to 5/6 nephrectomy (Nx). Adult male Wistar rats following a 5/6 Nx were treated with enalapril (NxE group, 10 mg/kg/day, n = 9) or vehicle (Nx group, n = 8) for two weeks. On the 15th day after Nx, rats were anaesthetized and submitted to mean arterial pressure (MAP) determination before and after receiving two intravenous injections of saline (vehicle, n = 9) or NPCdc (0.3 µg/kg dissolved in saline, n = 18) separated by a 20-min interval. The kidneys were submitted to oxidative stress analysis. The basal MAP of the NxE group was nearly 20% lower (P < 0.05) than non-treated rats. NPCdc administration decreased the MAP in both groups; however, in the NxE group, the effects were observed only in the second injection. The peptide also decreased the NADPH oxidase activity in the renal cortex. Additionally, the hydrolysis of NPCdc by recombinant neprilysin (NEP) was monitored by mass spectrometry. NPCdc was cleaved by NEP at different peptides with an inhibition constant (Ki) of 1.5 µM, determined by a competitive assay using the NEP fluorescence resonance energy transfer (FRET) peptide substrate Abz-(d)Arg-Gly-Leu-EDDnp. Docking experiments confirmed the high affinity of NPCdc toward NEP. These findings provide new insights into the antihypertensive and antioxidant mechanism of action of NPCdc. Altogether, the results presented here suggest that NPCdc must be further studied as a potential therapy for cardiorenal syndromes.

Humanização no cuidado em saúde mental: compreensões dos enfermeiros / Humanization in mental health care: nurses' understandings / Humanización en la atención de la salud mental: comprensión de las enfermeras

OBJETIVO: conhecer as compreensões dos enfermeiros sobre humanização no cuidado em saúde mental. MÉTODO: trata-se de uma pesquisa exploratória, de abordagem qualitativa, realizada com 12 enfermeiros em um hospital psiquiátrico do interior do Nordeste, Brasil, no período de setembro de 2014 a março de 2015. Para a coleta de dados, utilizou-se entrevista semiestruturada, observação não participante e observação dos registros de Enfermagem, analisando-os a partir da Análise de Conteúdo de Bardin. RESULTADOS: emergiram quatro categorias: acolhimento, autonomia, protagonismo e corresponsabilidade. O cuidado humanizado aparece atrelado ao modelo manicomial, culminando em práticas focadas no uso da medicação, ações desarticuladas e sem participação do paciente no tratamento. A percepção da humanização é de dificuldade de atenção às pessoas em crises psíquicas, o que inviabiliza a produção do cuidado integral. CONCLUSÃO: o estudo contribui para a reflexão do cuidado de Enfermagem em saúde mental onde é preciso modificar as relações que o discurso biomédico mantém com os que buscam uma prática humanizada.

OBJECTIVE: to know nurses' understandings of humanization in mental health care. METHOD: it is an exploratory research, with a qualitative approach, carried out with 12 nurses in a psychiatric hospital in the interior of the Northeast, Brazil, from September 2014 to March 2015. For data collection, semi-structured interviews were used, non-participant observation and observation of Nursing records, analyzing them from Bardin's Content Analysis. RESULTS: four categories emerged: welcoming, autonomy, protagonism and co-responsibility. Humanized care appears linked to the asylum model, culminating in practices focused on the use of medication, disjointed actions and without patient participation in the treatment. The perception of humanization is of difficulty in caring for people in psychic crises, which makes the production of comprehensive care unfeasible. CONCLUSION:the study contributes to the reflection of nursing care in mental health where it is necessary to modify the relationships that biomedical discourse maintains with those who seek a humanized practice.

