Aktiia cuffless blood pressure monitor yields equivalent daytime blood pressure measurements compared to a 24-h ambulatory blood pressure monitor: Preliminary results from a prospective single-center study.

In this preliminary study, we compared daytime blood pressure (BP) measurements performed by a commercially available cuffless-and continual-BP monitor (Aktiia monitor, Neuchâtel, Switzerland) and a traditional ambulatory BP monitor (ABPM; Dyasis 3, Novacor, Paris, France) from 52 patients enrolled in a 12-week cardiac rehabilitation (CR) program (Neuchâtel, Switzerland). Daytime (9am-9pm) systolic (SBP) and diastolic (DBP) BP from 7-day averaged data from Aktiia monitor were compared to 1-day averaged BP data from ABPM. No significant differences were found between the Aktiia monitor and the ABPM for SBP (µ ± σ [95% confidence interval]: 1.6 ± 10.5 [-1.5, 4.6] mmHg, P = 0.306; correlation [R2]: 0.70; ± 10/ ± 15 mmHg agreements: 60%, 84%). Marginally non-significant bias was found for DBP (-2.2 ± 8.0 [-4.5, 0.1] mmHg, P = 0.058; R2: 0.66; ±10/±15 mmHg agreements: 78%, 96%). These intermediate results show that daytime BP measurements using the Aktiia monitor generate data comparable to that of an ABPM monitor.

Use of digital technologies in mental health during COVID-19 / Uso de tecnologias digitais na saúde mental durante a COVID-19

Most countries did not have a consolidated digital health structure before the pandemic. Both social distancing and mental health problems resulting from the situation justify the urgency of discussions on web-mediated interventions. The objective of this work is to present the panorama of technological mediation in mental health services and their specificities in the context of the pandemic. This paper is grounded on a critical look at the migration from face-to-face care to the Internet environment, highlighting: the international experiences using digital technologies in the pandemic context; the challenges in online consultations, emphasizing the importance of the ethical, technical/technological, and clinical domains, which are recurring issues in the international literature; the challenges and perspectives in the use of technologies. It is essential to develop strategies aligned with government incentives, aiming at the quality of the offered services and the guarantee of an adequate hybrid qualification.

A maioria dos países não possuía uma estrutura de saúde digital consolidada antes da pandemia. Tanto o distanciamento social quanto os agravos psicológicos decorrentes da própria situação justificam a urgência de discussões científicas sobre intervenções mediadas pela web. O objetivo deste trabalho é apresentar o panorama da mediação tecnológica nos serviços de saúde mental e suas especificidades no contexto da pandemia. Parte-se de um olhar crítico diante da migração do cuidado face a face ao ambiente da Internet, ressaltando: experiências internacionais no uso das tecnologias digitais no contexto da pandemia; desafios nas consultas online, com destaque à importância dos domínios ético, técnico/tecnológico e da clínica recorrentes na literatura internacional; desafios e perspectivas do uso das tecnologias. É imprescindível desenvolver estratégias com incentivo governamental, visando a qualidade dos serviços oferecidos e a garantia de formação híbrida adequada.

Anti-Interleukin-5 in the Management of Eosinophilic Asthma: A Review of Effectiveness, Safety, and Budgetary Impact From the Perspective of the Brazilian Health System.

