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Purine nucleotides and nucleosides play critical roles in various pathological conditions, including tumor cell growth. Adenosine triphosphate (ATP) activates pro-tumor receptors, while adenosine (ADO) is a potent immunosuppressant and modulator of cell growth. This study aims to analyze the purinergic actions of ATP and its metabolites, associated enzymes, and P1 or P2 class receptors in primary central nervous system tumors. Additionally, we sought to correlate the levels of nucleosides and the density of P1, P2X, and P2Y receptors in cells with tumor progression. The results indicate that purinergic signaling depends on the receptor concentration and signaling molecules specific to each cell type, tissue, and tumor histology. The purinergic system may function as either a tumor-promoting agent or an antitumor factor, depending on the microenvironmental conditions and the concentrations of receptors and their respective activators. Notably, ATP emerges as the most significant extracellular signal, capable of being converted into other cellular stimulators pertinent to neoplasms, such as adenosine diphosphate, adenosine monophosphate, adenosine, and inosine. Consequently, a cascade of responses to these stimuli promotes tumor development, cell division, and metastasis. Purine nucleotides in central nervous system tumors are pivotal in cellular responses in glioblastoma multiforme, vestibular schwannoma, medulloblastoma, adenomas, gliomas, meningiomas, and pineal tumors. These findings hold the potential for developing novel therapeutic strategies and aiding in therapeutic management.
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Leishmaniases are a group of neglected vector-borne infectious diseases that are among the six priority endemic diseases worldwide. Visceral leishmaniasis (VL) is the most severe clinical manifestation, characterized by systemic and chronic visceral involvement and high mortality in immunosuppressed and untreated patients. VL can be complicated into post-kala-azar dermal leishmaniasis (PKDL), and when dermatologic disorders occur simultaneously with active VL, an intermediate clinical form called para-kala-azar dermal leishmaniasis (para-KDL) occurs. This clinical form is of great epidemiological relevance, as humans act as a source of infection for vectorial transmission. In the Americas, Brazil is among the seven countries responsible for more than 90% of VL cases, though reports of PKDL and para-KDL are rare. This paper presents three cases of VL-HIV co-infection with Leishmania-containing skin lesions resembling para-kala-azar dermal leishmaniasis. The cases were investigated by the team from the Infectious Diseases Department of University Hospital (HUMAP/UFMS) in Mato Grosso do Sul, Brazil. The three patients exhibited skin lesions where amastigote forms of L. (L.) infantum were identified. All cases exhibited similar clinical manifestations of para-KDL, including fever, hepatosplenomegaly, pancytopenia, and disseminated skin lesions. The study described the prevalence of comorbidities, the incidence of VL relapse, and the therapeutic regimen in relation to the outcomes. The study underscores the importance of follow-up and secondary prophylaxis in patients with VL, which are essential for the efficacy of the treatment. Furthermore, the study provides insight into the potential epidemiological profile of para-KDL cases in Brazil, which contributes to the development of more efficient clinical management strategies for patients.
