The Diagnostic Accuracy (DA) of ColonView Fecal Immunochemical Test (FIT) in Detecting Colorectal Adenoma (CRA) Can Be Improved by the Diagnostic Models (DM) that Include Triage and Risk Features of CRA.

BACKGROUND/AIM: This study assessed whether the diagnostic accuracy (DA) of ColonView (CV) fecal immunochemical test (FIT) in detecting colorectal adenoma (CRA) can be improved by the diagnostic models (DM) that include triage and risk features of CRA. PATIENTS AND METHODS: A total of 5,090 participants of colorectal neoplasia (CRN) screening were recruited prospectively between January 2014 and December 2016. The CRN cohort of 486 patients included 222 CRA patients and 264 non-CRA patients of whom three consecutive fecal samples were analyzed by two fecal occult blood (FOB) assays (CV FIT test, HemoccultSENSA test). Hierarchical multilevel logistic models were used to test the DA of CV test and DMs, visualised as hierarchical summary receiving operating characteristic (HSROC) curves. RESULTS: In conventional receiving operating characteristic (ROC) analysis, the area under the curve (AUC) values of the age, height, weight, and body mass index (BMI) were 0.60, 0.57, 0.54, and 0.51, respectively. The AUC values for different DMs ranged from 0.69 (for DM without triage I/II and SENSA), and the highest AUC value of 0.70 was reached for DM with all variables included. In HSROC analysis, the AUC values for i) lowR variables, ii) highR variables, and ii) DMs were as follows: i) AUC=0.506, ii) AUC=0.566 and iii) AUC=0.732. The differences in AUC values were: between i) and ii) p=0.008; between i) and iii) p<0.0001; between ii) and iii) p<0.0001. CONCLUSION: The results demonstrated that DMs, particularly those including risk factors, significantly improved the DA of the CV FIT test in detecting CRA compared to traditional low-risk (lowR) and high-risk (highR) features alone. This study provides novel evidence supporting the enhanced diagnostic performance of DMs in combination with CV FIT testing for the detection of CRA.

Biological and therapeutic implications of RKIP in Gastrointestinal Stromal Tumor (GIST): an integrated transcriptomic and proteomic analysis.

BACKGROUND: Gastrointestinal stromal tumors (GIST) represent a significant clinical challenge due to their metastatic potential and limited treatment options. Raf kinase inhibitor protein (RKIP), a suppressor of the MAPK signaling pathway, is downregulated in various cancers and acts as a metastasis suppressor. Our previous studies demonstrated low RKIP expression in GIST and its association with poor outcomes. This study aimed to expand on the previous findings and investigate the biological and therapeutic implications of RKIP loss on GIST. METHODS: To validate the RKIP prognostic significance, its expression was evaluated by immunohistochemistry in 142 bona fide GIST cases. The functional role of RKIP was evaluated in vitro, using the GIST-T1 cell line, which was knocked out for RKIP. The biological and therapeutic implications of RKIP were evaluated by invasion, migration, apoptosis, and 2D / 3D viability assays. Additionally, the transcriptome and proteome of RKIP knockout cells were determined by NanoString and mass spectrometry, respectively. RESULTS: Immunohistochemical analysis revealed the absence of RKIP in 25.3% of GIST cases, correlating with a tendency toward poor prognosis. Functional assays demonstrated that RKIP knockout increased GIST cells' invasion and migration potential by nearly 60%. Moreover, we found that RKIP knockout cells exhibited reduced responsiveness to Imatinib treatment and higher cellular viability in 2D and 3D in vitro models, as assessed by apoptosis-related protein expression. Through comprehensive genetic and proteomic profiling of RKIP knockout cells, we identified several putative RKIP-regulated proteins in GIST, such as COL3A1. CONCLUSIONS: Using a multidimensional integrative analysis, we identified, for the first time in GIST, molecules and pathways modulated by RKIP that may potentially drive metastasis and, consequently, poor prognosis in this disease.

Triage Process at Endoscopy With ColonView Fecal Immunochemical Test (FIT) Will Enhance Diagnostic Accuracy (DA) of Colorectal Cancer Screening.

BACKGROUND/AIM: This study assessed the diagnostic accuracy (DA) of the predictive features of colorectal cancer (CRC, predictCRC), triage process (triage), and ColonView (CV) fecal immunochemical test (FIT) in a CRC screening setting. The diagnostic score models (DMs) including predictCRC with triage and CV test were also calculated. PATIENTS AND METHODS: The study cohort of 544 patients included 58 CRC patients and 486 non-CRC patients who submitted three consecutive fecal samples for analysis, by two fecal occult blood (FOB) assays (CV FIT test, HemoccultSENSA test). Hierarchical multilevel logistic models were used to test the DA (for CRC) of each item of predictCRC (with triage I and II) and DMs, visualized as hierarchical summary receiving operating characteristic (HSROC) curves. RESULTS: The DA of the predictCRC location of neoplasm (Loc), triage I, and triage II showed 49%, 41%, and 93% sensitivity (Se), and 70%, 99.5%, and 88% specificity (Sp), respectively. The PPV+ of triage I (92%) was higher than that of Loc (22%) or triage II test (45%). In the conventional receiver operating characteristic (ROC) analysis, the area under the curve (AUC) values for the different DMs ranged from 0.880 (for DM without triage I and II), whereas the highest AUC value of 0.960 was reached for DM with triage I and II included in the formula. In the HSROC analysis, the AUC values were as follows: i) with all predictCRCs, AUC=0.717 and ii) with DMs, AUC=0.937. In the roccomp analysis, the difference in AUC values between i) and ii) was statistically significant (p<0.0001). CONCLUSION: In the detection of CRC, the DA of the new DMs with triage was far superior to that of DMs without triage. This is the first study to report evidence of improved DA in the detection of CRC using DMs including predictCRC with triage and CV FIT test.