OBJETIVO: se objetivó conocer las comprensiones de los enfermeros sobre humanización en el cuidado en salud mental. MÉTODO: se trata de una investigación exploratoria de abordaje cualitativo realizada con 12 enfermeros en un hospital psiquiátrico del interior del Nordeste, Brasil, en el período de septiembre de 2014 a marzo de 2015. Para la recolección de datos se utilizó entrevista semiestructurada, observación no participante y observación de los registros de enfermería, analizados a partir del análisis de contenido de Bardin. RESULTADOS: se plantearon cuatro categorías: acogida, autonomía, protagonismo y corresponsabilidad. El cuidado humanizado aparece atado al modelo manicomial, culminando en prácticas enfocadas en el uso de la medicación, acciones desarticuladas y sin participación del paciente en el tratamiento. La percepción de la humanización es de dificultad de atención a las personas en crisis psíquicas que inviabiliza la producción del cuidado integral. CONCLUSIÓN: el estudio contribuye a la reflexión del cuidado de enfermería en salud mental donde, hay que modificar las relaciones que el discurso biomédico mantiene con los que buscan una práctica humanizada.

Renal ischemia-reperfusion leads to hypertension and changes in proximal tubule Na+ transport and renin-angiotensin-aldosterone system: Role of NADPH oxidase.

Acute renal injury (AKI) is a risk factor for the development of hypertension, which involves oxidative stress, changes in Na+ handling, and the intrarenal renin-angiotensin-aldosterone system (RAAS) as underlying mechanisms. We investigated in rats whether renal ischemia-reperfusion (IR) leads to changes in the proximal tubule ATP-dependent Na+ transport and the intrarenal content of RAAS components, as well as the role of NADPH oxidase. Rats weighing 300-350 g were submitted to AKI by bilateral IR (n = 25). After IR injury, the animals were followed up for 4 weeks. One part (n = 7) received daily treatment with the NADPH oxidase inhibitor apocynin (100 mg/kg, drinking water), while another part (n = 9) received apocynin 24 h before and after IR. One group was submitted to sham surgery (n = 8). Four weeks after IR, the rats presented elevated systolic blood pressure, as well as increased lipid peroxidation, NADPH oxidase activity, (Na++K+)ATPase activity, and upregulation of type 1 angiotensin II receptor in the renal cortex. On the other hand, there was a decrease in Na+-ATPase activity and downregulation of the isoforms 1 and 2 of the angiotensin-converting enzyme, type 2 angiotensin II receptor, and of the α and ε isoforms of protein kinase C. Most of these alterations was prevented by both apocynin treatment protocols. Thus, we conclude that AKI-induced by IR may induce changes in proximal tubule ATPases and RAAS components compatible with renal Na+ retention and hypertension. These data also indicate that the NADPH oxidase represents a key factor in the origin of these alterations.

Estudo Pioneiro sobre a Presença de Clone de Hemoglobinúria Paroxística Noturna durante Acompanhamento Terapêutico de Leucemia Aguda / Pioneering Study about the Presence of Paroxysmal Nocturnal Hemoglobinuria Clone during Therapeutic Monitoring of Acute Leukemia / Estudio Pionero sobre la Presencia de un Clon de Hemoglobinuria Paroxística Nocturna durante el Seguimiento Terapéutico de la Leucemia Aguda

