Challenges in the use of NG2 antigen as a marker to predict MLL rearrangements in multi-center studies

AbstractRearrangements in MLL (MLL-r) are common within very young children with leukemia and affect the prognosis and treatment. Previous studies have suggested the use of the NG2 molecule as a marker for MLL-r but these studies were performed using a small number of infants. We analyzed 148 patients (all less than 24 months, 86 less than 12 months) from various centers in Brazil to determine the predictive power of NG2 within that cohort. We show that NG2 can be used for MLL-r prediction; however, proper staff training and standardized sampling procedures are essential when receiving samples from multiple centers as the accuracy of the prediction varies greatly on a per center basis

Aireación en la tecnología Biofloc (BTF): principios básicos, aplicaciones y perspectivas

In a globalized world with growing population avid for nutrients for their feeding, the aquatic originated protein emerges as the big nutritional alternative of the century. The reduction of their resources to the farming (water, field and human resource) implies that the fish and shrimp production has to be intensify and one of the possibilities for this development is Biofloc Technology (BFT). Nevertheless, this intensification has to be given with principles of economic and technical efficiency, therefore, a correct design of the aeration is a big principal to maintain the suspended particles, oxygenate and move the water correctly. The electricity (aeration included) join with the feed are the most important production costs using BFT. With water changes low or none of it, the number, type and distribution of the mechanical oxygenator devices are crucial to maintain the water quality for the cultivated species and for the microorganisms that are included on the system. In this context this revision pretends to present the basis for the study and implementation of the aeration systems on BFT, also drawing future perspectives for these components.En un mundo globalizado de creciente población ávido por nutrientes para su alimentación, la proteína de origen acuática emerge como la gran alternativa nutricional del siglo. La disminución de sus recursos para la explotación (agua, tierra y personal) implica que se deba intensificar la producción de peces y camarones y una posibilidad para dicho establecimiento es la tecnología de biofloc (BFT en su sigla en inglés). Sin embargo, esta intensificación debe ser dada con principios de eficiencia técnica y económica, por lo tanto, un correcto diseño de la aeración es de fundamental importancia para mantener las partículas en suspensión, oxigenar y mover correctamente el agua. Unido a los alimentos concentrados, el costo energético (incluyendo la aeración) son de los más importantes costos de producción usados en la tecnología BFT. Utilizando recambios mínimos o nulos, el número, tipo y distribución de los aparatos mecánicos de aeración son cruciales para el mantenimiento de la calidad de agua para las especies cultivadas y para los microorganismos que se encuentran inmiscuidos en el sistema. En este contexto, esta revisión pretende brindar una base teórica para el estudio e implementación de los sistemas de aireación en los sistemas BFT, además de trazar perspectivas futuras para estos componentes.En un mundo globalizado de creciente población ávido por nutrientes para su alimentación, la proteína de origen acuática emerge como la gran alternativa nutricional del siglo. La disminución de sus recursos para la explotación (agua, tierra y personal) implica que se deba intensificar la producción de peces y camarones y una posibilidad para dicho establecimiento es la tecnología de biofloc (BFT en su sigla en inglés). Sin embargo, esta intensificación debe ser dada con principios de eficiencia técnica y económica, por lo tanto, un correcto diseño de la aeración es de fundamental importancia para mantener las partículas en suspensión, oxigenar y mover correctamente el agua. Unido a los alimentos concentrados, el costo energético (incluyendo la aeración) son de los más importantes costos de producción utilizando la tecnología BFT. Utilizando recambios mínimos o nulos, el número, tipo y distribución de los aparatos mecánicos de aeración son cruciales para el mantenimiento de la calidad de agua para las especies cultivadas y para los microorganismos que se encuentran inmiscuidos en el sistema. En este contexto, esta revisión pretende brindar una base teórica para el estudio e implementación de los sistemas de aireación en los sistemas BFT, además de trazar perspectivas futuras para estos componentes.In a globalized world with growing population avid for nutrients for their feeding, the aquatic originated protein emerges as the big nutritional alternative of the century. The reduction of their resources to the farming (water, field and human resource) implies that the fish and shrimp production has to be intensify and one of the possibilities for this development is Biofloc Technology (BFT). Nevertheless, this intensification has to be given with principles of economic and technical efficiency, therefore, a correct design of the aeration is a big principal to maintain the suspended particles, oxygenate and move the water correctly. The electricity (aeration included) join with the feed are the most important production costs using BFT. With water changes low or none of it, the number, type and distribution of the mechanical oxygenator devices are crucial to maintain the water quality for the cultivated species and for the microorganisms that are included on the system. In this context this revision pretends to present the basis for the study and implementation of the aeration systems on BFT, also drawing future perspectives for these components