OBJECTIVES: To evaluate the efficacy and safety of anti-interleukin-5 class therapy agents in the treatment of eosinophilic asthma and the financial impact of these drugs on the Brazilian and Mato Grosso public health systems. METHODS: The literature review in important databases was guided by a structured research question including patient or population, intervention, comparator, outcome and type of study. The retrieved studies went through a screening, selection, data extraction, and methodological quality assessment process. A model with two scenarios, one with mepolizumab and the other with benralizumab, was created for budget impact analysis. RESULTS: Evidence indicated that anti-interleukins-5 have an acceptable safety profile and can reduce exacerbation rates by up to 50% in the population with eosinophilic asthma; however, they showed no significant difference in quality of life. The adoption of these drugs in the Brazilian health system can impact the budget from R$ 40,379,731.50 to R$ 140,301,211.34 depending on the drug incorporated, considering a time horizon of 5 years. From the perspective of the state of Mato Grosso, the budget impact may reach, in the fifth year, an amount of R$ 1,301,210.58 and R$ 2,050.687.62 for the scenarios with mepolizumab and benralizumab, respectively. CONCLUSION: Anti-interleukins-5 are promising treatments for eosinophilic asthma because they minimise exacerbations and are well tolerated and safe. The financial impact is large, implying that technology costs may be a barrier to accessing this treatment class.

Screening for Health-Promoting Fatty Acids in Ascidians and Seaweeds Grown under the Influence of Fish Farming Activities.

The present study aimed to contrast the fatty acid (FA) profile of ascidians (Ascidiacea) and seaweeds (sea lettuce, Ulva spp. and bladderwrack, Fucus sp.) occurring in a coastal lagoon with versus without the influence of organic-rich effluents from fish farming activities. Our results revealed that ascidians and seaweeds from these contrasting environments displayed significant differences in their FA profiles. The n-3/n-6 ratio of Ascidiacea was lower under the influence of fish farming conditions, likely a consequence of the growing level of terrestrial-based ingredients rich on n-6 FA used in the formulation of aquafeeds. Unsurprisingly, these specimens also displayed significantly higher levels of 18:1(n-7+n-9) and 18:2n-6, as these combined accounted for more than 50% of the total pool of FAs present in formulated aquafeeds. The dissimilarities recorded in the FAs of seaweeds from these different environments were less marked (≈5%), with these being more pronounced in the FA classes of the brown seaweed Fucus sp. (namely PUFA). Overall, even under the influence of organic-rich effluents from fish farming activities, ascidians and seaweeds are a valuable source of health-promoting FAs, which confirms their potential for sustainable farming practices, such as integrated multi-trophic aquaculture.

Pediatric Acute Promyelocytic Leukemia: Epidemiology, Molecular Features, and Importance of GST-Theta 1 in Chemotherapy Response and Outcome.

Previous studies have suggested a variation in the incidence of acute promyelocytic leukemia (APL) among the geographic regions with relatively higher percentages in the Latin American population. We aimed to explore the population burden of pediatric APL, gathering information from the population-based cancer registry (PBCR) and the diagnosis of APL obtained through incident cases from a hospital-based cohort. The homozygous deletion in glutathione S-transferases (GSTs) leads to a loss of enzyme detoxification activity, possibly affecting the treatment response. Mutations in the RAS pathway genes are also considered to be a key component of the disease both in the pathogenesis and in the outcomes. We have assessed mutations in a RAS-MAP kinase pathway (FLT3, PTPN11, and K-/NRAS) and GST variant predisposition risk in the outcome. Out of the 805 children and adolescents with acute myeloid leukemia (AML) who are registered in the PBCR, 35 (4.3%) were APL cases. The age-adjusted incidence rate (AAIR) was 0.03 per 100,000 person-years. One-hundred and sixty-three patients with APL were studied out of 931 AML cases (17.5%) from a hospital-based cohort. Mutations in FLT3, KRAS, and NRAS accounted for 52.1% of the cases. Patients with APL presented a 5-year probability of the overall survival (OS) of 67.3 ± 5.8%. A GST-theta 1 (GSTT1) null genotype conferred adverse prognosis, with an estimated hazard ratio of 2.8, 95% confidence interval (CI) 1.2-6.9. We speculate that the GSTT1 polymorphism is associated with therapeutics and would allow better OS of patients with APL with a GSTT1 null genotype.

Adaptation and validation of the EVENDOL scale to assess pain in neonates in Portuguese language.