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Coinfecção , Infecções por HIV , Leishmaniose Cutânea , Leishmaniose Visceral , Humanos , Leishmaniose Visceral/complicações , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/tratamento farmacológico , Masculino , Infecções por HIV/complicações , Adulto , Coinfecção/parasitologia , Coinfecção/epidemiologia , Brasil/epidemiologia , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/complicações , Feminino , Leishmania infantum/isolamento & purificação , Pele/patologia , Pele/parasitologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: There are few data reporting the needs and priorities of older adults in Brazil. This hampers the development and/or implementation of policies aimed at older adults to help them age well. The aim of this study was to understand areas of importance, priorities, enablers and obstacles to healthy ageing as identified by older adults and key stakeholders in both urban and rural environments. METHODS: Two locations were selected, one urban and one rural in the municipality of Santo André, in the metropolitan region of São Paulo (SP). Workshops for older adults (>60 y) and stakeholders were conducted separately in each location. The workshops incorporated an iterative process of discussion, prioritisation and ranking of responses, in roundtable groups and in plenary. Areas of commonality and differences between older adult and stakeholder responses were identified by comparing responses between groups as well as mapping obstacles and enablers to healthy ageing identified by older adults, to the priorities identified by stakeholder groups. The socio-ecologic model was used to categorise responses. RESULTS: There were few shared responses between stakeholders and older adults and little overlap between the top ranked responses of urban and rural groups. With respect to areas of importance, both stakeholder groups ranked policies for older people within their top five reponses. Both older adult groups ranked keeping physically and mentally active, and nurturing spirituality. There was a marked lack of congruence between older adults' obstacles and enablers to healthy ageing and stakeholder priorities, in both urban and rural settings. Most responses were located within the Society domain of the socio-ecologic model, although older adults also responded within the Individual/ Relationships domains, particularly in ranking areas of most importance for healthy ageing. CONCLUSIONS: Our results highlight substantial differences between older adults and stakeholders with respect to areas of importance, priorities, enablers and obstacles to healthy ageing, and point to the need for more engagement between those in advocacy and policymaking roles and the older people whose needs they serve.
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População Rural , População Urbana , Humanos , Brasil , Idoso , Masculino , Feminino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Participação dos Interessados , Prioridades em Saúde , Envelhecimento Saudável , Necessidades e Demandas de Serviços de SaúdeRESUMO
Introduction: The World Health Organization (WHO) has proposed to monitor intrinsic capacity (IC) in the older population as a public health strategy through the Integrated Care for Older People (ICOPE) program. Although the program has been developed based on solid concepts, scientific evidence on its practical applicability is still scarce. Objectives: To evaluate IC in Brazilian older adults, its progress over time, and its association with sociodemographic and health factors and outcomes. To evaluate the psychometric properties of the WHO/ICOPE screening tool. Methods: This is a prospective multicenter cohort study with a 36-month follow-up. We will recruit 3838 people aged ≥60 years, registered in the health care units included in the study by the participating centers. We will collect sociodemographic and health data and will administer tools to assess IC domains, both those provided for in the ICOPE screening tool and the sequence of confirmatory assessments provided for in the program. Participants will be reassessed every 6 months for 36 months. Expected results: To establish the profile of IC in the study population and to understand its progress and the variables associated with the clinical outcomes of interest. To reveal the diagnostic and psychometric properties of the WHO/ICOPE screening tool. The project is funded by the Brazilian National Council for Scientific and Technological Development (CNPq). Relevance: Understanding the potential use of the ICOPE public health strategy proposed by the WHO within the scope of the Brazilian Unified Health System (SUS) by integrating several research centers in the field of Geriatrics and Gerontology throughout Brazil. (AU)
Introdução: A Organização Mundial da Saúde (OMS) propõe o monitoramento da capacidade intrínseca (CI) da população idosa como estratégia de saúde pública por meio do Programa ICOPE (Integrated Care for Older People). Embora construído com base em conceitos sólidos, a evidência científica sobre a aplicabilidade prática da proposta ainda é escassa. Objetivo: Avaliar a capacidade intrínseca da população idosa brasileira, sua trajetória e sua associação com variáveis sociodemográficas, de saúde e desfechos. Avaliar as propriedades psicométricas da ferramenta de triagem da estratégia ICOPE da OMS. Metodologia: Coorte multicêntrica prospectiva com seguimento de 36 meses. Serão recrutadas 3.838 pessoas com 60 anos ou mais, cadastradas nas unidades de saúde incluídas no estudo pelos centros participantes. Serão coletados dados sociodemográficos e de saúde e aplicados instrumentos para avaliação dos domínios da CI, tanto aqueles previstos no instrumento de triagem do ICOPE quanto a sequência de avaliações confirmatórias previstas no programa. Os participantes serão acompanhados semestralmente ao longo de 36 meses. Resultados esperados: Estabelecer o perfil da CI na população estudada, entender a sua trajetória e as variáveis associadas aos desfechos clínicos avaliados. Revelar as propriedades diagnósticas e o perfil psicométrico da ferramenta de triagem do ICOPE da OMS. O projeto tem financiamento do Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Relevância: Compreensão sobre o potencial de utilização da estratégia ICOPE de saúde pública proposta pela OMS no âmbito do Sistema Único de Saúde (SUS) pela integração de diversos centros de pesquisa científica na área de Geriatria e Gerontologia de todo o Brasil. (AU)