IKZF1 Deletions with COBL Breakpoints Are Not Driven by RAG-Mediated Recombination Events in Acute Lymphoblastic Leukemia

IKZF1 deletion (ΔIKZF1) is an important predictor of relapse in both childhood and adult B-cell precursor acute lymphoblastic leukemia (B-ALL). Previously, we revealed that COBL is a hotspot for breakpoints in leukemia and could promote IKZF1 deletions. Through an international collaboration, we provide a detailed genetic and clinical picture of B-ALL with COBL rearrangements (COBL-r). Patients with B-ALL and IKZF1 deletion (n = 133) were included. IKZF1 ∆1-8 were associated with large alterations within chromosome 7: monosomy 7 (18%), isochromosome 7q (10%), 7p loss (19%), and interstitial deletions (53%). The latter included COBL-r, which were found in 12% of the IKZF1 ∆1-8 cohort. Patients with COBL-r are mostly classified as intermediate cytogenetic risk and frequently harbor ETV6, PAX5, CDKN2A/B deletions. Overall, 56% of breakpoints were located within COBL intron 5. Cryptic recombination signal sequence motifs were broadly distributed within the sequence of COBL, and no enrichment for the breakpoint cluster region was found. In summary, a diverse spectrum of alterations characterizes ΔIKZF1 and they also include deletion breakpoints within COBL. We confirmed that COBL is a hotspot associated with ΔIKZF1, but these rearrangements are not driven by RAG-mediated recombination

Distinctive genotypes in infants with T-cell acute lymphoblastic leukaemia

Infant T-cell acute lymphoblastic leukaemia (iT-ALL) is a very rare and poorly defined entity with a poor prognosis. We assembled a unique series of 13 infants with T-ALL, which allowed us to identify genotypic abnormalities and to investigate prenatal origins. Matched samples (diagnosis/remission) were analysed by single nucleotide polymorphism-array to identify genomic losses and gains. In three cases, we identified a recurrent somatic deletion on chromosome 3. These losses result in the complete deletion of MLF1 and have not previously been described in T-ALL. We observed two cases with an 11p13 deletion (LMO2-related), one of which also harboured a deletion of RB1. Another case presented a large 11q14·1-11q23·2 deletion that included ATM and only five patients (38%) showed deletions of CDKN2A/B. Four cases showed NOTCH1 mutations; in one case FBXW7 was the sole mutation and three cases showed alterations in PTEN. KMT2A rearrangements (KMT2A-r) were detected in three out of 13 cases. For three patients, mutations and copy number alterations (including deletion of PTEN) could be backtracked to birth using neonatal blood spot DNA, demonstrating an in utero origin. Overall, our data indicates that iT-ALL has a diverse but distinctive profile of genotypic abnormalities when compared to T-ALL in older children and adults

Effect of transcranial direct current stimulation combined with gait and mobility training on functionality in children with cerebral palsy: study protocol for a double-blind randomized controlled clinical trial

