RESUMO
Exercise is effective toward delaying or preventing chronic disease, with a large body of evidence supporting its effectiveness. However, less is known about the specific healthspan-promoting effects of exercise on blood biomarkers in the disease-free population. In this work, we examine 23,237 generally healthy individuals who self-report varying weekly running volumes and compare them to 4,428 generally healthy sedentary individuals, as well as 82 professional endurance runners. We estimate the significance of differences among blood biomarkers for groups of increasing running levels using analysis of variance (ANOVA), adjusting for age, gender, and BMI. We attempt and add insight to our observational dataset analysis via two-sample Mendelian randomization (2S-MR) using large independent datasets. We find that self-reported running volume associates with biomarker signatures of improved wellness, with some serum markers apparently being principally modified by BMI, whereas others show a dose-effect with respect to running volume. We further detect hints of sexually dimorphic serum responses in oxygen transport and hormonal traits, and we also observe a tendency toward pronounced modifications in magnesium status in professional endurance athletes. Thus, our results further characterize blood biomarkers of exercise and metabolic health, particularly regarding dose-effect relationships, and better inform personalized advice for training and performance.
Assuntos
Corrida , Humanos , Corrida/fisiologia , Exercício Físico/fisiologia , Atletas , Biomarcadores , Resistência FísicaRESUMO
Since next generation sequencing facilitated high-throughput and cost-efficient genomics analyses, the human gut metagenome has become an emerging frontier to explore toward precision nutrition. Significant progress has been made in identifying gut microbial features associated with a wide spectrum of human disease. However, other than a few microbiome-disease relations, there is a dearth of confirmed causal inferences, particularly in generally healthy populations. The relatively high unexplained variability in microbiome compositions in this group warrants caution in applying this complex biomarker toward precision nutrition, because our understanding of what constitutes a healthy microbiome is still rudimentary. Although gut microbiota harbor integrated environmental and host-specific information with the potential to facilitate personalized nutritional and lifestyle advice, these data cannot yet be confidently interpreted toward precise recommendations. Thus, nutritional advice for generally healthy individuals based on personal microbiome composition analysis might not yet be appropriate unless accompanied by established blood and physiological biomarkers.
RESUMO
O objetivo da pesquisa é apresentar os resultados de uma oficina, guiada pelo design thinking (DT), realizada com estudantes da área da Saúde para a produção de ideias de fomento à educação interprofissional (EIP) em Saúde em uma Instituição de Ensino Superior. Trata-se de uma pesquisa qualitativa, do tipo estudo de caso, realizada em junho de 2022. A oficina pedagógica baseou-se nas fases do DT: descoberta, interpretação, ideação e experimentação, e foi apoiada pelo uso de nove estratégias. Participaram seis estudantes de Enfermagem, um estudante de Saúde Coletiva e um de Farmácia. Como resultado, dois protótipos foram criados. Verificou-se que as fases e estratégias utilizadas no DT foram oportunas e eficientes para o debate da EIP. Os protótipos elaborados serão executados em continuidade à pesquisa. (AU)
This article presents the results of a design thinking workshop with health students to generate ideas for fostering interprofessional education (IPE) for health in a higher education institution. We conducted a qualitative case study in June 2022. The workshop followed the phases of the design thinking process (discovery, interpretation, ideation and experimentation) and was supported by the use of nine strategies. The workshop was attended by six nursing students, one public health student and one pharmacy student. The workshop resulted in the creation of two prototypes. It was found that the phases and strategies used were well-suited to and effective in promoting a debate about IPE. The prototypes will be executed as part of the continuation of the research. (AU)
El objetivo de la investigación es presentar los resultados de un taller, guiado por el design thinking (DT), realizado con estudiantes del área de la salud para la producción de ideas de fomento a la educación interprofesional en salud (EIP) en una Institución de Enseñanza Superior. Se trata de una investigación cualitativa, del tipo estudio de caso, realizada en junio de 2022. El taller pedagógico se basó en las fases del DT: descubrimiento, interpretación, ideación y experimentación y tuvo como apoyo el uso de nueve estrategias. Participaron seis estudiantes de Enfermería, un estudiante de Salud Colectiva y uno de Farmacia. Como resultado se crearon dos prototipos. Se verificó que las fases y estrategias utilizadas en el DT fueron oportunas y eficientes para el debate de la EIP. Los prototipos elaborados se realizarán en continuidad a la investigación. (AU)
RESUMO
To understand the molecular mechanisms underlying compound-induced hemangiosarcomas in mice, and therefore, their human relevance, a systems biology approach was undertaken using transcriptomics and Causal Network Modeling from mice treated with 2-butoxyethanol (2-BE). 2-BE is a hemolytic agent that induces hemangiosarcomas in mice. We hypothesized that the hemolysis induced by 2-BE would result in local tissue hypoxia, a well-documented trigger for endothelial cell proliferation leading to hemangiosarcoma. Gene expression data from bone marrow (BM), liver, and spleen of mice exposed to a single dose (4 h) or seven daily doses of 2-BE were used to develop a mechanistic model of hemangiosarcoma. The resulting mechanistic model confirms previous work proposing that 2-BE induces macrophage activation and inflammation in the liver. In addition, the model supports local tissue hypoxia in the liver and spleen, coupled with increased erythropoeitin signaling and erythropoiesis in the spleen and BM, and suppression of mechanisms that contribute to genomic stability, events that could be contributing factors to hemangiosarcoma formation. Finally, an immunohistochemistry method (Hypoxyprobe) demonstrated that tissue hypoxia was present in the spleen and BM. Together, the results of this study identify molecular mechanisms that initiate hemangiosarcoma, a key step in understanding safety concerns that can impact drug decision processes, and identified hypoxia as a possible contributing factor for 2-BE-induced hemangiosarcoma in mice.