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Humanos , Idoso , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: to map scientific knowledge on nursing students' attitudes and perceptions regarding ageism. METHOD: scoping review according to the recommendations of the Joanna Briggs Institute. The study question was: What are scientific evidence available on the attitudes and perceptions of nursing students regarding ageism? The search was conducted in 12 databases using the Rayyan application and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. The studies were selected by two reviewers using a data extraction tool. RESULTS: of the 4,595 files, 46 that were published between 1984 and 2022 were selected, and the quantitative method was the most used. The most commonly used instrument was the Kogan's Attitudes Toward Old People Scale. Positive, negative, mixed, neutral, and inconclusive attitudes and perceptions were identified. CONCLUSION: attitudes and perceptions about ageism are diverse and not conclusive. Future intervention studies are recommended to detect changes in the behavior of nursing students in the face of ageism. BACKGROUND: (1) Attitudes and perceptions about ageism are diverse and not conclusive. BACKGROUND: (2) Importance of discussing ageism in the training of nursing students. BACKGROUND: (3) Intervention studies to identify paradigm shifts in nursing students.
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Etarismo , Atitude do Pessoal de Saúde , Estudantes de Enfermagem , Etarismo/psicologia , Estudantes de Enfermagem/psicologia , HumanosRESUMO
Abstract Background: Real-world, primary data on the treatment of psoriasis are scarce, especially concerning the role of soluble biomarkers as outcome predictors. Objective: The authors evaluated the utility of Th1/Th17 serum cytokines along with clinical characteristics as predictors of drug survival in the treatment of psoriasis. Methods: The authors consecutively included participants with moderate to severe psoriasis who were followed up for 6 years. Baseline interferon-α, tumor necrosis factor-α, and inter-leukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A were measured using a cytometric bead array; clinical data were assessed. The authors calculated hazard ratios (HRs) for drug survival using a Cox proportional hazards model. Results: The authors included 262 patients, most of whom used systemic immunosuppressants or biologics. In the multivariate model, poor quality of life measured by the Dermatology Life Quality Index (HR = 1.04; 95% CI 1.01-1.07; p = 0.012) and elevated baseline IL-6 (HR = 1.99; 95% CI 1.29-3.08; p = 0.002) were associated with treatment interruption. Study limitations: The main limitation of any cohort study is the presence of confounders that could not be detected in clinical evaluation. Conclusions: Poor quality of life and elevated baseline serum IL-6 level predicted treatment interruption in patients with moderate to severe psoriasis. Although IL-6 is not the most important mediator of the inflammatory pathway in the skin environment, it is an interesting biomarker candidate for predicting psoriasis treatment response.
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Cutaneous leishmaniasis (CL) is a polymorphic and spectral skin disease caused by Leishmania spp. protozoan parasites. CL is difficult to diagnose because conventional methods are time-consuming, expensive, and low-sensitive. Fourier transform infrared spectroscopy (FTIR) with machine learning (ML) algorithms has been explored as an alternative to achieve fast and accurate results for many disease diagnoses. Besides the high accuracy demonstrated in numerous studies, the spectral variations between infected and noninfected groups are too subtle to be noticed. Since variability in sample set characteristics (such as sex, age, and diet) often leads to significant data variance and limits the comprehensive understanding of spectral characteristics and immune responses, we investigate a novel methodology for diagnosing CL in an animal model study. Blood serum, skin lesions, and draining popliteal lymph node samples were collected from Leishmania (Leishmania) amazonensis-infected BALB/C mice under experimental conditions. The FTIR method and ML algorithms accurately differentiated between infected (CL group) and noninfected (control group) samples. The best overall accuracy (â¼72%) was obtained in an external validation test using principal component analysis and support vector machine algorithms in the 1800-700 cm-1 range for blood serum samples. The accuracy achieved in analyzing skin lesions and popliteal lymph node samples was satisfactory; however, notable disparities emerged in the validation tests compared to results obtained from blood samples. This discrepancy is likely attributed to the elevated sample variability resulting from molecular compositional differences. According to the findings, the successful functioning of prediction models is mainly related to data analysis rather than the differences in the molecular composition of the samples.