Colorectal cancer spatial pattern in the northeast region of São Paulo, Brazil.

Background: This study examined the spatial pattern of the colorectal cancer (CRC) in the 18 municipalities that compose the Regional Health Department of Barretos (RHD-V), which is in the northeast of the state of São Paulo, Brazil. Methods: All incident cases and deaths from CRC between 2002 and 2016 were included. Age-standardized rates (ASR) for incidence and mortality per 100,000 person-years were used to evaluate the spatial distribution for the total and five-year periods. The lethality rates were also assessed. Excess risk maps compared the observed and expected events. Age-standardized net survival was used to evaluate CRC survival. Results: For CRC incidence, the ASR value for the general population over the entire period (2002-2016) was 17.7 (95% CI: 16.7, 18.6), ranging from 16.7 (95% CI: 14.9, 18.4) (2002-2006) to 20.0 (95% CI: 18.3, 21.7) (2012-2016) per 100,000. When males and females were compared, the ASR was 20.1 (95% CI: 18.6, 21.6) and 15.7 (95% CI: 14.5, 17.0) per 100,000, respectively. For CRC mortality (2002-2016), the ASR was 8.2 (95% CI: 7.6, 8.9), ranging from 9.0 (95% CI: 7.8, 10.3) (2002-2006) to 8.2 (95% CI: 7.2, 9.3) (2012-2016) per 100,000. Overall, the excess risk up to 2.0 was more frequent. In terms of survival, municipalities with large port populations had lower survival in comparison with medium port. Conclusions: This study showed a variation in CRC incidence and mortality, with differences considering five-year periods and gender, being the incidence higher in males than females in the entire period, with mortality equivalent to half the incidence. The survival was lower in municipalities with large port populations in comparison with medium port. Knowing spatial patterns of incidence, mortality, lethality, and survival can be necessary to support policymakers to advance or implement effective cancer control programs.

Fecal Immunochemical Test (FIT) in Triage of Bleed-positive (Crab+) and Bleed-negative Colorectal Adenoma (Crab-) Patients in Colorectal Neoplasia Screening.

BACKGROUND/AIM: Fecal immunochemical tests (FITs) are sensitive and specific for detecting colorectal cancer (CRC), but their diagnostic accuracy (DA) in bleed-positive (CRAb+) and bleed-negative colorectal adenomas (CRAb-) has been rarely tested. PATIENTS AND METHODS: A total of n=506 patients were included in the study, each collecting 3 consecutive stool samples for analysis. The stool samples were analyzed by the ColonView FIT (CV) and Hemoccult SENSA tests. A total of 484/5,090 (9.5%) patients returned all 3 samples and were subjected to final analysis. Hierarchical summary receiver operating characteristic (HSROC) analysis with different cut-offs for hemoglobin/haptoglobin (Hb and Hb/Hp) complex was performed to assess the DA of CV. RESULTS: In the HSROC analysis, the AUC values were as follows: i) bleed-positive adenoma patients by visual analysis mode (VA), AUC=0.566, ii) bleed-positive adenoma patients by automatic analysis mode (AA), AUC=0.546, iii) bleed-negative adenoma patients by VA, AUC=0.534 and iv) bleed-negative adenoma patients by AA, AUC=0.589: In roccomp analysis, there were significant differences in AUC values between iii) and iv) p=0.045. CONCLUSION: When stratified by the 'blood in stool' (as b+ or b- endpoint), the DA of the CV test is quite similar for CRAb+ and CRAb-. However, of the two modes (VA/AA) of the CV test, the AA reading gives a slightly higher DA both CRAb+ and CRAb-.

Combined SEPT9 and BMP3 methylation in plasma for colorectal cancer early detection and screening in a Brazilian population.

BACKGROUND: Colorectal cancer (CRC) screening can help to reduce its incidence and mortality. Noninvasive strategies, such as plasma analysis of epigenetic alterations, can constitute important biomarkers of CRC detection. OBJECTIVE: This study aimed to evaluate the plasma methylation status of SEPT9 and BMP3 promoters as biomarkers for detection of CRC and its precursor lesions in a Brazilian population. METHODS: Plasma samples from 262 participants of the CRC screening program of Barretos Cancer Hospital who had a positive fecal occult blood test and underwent colonoscopy and cancer patients were analyzed. Participants were grouped according to the worst lesion detected in the colonoscopy. Cell-free circulating DNA (cfDNA) was bisulfite treated followed by the analysis of SEPT9 and BMP3 methylation status using a droplet digital PCR system (ddPCR). The best methylation cutoff value for group discrimination was calculated by receiver operating characteristic (ROC) curve analysis. RESULTS: Among the 262 participants, 38 were diagnosed with CRC, 46 with advanced adenomas 119 with nonadvanced adenomas, three with sessile serrated lesions, and 13 with hyperplastic polyps. In 43 participants, no lesion was detected in the colonoscopy and were used as controls. The CRC group showed the highest cfDNA concentration (10.4 ng/mL). For the SEPT9 gene, a cutoff of 2.5% (AUC = 0.681) that discriminates between CRC and the control group resulted in CRC sensitivity and specificity of 50% and 90%, respectively. Concerning the BMP3 gene, a cutoff of 2.3% (AUC = 0.576) showed 40% and 90% of sensitivity and specificity for CRC detection, respectively. Combining SEPT9, BMP3 status, and age over 60 years resulted in a better performance for detecting CRC (AUC = 0.845) than the individual gene models, yielding 80% and 81% of sensitivity and specificity, respectively. CONCLUSION: The present study suggests that a combination of SEPT9 and BMP3 plasma methylation, along with age over 60 years, showed the highest performance in detecting CRC in a Brazilian population. These noninvasive biomarkers can potentially serve as useful tools for CRC screening programs.