Introdução: O potencial de transformação maligna de células-tronco hematopoiéticas portadoras de mutações no gene glicosilfostatidilinositolclasse A (PIG-A) para leucemias agudas, embora raro, já é bem descrito na literatura. Objetivo: Neste estudo, porém, buscou-se evidenciar pela primeira vez na literatura o surgimento ou a manutenção de clones de hemoglobinúria paroxística noturna (HPN) em pacientes diagnosticados com leucemia aguda ou ainda após o início do tratamento quimioterápico. Método: A pesquisa de clones de HPN foi realizada por citometria de fluxo em blastos, hemácias, granulócitos ou monócitos de 47 amostras de sangue periférico e medula óssea de pacientes submetidos à investigação diagnóstica ou acompanhamento terapêutico, provenientes de dois hospitais oncológicos e públicos de Belém, no período de dezembro de 2017 a dezembro de 2018. Resultados: A presença de clones de HPN foi observada em 19/47 (40,4%) amostras de pacientes, em investigação diagnóstica ou acompanhamento terapêutico, que realizaram pelo menos um estudo de acompanhamento terapêutico e ainda tiveram o surgimento ou a manutenção do clone de HPN mesmo após iniciado o tratamento quimioterápico. Conclusão: Foi possível evidenciar, de forma primária, a presença de clones de HPN em pacientes diagnosticados com leucemia aguda tanto no período de investigação diagnóstica como durante o acompanhamento terapêutico, independentemente da ontogenia celular. Sem, porém, que se possa ainda avaliar a importância da presença desses clones de HPN para a evolução da doença primária, prognóstico ou necessidade de tratamento específico.

Introduction: The potential for malignant transformation of hematopoietic stem cells carrying mutations in theglycosylphosphatidylinositol class A (PIG-A) gene for acute leukemias, although rare, is already well described in the literature. Objective: In this study, however, it was attempted to show for the first time in the literature the emergence or maintenance of paroxysmal nocturnal hemoglobinuria (PNH) clones in patients diagnosed with acute leukemia or even after the beginning of the chemotherapy treatment. Method: The search of PNH clones was performed by flow cytometry in blasts, erythrocytes, granulocytes or monocytes of 47 samples of peripheral blood and bone marrow from patients undergoing diagnostic investigation or therapeutic follow-up in two oncological and public hospitals in Belém, from December 2017 to December 2018. Results: The presence of PNH clones was observed in 19/47 (40.4%) patient samples, in diagnostic investigation or therapeutic follow-up, who participated of at least one therapeutic follow-up study and still experience the appearance or maintenance of the PNH clone even after the beginning of the chemotherapy treatment. Conclusion: Primarily, it was possible to demonstrate the presence of PNH clones in patients diagnosed with acute leukemia both during the diagnostic investigation period and therapeutic follow-up, regardless of cell ontogeny. However, the importance of the presence of these PNH clones for the evolution of the primary disease, prognosis or need for specific treatment was not evaluated yet.

Introducción: El potencial de transformación maligna de las células madre hematopoyéticas que portan mutaciones en el gen glicosofosfatidilinositol (GPI) clase A (PIGA) para las leucemias agudas, aunque raro, ya está bien descrito en la literatura. Objetivo: En este estudio, sin embargo, buscamos mostrar por primera vez en la literatura la aparición o mantenimiento de clones de HPN en pacientes diagnosticados de leucemia aguda o incluso después del inicio de la quimioterapia. Método: La investigación de clones de hemoglobinuria paroxística nocturna (HPN) se realizó mediante citometría de flujo en blastos, eritrocitos, granulocitos o monocitos de 47 muestras de sangre periférica y médula ósea de pacientes sometidos a investigación diagnóstica o seguimiento terapéutico de dos hospitales oncológicos y públicos de Belém, durante el período. de diciembre de 2017 a diciembre de 2018. Resultados: La presencia de clones HPN se observó en 19/47 (40,4%) muestras de pacientes, en investigación diagnóstica o seguimiento terapéutico, que realizaron al menos un estudio de seguimiento terapéutico y aún tenían la aparición o mantenimiento del clon HPN incluso después de iniciado el tratamiento de quimioterapia. Conclusión: Se pudo evidenciar, de forma primaria, la presencia de clones de HPN en pacientes diagnosticados de leucemia aguda tanto durante el período de investigación diagnóstica como durante el seguimiento terapéutico, independientemente de la ontogenia celular. Sin embargo, no podemos todavía evaluar la importancia de la presencia de estos clones de HPN para la evolución de la enfermedad primaria, el pronóstico o la necesidad de un tratamiento específico.