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Leishmania , Leishmaniose Cutânea , Animais , Camundongos , Espectroscopia de Infravermelho com Transformada de Fourier , Camundongos Endogâmicos BALB C , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/parasitologia , Modelos Animais , Aprendizado de MáquinaRESUMO
BACKGROUND: Real-world, primary data on the treatment of psoriasis are scarce, especially concerning the role of soluble biomarkers as outcome predictors. OBJECTIVE: The authors evaluated the utility of Th1/Th17 serum cytokines along with clinical characteristics as predictors of drug survival in the treatment of psoriasis. METHODS: The authors consecutively included participants with moderate to severe psoriasis who were followed up for 6 years. Baseline interferon-α, tumor necrosis factor-α, and interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A were measured using a cytometric bead array; clinical data were assessed. The authors calculated hazard ratios (HRs) for drug survival using a Cox proportional hazards model. RESULTS: The authors included 262 patients, most of whom used systemic immunosuppressants or biologics. In the multivariate model, poor quality of life measured by the Dermatology Life Quality Index (HR = 1.04; 95% CI 1.01â1.07; p = 0.012) and elevated baseline IL-6 (HR = 1.99; 95% CI 1.29â3.08; p = 0.002) were associated with treatment interruption. STUDY LIMITATIONS: The main limitation of any cohort study is the presence of confounders that could not be detected in clinical evaluation. CONCLUSIONS: Poor quality of life and elevated baseline serum IL-6 level predicted treatment interruption in patients with moderate to severe psoriasis. Although IL-6 is not the most important mediator of the inflammatory pathway in the skin environment, it is an interesting biomarker candidate for predicting psoriasis treatment response.
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Interleucina-6 , Psoríase , Humanos , Estudos de Coortes , Qualidade de Vida , Interrupção do Tratamento , Psoríase/patologia , BiomarcadoresRESUMO
Abstract This work aimed to carry out a literature review on Street Harassment, to defend the use of this term and propose its definition, while considering its limits, possibilities, and understanding through Social Psychology. A narrative review of the literature was performed, with non-systematic searches of national and international scientific productions that addressed street harassment. It was noted that there was no consensus in the literature regarding a universal term to name it. We emphasize that it is crucial to define a term and propose an inclusive definition for a phenomenon that is violent towards women, to properly frame the concept, and to promote scientific analyses and public policies that can confront this violence.
Resumo Este trabalho teve como objetivo realizar uma revisão de literatura sobre o Assédio de Rua, defender o uso deste termo e propor sua definição, sem deixar de considerar seus limites, possibilidades e compreensão por meio da Psicologia Social. Foi realizada uma revisão narrativa da literatura, com buscas não sistemáticas em produções científicas nacionais e internacionais que abordavam o assédio de rua. Observou-se que não houve consenso na literatura quanto a um termo universal para nomeá-lo. Ressaltamos que é fundamental definir um termo e propor uma definição inclusiva para um fenômeno que é violento contra as mulheres, para enquadrar adequadamente o conceito e promover análises científicas e políticas públicas que possam enfrentar essa violência.