Community mental health care network: an evaluative approach in a Brazilian state.

In recent decades, public policies of the Unified Health System (SUS) in Brazil have structured a community mental health care network (RAPS) based on various community actions and services. This study carried out evaluative research on the implementation of the structure and process dimensions of this care network in Minas Gerais, the second most populous state of Brazil, generating indicators that can enhance the strategic management of the public health system in the strengthening the psychosocial care in the state. The application of a multidimensional instrument, previously validated (IMAI-RAPS), in 795 of the 853 municipalities in Minas Gerais was carried out between June and August 2020. Regarding the structural dimension, we noticed an adequate implementation of services like 'Family Health Strategy,' 'Expanded Family Health Center,' and 'Psychosocial Care Centers' but a lack of 'Beds in General Hospitals' destinated to mental health care, 'Unified Electronic Medical Records' and 'Mental Health Training Activities for Professionals.' In the process dimension, adequate implementation of actions such as 'Multidisciplinary and Joint Care,' 'Assistance to Common Mental Disorders by Primary Health Care,' 'Management of Psychiatric Crises in Psychosocial Care Centers,' 'Offer of Health Promotion Actions,' and 'Discussion of Cases by Mental Health Teams' point to a form of work consistent with the guidelines. However, we detected difficulties in the implementation of 'Psychosocial Rehabilitation Actions,' 'Productive Inclusion,' 'User Protagonism,' 'Network Integration,' and practical activities for the effectiveness of collaborative care. We found a better implementation of the mental health care network in more populous, demographically dense, and socioeconomically developed cities, which shows the importance of regional sharing of services that are not possible for small cities. The evaluation practices of mental health care networks are scarce throughout the Brazilian territory, a fact also found in Minas Gerais, highlighting the need for its expansion not only in the scientific sphere but also in the daily life of the various levels of management.

Diagnostic Accuracy of Fecal Immunochemical Test (FIT) in Bleed-positive and Bleed-negative Colorectal Cancer (CRC) Among a Cohort of 5,090 Subjects who Participated in the Colorectal Neoplasia (CRN) Screening in Brazil.

BACKGROUND/AIM: This study assessed the diagnostic accuracy (DA) of fecal immunochemical test (FIT) ColonView (CV) and guaiac-based fecal occult blood test (HemoccultSENSA) among bleed-positive (history or signs of intestinal bleeding) and bleed-negative participants (no history or signs of intestinal bleeding) (n=5,090) in colorectal neoplasia (CRN) screening in Brazil. PATIENTS AND METHODS: The eligible patients for the study (n=506) collected three consecutive stool samples, to be analyzed by both assays (CV, SENSA). Finally, 421/5090 (8.3%) patients returned both samples, which were subjected to final analysis. Receiver operating characteristic (ROC) analysis with different cut-offs was performed to assess the DA. RESULTS: The area under curve (AUC) values for i) visually analyzed (VA) CV for bleed-positive CRC, ii) automatically analyzed (AA) CV for bleed-positive CRC, iii) VA CV for bleed-negative CRC, and iv) AA CV for bleed-negative CRC as endpoints were as follows: i) AUC=0.864, ii) AUC=0.933, iii) AUC=0.836, and iv) AUC=0.892. In roccomp analysis, the differences in AUC values were: between i) and ii) p=0.068; between i) and iii) p=0.497; between i) and iv) p=0.488; between ii) and iii) p=0.0058; between ii) and iv) p=0.229; and between iii) and iv) p=0.138. CONCLUSION: This is the first investigation where two modes of CV test, VA, and AA, for bleed-positive and bleed-negative CRC patients were used as the endpoint. The AA reading of the CV test showed higher DA in bleed-positive than in bleed-negative CRC patients.

Transcriptomic and biochemical analysis from the venom gland of the neotropical ant Odontomachus chelifer.

The genus Odontomachus is widely distributed in neotropical areas throughout Central and South America. It is a stinging ant that subdues its prey (insects) by injecting them a cocktail of toxic molecules (venom). Ant venoms are generally composed of formic acid, alkaloids, hydrocarbons, amines, peptides, and proteins. Odontomachus chelifer is an ant that inhabits neotropical regions from Mexico to Argentina. Unlike the venom of other animals such as scorpions, spiders and snakes, this ant venom has seldom been analyzed comprehensively, and their compositions are not yet completely known. In the present study, we performed a partial investigation of enzymatic and functional activities of O. chelifer ant venom, and we provide a global insight on the transcripts expressed in the venom gland to better understand their properties. The crude venom showed phospholipase A2 and antiparasitic activities. RNA sequencing (Illumina platform) of the venom gland of O. chelifer generated 61, 422, 898 reads and de novo assembly Trinity generated 50,220 contigs. BUSCO analysis against Arthropoda_db10 showed that 92.89% of the BUSCO groups have complete gene representation (single-copy or duplicated), while 4.05% are only partially recovered, and 3.06% are missing. The 30 most expressed genes in O. chelifer venom gland transcriptome included important transcripts involved in venom function such as U-poneritoxin (01)-Om1a-like (pilosulin), chitinase 2, venom allergen 3, chymotrypsin 1 and 2 and glutathione S-transferase. Analysis of the molecular function revealed that the largest number of transcripts were related to catalytic activity, including phospholipases. These data emphasize the potential of O. chelifer venom for prospection of molecules with biotechnological application.