BACKGROUND: EVENDOL scale (from the French Evaluation Enfant Douleur) is used to evaluate pain in children in any situation covering a wider age group than other pain scales (birth up to seven years). This study aimed to evaluate pain in hospitalized newborns, to adapt and validate the EVENDOL to Brazilian Portuguese. STUDY DESIGN: Cross-sectional, cross-cultural adaptation and validation study in a convenience sample from a tertiary hospital, Brazil. EVENDOL was translated and tested for reliability and validity using the PIPP and NFCS scales for comparison. For reliability testing, two observers independently evaluated 117 nociceptive procedures from 87 newborns. Internal consistency coefficient Cronbach's alpha, internal class agreement coefficient, and Kappa factor were appropriately measured. RESULTS: The scale's internal consistency reached a value of 0.82, and the estimates of internal consistency and reliability also reached acceptable or very good values. Two-way ANOVA determined statistically significant effect of gestational age on the total score of the EVENDOL (F = 4.14; p = 0.045), younger infants had the lowest values, as lower values of Apgar-5° minute lowered the indicator "Interaction with the Environment" (F = 5.066; p = 0.027). CONCLUSIONS: EVENDOL proved to be an easily applied tool and it was psychometrically robust, reliable and valid for use with both premature and term hospitalized newborns, who were clinically stable, being Apgar score and gestational age relevant factors. It is a reliable method of identifying pain in babies who need more support from the hospital staff and now is available for use in Portuguese language. TWEETABLE ABSTRACT: The EVENDOL pain scale is now validated for babies born at term and prematurely in Portuguese Language allowing its use in all Lusophone countries.

Medical students' knowledge of the human papillomavirus (HPV), cervical cancer, and HPV vaccination / Conhecimento dos alunos de medicina sobre papilomavírus humano (HPV), câncer cervical e vacinação contra HPV

Abstract: Introduction: Medical students still have many doubts regarding HPV (Human papillomavirus) and the vaccine against this virus. Objective: The study aimed to assess the University of Brasilia medical students' grasp of knowledge about HPV, its relationship with cancer, and the vaccine against the virus. Methods: A cross-sectional study was undertaken by applying a survey questionnaire on the topics. The evaluation involved 379 respondents, 72.7% of the 521 students from the 1st to the 6th years enrolled in the second semester of 2017. The statistical analyses included differences between means and proportions, effect size measures, and the correlation between the identified indicators. The study was approved by the Ethics Committee in Research on Human Beings of the School of Medicine (1,989,835). Results: The 50-item knowledge score increased progressively with the year attended by the medical students (r= .706, p< .001), and was higher among the sexually-active compared to celibate participants (t = 3.26, df = 275, p = 0.001, d = 0.37), as well as among participants with higher family income compared to those with lower family income (t= 2.91, df= 366, p= .004, d= .35). No significant score differences emerged between participants grouped by gender, sexual behavior, or HPV vaccination status. Furthermore, gender (female; OR= 6.5, p<.001), age range (<24 years; OR= 3.3, p= .001), sexuality (active; OR= 2.7, p= .002), but not overall knowledge were predictors of the wish to be vaccinated among the 297 unvaccinated students. Conclusion: The study revealed a strong correlation of medical students' HPV-related knowledge with medical school year and significantly higher scores among sexually active and higher-income respondents, but there were no essential differences between males and females or between vaccinated and unvaccinated students. Among the latter participants, gender, age, and sexuality, but not knowledge, were the best predictors of the wish to be vaccinated. The findings suggest the need for improving HPV screening and vaccination programs and educational strategies regarding HPV-related diseases.

