Myeloproliferative Neoplasms Transcriptome Reveals Pro-Inflammatory Signature and Enrichment in Peripheral Blood Monocyte-Related Genes.

Myeloproliferative neoplasms (MPN) are hematological diseases associated with genetic driver mutations in the JAK2, CALR, and MPL genes and exacerbated oncoinflammatory status. Analyzing public microarray data from polycythemia vera (n = 41), essential thrombocythemia (n = 21), and primary myelofibrosis (n = 9) patients' peripheral blood by in silico approaches, we found that pro-inflammatory and monocyte-related genes were differentially expressed in MPN patients' transcriptome. Genes related to cell activation, secretion of pro-inflammatory and pro-angiogenic mediators, activation of neutrophils and platelets, coagulation, and interferon pathway were upregulated in monocytes compared to controls. Together, our results suggest that molecular alterations in monocytes may contribute to oncoinflammation in MPN.

Kinetics of BCR::ABL1 transcript levels and molecular relapse after tyrosine kinase inhibitors discontinuation in chronic myeloid leukemia patients: preliminary results from the DES-CML study.

Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of patients with chronic myeloid leukemia. Patients who achieve sustained deep molecular response are eligible for treatment discontinuation. DES-CML is an ongoing, phase 2 multicentric discontinuation trial. Adult patients with CML in chronic phase with typical BCR::ABL1 transcripts, stable deep molecular response (MR4.5 IS) for two years, and no previous resistance were eligible. Patients underwent a phase of TKI dose de-escalation for six months before discontinuation. TKI was reintroduced at the previous dose if the patient lost major molecular response (MMR) at any time. This study aimed to assess the impact of BCR-ABL transcript kinetics during TKI de-escalation and discontinuation phases on treatment-free survival. So far, the study recruited 41 patients, and 38 patients discontinued therapy (4 were in the second discontinuation attempt). Eleven patients lost MMR, one during the de-escalation phase and ten after discontinuation. 24-month treatment-free survival was 66% (95% CI: 48-84%) in a median follow-up of 7 (1-30) months. No patient lost hematological response or had disease progression. A higher rate of molecular relapses occurred in patients with fluctuating BCR::ABL1 levels after the discontinuation phase (with loss of MR4.5, but no loss of MMR) (P=0.04, HR-4.86 (1.03-22.9) but not confirmed in the multivariate analysis. The longer duration of TKI treatment (P=0.03, HR-1.02, 95%CI - 1.00-1.04) and MMR (P=0.004, HR-0.95, 95%CI - 0.92-098) were independent factors of a lower relapse rate.

The pain reported by postpartum women in rooming-in according to the mode of delivery / Dor relatada por puérperas no alojamento conjunto segundo a via de nascimento