Tensionamentos no cuidado em Saúde Mental relacionados ao uso de Substâncias Psicoativas: dificuldades identificadas por profissionais da saúde pública / Tensioning in Mental Healthcare related to Psychoactive Substance use: difficulties reported by public health professionals

RESUMO Analisaram-se, na percepção de profissionais da Atenção Primária à Saúde (APS), as dificuldades no cuidado em Saúde Mental relacionadas ao uso de Substâncias Psicoativas (SPA), à luz de reflexões sobre os tensionamentos presentes na saúde pública no que se refere ao seu uso. Foi conduzido estudo exploratório qualitativo em 11 municípios da Macrorregião de Saúde Oeste do estado de Minas Gerais, com entrevistas semiestruturadas e Grupos Focais com 145 profissionais da APS. O material foi analisado a partir do referencial de Análise de Conteúdo. As principais dificuldades identificadas estavam relacionadas à organização e à gestão do trabalho em saúde, ao estigma sobre usuários com demandas relacionadas ao uso de SPA, à falta de reflexões e práticas em saúde que considerem a realidade dos usuários em uso de SPA, à 'cultura da medicação' e à desarticulação da Rede de Atenção Psicossocial. É fundamental o desenvolvimento de políticas e práticas que permitam aos trabalhadores e às estruturas de saúde uma maior reflexão acerca da relação entre o uso de SPA e as possibilidades de lidar com o sofrimento, expresso de diferentes formas pelos usuários dos serviços de saúde.

ABSTRACT Difficulties found by healthcare professionals working at Primary Health Care (PHC) with respect to Mental Healthcare issues regarding Psychoactive Substances (PS) were analyzed considering a tensioning which pervaded those issues. An exploratory qualitative study was performed in 11 municipalities of the west macroregion of Minas Gerais state. Semi-structured interviews and focal groups with 145 PHC professionals. Data was analyzed through content analysis. The most relevant difficulties were related to health work organization and management, the stigma against users with demands related do the use of PS, the lack of reflections health practices which consider the user's reality, the 'medicine culture' and a disjointed Psychosocial Attention Network. It is fundamental to develop policies and practices that allow workers and health structures to reflect more on the relationship between PS use and possibilities to cope with suffering, expressed in different ways by healthcare users.

Rede de Atenção Psicossocial: desenvolvimento e validação de um instrumento multidimensional para avaliação da implantação (IMAI-RAPS) / Psychosocial Care Network: development and validation of a multidimensional instrument to assess implementation (IMAI-RAPS)

Resumo Trata-se de um estudo metodológico para desenvolvimento e validação do Instrumento Multidimensional para Avaliação da Implantação da RAPS (IMAI-RAPS) em Minas Gerais (MG)/Brasil. O estudo foi executado em três etapas: estudo de avaliabilidade, desenvolvimento do IMAI-RAPS, aplicação da Técnica Delphi para validação de conteúdo e aparência das questões. Foram realizados a análise de documentos oficiais, revisão da literatura e um engajamento estruturado com membros do programa para esclarecer sua operacionalização e focalizar os aspectos centrais a serem avaliados. Um modelo teórico-lógico da RAPS foi construído de acordo com a tríade donabediana: estrutura, processo e resultado e organizado em: Unidades Mínimas (Assistência à Saúde Mental e Reabilitação Psicossocial), Conectividade (Articulação da Rede), Integração (Governança e Gestão do Cuidado), Normatividade (Política de Saúde Mental e Participação e Controle Social), Subjetividade e Estrutura (Serviços, Sistema Logístico e Educação em Saúde). Desse modelo derivou-se o IMAI-RAPS que foi validado por 44 experts da área indicando a abordagem de questões relevantes, úteis e viáveis para avaliação da estrutura e processo de implantação do programa em MG. A utilização da Técnica Delphi possibilitou que os produtos desenvolvidos fossem balizados por estudiosos ou profissionais da RAPS de diversas regiões do país aumentando o poder analítico da ferramenta.

Abstract This is a methodological study for the development and validation of the Multidimensional Instrument for Evaluating of the Implementation of Psychosocial Care Network (IMAI-RAPS) in Minas Gerais (MG)/Brazil. The study was carried out in three stages: evaluability study, development of the IMAIRAPS, application of the Delphi Technique for content and appearance validation of the questions. The analysis of official documents, literature review and a structured engagement with program members were carried out to clarify its operationalization and focus on the central aspects to be evaluated. A theoreticallogical model of RAPS was built according to the Donabedian triad: structure, process and result and organized into: Minimum Units (Mental Health Care and Psychosocial Rehabilitation), Connectivity (Network Articulation), Integration (Governance and Management of the Care), Normativity (Mental Health Policy and Participation and Social Control), Subjectivity and Structure (Services, Logistics System and Health Education). The IMAI-RAPS was derived from this model, which was validated by 44 experts in the field, indicating the approach of relevant, useful and viable questions for evaluating the structure and process of implementing the program in MG. The use of the Delphi Technique made it possible for the developed products to be marked out by Psychosocial Care Network scholars or professionals from different regions of the country, increasing the analytical power of the tool.