Resumo: Introdução: Há ainda, entre os estudantes de Medicina, muitas dúvidas com relação ao papilomavírus humano (HPV) e à vacina contra esse vírus. Objetivo: Este estudo teve como objetivo avaliar a compreensão dos estudantes de Medicina da Universidade de Brasília acerca do HPV, da sua relação com o câncer e da vacina contra o vírus. Método: Foi realizado um estudo transversal por meio da aplicação de um questionário teste sobre os temas. A avaliação envolveu 379 respondentes, o que representava 72,7% dos 521 alunos do primeiro ao sexto ano matriculados no segundo semestre de 2017. As análises estatísticas incluíram diferenças entre médias e proporções, medidas de tamanho de efeito e a correlação entre os indicadores identificados. O estudo foi aprovado pelo Comitê de Ética em Pesquisa em Seres Humanos da Faculdade de Medicina (1,989,835). Resultado: A pontuação de conhecimento de 50 itens aumentou progressivamente com o ano do curso médico (r = 0,706, p <0,001) e foi maior entre os participantes sexualmente ativos em comparação com os celibatários (t = 3,26, df = 275, p = 0,001, d = 0,37), e entre os participantes com renda familiar mais alta em comparação com aqueles com renda mais baixa (t = 2,91, df = 366, p = 0,004, d = 0,35). Nenhuma diferença significativa de pontuação foi observada entre os participantes agrupados por gênero, comportamento sexual ou estado de vacinação contra o HPV. Além disso, sexo (feminino; OR = 6,5, p <0,001), faixa etária (<24 anos; OR = 3,3, p = 0,001) e sexualidade (ativo; OR = 2,7, p = 0,002), mas não o conhecimento geral, foram preditores do desejo de vacinação entre 297 alunos não vacinados. Conclusão: O estudo revelou uma forte correlação entre o conhecimento relacionado ao HPV dos estudantes de Medicina e o ano de estudo, e pontuações significativamente mais altas entre os respondentes sexualmente ativos e de renda superior, mas não houve nenhuma diferença essencial entre homens e mulheres ou entre alunos vacinados e não vacinados. Entre estes últimos, gênero, idade, sexualidade, e não o conhecimento foram os melhores preditores do desejo de vacinação. Os achados sugerem a necessidade de aperfeiçoamento em programas de triagem e vacinação para HPV e nas estratégias educacionais referentes às doenças relacionadas ao vírus.

Development of CAR-T cell therapy for B-ALL using a point-of-care approach.

Recently approved by the FDA and European Medicines Agency, CAR-T cell therapy is a new treatment option for B-cell malignancies. Currently, CAR-T cells are manufactured in centralized facilities and face bottlenecks like complex scaling up, high costs, and logistic operations. These difficulties are mainly related to the use of viral vectors and the requirement to expand CAR-T cells to reach the therapeutic dose. In this paper, by using Sleeping Beauty-mediated genetic modification delivered by electroporation, we show that CAR-T cells can be generated and used without the need for ex vivo activation and expansion, consistent with a point-of-care (POC) approach. Our results show that minimally manipulated CAR-T cells are effective in vivo against RS4;11 leukemia cells engrafted in NSG mice even when inoculated after only 4 h of gene transfer. In an effort to better characterize the infused CAR-T cells, we show that 19BBz T lymphocytes infused after 24 h of electroporation (where CAR expression is already detectable) can improve the overall survival and reduce tumor burden in organs of mice engrafted with RS4;11 or Nalm-6 B cell leukemia. A side-by-side comparison of POC approach with a conventional 8-day expansion protocol using Transact beads demonstrated that both approaches have equivalent antitumor activity in vivo. Our data suggest that POC approach is a viable alternative for the generation and use of CAR-T cells, overcoming the limitations of current manufacturing protocols. Its use has the potential to expand CAR immunotherapy to a higher number of patients, especially in the context of low-income countries.

Transposon-mediated generation of CAR-T cells shows efficient anti B-cell leukemia response after ex vivo expansion.