Background: The project proposes three innovative intervention techniques (treadmill training, mobility training with virtual reality and transcranial direct current stimulation that can be safely administered to children with cerebral palsy. The combination of transcranial stimulation and physical therapy resources will provide the training of a specific task with multiple rhythmic repetitions of the phases of the gait cycle, providing rich sensory stimuli with a modified excitability threshold of the primary motor cortex to enhance local synaptic efficacy and potentiate motor learning. Methods/design A prospective, double-blind, randomized, controlled, analytical, clinical trial will be carried out.Eligible participants will be children with cerebral palsy classified on levels I, II and III of the Gross Motor Function Classification System between four and ten years of age. The participants will be randomly allocated to four groups: 1) gait training on a treadmill with placebo transcranial stimulation; 2) gait training on a treadmill with active transcranial stimulation; 3) mobility training with virtual reality and placebo transcranial stimulation; 4) mobility training with virtual reality and active transcranial stimulation. Transcranial direct current stimulation will be applied with the anodal electrode positioned in the region of the dominant hemisphere over C3, corresponding to the primary motor cortex, and the cathode positioned in the supraorbital region contralateral to the anode. A 1 mA current will be applied for 20 minutes. Treadmill training and mobility training with virtual reality will be performed in 30-minute sessions five times a week for two weeks (total of 10 sessions). Evaluations will be performed on four occasions: one week prior to the intervention; one week following the intervention; one month after the end of the intervention;and 3 months after the end of the intervention. The evaluations will involve three-dimensional gait analysis, analysis of cortex excitability (motor threshold and motor evoked potential), Six-Minute Walk Test, Timed Up-and-Go Test, Pediatric Evaluation Disability Inventory, Gross Motor Function Measure, Berg Balance Scale, stabilometry, maximum respiratory pressure and an effort test. Discussion This paper offers a detailed description of a prospective, double-blind, randomized, controlled, analytical, clinical trial aimed at demonstrating the effect combining transcranial stimulation with treadmill and mobility training on functionality and primary cortex excitability in children with Cerebral Palsy classified on Gross Motor Function Classification System levels I, II and III. The results will be published and will contribute to evidence regarding the use of treadmill training on this population. Trial registration ReBEC RBR-9B5DH

Validation of the United Kingdom copy-number alteration classifier in 3239 children with B-cell precursor ALL

Genetic abnormalities provide vital diagnostic and prognostic information in pediatric acute lymphoblastic leukemia (ALL) and are increasingly used to assign patients to risk groups. We recently proposed a novel classifier based on the copy-number alteration (CNA) profile of the 8 most commonly deleted genes in B-cell precursor ALL. This classifier defined 3 CNA subgroups in consecutive UK trials and was able to discriminate patients with intermediate-risk cytogenetics. In this study, we sought to validate the United Kingdom ALL (UKALL)-CNA classifier and reevaluate the interaction with cytogenetic risk groups using individual patient data from 3239 cases collected from 12 groups within the International BFM Study Group. The classifier was validated and defined 3 risk groups with distinct event-free survival (EFS) rates: good (88%), intermediate (76%), and poor (68%) (P < .001). There was no evidence of heterogeneity, even within trials that used minimal residual disease to guide therapy. By integrating CNA and cytogenetic data, we replicated our original key observation that patients with intermediate-risk cytogenetics can be stratified into 2 prognostic subgroups. Group A had an EFS rate of 86% (similar to patients with good-risk cytogenetics), while group B patients had a significantly inferior rate (73%, P < .001). Finally, we revised the overall genetic classification by defining 4 risk groups with distinct EFS rates: very good (91%), good (81%), intermediate (73%), and poor (54%), P < .001. In conclusion, the UKALL-CNA classifier is a robust prognostic tool that can be deployed in different trial settings and used to refine established cytogenetic risk groups