Dificuldades no trabalho em saúde mental: percepção de trabalhadores do Núcleo de Apoio à Saúde da Família na Macrorregião Oeste de Minas Gerais / Difficulties in mental health work: the perception of Family Health Support Center workers in the Western Region of Minas Gerais state, Brazil

Resumo No atual cenário de manobras neoliberais no país, mudanças nas Políticas de Atenção em Saúde alteram formas de organização e financiamento dos serviços, desdobram-se em formas precarizadas de trabalho e ameaçam conquistas da Reforma Psiquiátrica e Atenção Psicossocial. Buscou-se identificar e analisar, na percepção de profissionais de 11 equipes de Núcleo de Apoio a Saúde da Família (NASF), dificuldades no processo de construção de uma política de Saúde Mental (SM) na Atenção Básica em Saúde (ABS). Realizou-se estudo qualitativo, a partir de entrevistas com 11 profissionais de SM dos NASF, e estas foram analisadas considerando-se o referencial da Análise de Conteúdo. As dificuldades identificadas foram: formas precárias de contratação; alta rotatividade; carga horária insuficiente; baixa remuneração; concentração da carga horária em atividades de assistência; falta de compartilhamento e integração de serviços e profissionais; desarticulação da Rede de Atenção Psicossocial (RAPS). O Apoio Matricial não estava incorporado e não havia políticas de Educação Permanente em Saúde (EPS) no conjunto dos municípios estudados. No entanto, os NASF contribuíam para melhorar o cuidado em SM. Conclui-se que as mudanças em curso impõem desafios para a sustentação de conquistas em SM e consolidação da política de SM na ABS dos municípios estudados.

Abstract The current scenario of neoliberal political maneuvers in Brazil brought several legislative changes regarding health care policies which alter many services' organizational forms and funding. These changes also come through as precarious work and threaten advances and accomplishments related to the Brazilian Psychiatric Reform and mental health care. This study aimed to identify and analyse difficulties regarding the construction of a mental health (MH) policy in Primary Health Care (PHC) according to professionals working at 11 teams of the Family Health Support Center (NASF). We developed a qualitative study through 11 semi-structured interviews conducted with 11 MH workers in PHC and explored the results using content analysis. The identified difficulties were precarious forms of employment; high professional turnover; insufficient working hours; low wages; working hours concentrated in care activities; lack of integration and communication among services and workers and disarticulation of the psychosocial attention network (RAPS). Matrix support was not present and there were no Permanent Health Education policies in the municipalities studied. Nevertheless, the NASF contributed to improve mental healthcare. The conclusion is that ongoing changes impose challenges to sustain mental health accomplishments and consolidation of mental healthcare policies at PHC at the studied municipalities.Resumo: No atual cenário de manobras neoliberais no país, mudanças nas Políticas de Atenção em Saúde alteram formas de organização e financiamento dos serviços, desdobram-se em formas precarizadas de trabalho e ameaçam conquistas da Reforma Psiquiátrica e Atenção Psicossocial. Buscou-se identificar e analisar, na percepção de profissionais de 11 equipes de Núcleo de Apoio a Saúde da Família (NASF), dificuldades no processo de construção de uma política de Saúde Mental (SM) na Atenção Básica em Saúde (ABS). Realizou-se estudo qualitativo, a partir de entrevistas com 11 profissionais de SM dos NASF, e estas foram analisadas considerando-se o referencial da Análise de Conteúdo. As dificuldades identificadas foram: formas precárias de contratação; alta rotatividade; carga horária insuficiente; baixa remuneração; concentração da carga horária em atividades de assistência; falta de compartilhamento e integração de serviços e profissionais; desarticulação da Rede de Atenção Psicossocial (RAPS). O Apoio Matricial não estava incorporado e não havia políticas de Educação Permanente em Saúde (EPS) no conjunto dos municípios estudados. No entanto, os NASF contribuíam para melhorar o cuidado em SM. Conclui-se que as mudanças em curso impõem desafios para a sustentação de conquistas em SM e consolidação da política de SM na ABS dos municípios estudados.

Abordagem da morte na graduação médica: percepções de estudantes à luz de contribuições freudianas / Approach to death in medical graduation: students' perceptions in light of Freudian contributions