CAR-T-cell therapy has shown considerable advance in recent years, being approved by regulatory agencies in US, Europe, and Japan for the treatment of refractory patients with CD19+ B-cell leukemia or diffuse large B-cell lymphoma. Current methods for CAR-T-cell production use viral vectors for T-cell genetic modification and can take up to 15 days to generate the infusion product. The development of simple and less costly manufacturing protocols is needed in order to meet the increasing demand for this therapy. In this present work, we generated 19BBz CAR-T cells in 8 days using a protocol based on the non-viral transposon-based vector Sleeping Beauty. The expanded cells display mostly a central memory phenotype, expressing higher levels of inhibitory receptors when compared with mock cells. In addition, CAR-T cells were cytotoxic against CD19+ leukemia cells in vitro and improved overall survival rates of mice xenografted with human RS4;11 or Nalm-6 B-cell leukemias. Infused CAR-T cells persisted for up to 28 days, showing that they are capable of long-term persistence and antitumor response. Altogether, these results demonstrate the effectiveness of our protocol and pave the way for a broader application of CAR-T-cell therapy.

Corrigendum: The Profile of Immunophenotype and Genotype Aberrations in Subsets of Pediatric T-Cell Acute Lymphoblastic Leukemia.

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Accuracy testing of a new optical device for noninvasive estimation of systolic and diastolic blood pressure compared to intra-arterial measurements.

OBJECTIVE: The objective of this study was to compare the systolic (S) and diastolic (D) blood pressure (BP) estimations from a new optical device at the wrist with invasive measurements performed on patients scheduled for radial arterial catheterization in the ICU. Optical signals were automatically processed by a library of algorithms from Aktiia SA (OBPM - optical blood pressure monitoring algorithms). METHODS: A total of 31 participants from both sexes, aged 32-87 years, were enrolled in the study (NCT03837769). The measurement protocol consisted of the simultaneous recording of reflective photoplethysmographic signals (PPG) from the cuffless optical device and the reference BP values recorded by a contralateral radial arterial catheter. From the 31 participants, 23 subjects whose reference data quality requirements were adequate were retained for further analysis. The PPG signals from these patients were then automatically processed by the Aktiia OBPM library of algorithms, which generated uncalibrated estimates of SBP and DBP. After the automatic assessment of optical signal quality, 326 pairs of uncalibrated SBP and DBP determinations from 16 patients were available for analysis. These values were finally transformed into calibrated estimations (in mmHg) using arterial catheter SBP and DBP values, respectively. RESULTS: For SBP, a mean difference (±SD) of 0.0 ± 7.1 mmHg between the arterial catheter and the optical device values was found, with 95% limits of agreement in the Bland-Altman method of -11.9 to + 12.2 mmHg (correlation of r = 0.87, P < 0.001). For DBP, a mean difference (±SD) of 0.0 ± 2.9 mmHg between arterial catheter and the optical device values was found, with 95% limits of agreement in the Bland-Altman method of -4.8 to + 5.5 mmHg (correlation of r = 0.98, P < 0.001). CONCLUSION: SBP and DBP values obtained by radial artery catheterization and those obtained from optical measurements at the wrist were compared. The new optical technique appears to be capable of replacing more traditional methods of BP estimation.

Students' HPV vaccination rates are associated with demographics, sexuality, and source of advice but not level of study in medical school.

This study aimed to explore how medical students differ regarding the HPV vaccination status according to their demographics, sexuality, medical school year and sources of information regarding the vaccine. The cross-sectional survey included 379 participants from medical school year 1 to 6, in a medical school in Brasilia. Statistical analyses of the data obtained from a questionnaire analyzed contingency tables and highlighted odds ratios effect sizes. The results showed that among all the participants, 80 (21.1%) were vaccinated against HPV, 215 (58.7%) were not vaccinated but wanted to be and 84 (22.2%) were neither vaccinated nor wanted to be vaccinated. . Female gender (OR= 5.88, 95% CI 3.36-10.30), parental advice (OR= 6.95, 95% CI= 3.97-12.16), and absence of sexual initiation before 16 years of age (OR= 3.04, 95% CI= 1.05-8.77) were positively associated with HPV-vaccinated students. In parallel, female gender (OR= 4.74, 95% CI= 2.38-9.44), parental advice (OR= 3.50, 95% CI=1.20-10.22), and reporting two or more recent sexual partners (OR= 2.03, 95% CI= 1.06-3.88) were positively associated with the intention to be vaccinated among unvaccinated students. The high cost of the vaccine was perceived as a barrier among those respondents who wished to be vaccinated. Additionally, among the 84 (81.3% male) students who admitted unwillingness to be vaccinated, approximately two-thirds cited the feeling to be safe, lack of counseling, or low efficacy of the vaccine as the reasons for their reluctance. In conclusion, vaccination coverage was low among these medical students. Nevertheless, female gender, personal advice, and safe sex were the main factors associated with higher levels of vaccination and vaccine acceptance.

