Predictive genetic panel for adult asthma using machine learning methods.

Background: Asthma is a chronic inflammatory disease of the airways that is heterogeneous and multifactorial, making its accurate characterization a complex process. Therefore, identifying the genetic variations associated with asthma and discovering the molecular interactions between the omics that confer risk of developing this disease will help us to unravel the biological pathways involved in its pathogenesis. Objective: We sought to develop a predictive genetic panel for asthma using machine learning methods. Methods: We tested 3 variable selection methods: Boruta's algorithm, the top 200 genome-wide association study markers according to their respective P values, and an elastic net regression. Ten different algorithms were chosen for the classification tests. A predictive panel was built on the basis of joint scores between the classification algorithms. Results: Two variable selection methods, Boruta and genome-wide association studies, were statistically similar in terms of the average accuracies generated, whereas elastic net had the worst overall performance. The predictive genetic panel was completed with 155 single-nucleotide variants, with 91.18% accuracy, 92.75% sensitivity, and 89.55% specificity using the support vector machine algorithm. The markers used range from known single-nucleotide variants to those not previously described in the literature. Our study shows potential in creating genetic prediction panels with tailored penalties per marker, aiding in the identification of optimal machine learning methods for intricate results. Conclusions: This method is able to classify asthma and nonasthma effectively, proving its potential utility in clinical prediction and diagnosis.

Análise bibliométrica da produção científica global em chikungunya: perspectiva da Vigilância em Saúde / Bibliometric analysis of global scientific production on chikungunya: Health Surveillance perspective / Análisis bibliométrico de la producción científica mundial sobre chikungunya: una perspectiva de Vigilancia Sanitária

Chikungunya, arbovirose que provoca febre e artralgia debilitante, demonstra potencial crônico e incapacitante por longos períodos, não havendo vacinas ou terapias específicas. Recentemente, a doença evoluiu da condição negligenciada para uma ameaça à saúde pública, impactando milhões de pessoas em regiões tropicais e subtropicais. Este estudo analisa a produção do conhecimento sobre a Chikungunya, na perspectiva da Vigilância em Saúde. Trata-se de metodologia exploratória-descritiva, com análise bibliométrica. Realizou-se a coleta nas bases Scopus e Web of Science para artigos de 2008 a 2022. A análise revelou uma série temporal de produção destacando a contribuição de Estados Unidos, Brasil e França. Identificaram-se como áreas mais produtivas: doenças transmissíveis, medicina tropical e parasitologia, fundamentais à Vigilância em Saúde e ao planejamento de políticas públicas. Quanto aos pesquisadores, Weaver, Scott C., Failloux, Anna-Bella e De Lamballerie, Xavier foram relevantes no cenário global, indicando a importância da colaboração e da abordagem interdisciplinar.

Chikungunya, an arbovirus that causes fever and debilitating arthralgia, has potential to be chronic and incapacitating for long periods, and there are no vaccines or therapies available for it. Recently, the disease has evolved from a neglected condition to public health threat, impacting millions in tropical and subtropical regions. This study analyzed the knowledge production about chikungunya, from the perspective of Health Surveillance, using an exploratory-descriptive methodology and bibliometric analysis. Articles from 2008 to 2022 were collected from Scopus and Web of Science databases. The analysis showed a production time series, highlighting the contribution of United States, Brazil, and France. The most productive areas were identified as: communicable diseases, tropical medicine and parasitology, which are fundamental to Health Surveillance and public policy planning. Regarding researchers, Weaver, Scott C., Failloux, Anna-Bella, and De Lamballerie, Xavier were relevant in the global scenario, indicating the importance of collaboration and of the interdisciplinary approach.

El chikungunya, arbovirus que causa fiebre y artralgia debilitante, tiene potencial de ser crónico e incapacitante por largos periodos, todavía no hay vacunas ni terapias. Recientemente, la enfermedad ha pasado de afección desatendida a amenaza para la salud pública, afectando a millones en regiones tropicales y subtropicales. Este estudio analiza la producción de conocimientos sobre chikungunya, desde la perspectiva de la Vigilancia Sanitaria. Se utilizó una metodología exploratoria-descriptiva con análisis bibliométrico. Se recompilaron artículos de Scopus y Web of Science, 2008-2022. El análisis reveló una serie temporal de producción, destacando la contribución de EEUU, Brasil y Francia. Se identificaron como áreas más productivas: enfermedades transmisibles, medicina tropical y parasitología, fundamentales para la Vigilancia Sanitaria y la planificación de políticas públicas. En cuanto a los investigadores, Weaver, Scott C., Failloux, Anna-Bella y De Lamballeire, Xavier fueron relevantes en el escenario global, indicando la importancia de la colaboración y del enfoque interdisciplinario.