Resumo Introdução: Na sociedade ocidental contemporânea, as tentativas de evitar a morte e o sofrimento impulsionam a formação de médicos voltados para lidar majoritariamente com aspectos biológicos do adoecimento e da morte, em detrimento dos aspectos psicossociais relacionados a essas questões. Objetivo: Buscou-se identificar a percepção de estudantes de Medicina sobre a abordagem da morte e do morrer na graduação à luz de estudos atuais sobre a formação médica no país e algumas contribuições da teoria freudiana sobre a morte. Método: Trata-se de pesquisa qualitativa de caráter exploratório, desenvolvida a partir de seis grupos focais compostos por 55 estudantes de todos os períodos do curso de Medicina de uma universidade federal do interior de Minas Gerais. O material produzido foi analisado a partir do referencial de análise de conteúdo temática ou categorial, e emergiram categorias: 1. a morte na formação médica; 2. o médico diante da morte. Resultado: Discutir a morte e o morrer no processo formativo é falar da angústia diante da finitude. Os estudantes identificaram a abordagem da morte e do morrer na graduação, mas de forma limitada e insuficiente. Apontaram a necessidade de ampliar o contato com os temas no currículo, melhorar as metodologias utilizadas e inserir de forma obrigatória os conteúdos de cuidados paliativos. O papel do médico comporta tanto o cuidado com foco na cura quanto a assistência nas situações em que a cura não for possível. A preparação para lidar com a morte ao longo da graduação envolve concepções e experiências pessoais, experiências na graduação, acesso aos conteúdos teóricos, especificidades e aspectos subjetivos relacionados a cada situação. Os recursos mencionados para lidar com a morte, além dos estudos, foram a religiosidade e psicoterapias. Conclusão: Abordar a morte nos currículos de graduação em Medicina envolve grande complexidade e desafios. Do ponto de vista da realidade psíquica, os seres humanos tentam negar a morte e evitar os sofrimentos. Dessa forma, os desafios da formação e da prática médica consistem em assumir a articulação indissociável entre aspectos biológicos, culturais e psicossociais. Cuidar da vida é também cuidar da morte, e evitá-la pode desencadear maior sofrimento aos pacientes, familiares, estudantes e médicos.

Abstract: Introduction: In western contemporary society, attempts to prevent death and suffering promote a medical training focused on dealing mostly with the biological aspects of illness and death, to the detriment of the psychosocial aspects related to those issues. Objective: The authors intended to identify medical students' perceptions about the approach to death and dying in the light of Freudian theory about death. Method: This was a qualitative study with an exploratory approach, developed based on six focal groups consisting of 55 students from all the undergraduate medical school semesters from a federal university in the interior of the state Minas Gerais. The data produced was analyzed according to the thematic or category-based content analysis, from which the following categories emerged: 1- The death topic in undergraduate medical school; 2- The medical professional facing death. Results: To discuss death and dying in the formative process is to talk about the anguish in the face of human finitude. The students identified the approach to death and dying in undergraduate school, but in a limited and insufficient way. They indicated the need to increase contact with the topic in the curriculum, and to include, in a mandatory way, the contents on Palliative Care. The medical role encompasses both the care focused on healing and the assistance in moments when healing is not possible. The preparation to deal with death throughout undergraduate training involves personal conceptions and experiences, undergraduate practice, access to theoretical contents, specificities and subjective aspects related to each situation. The mentioned resources to deal with death, in addition to the studies, were religiosity and psychotherapy. Conclusion: To approach death in undergraduate medical curricula involves great complexity and challenges. From the viewpoint of psychological reality, human beings try to deny death and avoid suffering. Thus, the challenges in medical formation and practices consist in assuming the indissociable articulation between the biological, cultural and psychosocial aspects. To take care of life is also to take care of death and avoiding it may cause greater suffering to the patients, family members, students and medical professionals.

The Barretos Cancer Hospital Animal Facility: Implementation and Results of a Dedicated Platform for Preclinical Oncology Models.

The Barretos Cancer Hospital Animal Facility (BCHAF) is a unique facility in Brazil exclusively dedicated to working with animal models for cancer research. In this article, we briefly present our modern facility and the main experiments performed, focusing on mutant strains of mice (PTCH-knockout and ApcMin mice), xenograft models, and patient-derived xenografts (PDXs). Our results show the progress and challenges in establishing these models and the need for having an appropriate representation of our cancer population to better understand tumor biology and to identify cancer biomarkers, which could be putatively targeted, allowing for personalized therapy.

Site-specific Performance of ColonView (CV) Fecal Immunochemical Test (FIT) With Differences Between Proximal and Distal Colorectal Adenoma.

BACKGROUND/AIM: The aim of this study was to assess the diagnostic accuracy (DA) of a ColonView (CV) test in proximal versus distal colorectal adenoma (pCRA versus dCRA). PATIENTS AND METHODS: The colorectal neoplasia (CRN) screening cohort included 5,090 individuals and 506/5,090 (10%) were eligible for the study. Finally, only 127/506 were included in the CRA analysis and hierarchical summary ROC (HSROC) curves were used to show the pooled overall DA of visually analyzed (VA) and automatically analyzed (AA) techniques in pCRA and dCRA detection. RESULTS: The overall specificity (Sp) of the AA technique for the pCRA and dCRA endpoint was 46% and 43%, respectively. The most sensitive AA test in pCRA patients showed 76% sensitivity (Se) versus 58% Se in dCRA patients. In the HSROC analysis, area under the curve (AUC) values were as follows: i) VA in pCRA: AUC=0.503, ii) AA in pCRA: AUC=0.560, iii) VA in dCRA: AUC=0.552 and iv) AA in dCRA: AUC=0.486. In Roccomp analysis, the statistically significant AUC values were available between VA and AA reading modes in pCRA (p=0.044) and in AA reading between pCRA and dCRA (p=0.024). CONCLUSION: As compared with the CRC endpoint, the DA value of the CV test is far inferior for the CRA endpoint, as determined by the AUC values.

Somatic targeted mutation profiling of colorectal cancer precursor lesions.