ABSTRACT BACKGROUND AND OBJECTIVES: Pain is the most frequently reported symptom in the immediate puerperium. The aim of this study was to quantify pain levels and sociodemographic, obstetric, and care characteristics associated with severe pain and inadequate analgesia according to the mode of delivery. METHODS: Observational, descriptive, cross-sectional study conducted between October and December 2020, with a sample of 229 postpartum women considered eligible (baby born alive, weighing > 500 g and/or gestational age > 22 weeks) to answer the study questionnaire. RESULTS: The mean reported pain was 5.34 by Visual Analogue Scale (VAS) and there was a difference (p<0.001) between modes of delivery. Cesarean section was associated with severe pain (p=0.006) and pain above eight on the VAS (p=0.02). Vaginal delivery was associated with the perception of inadequate analgesia (p=0.04). Severe pain reported was associated with the admission of the baby to the ICU (p=0.01) and cases of postpartum hemorrhage (p=0.002). Among women who gave birth vaginally, there was an association between severe pain and instrumental delivery (p=0.05). Reported severe pain was associated with difficulties in self-care (p<0.001) and care of the newborn (p= 0.02), sensation of weakness (p<0.001), and fainting (p=0.002). The perception of inadequate analgesia was associated with vaginal birth (p=0.04) end non-white skin color (p=0,03). CONCLUSION: The average reported pain was moderate. Intense pain and the perception of inadequate analgesia were associated with instrumental delivery, newborns being referred to the NICU, postpartum hemorrhage, and non-white skin color.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor é o sintoma mais frequentemente relatado no puerpério imediato. O objetivo deste estudo foi quantificar os níveis de dor e as características sociodemográficas, obstétricas e da assistência associadas à dor intensa e à percepção de analgesia inadequada segundo a via de nascimento. MÉTODOS: Estudo observacional, descritivo, transversal, conduzido entre outubro e dezembro de 2020, com uma amostra de 229 puérperas consideradas elegíveis (nativivos com peso > 500g e/ou idade gestacional > 22 semanas) para responder ao questionário do estudo. RESULTADOS: A média de dor relatada foi 5,3 pela Escala Analógica Visual (EAV) e houve diferença (p<0,001) entre as vias de nascimento. A cesariana apresentou associação com dor intensa referida (p=0,006) e dor acima de oito pela EAV (p=0,02). O parto vaginal obteve associação com percepção de analgesia inadequada (p=0,04). Entre as mulheres que referiram dor intensa, houve associação com recém-nascido encaminhado à unidade de terapia intensiva neonatal (UTIN) (p=0,01) e nos casos de hemorragia pós-parto (p=0,002). Entre as mulheres que tiveram parto vaginal, também houve associação entre dor intensa e o parto instrumental (p=0,05). Dor intensa referida teve associação com dificuldades para o autocuidado (p<0,001) e do recém-nascido (p=0,02), sensação de fraqueza (p<0,001) e de desmaio (p= 0,002). A percepção de analgesia inadequada esteve associada a parto vaginal (p=0,04) e cor da pele não branca (p=0,03). CONCLUSÃO: A média de dor relatada foi moderada. Dor intensa e percepção de analgesia inadequada estiveram associadas com parto instrumental, recém-nascido encaminhado à UTIN, hemorragia pós-parto e cor de pele não branca.

Measurement of the prevalence of intervention/complication in puerperal women attending a university hospital during the pandemic of COVID-19 by the maternity safety thermometer / Medida da prevalência de intervenção/complicação em puérperas atendidas em hospital universitário durante a pandemia de COVID-19 pelo termômetro de segurança da maternidade

Abstract Objectives: measuring the prevalence of interventions and/or complications based on the Maternity Safety Thermometer (MST) criteria and verifying associations with sociodemographic, clinical, and obstetric factors. Methods: prospective observational study conducted with postpartum women admitted to the maternity ward of a tertiary hospital, from October 10th to December 30th, 2020. Data were collected from medical records and self-administered questionnaires from 260 patients. Results: harm-free care was detected in 17.7% of participants, 66.9% had low-temperature damage (one or less intervention/complication) and 33.1% of patients had elevated temperature damage (two or more intervention/complication). The most frequent intervention was the "scar", given that 38.5% had abdominal scarring (cesarean section) and 26.5% had perineal scarring (2nd-degree tear or greater - spontaneous or by episiotomy). The second most frequent MST item was related to the perception of safety (30%), followed by complications to the newborn (12.3%), infection (11.2%), and hemorrhage (9.2%). Factors related to high temperature were: being of social class A or B, having a previous cesarean section, and being hospitalized during pregnancy. Conclusions: one-third of the participating women had two or more complications/interventions (high temperature by the MST), factors that are related to this temperature were: being of social class A or B, having a previous cesarean section, and being hospitalized during pregnancy.