The role of IL10 and IL17 gene polymorphisms in treatment response in children and adolescents with severe asthma.

OBJECTIVE: To determine whether polymorphisms of the IL10 and IL17 genes are associated with severe asthma control and bronchodilator reversibility in children and adolescents with severe asthma. METHODS: This was a cross-sectional study, nested within a prospective cohort study of patients with severe asthma. Two outcomes were evaluated: asthma control and bronchodilator reversibility. We extracted DNA from peripheral blood and genotyped three single nucleotide polymorphisms: rs3819024 and rs2275913 in the IL17A gene; and rs3024498 in the IL10 gene. For the association analyses, we performed logistic regression in three genetic models (allelic, additive, and dominant). RESULTS: The rs3024498 C allele in the IL10 gene was associated with failure to achieve asthma control despite regular treatment (p = 0.02). However, the G allele of the IL17A rs3819024 polymorphism was associated with failure to respond to stimulation with a b2 agonist. The rs2275913 polymorphism of the IL17A gene showed no relationship with asthma control or bronchodilator reversibility. CONCLUSIONS: In pediatric patients with severe asthma, the IL10 polymorphism appears to be associated with failure to achieve clinical control, whereas the IL17A polymorphism appears to be associated with a worse bronchodilator response. Knowledge of the involvement of these polymorphisms opens future directions for pharmacogenetic studies and for the implementation of individualized therapeutic management of severe asthma in pediatric patients.

Elucidating the role played by bone marrow in visceral leishmaniasis.

Leishmaniasis is a widespread group of infectious diseases that significantly impact global health. Despite high prevalence, leishmaniasis often receives inadequate attention in the prioritization of measures targeting tropical diseases. The causative agents of leishmaniasis are protozoan parasites of the Leishmania genus, which give rise to a diverse range of clinical manifestations, including cutaneous and visceral forms. Visceral leishmaniasis (VL), the most severe form, can be life-threatening if left untreated. Parasites can spread systemically within the body, infecting a range of organs, such as the liver, spleen, bone marrow and lymph nodes. Natural reservoirs for these protozoa include rodents, dogs, foxes, jackals, and wolves, with dogs serving as the primary urban reservoir for Leishmania infantum. Dogs exhibit clinical and pathological similarities to human VL and are valuable models for studying disease progression. Both human and canine VL provoke clinical symptoms, such as organ enlargement, fever, weight loss and abnormal gamma globulin levels. Hematologic abnormalities have also been observed, including anemia, leukopenia with lymphocytosis, neutropenia, and thrombocytopenia. Studies in dogs have linked these hematologic changes in peripheral blood to alterations in the bone marrow. Mouse models of VL have also contributed significantly to our understanding of the mechanisms underlying these hematologic and bone marrow abnormalities. This review consolidates information on hematological and immunological changes in the bone marrow of humans, dogs, and mice infected with Leishmania species causing VL. It includes findings on the role of bone marrow as a source of parasite persistence in internal organs and VL development. Highlighting gaps in current knowledge, the review emphasizes the need for future research to enhance our understanding of VL and identify potential targets for novel diagnostic and therapeutic approaches.

Does radiotherapy treatment alter the pulp condition in patients with head and neck cancer? A systematic review.

The main purpose of this study was to answer the question: "Can radiotherapy cause changes in the dental pulp condition of patients treated with irradiation in the head and neck region?" Clinical observational studies in adults with head and neck cancer undergoing treatment with ionizing radiation, longitudinal or cross-sectional follow-up to measure oxygen saturation (SpO2), and/or pulp sensitivity test to cold stimulation, were considered eligible. A systematic literature search was performed in six different databases, including the gray literature, and in article references. Two independent evaluators selected the studies, extracted the data, recorded the data on electronic spreadsheets, and then evaluated the methodological quality using the Checklist for Quasi-Experimental Studies tool devised by JBI. The data were assessed qualitatively using the Synthesis Without Metanalysis (SWiM) guidelines. After removing the duplicate articles, carefully analyzing the titles and abstracts, and reading the papers in full, seven studies were included. Four of the studies evaluated applied the cold sensitivity test, two associated pulse oximetry and cold sensitivity, and only one used just pulse oximetry. Evaluation using the cold sensitivity test and pulse oximetry in the initial periods before radiotherapy showed a decrease in the sensitive response and in SpO2 levels during a maximum period of 1 year. However, analyses thereafter indicated a normal response in both tests from 5 to 6 years after the end of radiotherapy treatment. Radiotherapy causes changes in pulp behavior patterns in the short term; however, recovery and return to average values occurs after long periods.

The rs2601796 variant in ADCY9 gene is associated with severe asthma and less bronchodilator response.