Assuntos
Medula Óssea/metabolismo , Transformação Celular Neoplásica/metabolismo , Hemangiossarcoma/metabolismo , Fígado/metabolismo , Modelos Biológicos , Transdução de Sinais , Baço/metabolismo , Biologia de Sistemas , Animais , Medula Óssea/patologia , Ciclo Celular , Diferenciação Celular , Hipóxia Celular , Proliferação de Células , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Eritropoese , Eritropoetina/metabolismo , Etilenoglicóis , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Instabilidade Genômica , Hemangiossarcoma/induzido quimicamente , Hemangiossarcoma/genética , Hemangiossarcoma/patologia , Células-Tronco Hematopoéticas/metabolismo , Hemólise , Hepatite/metabolismo , Hepatite/patologia , Imuno-Histoquímica , Fígado/patologia , Ativação de Macrófagos , Masculino , Camundongos , Baço/patologia , Fatores de TempoRESUMO
Trypanosoma cruzi, the agent of Chagas' disease, is an obligate intracellular parasite that invades various organs including several cell types in the nervous system that express the Trk receptor tyrosine kinase. Activation of Trk is a major cell-survival and repair mechanism, and parasites could use Trks to invade cells as a strategy to protect their habitat and prolong parasitism of vertebrate hosts. We show that T. cruzi binds to TrkA specifically and activates TrkA-dependent survival mechanisms. This interaction facilitates parasite adherence and promotes efficient invasion of neuronal, epithelial, and phagocytic cells via a process that requires TrkA kinase activity. Diffusible TrkA and TrkA-blocking agents neutralized infection in cellular and animal models of acute Chagas' disease, suggesting cellular receptors as therapeutic targets against parasitic diseases. Thus, TrkA, the nerve growth factor receptor commonly associated with neural survival and protection, may also underlie clinical progression of an important human parasitic disease.
Assuntos
Doença de Chagas/parasitologia , Doença de Chagas/transmissão , Fenômenos Fisiológicos do Sistema Nervoso , Receptor trkA/antagonistas & inibidores , Receptor trkA/fisiologia , Trypanosoma brucei brucei/fisiologia , Animais , Doença de Chagas/fisiopatologia , Humanos , Mamíferos , Sistema Nervoso/parasitologia , Neurônios/parasitologia , Células PC12 , Ratos , Trypanosoma brucei brucei/patogenicidadeRESUMO
BACKGROUND: The transmission of parasites, including Babesia, plasmodia, and Trypanosoma cruzi, via transfusions is an important public health concern. INACTINE technology is a pathogen-reduction process that utilizes PEN110, an electrophilic agent that inac-tivates a wide range of pathogens by disrupting nucleic acid replication. The present study investigated the effect of PEN110 treatment on the viability of protozoa in RBCs. STUDY DESIGN AND METHODS: B. microti-parasitized RBCs from infected hamsters were treated with PEN110 and inoculated to naïve animals. Parasitemia was detected by blood smears and PCR. Human RBCs infected with P. falciparum were treated with PEN110 and incubated with fresh RBCs. P. falciparum multiplication was detected by blood smears. Human RBCs spiked with T. cruzi and treated with PEN110 were analyzed for the presence of live parasites using in-vitro infectivity assay or by inoculating susceptible mice. RESULTS: Treatment of RBCs infected with B. microti or P. falciparum with 0.01 to 0.1 percent (vol/vol) PEN110 resulted in parasite inactivation to below the limit of detection during 24 hours. T. cruzi inoculated into human RBCs was inactivated below the limit of detection by 0.1 percent PEN110 after 3 hours. CONCLUSION: The study demonstrates that treatment of blood with PEN110 is highly effective in eradicating transfusion-transmitted protozoan parasites.
Assuntos
Babesia microti/efeitos dos fármacos , Eritrócitos/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Poliaminas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , HumanosRESUMO
Somatic hypermutation contributes to the generation of antibody diversity and is strongly associated with the maturation of antigen-specific immune responses. We asked whether somatic hypermutation also plays a role in the generation of the murine immunoglobulin repertoire during B cell development. To facilitate identification of somatic mutations, we examined mouse systems in which only antibodies expressing lambda1, lambda2, and lambdax light chains can be generated. Somatic mutations were found in cells, which, by surface markers, RAG expression, and rapid turnover, had the phenotype of immature B cells. In addition, expression of AID was detected in these cells. The mutations were limited to V regions and were localized in known hotspots. Mutation frequency was not diminished in the absence of T cells. Our results support the idea that somatic hypermutation can occur in murine immature B cells and may represent a mechanism for enlarging the V gene repertoire.