Resumo Objetivos: mensurar a prevalência de intervenções e/ou complicações a partir dos critérios estabelecidos pelo Termômetro de Segurança da Maternidade (TSM) e avaliar associações com fatores sociodemográficos, clínicos e obstétricos. Métodos: estudo observacional prospectivo realizado com puérperas internadas na maternidade de hospital terciário, de 10 de outubro a 30 de dezembro de 2020. Foram coletados dados do prontuário e de questionários autoaplicáveis de 260 pacientes. Resultados: um cuidado livre de intervenções/complicações foi detectado em 17,7% das participantes, 66,9% apresentaram baixa temperatura (até uma intervenção/complicação) e 33,1% tiveram alta temperatura de intervenções/complicações (2 ou mais). A intervenção mais frequente foi a denominada "cicatriz", sendo que 38,5% tiveram cicatriz abdominal (cesariana) e 26,5% tiveram "cicatriz" perineal (laceração de 2º grau ou mais - espontânea ou por episiotomia). O segundo dano mais frequente foi o relacionado à percepção de segurança (30%), seguido de complicações do recémnascido (12,3%), infecção (11,2%), e hemorragia (9,2%). Houve associação de ter alta temperatura com ser de classe social A ou B, ter cesárea anterior e ser internada na gestação. Conclusões: das mulheres participantes, um terço teve duas ou mais complicações/intervenções (alta temperatura no TSM), estiveram relacionados a essa temperatura: ser de classe social A ou B, ter cesárea anterior e ser internada ao longo da gestação.

Philadelphia-negative myeloproliferative neoplasms display alterations in monocyte subpopulations frequency and immunophenotype.

Philadelphia-negative myeloproliferative neoplasms (MPN) are clonal hematological diseases associated with driver mutations in JAK2, CALR, and MPL genes. Moreover, several evidence suggests that chronic inflammation and alterations in stromal and immune cells may contribute to MPN's pathophysiology. We evaluated the frequency and the immunophenotype of peripheral blood monocyte subpopulations in patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (MF). Peripheral blood monocytes from PV (n = 16), ET (n = 16), and MF (n = 15) patients and healthy donors (n = 10) were isolated and submitted to immunophenotyping to determine the frequency of monocyte subpopulations and surface markers expression density. Plasma samples were used to measure the levels of soluble CD163, a biomarker of monocyte activity. PV, ET, and MF patients presented increased frequency of intermediate and non-classical monocytes and reduced frequency of classical monocytes compared to controls. Positivity for JAK2 mutation was significantly associated with the percentage of intermediate monocytes. PV, ET, and MF patients presented high-activated monocytes, evidenced by higher HLA-DR expression and increased soluble CD163 levels. The three MPN categories presented increased frequency of CD56+ aberrant monocytes, and PV and ET patients presented reduced frequency of CD80/86+ monocytes. Therefore, alterations in monocyte subpopulations frequency and surface markers expression pattern may contribute to oncoinflammation and may be associated with the pathophysiology of MPN.

Bioactive Lipids as Chronic Myeloid Leukemia's Potential Biomarkers for Disease Progression and Response to Tyrosine Kinase Inhibitors.

Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm that expresses the Philadelphia chromosome and constitutively activated Bcr-Abl tyrosine kinase in hematopoietic progenitor cells. Bcr-Abl tyrosine-kinase inhibitors (TKI) do not definitively cure all CML patients. The efficacy of TKI is reduced in CML patients in the blastic phase-the most severe phase of the disease-and resistance to this drug has emerged. There is limited knowledge on the underlying mechanisms of disease progression and resistance to TKI beyond BCR-ABL1, as well as on the impact of TKI treatment and disease progression on the metabolome of CML patients. The present study reports the metabolomic profiles of CML patients at different phases of the disease treated with TKI. The plasma metabolites from CML patients were analyzed using liquid chromatography, mass spectrometry, and bioinformatics. Distinct metabolic patterns were identified for CML patients at different phases of the disease and for those who were resistant to TKI. The lipid metabolism in CML patients at advanced phases and TKI-resistant patients is reprogrammed, as detected by analysis of metabolomic data. CML patients who were responsive and resistant to TKI therapy exhibited distinct enriched pathways. In addition, ceramide levels were higher and sphingomyelin levels were lower in resistant patients compared with control and CML groups. Taken together, the results here reported established metabolic profiles of CML patients who progressed to advanced phases of the disease and failed to respond to TKI therapy as well as patients in remission. In the future, an expanded study on CML metabolomics may provide new potential prognostic markers for disease progression and response to therapy.