Asthma is a respiratory disease caused by the interaction of genetic and environmental factors. The adenylyl cyclase type 9 (ADCY9) enzyme produces the cyclic-adenosinemonophosphate (cAMP), important mediator involved in bronchodilation and immunomodulatory response. The aim of this study was to investigate if rs2601796 and rs2532019 variants in the ADCY9 gene are associated with asthma and lung function. The study comprised 1,052 subjects. Logistic regressions were done using PLINK 1.9 adjusted by sex, age, BMI, smoke and principal components. Bronchodilator responsiveness was assessed using the percentage of difference in FEV1 before and after the bronchodilator use. The in silico analysis for gene expression was performed in the GTEx Portal. The variant rs2601796 (AA/AG genotype) was positively associated with asthma severity (OR: 1.60 IC95%: 1.08-2.39) and with obstruction in individuals with severe asthma (OR: 3.10, IC95%: 1.11-8.62). Individuals with severe asthma and the AA/AG genotype of rs2601796 had less responsiveness to bronchodilators and also a lower expression of ADCY9 in lung and whole blood. The variant rs2532019 (TT/GT genotype) also downregulated the ADCY9 gene expression, but no significant association with the studied phenotypes was found. Thus, the variant in ADCY9 was associated with worse asthma outcomes, including a lower response to bronchodilators, likely due to the impact on its gene expression rate. This variant may be useful in the future to assist in personalized management of patients with asthma.

Intra-Articular Hyaluronic Acid in Osteoarthritis and Tendinopathies: Molecular and Clinical Approaches.

Musculoskeletal diseases continue to rise on a global scale, causing significant socioeconomic impact and decreased quality of life. The most common disorders affecting musculoskeletal structures are osteoarthritis and tendinopathies, complicated orthopedic conditions responsible for major pain and debilitation. Intra-articular hyaluronic acid (HA) has been a safe, effective, and minimally invasive therapeutic tool for treating these diseases. Several studies from bedside to clinical practice reveal the multiple benefits of HA such as lubrication, anti-inflammation, and stimulation of cellular activity associated with proliferation, differentiation, migration, and secretion of additional molecules. Collectively, these effects have demonstrated positive outcomes that assist in the regeneration of chondral and tendinous tissues which are otherwise destroyed by the predominant catabolic and inflammatory conditions seen in tissue injury. The literature describes the physicochemical, mechanical, and biological properties of HA, their commercial product types, and clinical applications individually, while their interfaces are seldom reported. Our review addresses the frontiers of basic sciences, products, and clinical approaches. It provides physicians with a better understanding of the boundaries between the processes that lead to diseases, the molecular mechanisms that contribute to tissue repair, and the benefits of the HA types for a conscientious choice. In addition, it points out the current needs for the treatments.

Does irradiation of the tooth structure interfere with oxygen saturation measured by pulse oximetry?-An ex vivo laboratorial study.

The effect of tooth structure subjected to ionising radiation on oxygen saturation levels (SpO2 ) measured by pulse oximetry was investigated. Fifty-four extracted human third molars were sectioned mesiodistally. Pulse oximeter diodes were placed in prefabricated silicone moulds, secured on a vise with tooth surfaces placed between the diodes and the participant's finger, and SpO2 levels were measured. After that, the tooth surfaces were subjected to ionising radiation in fractionated doses of up to 70 Gy, and SpO2 was measured according to the protocol described. The Kolmogorov-Smirnov test was used for the analysis of normality of the quantitative variables, and Student's t-test compared mean SpO2 levels before and after irradiation. Mean SpO2 after irradiation was 94.6 ± 0.9%, without a statistically significant difference from SpO2 before irradiation, which was 94.7 ± 0.6%. Irradiation of the tooth structure did not interfere with SpO2 levels measured by pulse oximetry.

Anticoncepção oral e hipotrofia muscular: existe correlação? / Oral contraception and muscle atrophy: is there a correlation?

As pílulas anticoncepcionais consistem na formulação combinada de um estrogênio e um progestagênio ou em apresentações simples de progestagênio isolado com a finalidade de bloquear a ovulação e alterar as condições do útero e das tubas uterinas, bloqueando parcialmente a foliculogênese e a inibição do pico de gonadotrofinas. Desse modo, no que concerne à temática, diversas publicações na mídia de ampla divulgação afirmam que os anticoncepcionais orais têm papel importante na sarcopenia e na hipotrofia, incluindo perda de força muscular e redução do desempenho físico. Assim, o presente trabalho tem por objetivo avaliar, por meio de pesquisas de artigos, a correlação entre anticoncepcionais hormonais orais e hipotrofia muscular. Foi concluído que os artigos científicos especializados no tema são ainda bastante inconclusivos, sugerindo que há indicações de que usuárias de anticoncepcional oral sejam mais suscetíveis ao dano muscular induzido por exercícios, contudo ainda não há consenso.