BACKGROUND: Most colorectal cancers (CRC) arise from precursor lesions. This study aimed to characterize the mutation profile of colorectal cancer precursor lesions in a Brazilian population. METHODS: In total, 90 formalin-fixed paraffin-embedded colorectal precursor lesions, including 67 adenomas, 7 sessile serrated lesions, and 16 hyperplastic polyps, were analyzed by next-generation sequencing using a panel of 50 oncogenes and tumor suppressor genes. The genetic ancestry of the patients was estimated. RESULTS: Somatic driver mutations were identified in 66.7% of cases, including alterations in APC (32.2%), TP53 (20.0%), KRAS (18.9%), BRAF (13.3%) and EGFR (7.8%). Adenomas displayed a higher number of mutations, mainly in APC, compared to serrated polyps (73.1% vs. 47.8%, p = 0.026). Advanced adenomas had a significantly higher frequency of mutation in KRAS and a high overall mutation rate than early adenomas (92.9% vs. 59%, p = 0.006). A high degree of ancestry admixture was observed in the population studied, with a predominance of European components (mean of 73%) followed by African (mean of 11.3%). No association between genetic ancestry and type of lesions was found. The mutation profile of Brazilian colorectal precursor lesions exhibits alteration in APC, KRAS, TP53, and BRAF at different frequencies according to lesion type. CONCLUSIONS: These results bestow the knowledge of CRC's biologic history and support the potential of these biomarkers for precursor lesions detection in CRC screening of the Brazilian population.

Morte e morrer na formação médica brasileira: revisão integrativa / Death and dying in Brazilian medical training: an integrative review / La murte y el morir em la formación médica brasileña: uma revisión integradora

Resumo A fim de descrever como a morte e o morrer são abordados na graduação médica no Brasil e suas repercussões para estudantes, realizou-se revisão integrativa de publicações ocorridas entre 2008 e 2019, resultando na seleção de 36 artigos. Identificaram-se dificuldades na abordagem do tema relacionadas ao modelo biomédico de formação, à organização dos currículos e à formação dos professores. Estas afetam os estudantes, trazendo sofrimento psíquico e prejudicando o processo de formação. Poucos currículos abordam aspectos psicossociais relacionados à morte e ao morrer, sendo frequentemente abordados com carga horária insuficiente, métodos inadequados ou como atividades extracurriculares. Propostas de solução apontam a necessidade de investimentos em cuidados paliativos na graduação. Conclui-se que essas temáticas precisam ser mais bem contempladas nas Diretrizes Curriculares Nacionais de cursos de medicina, de modo a garantir uma formação mais humanitária, pautada em princípios éticos, e que prepare estudantes e profissionais para lidar com situações de terminalidade.

Abstract To describe how death and dying are approached in the medical undergraduate programs in Brazil and their repercussions for students, an integrative review of publications from 2008 to 2019 was carried out, resulting in a selection of 36 articles. The difficulties in approaching the theme related to the biomedical model of training, the organization of the curriculum, and the training of teacher were identified. Those affect students, causing psychic suffering and hindering the training process. Few curriculums approach psychosocial aspects related to death and dying, which are often approached for insufficient credit hours, inadequate methods, or as extracurricular activities. Solution proposals point to the necessity of investments in palliative care in the undergraduate programs. In conclusion, these themes need to be more thoroughly included in the National Curricular Directives of medicine programs, to foster a more humanitarian training, based on ethical principles, and which prepares students and professionals to deal with end-of-life situations

Resumen Este texto describe cómo la graduación en Medicina en Brasil aborda la muerte y el morir y sus repercusiones al alumnado; para ello, se realizó una revisión integradora de 36 artículos publicados entre 2008 y 2019. Se identificaron las dificultades en el enfoque del tema relacionadas con el modelo biomédico de formación, la organización curricular y la formación docente. Esas dificultades generan sufrimiento psíquico a los estudiantes y perjudican su formación. Pocos currículos abordan los aspectos psicosociales en este tema y, muchas veces, lo hacen con inadecuados métodos, desde una insuficiente carga horaria o desde actividades extracurriculares. Para solucionarlo, es necesario plantear los cuidados paliativos en la graduación. Esta temática debe abordarse mejor en las Directrices Curriculares Nacionales de la carrera de medicina para garantizar una formación más humanitaria, basada en principios éticos y que prepara a los estudiantes y profesionales para enfrentar situaciones de final de la vida.

Regionalization of psychosocial care: a panoramic view of the Psychosocial Care Network of Minas Gerais state, Brazil. / Regionalização da atenção psicossocial: uma visão panorâmica da Rede de Atenção Psicossocial de Minas Gerais, Brasil.

The present study aims at analyzing the regionalization of the services carried out by the Psychosocial Care Network (RAPS in Portuguese) in the state of Minas Gerais (MG) in Brazil, yielding indicators that may enhance the SUS strategic management towards the strengthening of the psychosocial care provided by the state. It is a cross-sectional study, based on the data collected in May 2019 from government websites, considering the state's Macro-Regions and Health Regions as units of analysis. Indicators of service coverage in relation to the population in accordance to normative parameters determined by the Ministry of Health for a better understanding of the effective coverage were produced, and a general indicator (iRAPS) of the supply of services in this network in Minas Gerais state was validated. The outcomes allow a detailed analysis of the structural aspect of the RAPS in MG and unveil the development of a robust network. However, important regional heterogeneities were noticed and also a lack of services aiming at specific populations providing assistance 24 hours a day, which weakens the proper access to RAPS in several parts of the state. Higher values of iRAPS were found in health regions with low socioeconomic development and low general offer of health services, a fact that differs from the national scenario, which may imply state policy investments aiming at offering RAPS within the state hinterland areas.