Variability in nearshore fish biodiversity indicators after a mining disaster in eastern Brazil.

The rupture of the Fundão mining dam (Doce river basin, Brazil) caused a wide range of negative impacts. Yet, assemblage-level implications to estuarine and coastal fishes remain unclear, partly due to the lack of pre-disaster information. Based on monthly otter trawl surveys, we analyzed spatial and seasonal variability in univariate (total biomass, biomass of species vulnerable to exploitation, rarefied richness and evenness) and multivariate (species composition and trophic composition) indicators of fish biodiversity in the Doce river delta, eastern Brazil. We determined the independent and interactive effects of environmental, seasonal and spatial variables on species composition to test whether environmental alterations provoked by mine tailings could affect assemblage's organization. Most indicators present idiosyncratic spatiotemporal patterns, suggesting they have complementary roles in revealing changes in fish biodiversity. Environmental variables, including those affected by the Fundão dam collapse such as turbidity, dissolved oxygen and pH, were much more important than seasonal and spatial predictors in explaining the variation in fish species composition. These findings highlight the potential from mine tailings to disrupt local ichthyofauna and indicate a preponderant role of environmental conditions in assemblage structuring. Given the lack of data prior to rupture, our results may be used as a baseline against which to assess temporal trends in fish biodiversity relative to changes detected in less disturbed estuarine and coastal assemblages.

Controle Postural em Crianças com Síndrome de Down: Avaliação do Equilíbrio e da Mobilidade Funcional / Postural Control in Children with Down Syndrome: Evaluation of Functional Balance and Mobility

RESUMO: O atraso do desenvolvimento motor em crianças com Síndrome de Down (SD), em consequência das características e da presença dos distúrbios associados, pode levar à lentidão na aquisição ou a limitações das habilidades funcionais. Assim, este estudo teve como objetivo caracterizar o equilíbrio e a mobilidade funcional de crianças com SD, uma vez que possibilitam a execução de atividades do cotidiano. O estudo transversal com amostra de conveniência foi realizado com crianças com SD, confirmado por cariótipo, na faixa etária entre oito e 12 anos. A avaliação do controle postural foi realizada com dois instrumentais: Escala de Equilíbrio Pediátrica (EEP) e Teste de Alcance (TA). Foram avaliados 21 participantes com SD, 12 (57%) meninos e nove (43%) meninas, mediana de idade de 10 [8-11] anos. O escore obtido na EEP foi de 53 (51-54). A distância obtida no TA foi de 19 cm (17-23,5). Os resultados mostraram que a realização de atividades funcionais foi pouco afetada, conforme a mediana do escore na EEP; no entanto, alguns participantes pontuaram entre 48 a 51. As medidas atingidas no TA implicam redução da mobilidade funcional.

ABSTRACT: The delay in motor development in children with Down Syndrome (DS), as a consequence of the characteristics and presence of associated disorders, may lead to slowness in the acquisition or limitations of functional abilities. Thus, this study aims to characterize the balance and functional mobility of children with DS, since they enable the execution of daily activities. The cross-sectional study with sample convenience was performed with children with DS, confirmed through karyotype, between the ages of 8 and 12 years old. The evaluation of postural control was performed with two instruments: Pediatric Balance Scale (PBS) and Reach Test (RT). Twenty-one participants with DS, 12 (57%) boys and nine (43%) girls, median age of 10 [8-11] years old, were evaluated. The score obtained in the PBS was 53 (51-54). The distance obtained in the RT was 19 cm (17-23.5). The results showed that the performance of functional activities was little affected, according to the median of the score in the PBS; however, some participants scored between 48 to 51. The measurements obtained in the RT imply a reduction in functional mobility.