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Este estudo objetivou analisar a percepção do assédio de rua no contexto brasileiro. Participaram 323 pessoas da população geral, com idades variando entre 18 e 65 anos (M=27,5; DP=8,10), as quais responderam a um questionário online com situações fictícias de assédio de rua, medidas de percepção do assédio, uma questão aberta e perguntas sociodemográficas. Os resultados quantitativos mostraram que os participantes percebem o assédio como um comportamento sexista; contudo, mulheres percebem mais do que homens. Essa percepção varia de acordo com o contexto em que o assédio ocorre, ou seja, o assédio que acontece na rua é visto como mais sexista do que quando ocorre em uma festa. Ademais, os resultados mostram que o sexismo hostil influencia significativamente de forma negativa a percepção do assédio de rua. Além disso, os resultados qualitativos convergem com o que foi encontrado nos dados quantitativos, de modo que as pessoas percebem e justificam a situação ocorrida como assédio
This study aimed to analyze the perception of street harassment in the Brazilian context. A total of 323 people from the general population, aged between 18 and 65 years old (M=27.5; SD=8.10), who answered an online questionnaire with fictitious situations of street harassment, measures of harassment perception, a study participated, open question and sociodemographic questions. Quantitative results showed that participants perceive harassment as sexist behavior; howe-ver, women perceive more than men do. This perception varies according to the context in which the harassment occurs, that is, harassment that takes place in the street is seen as more sexist than when it occurs at a party. Furthermore, the results show that hostile sexism significantly negatively influences the perception of street harassment. Furthermore, the qualitative results converge with what was found in the quantitative data, so that people perceive and justify the situation that occurred as harassment
Este estudio tuvo como objetivo analizar la percepción del acoso callejero en el contexto brasileño. Participaron en este estudio un total de 323 personas de la población general, con edades comprendidas entre 18 y 65 años (M = 27,5; DT = 8,10), que respondieron un cuestionario online con situaciones ficticias de acoso callejero, medidas de percepción del acoso, participaron en este estudio. Pregunta abierta y cuestiones sociodemográficas. Los resultados cuantitativos mostraron que los participantes perciben el acoso como un comportamiento sexista; sin embargo, las mujeres perciben más que los hombres. Esta percepción varía según el contexto en el que se produce el acoso, es decir, el acoso que se da en la calle se percibe más sexista que cuando se da en una fiesta. Además, los resultados muestran que el sexismo hostil influye significa- tivamente de forma negativa en la percepción del acoso callejero. Además, los resultados cualitativos convergen con lo encontrado en los datos cuantitativos, de manera que las personas perciben y justifican la situación ocurrida como acoso
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Humanos , Assédio Sexual , SexismoRESUMO
Objective: to map scientific knowledge on nursing students' attitudes and perceptions regarding ageism. Method: scoping review according to the recommendations of the Joanna Briggs Institute. The study question was: What are scientific evidence available on the attitudes and perceptions of nursing students regarding ageism? The search was conducted in 12 databases using the Rayyan application and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. The studies were selected by two reviewers using a data extraction tool. Results: of the 4,595 files, 46 that were published between 1984 and 2022 were selected, and the quantitative method was the most used. The most commonly used instrument was the Kogan's Attitudes Toward Old People Scale. Positive, negative, mixed, neutral, and inconclusive attitudes and perceptions were identified. Conclusion: attitudes and perceptions about ageism are diverse and not conclusive. Future intervention studies are recommended to detect changes in the behavior of nursing students in the face of ageism.
Objetivo: mapear el conocimiento científico sobre las actitudes y percepciones de los estudiantes de enfermería respecto al edadismo. Método: La pregunta del estudio fue: ¿Qué evidencia científica está disponible sobre las actitudes y percepciones de los estudiantes de enfermería respecto al edadismo? La búsqueda se realizó en 12 bases de datos utilizando la aplicación Rayyan y la Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews . Los estudios fueron seleccionados por dos revisores mediante una herramienta de extracción de datos. Resultados: de los 4.595 artículos, se seleccionaron 46 publicados entre 1984 y 2022, siendo el método cuantitativo el más utilizado. La herramienta más utilizada fue el Kogan's Attitudes Toward Old People Scale . Se identificaron actitudes y percepciones positivas, negativas, mixtas, neutras y no concluyentes. Conclusión: las actitudes y percepciones sobre la discriminación por edad son diversas y no concluyentes. Se recomiendan futuros estudios de intervención para detectar cambios en el comportamiento de los estudiantes de enfermería ante el edadismo.