Propriedade intelectual do soro antiofídico: a efetividade a partir da correlação entre os investimentos do governo federal nos principais institutos responsáveis pela produção do soro e realização de pesquisas para o tratamento de acidentes ofídicos no brasil, com relação ao número de vítimas fatais dos acidentes / Intellectual property of antiophidic serum: the effectiveness from the correlation between federal government investments in the main institutes responsible for the production of serum and conducting researches for the treatment of official accidents in Brazil, with regard to the accident of disease acts

Resumo Introdução O envenenamento por picada de serpentes é um latente problema de saúde pública em nível global. Neste contexto, o Brasil se apresenta como referência mundial no tratamento deste tipo de acidente. É importante destacar que o tratamento de acidentes ofídicos no país foi evidenciado a partir dos estudos do sanitarista Vital Brazil, que patenteou o tratamento e doou para o Estado brasileiro. Mas, qual o impacto este ato gerou para a sociedade, já que a gestão da patente se tornou obrigação do Estado? Objetivo A partir de uma análise da evolução do tratamento do ofidismo, verificar a correlação entre os investimentos do Governo Federal nos principais institutos responsáveis pela produção do soro e realização de pesquisas para o tratamento de acidentes ofídicos no Brasil, com relação ao número de vítimas fatais dos acidentes. Método Realizou-se uma análise de correlação estatística, tendo como base acidentes e óbitos decorrentes dos acidentes ofídicos e os investimentos do governo nos principais institutos produtores de soros antipeçonhentos, no período de 1998 a 2017. Resultados Os resultados mostraram que há uma franca evolução no número de acidentes decorrentes dos acidentes ofídicos no Brasil entre 1998 e 2017. Conclusão Existe correlação positiva entre os investimentos do Governo Federal nos principais institutos responsáveis pela produção do soro e realização de pesquisas para o tratamento de acidentes ofídicos no Brasil, com relação ao número de vítimas fatais dos acidentes.

Abstract Background Snakebite poisoning is a latent global public health problem. In this context, Brazil is a world reference in the treatment of this type of accident. It is important to highlight that the treatment of ophidian accidents in the country was evidenced by the studies of the sanitary veterinarian Vital Brazil, who patented the treatment and donated to the Brazilian state. But what impact did this act have on society since patent management became a state obligation? Objective Based on an analysis of the evolution of the treatment of ophidism, we aimed to verify the correlation between the investments of the Federal Government in the main institutes responsible for the production of serum and researching the treatment of ophidian accidents in Brazil, number of fatal accident victims. Method A statistical correlation analysis was performed based on accidents and deaths resulting from ophidian accidents and government investments in the main institutes producing anti-blind sera from 1998 to 2017. Results The results showed that there is a clear evolution in the number of accidents resulting from ophidian accidents in Brazil. Conclusion there is a positive correlation between the investments of the Brazilian government to control the mortality resulting from these accidents.

Maternal endotoxemia induces renal collagen deposition in adult offspring: Role of NADPH oxidase/TGF-ß1/MMP-2 signaling pathway.

Maternal endotoxemia has been shown to increase renal collagen deposition in the offspring. Renal fibrosis is a hallmark of progressive chronic kidney disease. It was investigated whether maternal reactive oxygen species (ROS) leads to renal fibrosis or exacerbates unilateral ureteral obstruction (UUO)-induced renal fibrosis in the offspring of dams treated with lipopolysaccharide (LPS). Furthermore, it was studied the role of matrix metalloproteinases (MMPs) in these changes. Adults Wistar rats were obtained from dams submitted to LPS administration through the third part of gestation. To evaluate the role of maternal ROS, part of the dams received α-tocopherol simultaneously with LPS. Part of the offspring in each group was submitted to UUO at adulthood when sub-groups were treated with NADPH oxidase inhibitor, apocynin. Maternal LPS administration increased proteinuria, systolic arterial pressure and renal collagen deposition in adult offspring. LPS offspring rats also presented higher MMP-2 activity in parallel to a decreased renal cortical TIMP-2 content. These changes were correlated to increased amounts of TGF-ß1 and NOX2. Maternal α-tocopherol treatment prevented collagen deposition and reduced arterial pressure in adult offspring. α-Tocopherol also inhibited maternal endotoxemia-induced changes in TGF-ß1/NOX2/MMP-2 signaling. UUO led to increased collagen deposition in the contralateral kidneys of LPS offspring, which was correlated to increased NADPH oxidase activity and prevented by NADPH oxidase inhibition. In summary, maternal endotoxemia led to alterations in the TGF-ß1/NOX2/MMP-2 signaling pathway in renal tissue concomitant with collagen deposition, therefore contributing to hypertension in adult offspring.