Anticonception pills consist of a combined formulation of an estrogen and a progestogen or simple presentations of progestogen alone with the purpose of blocking ovulation and altering the conditions of the uterus and uterine tubes, partially blocking folliculogenesis and inhibiting the gonadotropin peak. Thus, with regard to the subject, several widely publicized media publications claim that oral contraceptives play an important role in sarcopenia and hypotrophy, including loss of muscle strength and reduced physical performance. So, the present work aims to evaluate through article searches the correlation between oral hormonal contraceptives and muscle hypotrophy. It was concluded that scientific articles specialized on the subject are still quite inconclusive, suggesting that there are indications that oral contraceptive users are more susceptible to exercise-induced muscle damage, however there is still no consensus.

The role of IL10 and IL17 gene polymorphisms in treatment response in children and adolescents with severe asthma / O papel de polimorfismos dos genes IL10 e IL17 na resposta ao tratamento em crianças e adolescentes com asma grave

ABSTRACT Objective: To determine whether polymorphisms of the IL10 and IL17 genes are associated with severe asthma control and bronchodilator reversibility in children and adolescents with severe asthma. Methods: This was a cross-sectional study, nested within a prospective cohort study of patients with severe asthma. Two outcomes were evaluated: asthma control and bronchodilator reversibility. We extracted DNA from peripheral blood and genotyped three single nucleotide polymorphisms: rs3819024 and rs2275913 in the IL17A gene; and rs3024498 in the IL10 gene. For the association analyses, we performed logistic regression in three genetic models (allelic, additive, and dominant). Results: The rs3024498 C allele in the IL10 gene was associated with failure to achieve asthma control despite regular treatment (p = 0.02). However, the G allele of the IL17A rs3819024 polymorphism was associated with failure to respond to stimulation with a b2 agonist. The rs2275913 polymorphism of the IL17A gene showed no relationship with asthma control or bronchodilator reversibility. Conclusions: In pediatric patients with severe asthma, the IL10 polymorphism appears to be associated with failure to achieve clinical control, whereas the IL17A polymorphism appears to be associated with a worse bronchodilator response. Knowledge of the involvement of these polymorphisms opens future directions for pharmacogenetic studies and for the implementation of individualized therapeutic management of severe asthma in pediatric patients.

RESUMO Objetivo: Determinar se existe relação entre polimorfismos dos genes IL10 e IL17 e controle da asma grave e reversibilidade com broncodilatador em crianças e adolescentes com asma grave. Métodos: Estudo transversal, aninhado em um estudo prospectivo de coorte com pacientes com asma grave. Foram avaliados dois desfechos: controle da asma e reversibilidade com broncodilatador. Extraímos DNA do sangue periférico e genotipamos três polimorfismos de nucleotídeo único: rs3819024 e rs2275913 no gene IL17A e rs3024498 no gene IL10. Para as análises de associação, realizamos regressão logística em três modelos genéticos (alélico, aditivo e dominante). Resultados: O alelo C do polimorfismo rs3024498 do gene IL10 apresentou relação com asma que permaneceu descontrolada mesmo com tratamento regular (p = 0,02). No entanto, o alelo G do polimorfismo rs3819024 do gene IL17A apresentou relação com ausência de resposta ao estímulo com b2-agonista. O polimorfismo rs2275913 do gene IL17A não apresentou relação com controle da asma ou reversibilidade com broncodilatador. Conclusões: Em pacientes pediátricos com asma grave, o polimorfismo do gene IL10 parece estar relacionado com ausência de controle clínico, ao passo que o polimorfismo do gene IL17A parece estar relacionado com pior resposta ao broncodilatador. O conhecimento a respeito do envolvimento desses polimorfismos abre perspectivas futuras para estudos farmacogenéticos e para a implantação de manejo terapêutico individualizado da asma grave em pacientes pediátricos.

Alteración de la marcha y poliartralgia como manifestación de escorbuto en un niño. Presentación de un caso / Gait disturbance and polyarthralgia as a manifestation of scurvy in a pediatric patient. Case report

La vitamina C o ácido ascórbico es imprescindible para el correcto funcionamiento del organismo. Los seres humanos no pueden sintetizarla; en consecuencia, dependen estrictamente de su aporte exógeno. Su déficit causa escorbuto, un cuadro que se manifiesta con fatiga, mialgias y poliartralgias, hemorragias en la piel y sangrado de las encías. Es una enfermedad infrecuente. La mayoría de los casos publicados corresponden a niños con restricciones alimentarias por trastornos del neurodesarrollo. La respuesta satisfactoria al aporte de ácido ascórbico confirma el diagnóstico. La sospecha de esta enfermedad evitaría exámenes complementarios innecesarios y el tratamiento temprano ayudaría a revertir los síntomas y prevenir complicaciones. Se presenta el caso de un varón de 13 años que consulta por dolor en ambas caderas con progresión hacia las rodillas, sumado a pérdida de la fuerza y hematomas en los miembros inferiores. El objetivo de esta presentación es resaltar la importancia de la anamnesis alimentaria completa y evitar un abordaje tardío con múltiples intervenciones. Nivel de Evidencia: IV