Objetivo: mapear o conhecimento científico sobre as atitudes e percepções dos estudantes de enfermagem em relação ao idadismo. Método: revisão de escopo segundo as recomendações do Joanna Briggs Institute . A pergunta de estudo foi: Quais são as evidências científicas disponíveis sobre as atitudes e percepções dos estudantes de enfermagem no que diz respeito ao idadismo? A busca foi realizada em 12 bases de dados utilizando o aplicativo Rayyan e o Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews . Realizou-se a seleção dos estudos por dois revisores, com uso de um instrumento para a extração dos dados. Resultados: dos 4.595 arquivos, selecionaram-se 46 publicados entre 1984 e 2022, sendo que a maioria utilizou o método quantitativo. O instrumento mais utilizado foi o Kogan's Attitudes Toward Old People Scale e os estudos mostraram que os estudantes apresentaram atitudes e percepções positivas, negativas, mistas, neutras e não conclusivas. Conclusão: as atitudes e percepções sobre idadismo são diversificadas e não conclusivas. Recomenda-se estudos futuros de intervenção para detecção de mudanças de comportamento dos estudantes de enfermagem frente ao idadismo.
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Humanos , Idoso , Percepção , Estudantes de Enfermagem , Atitude , EtarismoRESUMO
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.
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COVID-19 , SARS-CoV-2 , Humanos , Linfócitos T CD8-Positivos , Linfócitos T Auxiliares-Indutores , PulmãoRESUMO
This study compared mirtazapine with megestrol in the management of cancer-related anorexia-cachexia syndrome in patients with advanced cancer. A randomized, double-blind, controlled clinical trial involving patients with advanced cancer and anorexia-cachexia syndrome was performed. Participants received mirtazapine 30 mg/day or megestrol 320 mg/day for eight weeks. The primary endpoint was the effect of mirtazapine on weight gain and the secondary endpoints were its effect on appetite, muscle strength, physical performance, body composition, adverse events, and medication adherence. Linear regression model with mixed effects was applied and a significance level of 5% was adopted. Fifty-two patients were randomized. Mean age was 65.8 ± 8.4 years. There was weight gain in 52% of the participants in the megestrol group and in 38% in the mirtazapine group after four weeks (p = 0.040). Appetite improved in 92% of the participants in the megestrol group and in 56% in the mirtazapine group after eight weeks (p = 0.007). In the sub-analysis by sex, women showed improvement in appetite (p < 0.001) and weight gain (p < 0.005) in the mirtazapine group, which was not observed in men. Mirtazapine appears to be inferior to megestrol in weight and appetite improvement. However, there may be a difference in the therapeutic response between sexes.
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A structural variant (SV) in the agouti signaling protein gene (ASIP), namely ASIP-SV1, has been found to strongly correlate with the darkness of hair coat in specific regions of the body of bulls from the zebu (Bos indicus) Nellore breed. Here we visually analyzed the whole-genome sequence of zebu and taurine (Bos taurus) cattle to elucidate the extent of spread of ASIP-SV1 in different cattle populations. Of 216 sequences analyzed, 63 zebu (45.9%) and five taurine (6.3%) animals had at least one copy of ASIP-SV1. Four of the taurine animals presenting the SV were Romagnola cattle, a breed with history of zebu introgression. The remaining taurine animal was a Simmental, a breed frequently used in crossbreeding. These data provide evidence that ASIP-SV1 is commonly found in zebu populations, in addition to taurine animals with zebu admixture.