The Profile of Immunophenotype and Genotype Aberrations in Subsets of Pediatric T-Cell Acute Lymphoblastic Leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous malignancy, which reflects distinctive stages of T-cell differentiation arrest. We have revisited a cohort of pediatric T-ALL, in order to test if immunophenotypes associated with molecular alterations would predict the patient's outcome. Genetic mutations, translocations and copy number alterations were identified through Sanger sequencing, RT-PCR, FISH and multiplex ligation-dependent probe amplification (MLPA). We defined 8 immunophenotypic T-ALL subtypes through multiparametric flow cytometry: early T-cell precursor (ETP, n = 27), immature (n = 38), early cortical (n = 15), cortical (n = 50), late cortical (n = 53), CD4/CD8 double negative mature (n = 31), double positive mature (n = 35) and simple positive mature (n = 31) T-ALL. Deletions (del) or amplifications (amp) in at least one gene were observed in 87% of cases. The most frequent gene alterations were CDKN2A/Bdel (71.4%), NOTCH1mut (47.6%) and FBXW7mut (17%). ETP-ALL had frequent FLT3mut (22.2%) and SUZ12del (16.7%) (p < 0.001), while CDKN2A/Bdel were rarely found in this subtype (p < 0.001). The early cortical T-ALL subtype had high frequencies of NOTCH1mut and IL7Rmut (71%, 28.6%, respectively), whereas, mature T-ALL with double positive CD4/CD8 had the highest frequencies of STIL-TAL1 (36.7%), LEF1del (27.3%) and CASP8AP2del (22.7%). The co-existence of two groups of T-ALL with NOTCH1mut/IL7Rmut, and with TLX3/SUZ12del/NF1del/IL7Rmut, were characterized with statistical significance (p < 0.05) but only STIL-TAL1 (pOS 47.5%) and NOTCH1WT/FBXW7WT (pOS 55.3%) are predictors of poor T-ALL outcomes. In conclusion, we have observed that 8 T-ALL subgroups are characterized by distinct molecular profiles. The mutations in NOTCH1/FBXW7 and STIL-TAL1 rearrangement had a prognostic impact, independent of immunophenotype.

Advancements and achievements in the Brazilian Federal District public health: an essential contribution by family and community medicine. / Avanços e conquistas na saúde pública do DF, Brasil: uma contribuição essencial da medicina de família e comunidade.

The history of Primary Health Care (PHC) in the Federal District (DF) is as old as the history of the Federative Unit. The history of Family and Community Medicine (MFC), however, is relatively recent, both locally and nationally. This paper proposes to focus on the fundamental contribution of MFC to advances in Public Health in the Federal District, especially in the last 10 years, after the founding of the Family and Community Medicine Association of Brasília (ABMFC). In order to do so, the most relevant historical events and contexts related to Health Care, Management, Social Control and Medical Education - including Undergraduate course and Residency - were documented, which support this position, in parallel with the evolution of the specialty in the Federal District. Therefore, its organization was divided into four historical stages: until 2008, from 2008 to 2011, from 2011 to 2016, and from 2016 to 2018.