Avaliação do controle postural em crianças e adolescentes com síndrome de down na faixa etária entre oito e doze anos / Evaluation of postural control in children and adolescents with down syndrome aged eight to twelve years old

INTRODUCTION: Down Syndrome is a genetic disorder caused by the presence of the third copy of chromosome 21 (total or partial). The syndrome occurs in approximately one out of every 700 - 1000 newborns per year. OBJECTIVE: To analyze postural control (PC) of children and adolescents with Down Syndrome (DS) and to compare differences regarding age, sex, nutritional status, and physical activity (PA) levels METHODS: In this cross-sectional study, a convenience sample composed of 21 children and adolescents (9 girls) was categorized according to age: G1 (8 to 9 years old; n = 8), G2 (10 years old; n = 7), and G3 (11 to 12 years old; n = 6), Score-Z: eutrophic (n = 9) and overweight (n = 12), and PA level: practitioners (n = 7) and non-practitioners (n = 14). PC was assessed in the force platform (FP), in the standing position, with feet together during 30 seconds. The variables analyzed were the center of pressure area (COP) and the mean velocities of anteroposterior and mediolateral oscillation (VEL-AP and VEL-ML). Shapiro-Wilk test was used to test the normality of data. Kruskal-Wallis, Dunn's, and Mann Whitney tests were performed to analyze associations with PC. Statistical significance was set at p<0.05 RESULTS: The median COP, VEL-AP and VEL-ML were 3.55 [2.13 - 6.82] , 2.81 [2.32 - 3.16], and 2.98 [2.42 - 3.43], respectively. There were no differences in PC regarding sex, body mass index and PA level. The adolescents in G3 presented lower values of VEL-AP (G1=2,88 [2,82 - 3,21]; G2= 2,94 [2,35 - 3,39]; G3= 2,27 [2 - 2,3]) and VEL-ML (G1= 3,22 [3,14 - 3,68]; G2= 2,91 [2,52 - 3,63]; G3= 2,34 [2,1 - 2,39]. CONCLUSION: Sex, nutritional status, and PA level did not affect COP area and AP-VEL and ML-VEL. However, strategies were affected by age, as observed by differences in velocity, but did not affect the COP area.

INTRODUÇÃO: A Síndrome de Down (SD) é considerada condição genética, resultante da presença de cópia extra do material genético do cromossomo 21, com prevalência mundial de um a cada 700-1000 nascidos vivos. OBJETIVO: Avaliar o controle postural (CP) de crianças e adolescentes com SD e comparar com a idade, sexo, classificação nutricional e prática de atividade física (PAF MÉTODO: Estudo transversal, amostra de conveniência, com 21 particpantes, 12 meninos e 9 meninas. As crianças foram subdivididas quanto à idade: G1 - 8 a 9 anos (n=8); G2 - 10 (n= 7); e G3 - 11 a 12 anos (n=6); score-Z, em eutróficas (n= 9) e acima do peso (n=12); praticantes (n= 7) e não praticantes (n=14) de atividade física regular. O CP foi avaliado na plataforma de força (PF), na posição pés juntos, permanência de 30 segundos. As variáveis analisadas foram área centro de pressão (COP) e as velocidades médias de oscilação anteroposterior e médio lateral (VEL-AP e VEL-ML). Para análise de normalidade dos dados, foi utilizado o teste Shapiro-Wilk. Os testes KrusKal-Wallis, pós teste de Dunn's e Mann Whitney foram realizados para análise das associações com o CP. A significância estatística foi de p<0.05. RESULTADOS: As medianas de COP, VEL-AP e VEL-ML foram 3,55 [2,13-6,82], 2,81 [2,32-3,16] e 2,98 [2,42-3,43], respectivamente. Não houve diferença no CP em relação ao sexo, classificação nutricional e PAF. As crianças do G3 apresentaram valores menores de VEL-AP (G1=2,88 [2,82-3,21]; G2= 2,94 [2,35-3,39]; G3= 2,27 [2-2,3]) e VEL-ML (G1= 3,22 [3,14-3,68]; G2= 2,91 [2,52-3,63]; G3= 2,34 [2,1-2,39]. CONCLUSÃO: O sexo, classificação nutricional e PAF não afetaram o CP, no entanto, a idade modificou as estratégias, visto a diferença na velocidade, mas não interferiu o desempenho em relação a área de COP.