Vitamin C or ascorbic acid is essential for the correct functioning of the organism. As it cannot be synthesized by humans, it is obtained from external food sources. Deficiency of ascorbic acid produces scurvy, which includes symptoms as fatigue, myalgia and polyarthralgia, associated with skin hemorrhage and bleeding gums. Scurvy is a rare entity. Most of the reported cases involve children with food restrictions due to neurodevelopmental disorders. The early detection of the clinical signs of this condition would avoid unnecessary complementary tests, and early treatment would help reverse symptoms and prevent complications. Case Report: a 13-year-old male patient presented with pain in both hips radiating to the knees associated with loss of strength and hematomas in the lower limbs. Objective: to highlight the importance of a complete nutritional assessment to avoid a late approach with multiple interventions. Level of Evidence: IV

Does radiotherapy treatment alter the pulp condition in patients with head and neck cancer? A systematic review

Abstract The main purpose of this study was to answer the question: "Can radiotherapy cause changes in the dental pulp condition of patients treated with irradiation in the head and neck region?" Clinical observational studies in adults with head and neck cancer undergoing treatment with ionizing radiation, longitudinal or cross-sectional follow-up to measure oxygen saturation (SpO2), and/or pulp sensitivity test to cold stimulation, were considered eligible. A systematic literature search was performed in six different databases, including the gray literature, and in article references. Two independent evaluators selected the studies, extracted the data, recorded the data on electronic spreadsheets, and then evaluated the methodological quality using the Checklist for Quasi-Experimental Studies tool devised by JBI. The data were assessed qualitatively using the Synthesis Without Metanalysis (SWiM) guidelines. After removing the duplicate articles, carefully analyzing the titles and abstracts, and reading the papers in full, seven studies were included. Four of the studies evaluated applied the cold sensitivity test, two associated pulse oximetry and cold sensitivity, and only one used just pulse oximetry. Evaluation using the cold sensitivity test and pulse oximetry in the initial periods before radiotherapy showed a decrease in the sensitive response and in SpO2 levels during a maximum period of 1 year. However, analyses thereafter indicated a normal response in both tests from 5 to 6 years after the end of radiotherapy treatment. Radiotherapy causes changes in pulp behavior patterns in the short term; however, recovery and return to average values occurs after long periods.

Platelet-Rich Plasma Gel Matrix (PRP-GM): Description of a New Technique.

Several musculoskeletal conditions are triggered by inflammatory processes that occur along with imbalances between anabolic and catabolic events. Platelet-rich plasma (PRP) is an autologous product derived from peripheral blood with inherent immunomodulatory and anabolic properties. The clinical efficacy of PRP has been evaluated in several musculoskeletal conditions, including osteoarthritis, tendinopathy, and osteonecrosis. When used in combination with hyaluronic acid (HA), a common treatment alternative, the regenerative properties of PRP are significantly enhanced and may provide additional benefits in terms of clinical outcomes. Recently, a new PRP-derived product has been reported in the literature and is being referred to as "plasma gel". Plasma gels are obtained by polymerizing plasmatic proteins, which form solid thermal aggregates cross-linked with fibrin networks. Plasma gels are considered to be a rich source of growth factors and provide chemotactic, migratory, and proliferative properties. Additionally, clot formation and the associated fibrinolytic reactions play an additional role in tissue repair. There are only a few scientific articles focusing on plasma gels. Historically, they have been utilized in the fields of aesthetics and dentistry. Given that the combination of three products (PRP, HA, and plasma gel) could enhance tissue repair and wound healing, in this technical note, we propose a novel regenerative approach, named "PRP-HA cellular gel matrix" (PRP-GM), in which leukocyte-rich PRP (LR-PRP) is mixed with a plasma gel (obtained by heating the plasma up) and HA in one syringe using a three-way stopcock. The final product contains a fibrin-albumin network entangled with HA's polymers, in which the cells and biomolecules derived from PRP are attached and released gradually as fibrinolytic reactions and hyaluronic acid degradation occur. The presence of leukocytes, especially monocytes and macrophages, promotes tissue regeneration, as type 2 macrophages (M2) possess an anti-inflammatory feature. In addition, HA promotes the viscosuplementation of the joint and induces an anti-inflammatory response, resulting in pain relief. This unique combination of biological molecules may contribute to the optimization of regenerative protocols suitable for the treatment of degenerative musculoskeletal diseases.