Objetivou-se analisar a regionalização dos serviços da Rede de Atenção Psicossocial (RAPS) em Minas Gerais (MG), Brasil, gerando indicadores que possam potencializar a gestão estratégica do SUS no fortalecimento da atenção psicossocial do estado. É um estudo transversal, realizado a partir de dados coletados em maio de 2019 em sites governamentais, tendo as Macrorregiões e Regiões de Saúde do estado como unidades de análise. Foram produzidos indicadores da cobertura de serviços em relação à população, de acordo com parâmetros normativos estipulados pelo Ministério da Saúde, para melhor compreensão da cobertura efetivada e validou-se um indicador geral (iRAPS) da oferta dos serviços dessa rede em MG. Os resultados encontrados possibilitam uma análise detalhada do aspecto estrutural da RAPS em MG e demonstram a implantação de uma rede robusta. Entretanto, percebem-se importantes heterogeneidades regionais e também uma carência de serviços voltados para populações específicas e com funcionamento 24 horas, o que fragiliza o adequado acesso à RAPS em diversos territórios do estado. Foram encontrados maiores valores do iRAPS nas regiões de saúde com baixo desenvolvimento socioeconômico e baixa oferta geral de serviços de saúde, fato que difere do cenário nacional.

Regionalização da atenção psicossocial: uma visão panorâmica da Rede de Atenção Psicossocial de Minas Gerais, Brasil / Regionalization of psychosocial care: a panoramic view of the Psychosocial Care Network of Minas Gerais state, Brazil

Resumo Objetivou-se analisar a regionalização dos serviços da Rede de Atenção Psicossocial (RAPS) em Minas Gerais (MG), Brasil, gerando indicadores que possam potencializar a gestão estratégica do SUS no fortalecimento da atenção psicossocial do estado. É um estudo transversal, realizado a partir de dados coletados em maio de 2019 em sites governamentais, tendo as Macrorregiões e Regiões de Saúde do estado como unidades de análise. Foram produzidos indicadores da cobertura de serviços em relação à população, de acordo com parâmetros normativos estipulados pelo Ministério da Saúde, para melhor compreensão da cobertura efetivada e validou-se um indicador geral (iRAPS) da oferta dos serviços dessa rede em MG. Os resultados encontrados possibilitam uma análise detalhada do aspecto estrutural da RAPS em MG e demonstram a implantação de uma rede robusta. Entretanto, percebem-se importantes heterogeneidades regionais e também uma carência de serviços voltados para populações específicas e com funcionamento 24 horas, o que fragiliza o adequado acesso à RAPS em diversos territórios do estado. Foram encontrados maiores valores do iRAPS nas regiões de saúde com baixo desenvolvimento socioeconômico e baixa oferta geral de serviços de saúde, fato que difere do cenário nacional.

Abstract The present study aims at analyzing the regionalization of the services carried out by the Psychosocial Care Network (RAPS in Portuguese) in the state of Minas Gerais (MG) in Brazil, yielding indicators that may enhance the SUS strategic management towards the strengthening of the psychosocial care provided by the state. It is a cross-sectional study, based on the data collected in May 2019 from government websites, considering the state's Macro-Regions and Health Regions as units of analysis. Indicators of service coverage in relation to the population in accordance to normative parameters determined by the Ministry of Health for a better understanding of the effective coverage were produced, and a general indicator (iRAPS) of the supply of services in this network in Minas Gerais state was validated. The outcomes allow a detailed analysis of the structural aspect of the RAPS in MG and unveil the development of a robust network. However, important regional heterogeneities were noticed and also a lack of services aiming at specific populations providing assistance 24 hours a day, which weakens the proper access to RAPS in several parts of the state. Higher values of iRAPS were found in health regions with low socioeconomic development and low general offer of health services, a fact that differs from the national scenario, which may imply state policy investments aiming at offering RAPS within the state hinterland areas.

Association of microsatellite instability (MSI) status with the 5-year outcome and genetic ancestry in a large Brazilian cohort of colorectal cancer.

Colorectal cancer (CRC) has a high incidence and mortality worldwide. Microsatellite instability (MSI) is crucial in CRC, with distinct molecular and clinicopathological features in patients. Nowadays, it is a predictive marker for immunotherapy. We proposed to evaluate the 5-year outcome of MSI status in 1002 Brazilian CRC, and associate it with genetic ancestry, molecular and clinicopathological features. MSI evaluation was performed using molecular markers. MSI+ tumors were analyzed for alterations in 23 MSI-targeted genes. Genetic ancestry was evaluated using an Ancestry-Informative markers panel. MSI status was analyzed in relation to CRC specific survival and other clinical and genetic variables. MSI+ status was observed in 10.5% of cases. MSI+ status was significantly associated with the anatomic site right colon, mucinous histological type, clinical stage II, histological grade III/undifferentiated, no recurrence of disease, and live cases without cancer. No association of MSI status with genetic ancestry components was observed. MSI-targeted genes analyses showed the most frequently altered genes: ATM, EGFR, MRE11, ROCK1, and TGFBRII. There was a statistically significant difference in cancer-specific survival between cases according to MSI status. This study constitutes the most comprehensive analyses of the MSI impact on the Brazilian CRC. MSI+ frequency in Brazilian CRC agreed with the literature and was associated with several clinicopathological features related with less aggressive tumors, independently of their genetic ancestry.