Prevalência de hipermobilidade articular em crianças pré-escolares / Prevalence joint hypermobility in preschool children / Prevalencia de hipermobilidad articular en niños pre-escolares

A hipermobilidade articular é a capacidade de realizar movimentos em amplitudes maiores que a normal. O presente estudo teve como objetivo estabelecer a prevalência de hipermobilidade articular em crianças pré-escolares da Rede Municipal de Educação de Londrina/PR. O estudo foi do tipo transversal com amostra constituída de 366 crianças, de 5 e 6 anos de idade. Verificou-se que, das crianças pré-escolares avaliadas, 198 (54,1%) apresentaram hipermobilidade articular, sendo 96 (59,6%) do sexo feminino e 102 (49,8%) do masculino. A hipermobilidade articular foi encontrada com maior frequência nas articulações de cotovelo e joelho, onde ocorreu a hiperextensão. Não houve diferença estatisticamente significante entre os grupos masculino e feminino em relação à hipermobilidade articular (χ²=3,539, p=0,072). Pode-se concluir que a hipermobilidade articular nas crianças pré-escolares foi achado comum, compatível com a faixa etária da população avaliada no estudo...

Joint hypermobility is the ability to perform movements with a range of motion that is wider than normal. This study aimed at establishing the prevalence of joint hypermobility in junior kindergarten and senior kindergarten children from the Municipal Education System of Londrina, Paraná, Brasil. The study was cross-­sectional, with a sample of 366 children aged between 5 and 6 years. The detection of joint hypermobility was based on the criteria proposed in literature. It was found that 198 (54.1%) of the children evaluated had joint hypermobility, 96 (59.6%) were girls and 102 (49.8%) were boys. Joint hypermobility was found more frequently in the elbow and knee joints, where hyperextension occurred. There was no statistically significant difference between the male and female groups in relation to joint hypermobility (χ²=3.539, p=0.072). We can conclude that joint hypermobility found in the junior kindergarten and senior kindergarten children evaluated was common and compatible with the age of the population evaluated in this study...

La hipermovilidad articular es la capacidad de realizar movimientos en amplitudes mayores que lo normal. El presente estudio tuvo como objetivo establecer la prevalencia de hipermovilidad articular en niños pre-escolares de la Red Municipal de Educación de Londrina/PR. El estudio fue de tipo transversal con una muestra constituida de 366 niños, de 5 a 6 años de edad. Se verificó que los niños pre-escolares evaluados, 198 (54,1%) presentaron hipermovilidad articular, siendo 96 (59,6%) de sexo femenino y 102 (49,8%) de sexo masculino. La hipermovilidad articular fue encontrada con mayor frecuencia en las articulaciones del tobillo y rodilla, donde ocurre la hiperextensión. No hubo diferencia estadísticamente significativa entre los grupos masculino y femenino en relación a la hipermovilidad articular (χ²=3,539, p=0,072). Se puede concluir que la hipermovilidad articular en los niños pre-escolares fue encontrada normal, compatible con la línea etaria de la población evaluada en el estudio...

Morphometry of the human bicipital groove (sulcus intertubercularis).

BACKGROUND: The bicipital groove is located between the greater and lesser tubercles at the proximal extremity of the humerus and extends inferiorly. Citations that anatomic variations of the groove could give rise to sliding of the biceps brachii muscle tendon led us to initiate a morphometric study on this groove. MATERIALS AND METHODS: The study was done on 50 dry humeral bones from adults of both genders and from both sides. A digital caliper rule was used to measure the length, thickness and width of the bicipital groove and the humerus. The angles of the bicipital groove were measured with a goniometer. RESULTS: The average length of the groove was 8.1 cm and it corresponded to 25.2% of the length of the humerus. The width at the midpoint of the groove was 10.1 mm and corresponded to 49.7% to 54.5% of the width of the humerus. The depth was 4.0 mm and corresponded to 18.8% of the depth of the humerus. The mean angle formed by the groove lips was 106 degrees . CONCLUSION: This study confirmed the variability of the measurements presented by the groove in relation to all the aspects considered. LEVEL OF EVIDENCE: Basic Science.