Criação de uma comunicação interatrial com implante de stent como tratamento paliativo em pacientes com hipertensão arterial pulmonar primária grave ­ avaliação de longo prazo / Creation of an atrial septal defect with stent implantation as a palliative treatment in patients with severe primary pulmonary arterial hypertension ­ long-term evaluation

INTRODUÇÃO E/OU FUNDAMENTOS: A história natural da hipertensão arterial pulmonar primária (HPP) grave culmina em insuficiência cardíaca direita refratária ao tratamento otimizado. A comunicação interatrial (CIA) alivia a sobrecarga direita na HP secundária à cardiopatia congênita de hiperfluxo e é uma alternativa na falência ventricular direita associada a HPP. Avaliamos a segurança e eficácia da criação de uma CIA nestes pacientes, com ênfase no impacto clínico de longo prazo. MÉTODOS: Estudo clínico observacional e retrospectivo de uma coorte de pacientes com HPP e classe funcional (CF) > II, em tratamento otimizado, submetidos a abertura de CIA com stent de 2014-2022. O procedimento se deu através de punção transseptal. Foram avaliados os desfechos: mortalidade, sucesso na criação e manutenção da CIA, complicações e melhora da classe funcional e do teste de caminhada de 6 min. RESULTADOS E CONCLUSÕES: Amostra de 8 pacientes com médias de idade e peso de 29,5±13,0 anos e 71,0±15,5kg. No cateterismo, tinham média basal de pressão atrial direita de 16,9±5,9mmHg e pressão sistólica na artéria pulmonar (PSAP) de 98,8±25,2mmHg. Todos classificados como HAP de alto risco. Imediatamente após o procedimento houve queda da saO2 de 96,7±2,9 para 84,3±1,1% (p<0,01) com uma CIA de diâmetro médio de 6,2±1,1mm. Não houve óbito relacionado ao procedimento. Um paciente apresentou taquicardia supraventricular revertida com cardioversão elétrica e 1 paciente apresentou imagem de trombo aderido ao stent imediatamente após o seu implante, que reverteu após 48h de uso de heparina. O seguimento clínico foi realizado em 100% da série e o seu tempo médio foi de 3,5±1,8 anos. Neste período, a hipoxemia obtida se manteve (queda de 96,7±2,9 para 89,3±2,1%, p0,02). Não houve diferença nos parâmetros ecocardiográficos avaliados (PSAP, TAPSE e onda s'), da CF (mantida em III) ou do teste de caminhada (321,8±105,0 para 304,9±61,0m p0,50). Houve 4 internações por IC grave, com melhora após tratamento inotrópico endovenoso em 1 paciente, que recebeu alta hospitalar e 3 óbitos em decorrência de choque cardiogênico refratário. No entanto, o tempo médio de sobrevida foi de 4,2±0,7 anos (IC 95%: 2,8-5,6), com sobrevida em 5 anos de 60%, superior à média descrita na literatura (32,4%). CONCLUSÃO: A criação da CIA nestes pacientes é segura e eficaz no alívio da hipertensão atrial direita. Apesar de não mostrar diferença nas variáveis clínicas e ecocardiográficas avaliadas, contribuiu para melhora significativa da sobrevida nesta grave condição.

Metabolic alterations impair differentiation and effector functions of CD8+ T cells.

CD8+ T lymphocytes are one of the main effector cells of the immune system, they protect the organism against intracellular threats such as viruses and bacteria, as well as neoplasms. It is currently well established that CD8+ T cells have distinct immune responses, given by their phenotypes Tc1, Tc2, Tc17, and TcReg. The cellular plasticity of such phenotypes depends on the presence of different combinations of cytokines in the extracellular medium. It is known that metabolic imbalances play an important role in immune response, but the precise role of metabolic disturbances on the differentiation and function of CD8+ T cells, however, has not been explored. In this work, we used a computational model to explore the potential effect of metabolic alterations such as hyperglycemia, high alcohol consumption, dyslipidemia, and diabetes on CD8+ T cell differentiation. Our model predicts that metabolic alterations preclude the effector function of all CD8+ T cell phenotypes except for TcReg cells. It also suggests that such inhibition originates from the increase of reactive oxygen species in response to metabolic stressors. Finally, we simulated the outcome of treating metabolic-inhibited CD8+ T cells with drugs targeting key molecules such as mTORC1, mTORC2, Akt, and others. We found that overstimulation of mTORC2 may restore cell differentiation and functions of all effector phenotypes, even in diabetic patients. These findings highlight the importance of our predictive model to find potential targets to strengthen immunosuppressed patients in chronic diseases, like diabetes.

Mortality from chronic respiratory disease in Brazil: time trend and forecasts.