ANÁLISE DO USO DO SLEEVE GÁSTRICO NO TRATAMENTO DA OBESIDADE MÓRBIDA

The present study aims to analyze the effectiveness and safety of Sleeve Gastrectomy as a surgical technique for treating morbid obesity, comparing its outcomes with other bariatric methods and evaluating its impact on patients' quality of life. This research utilized a comprehensive literature review, encompassing studies published between 2000 and 2024 in English, Portuguese, and Spanish. Databases such as PubMed, Google Scholar, SciELO, as well as specialized scientific journals and academic repositories were consulted. The results indicate that Sleeve Gastrectomy is an effective technique for weight loss, showing outcomes comparable to other bariatric surgeries such as Roux-en-Y Gastric Bypass. Literature analysis revealed that Sleeve Gastrectomy provides significant short-term and long-term weight loss with lower incidence of postoperative complications compared to other techniques. Furthermore, patients' quality of life improved considerably after surgery, covering physical, psychological, and social aspects. It is concluded that Sleeve Gastrectomy is a viable and safe surgical option for treating morbid obesity, offering significant advantages in terms of weight loss and patient quality of life. However, further long-term studies are needed to fully compare this technique with other bariatric treatment modalities and assess the maintenance of weight loss and improvement of associated comorbidities.O presente estudo visa analisar a eficácia e a segurança do Sleeve Gástrico como técnica cirúrgica no tratamento da obesidade mórbida, comparando seus resultados com outros métodos bariátricos e avaliando seu impacto na qualidade de vida dos pacientes. Esta pesquisa utilizou uma revisão da literatura abrangente, incluindo estudos publicados entre 2000 e 2024 em inglês, português e espanhol. Foram consultadas bases de dados como PubMed, Google Acadêmico, SciELO, além de revistas científicas especializadas e repositórios acadêmicos. Os resultados indicam que o Sleeve Gástrico é uma técnica eficaz para a perda de peso, apresentando resultados comparáveis a outras cirurgias bariátricas como o Bypass Gástrico em Y de Roux. A análise da literatura revelou que o Sleeve Gástrico proporciona uma perda de peso significativa a curto e longo prazo, com menor incidência de complicações pós-operatórias em comparação com outras técnicas. Além disso, a qualidade de vida dos pacientes melhorou consideravelmente após a cirurgia, abrangendo aspectos físicos, psicológicos e sociais. Conclui-se que o Sleeve Gástrico é uma opção cirúrgica viável e segura para o tratamento da obesidade mórbida, oferecendo vantagens significativas em termos de perda de peso e qualidade de vida dos pacientes. No entanto, é necessário mais estudo de longo prazo para comparar plenamente esta técnica com outras modalidades de tratamento bariátrico e avaliar a manutenção da perda de peso e a melhoria das comorbidades associadas

Combined therapy with the use of transcranial direct current stimulation associated with aerobic training for fibromialgic patients: A randomized, double-blind, clinical trial