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Cabelo , Hibridização Genética , Bovinos/genética , Masculino , Animais , Escuridão , AlelosRESUMO
Abstract Objective: To investigate the effects of different physical exercise programs and polymorphisms of the FTO (fat mass and obesity-associated gene) on body composition and cardiovascular risk factors in adolescents with overweight and obesity. Methods: A randomized, parallel, double-blind clinical trial consisting of the adolescent overweight from the state public network, in a simple representative random sample, who participated in an aerobic exercise or weight training intervention for 10 weeks. Anthropometry, body composition, biochemical markers, sexual maturation, and rs9939609 polymorphism in the FTO gene were assessed. 347 adolescents had their characterization of nutritional status. 72 individuals with overweight and obesity were invited to participate. 39 remained for the start of the program and were randomly allocated to both types of intervention. In the end, 26 subjects participated in the intervention programs, with 12 and 14 in the aerobic and weight training programs, respectively. Results: Heterozygous and homozygous bearers of risk allele A participating in the aerobic program showed improvements in glycemia (p = 0.002) and total cholesterol (p = 0.023) and a reduction in body fat mass (p = 0.041). The weight training program reduced glycemia in patients with the risk allele A (p = 0.027). Cameron's stage four sexual maturation participants were 2.1 times more likely to improve their body fat (CI = 1.31-3.39). Conclusion: Aerobic exercises produced exclusively a significant decrease in fat mass and total cholesterol in patients with risk allele A. Distinct physical exercise programs may cause diverse changes in risk variables related to the health of adolescents.
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Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer (BC). Neoadjuvant chemotherapy has proven efficacy in its treatment, and a pathological complete response (pCR) to therapy is predictive of improved long-term survival. The immune response is key to successful neoadjuvant chemotherapy, as indicated by the relation between the percentage of stromal tumour-infiltrating lymphocytes (TILs) in pre-treated tumour tissue samples and the likelihood of achieving pCR. Here we studied systemic immune mediators from volunteer TNBC patients before undergoing neoadjuvant chemotherapy to determine the systemic response association with TIL intensity, treatment response and survival. Patients were classified into pCR responder or non-responder at time of surgery. We found higher levels of immune mediators before treatment began in patients that went on to be pCR responders versus non-pCR, with area under the curve (AUC) values of 0.64-0.80. We also observed a positive correlation between inflammatory systemic immune mediators and the percentage of TILs in pCR responder patients. Combining TILs and systemic immune mediator levels provided stronger AUC values (range of 0.72-0.82). Last, performing a progression-free survival analysis with several of the systemic cytokines that predict pCR, segregated the patients into long- and short-survival groups based on high and low production of the cytokines, respectively. Our study demonstrates that circulating cytokines, before treatment begins, predict pCR in TNBC patients treated with neoadjuvant chemotherapy. Moreover, they may act as a surrogate marker of high TILs or together with TILs to better predict pCR and survival.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Linfócitos do Interstício Tumoral , Neoplasias da Mama/terapia , Terapia Neoadjuvante , Citocinas , PrognósticoRESUMO
OBJECTIVE: To investigate the effects of different physical exercise programs and polymorphisms of the FTO (fat mass and obesity-associated gene) on body composition and cardiovascular risk factors in adolescents with overweight and obesity. METHODS: A randomized, parallel, double-blind clinical trial consisting of the adolescent overweight from the state public network, in a simple representative random sample, who participated in an aerobic exercise or weight training intervention for 10 weeks. Anthropometry, body composition, biochemical markers, sexual maturation, and rs9939609 polymorphism in the FTO gene were assessed. 347 adolescents had their characterization of nutritional status. 72 individuals with overweight and obesity were invited to participate. 39 remained for the start of the program and were randomly allocated to both types of intervention. In the end, 26 subjects participated in the intervention programs, with 12 and 14 in the aerobic and weight training programs, respectively. RESULTS: Heterozygous and homozygous bearers of risk allele A participating in the aerobic program showed improvements in glycemia (p = 0.002) and total cholesterol (p = 0.023) and a reduction in body fat mass (p = 0.041). The weight training program reduced glycemia in patients with the risk allele A (p = 0.027). Cameron's stage four sexual maturation participants were 2.1 times more likely to improve their body fat (CI = 1.31-3.39). CONCLUSION: Aerobic exercises produced exclusively a significant decrease in fat mass and total cholesterol in patients with risk allele A. Distinct physical exercise programs may cause diverse changes in risk variables related to the health of adolescents.