A história da Atenção Primária à Saúde (APS) no Distrito Federal (DF) é tão antiga quanto a história da unidade federativa. A história da especialidade Medicina de Família e Comunidade (MFC), porém, é relativamente recente, tanto em âmbito local como nacional. O presente artigo se propõe a focar na fundamental contribuição da MFC para os avanços na Saúde Pública do DF, sobretudo nos últimos 10 anos, após a fundação da Associação Brasiliense de Medicina de Família e Comunidade (ABMFC). Para tanto, foram rememorados os eventos e os contextos históricos mais relevantes, relacionados às áreas de Assistência à Saúde, Gestão, Controle Social e Ensino Médico ­ incluindo Graduação e Residência ­, que embasam essa posição, paralelamente à evolução da própria especialidade no DF. Sua organização foi, portanto, dividida em quatro etapas históricas: até 2008, de 2008 a 2011, de 2011 a 2016, e de 2016 até 2018.

Avanços e conquistas na saúde pública do DF, Brasil: uma contribuição essencial da medicina de família e comunidade / Advancements and achievements in the Brazilian Federal District public health: an essential contribution by family and community medicine

Resumo A história da Atenção Primária à Saúde (APS) no Distrito Federal (DF) é tão antiga quanto a história da unidade federativa. A história da especialidade Medicina de Família e Comunidade (MFC), porém, é relativamente recente, tanto em âmbito local como nacional. O presente artigo se propõe a focar na fundamental contribuição da MFC para os avanços na Saúde Pública do DF, sobretudo nos últimos 10 anos, após a fundação da Associação Brasiliense de Medicina de Família e Comunidade (ABMFC). Para tanto, foram rememorados os eventos e os contextos históricos mais relevantes, relacionados às áreas de Assistência à Saúde, Gestão, Controle Social e Ensino Médico - incluindo Graduação e Residência -, que embasam essa posição, paralelamente à evolução da própria especialidade no DF. Sua organização foi, portanto, dividida em quatro etapas históricas: até 2008, de 2008 a 2011, de 2011 a 2016, e de 2016 até 2018.

Abstract The history of Primary Health Care (PHC) in the Federal District (DF) is as old as the history of the Federative Unit. The history of Family and Community Medicine (MFC), however, is relatively recent, both locally and nationally. This paper proposes to focus on the fundamental contribution of MFC to advances in Public Health in the Federal District, especially in the last 10 years, after the founding of the Family and Community Medicine Association of Brasília (ABMFC). In order to do so, the most relevant historical events and contexts related to Health Care, Management, Social Control and Medical Education - including Undergraduate course and Residency - were documented, which support this position, in parallel with the evolution of the specialty in the Federal District. Therefore, its organization was divided into four historical stages: until 2008, from 2008 to 2011, from 2011 to 2016, and from 2016 to 2018.

T-lymphoid/myeloid mixed phenotype acute leukemia and early T-cell precursor lymphoblastic leukemia similarities with NOTCH1 mutation as a good prognostic factor.