A Fibromialgia (FM) é uma síndrome de dor crônica caracterizada pelo aparecimento de dor difusa, intermitente e crônica por todo o corpo. A prática de exercícios aeróbicos demonstra resultados no alívio da dor, porém com uma dificuldade de aderência aos protocolos. A Estimulação Transcraniana com Corrente Contínua (ETCC), promove modulação da atividade cerebral e tem demonstrado resultados positivos para redução da dor. O objetivo deste estudo foi determinar o efeito da terapia combinada utilizando a técnica de ETCC associada ao treino de Exercício Aeróbico (EA) em pacientes portadores de fibromialgia. Para tanto, 45 pacientes foram randomizados em um dos seguintes três grupos: Grupo ETCC / EA, Grupo EA (com ETCC simulada), e Grupo ETCC (com EA simulado). Durante a intervenção os sujeitos passaram por uma etapa de uma semana de ETCC (cinco dias consecutivos) associado ao treino de EA por três dias desta semana; e uma segunda etapa de quatro semanas (sendo realizadas três vezes em cada semana) apenas com o treino de EA. A ETCC foi aplicada posicionando o eletrodo anodal sobre o córtex motor primário e o eletrodo catodal sobre a região supra-orbital contralateral com 2mA por 20 minutos. O EA utilizou uma intensidade de 60 a 70% da frequência cardíaca máxima. A escala visual numérica de dor foi utilizada como desfecho primário, sendo utilizadas avaliações de ansiedade, limiar de dor à pressão, resposta condicionada a dor (DNIC), preenchimento de mapa corporal, questionário de qualidade de vida SF-36, inventário de depressão de Beck, tarefa go-no-go, teste de caminhada de seis minutos, timed up-and-go, e avaliação da excitabilidade cortical utilizando estimulação magnética transcraniana. Houve efeito significativo para a interação tempo X grupo para a intensidade da dor, demonstrando que ETCC / EA foi superior ao AE apenas (F (13,364) = 2.25, p = 0,007) e ETCC (F (13,364) = 2.33, p = 0,0056). Análise ajustada do post hoc demostrou uma diferença entre ETCC / AE e grupo ETCC após a primeira semana de estimulação e depois do período de um mês de intervenção (p = 0,02 e p = 0,03, respectivamente). Além disso, após o tratamento houve uma diferença significativa entre os grupos nos níveis de ansiedade e de humor. O tratamento combinado apresentou a maior resposta. Nenhum dos grupos apresentou diferenças significativas em relação a respostas da plasticidade do córtex motor, tal como avaliado pela EMT. A combinação de ETCC com o exercício aeróbico é superior em comparação com cada intervenção individual (tamanho do efeito pelo teste d de Cohen> 0,55). Este estudo demonstrou que a neuromodulação com ETCC associado ao treino de EA levou a uma melhora na resposta de dor mais intensa do que quando comparado a cada modalidade de intervenção isolada. Os níveis de ansiedade também demonstraram melhora no grupo de associação. Notavelmente, o nível inicial de dor e humor parece ser um preditor do resultado. Observou-se que os indivíduos com níveis de dor mais altos e níveis mais elevados de depressão responderam melhor ao tratamento. Por fim, a intervenção combinada teve um efeito significativo sobre a dor, ansiedade e humor. É provável que a intervenção combinada pode ter afetado outros circuitos neurais, tais como aqueles que controlam os aspectos afetivo-emocionais de dorFibromyalgia (FM) is a chronic pain syndrome characterized by the appearance of diffuse pain, intermittent and chronic throughout the body. The aerobic exercise demonstrates results in relieving but with a difficulty of adherence to protocols. The transcranial direct current stimulation (tDCS) promotes modulation of brain activity and have demonstrated positive results in reducing pain. The aim of this study was to determine the effect of a combination therapy protocol using tDCS technique associated with Aerobic Exercise training (AE) in fibromyalgia patients. Therefore, 45 patients were randomized into one of three groups: tDCS/AE group, AE group (sham tDCS), and tDCS group (sham AE). During the intervention subjects went through a stage of a week of tDCS (five consecutive days) associated with AE training for three days per week; and a second step with four weeks duration (being performed three times per week) only with AE training. The tDCS was applied by placing the anodal electrode on the primary motor cortex and catodal electrode on the contralateral supraorbital region, using 2mA for 20 minutes. AE used an intensity of 60 to 70% of maximum heart rate. The visual numeric pain scale was used as the primary outcome, and as secondary outcome: VNS anxiety ratings, pressure pain threshold, conditioned pain modulation (DNIC), SF-36 questionnaire, beck depression inventory, an emotional go-no-go task, six-minute walk test, timed up-and-go test, and evaluation of cortical excitability using TMS. There was a significant effect for the interaction time X group to the intensity of pain, demonstrating that tDCS / AE was higher than the AE only (F (13.364) = 2.25, p = 0.007) and tDCS (F (13.364) = 2.33, p = 0, 0056). Adjusted post hoc analysis demonstrated a difference between tDCS / AE and tDCS group after first week of stimulation, and after one month\'s intervention (p = 0.02 and p = 0.03, respectively). In addition, after treatment there was a significant difference between the groups in the level of anxiety and mood. The combined treatment showed the greatest response. Neither group showed significant differences from the motor cortex plasticity responses, as assessed by EMT. The combination of tDCS with aerobic exercise is higher compared to each individual intervention (effect size for the test Cohen d> 0.55). This study demonstrated that neuromodulation with tDCS associated with AE training led to an improvement in the intensity of pain greater than when compared to each intervention modality alone. Anxiety levels also showed improvement in the combination group. Notably, the initial level of pain and mood seems to be a predictor of the outcome. It was observed that individuals with higher levels of pain and higher levels of depression responded better to the treatment. Finally, the combined intervention had a significant effect on pain, anxiety and mood. It is likely that the combined intervention may have affected other neural circuits, such as those that control the affective and emotional aspects of pai