NO mediates the effect of the synthetic natriuretic peptide NPCdc on kidney and aorta in nephrectomised rats.

NPCdc is a synthetic natriuretic peptide that was originally derived from another peptide, the NP2_Casca, isolated from Crotalus durissus cascavella venom. These molecules share 70% structural homology with natriuretic peptides obtained from different species, including humans. NP2_Casca induces vasorelaxation and increases nitric oxide levels independently of natriuretic peptide receptors A and B. This study aimed to investigate whether NPCdc-induced hypotension in control rats and rats with a reduced kidney mass is associated with effects on the glomerular filtration rate, NADPH oxidase activity and components downstream of natriuretic peptide receptor C (NPR-C). Anaesthetized Wistar rats that were subjected to a sham operation and 5/6 nephrectomy (5/6Nx) were infused with saline (vehicle) or NPCdc (7.5 µg/kg/min) for 70 min. The NPCdc treatment decreased the mean arterial pressure and NADPH oxidase activity while simultaneously increasing the glomerular filtration rate, fractional Na+ excretion and nitric oxide level. After 70 min, the levels of p-AKT Ser-473, p-eNOS Ser-1177, p-nNOS Ser-1417 and p-iNOSTyr-151 were not affected. However, p-ERK1/2 Thr-202/Tyr-204 levels were altered. Thus, nitric oxide and components of NPR-C signalling mediate the effects of NPCdc. The results suggest a potential therapeutic application of this peptide for cardiorenal syndrome.

Alpha-Tocopherol during lactation and after weaning alters the programming effect of prenatal high salt intake on cardiac and renal functions of adult male offspring.

Maternal salt overload programs cardiovascular and renal alterations in the offspring. However, beneficial and harmful effects of high dose vitamin E supplementation have been described in humans and animals. We investigated the hypothesis as to whether cardiac and renal alterations can be programmed by gestational salt overload, and can become further modified during lactation and after weaning. Male Wistar rats were used, being the offspring of mothers that drank either tap water or 0.3 mol/L NaCl for 20 days before and during pregnancy. α-Tocopherol (0.35 g/kg) was administered to mothers daily during lactation or to their offspring for 3 weeks post-weaning. Systolic blood pressure (tcSBP) was measured in juvenile rats aged 210 days. The response of mean arterial pressure (MAP) and heart rate (HR) to intravenous infusion of angiotensin II (Ang II) was also examined. Left ventricle plasma membrane (PMCA) and sarcoplasmic reticulum Ca2+ -ATPase (SERCA) activities, and certain parameters of renal function, were measured. Maternal saline programmed for increased body mass and kidney mass/body mass ratio, increased tcSBP, increased mean arterial pressure and heart rate with anomalous response to infused Ang II. In the heart, saline increased PMCA and α-Tocopherol per se increased PMCA/SERCA. In the kidney, the most remarkable result was the silent saline programming of CrCl , which was sensitized for a sharp decrease after α-Tocopherol. In conclusion, the combination of maternal saline overload and high α-Tocopherol immediately after birth leads to simultaneous cardiovascular and renal alterations in the young offspring, like those encountered in type V cardiorenal syndrome.