Purpose: T-lymphoid/Myeloid Mixed phenotype acute leukemia (T/M-MPAL) is ambiguous leukemia which overlaps with early T-cell precursor lymphoblastic leukemia (ETP-ALL). We have revisited the immunophenotyping profile of T/M-MPAL and ETP-ALL to identify differences and/or similarities, as these entities represent a therapeutic challenge in clinical practice. Patients and methods: A total of 26 ETP-ALL and 10 T/M-MPAL cases were identified among 857 cases of childhood leukemia (T-ALL, n=266 and AML, n=591) before any treatment decisions. The variables analyzed were age strata, sex, clinical features, immunophenotyping, and molecular aberrations. Immunophenotyping was performed in all samples using a panel of cytoplasm and membrane antibodies to identify the lineage and blast differentiation. The mutational status of STIL-TAL1, TLX3, RUNX1, NOTCH1, FBXW7, FLT3, IL7R, RAS, KTM2A, and CDKN2A/B was tested using RT-PCR, FISH, and PCR sequencing methods. The outcomes were assessed in terms of overall survival (OS). Results: The immunophenotypes were similar in ETP-ALL and T/M-MPAL, regarding the cellular expression of CD34, CD117, CD13/CD33, and CD11b, although CD2 and HLA-DR were more frequent in T/M-MPAL (p<0.01). aMPO positivity and myelomonocyte differentiation were definitive in separating both entities. NOTCH1, FLT3-ITD, and N/KRAS mutations as well as TLX3 and KMT2A rearrangements were found in both ETP-ALL and T/M-MPAL. Thirty-one patients received ALL protocol whereas five had AML therapy. The overall 5-year survival rate (pOS) was 56.4% for patients treated using ALL protocols. No differences were observed between T/M-MPAL (pOS of 57%) and ETP-ALL (pOS of 56%) patients. The prognostic value of NOTCH1mut was associated with significantly better OS (pOS 90%) than NOTCH1 wt (pOS 37%) (p=0.017). Conclusion: This research can potentially contribute to NOTCH1 as targeted therapy and prognostic assessment of T-cell mixed phenotype leukemia.

CD44 Expression Profile Varies According to Maturational Subtypes and Molecular Profiles of Pediatric T-Cell Lymphoblastic Leukemia.

CD44 is a glycoprotein expressed in leucocytes and a marker of leukemia-initiating cells, being shown to be important in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). In this study, we have (i) identified the aberrant antigenic pattern of CD44 and its isoform CD44v6 in T-ALL; (ii) tested the association with different T-cell subtypes and genomic alterations; (iii) identified the impact of CD44 status in T-ALL outcome. Samples from 184 patients (123 T-ALL and 61 AML; <19 years) were analyzed throughout multiparametric flow cytometry. Mutations in N/KRAS, NOTCH1, FBXW7 as well as STIL-TAL1 and TLX3 rearrangements were detected using standard molecular techniques. CD44 expression was characterized in all T-ALL and AML cases. Compared with AML samples in which the median fluorescence intensity (MFI) was 79.1 (1-1272), T-ALL was relatively low, with MFI 43.2 (1.9-1239); CD44v6 expression was rarely found, MFI 1 (0.3-3.7). T-ALL immature subtypes (mCD3/CD1aneg) had a lower CD44 expression, MFI 57.5 (2.7-866.3), whereas mCD3/TCRγδpos cases had higher expressions, MFI 99.9 (16.4-866.3). NOTCH1 mut and STIL-TAL1 were associated with low CD44 expression, whereas N/KRAS mut and FBXW7 mut cases had intermediate expression. In relation to clinical features, CD44 expression was associated with tumor infiltrations (p = 0.065). However, no association was found with initial treatment responses and overall survival prediction. Our results indicate that CD44 is aberrantly expressed in T-ALL being influenced by different genomic alterations. Unraveling this intricate mechanism is required to place CD44 as a therapeutic target in T-ALL.

Curso para mudança do modelo da atenção primária em região de saúde do distrito federal / Course to change the model of primary care in the federal district health region

INTRODUÇÃO: Alicerçado no SUS e na PNAB, o Distrito Federal, por meio das Portarias 77 e 78, sistematizou o Converte. A Região de Saúde Norte realizou um curso diferenciado para esse processo. OBJETIVO: Apresentar a operacionalização do curso. MÉTODO: Utilizou-se a Residência em Medicina de Família e Comunidade e os Gerentes de Território, e propôs-se, coletivamente, a reestruturação do módulo prático e das reuniões de equipe. RESULTADOS: Construiu-se um ambiente semelhante à Residência, regatando-se valores e diretrizes da APS. CONCLUSÃO: O planejamento participativo com a aproximação de diferentes atores tornou-se diferencial e potencializador do curso do Converte na Região Norte.