OBJECTIVE: To analyze the time trend of monthly mortality rates from chronic respiratory diseases in Brazil from 1996 to 2017, with forecasts for 2022, besides analyzing the possibility of achieving the goal of the Plano de Ações Estratégicas para o Enfrentamento das Doenças Crônicas Não Transmissíveis no Brasil (Strategic Action Plan to Tackle Chronic Noncommunicable Diseases in Brazil) from 2011 to 2022. METHODS: This is an ecological study that uses data from Sistema de Informações sobre Mortalidade (SIM - Mortality Information System), Sistema de Informações Demográficas e Socioeconômicas (Demographic and Socioeconomic Information System) and Pesquisa Nacional por Amostra de Domicílios Contínua (PNAD Contínua - Continuous National Household Sample Survey). We established the age range between 30 and 69 years old and the evolution of the rates over time was made by autoregressive integrated moving average models in R statistical tool. RESULTS: Premature mortality rates from chronic respiratory diseases are decreasing in Brazil as a whole, mostly in state capitals. There is also a trend to reach the Ministry of Health's goal in most of the country. For capitals that tend not to reach the goal, there is an association between mortality and social indicators, healthcare network and frequency of smoking. CONCLUSION: This study intends to improve planning of the public health system for the control of chronic respiratory diseases.

Opciones e indicaciones en el manejo del istmocele / Options and indications in the management of isthmocele

INTRODUCCIÓN: El istmocele es un defecto en la cicatrización del sitio de una histerotomía, que puede cursar con sangrado posmenstrual, dolor pélvico, dismenorrea, dispareunia e infertilidad secundaria. Esta patología ha ido incrementando su prevalencia dado el aumento de la tasa de cesáreas en todo el mundo. OBJETIVO: Se realizó una revisión sobre el istmocele y su manejo, presentando sus indicaciones específicas y las complicaciones asociadas a esta patología. MÉTODO: Se llevó a cabo una búsqueda en PubMed, Embase, Scopus y Google Scholar, en la que se encontraron 868 artículos, de los cuales se revisaron 30 al aplicar los criterios de inclusión y exclusión. DISCUSIÓN: El istmocele es cada vez más frecuente. Tiene una prevalencia cercana al 60% posterior a la realización de una cesárea y aumenta hasta valores del 100% con tres de ellas. Los métodos diagnósticos más utilizados son la ecografía transvaginal y la histerosonografía. Su abordaje es habitualmente quirúrgico, aunque existe la posibilidad de intentar tratamiento médico en algunos casos. CONCLUSIONES: Es necesario determinar el grosor miometrial para poder establecer un plan de manejo adecuado. Además, se ameritan estudios que realicen un seguimiento a largo plazo y que aporten mayor evidencia para la realización de cada procedimiento. Después de clasificar el tipo de defecto, el tratamiento quirúrgico del istmocele se debe ofrecer a pacientes sintomáticas y a aquellas con defectos grandes y que desean mantener la fertilidad.

INTRODUCTION: The isthmocele is a defect in the healing of the site of a hysterotomy, which can present with post-menstrual bleeding, pelvic pain, dysmenorrhea, dyspareunia and secondary infertility. This pathology has been increasing its prevalence given the increase in the rate of cesarean sections worldwide. OBJECTIVE: A review will be carried out of the isthmocele and its management, presenting its specific indications and the complications associated with this pathology. METHOD: A search was carried out in databases such as PubMed, Embase, Scopus and Google Scholar, finding a total of 868 articles, of which 30 of them were reviewed when applying the inclusion and exclusion criteria. DISCUSSION: Isthmocele is an increasingly frequent pathology, having a prevalence of 60% after performing a cesarean section and increasing to 100% with 3 of them. There are multiple diagnostic methods, mainly transvaginal ultrasound and sono-hysterosonography. The approach to this pathology is usually surgical, although there is the possibility of trying medical treatment in some cases. CONCLUSIONS: It is necessary to determine the myometrial thickness in order to establish an adequate management plan. Additionally, long-term follow-up studies are warranted and provide more evidence for the performance of each procedure. After classifying the type of defect, surgical treatment of the isthmocele should be offered to symptomatic patients or those with large defects and who desire future fertility.

Role of 5-HT2A receptors in the effects of ayahuasca on ethanol self-administration using a two-bottle choice paradigm in male mice.

RATIONALE: Ayahuasca has been proposed as a potential treatment of alcohol (ethanol) use disorder (AUD). The serotonin 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT) is the main psychoactive component of ayahuasca, suggesting that its therapeutic effects may be mediated by 5-HT2A receptors. OBJECTIVES: The aim of the present study was to investigate the effects of ayahuasca on the expression of ethanol self-administration using a two-bottle choice procedure and the role of 5-HT2A receptors in those effects. METHODS: Male mice had intermittent access to ethanol (10% v/v) in a two-bottle choice procedure for 30 days. Animals were then submitted to 3 treatment phases, each followed by ethanol re-exposure tests. During the treatment phase, every 3 days, animals received i.p. injections of either vehicle or the 5-HT2A receptor antagonist M100907 (M100, 1 mg/kg) followed by an i.g. (gavage) administration of vehicle or ayahuasca (100 mg/kg) and were exposed to the self-administration apparatus with no ethanol availability. During re-exposure tests, animals were submitted to the same conditions as during acquisition, with no treatments prior to those sessions. RESULTS: Treatment with ayahuasca blocked the expression of ethanol self-administration, decreasing ethanol intake and preference during re-exposure tests. Pretreatment with M100 blocked the effects of ayahuasca on ethanol drinking without significantly attenuating ethanol self-administration. CONCLUSIONS: Treatment with ayahuasca during alcohol abstinence blocked the expression of alcohol self-administration in mice, and 5-HT2A receptor activation is critical for those effects to emerge. Our findings support a potential for ayahuasca and other 5-HT2A receptor agonists as adjunctive pharmacotherapies for the treatment of AUD.

As três versões do pai: o parricídio, o nome e o dizer / The three versions of the father: the parricide, the name and the existential saying

RESUMO: O presente artigo desenvolve as respostas freudianas à questão "O que é um pai?", partindo da observação de Lacan no Seminário, livro 11 de que Freud encontrou a regulação do seu desejo nos mitos da morte do pai. Divide-se em três partes: Édipo, primeiro parricídio; Totem, o retorno do pai como nome; Moisés, o pai como Um dizer. Por fim, levanta-se a questão de que o desejo em Lacan estaria subjacente a suas elaborações sobre a relação entre o pai e o nome.

Abstract: This article develops freudians' answers to the question "What is a father?" starting from Lacan's observation in Seminar book 11 that Freud finds the regulation of his desire in the myths of the father's death. It is divided into three parts: Oedipus, the first parricide; Totem, the return of the father as a name: Moses, the father as One saying. Finally, it raises the question of what desire would underlie Lacan's elaborations on the relationship between the father and the name

Mortality from chronic respiratory disease in Brazil: time trend and forecasts / Mortalidade por doença respiratória crônica no Brasil: tendência temporal e projeções

ABSTRACT OBJECTIVE To analyze the time trend of monthly mortality rates from chronic respiratory diseases in Brazil from 1996 to 2017, with forecasts for 2022, besides analyzing the possibility of achieving the goal of the Plano de Ações Estratégicas para o Enfrentamento das Doenças Crônicas Não Transmissíveis no Brasil (Strategic Action Plan to Tackle Chronic Noncommunicable Diseases in Brazil) from 2011 to 2022. METHODS This is an ecological study that uses data from Sistema de Informações sobre Mortalidade (SIM - Mortality Information System), Sistema de Informações Demográficas e Socioeconômicas (Demographic and Socioeconomic Information System) and Pesquisa Nacional por Amostra de Domicílios Contínua (PNAD Contínua - Continuous National Household Sample Survey). We established the age range between 30 and 69 years old and the evolution of the rates over time was made by autoregressive integrated moving average models in R statistical tool. RESULTS Premature mortality rates from chronic respiratory diseases are decreasing in Brazil as a whole, mostly in state capitals. There is also a trend to reach the Ministry of Health's goal in most of the country. For capitals that tend not to reach the goal, there is an association between mortality and social indicators, healthcare network and frequency of smoking. CONCLUSION This study intends to improve planning of the public health system for the control of chronic respiratory diseases.

RESUMO OBJETIVO Analisar a tendência temporal das taxas mensais de mortalidade por doenças respiratórias crônicas no Brasil de 1996 até 2017, com projeções para 2022, além de analisar a possibilidade de cumprimento da meta do Plano de Ações Estratégicas para o Enfrentamento das Doenças Crônicas Não Transmissíveis no Brasil de 2011 até 2022. MÉTODOS Trata-se de estudo ecológico que utiliza dados do Sistema de Informações sobre Mortalidade, do Sistema de Informações Demográficas e Socioeconômicas e da Pesquisa Nacional por Amostra de Domicílios Contínua. O recorte etário foi estabelecido entre 30 e 69 anos e a evolução das taxas no tempo foi feita por meio de modelos autorregressivos integrados de média móvel em plataforma estatística R. RESULTADOS As taxas de mortalidade precoce por doenças respiratórias crônicas apresentam-se decrescentes no Brasil como um todo e na maior parte das capitais, assim como, há tendência a atingir a meta do Ministério da Saúde na maior parte do país. Para capitais que tendem a não atingir a meta, verifica-se associação entre mortalidade e indicadores sociais, rede assistencial de saúde e frequência do tabagismo. CONCLUSÃO Pretende-se que o estudo possibilite um melhor planejamento do sistema público de saúde para o controle das doenças respiratórias crônicas.