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1.
Stud Health Technol Inform ; 270: 267-271, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32570388

RESUMO

Information relevant to pharmacogenomics studies is available in several open databases, which makes it difficult to synthetize the available data. Within the PractikPharma project, several databases were integrated to PGxLOD, a resource dedicated to the generation and verification of pharmacogenomic influence on drug responses. The Comparative Toxicogenomic Database (CTD) describes the toxic effects of many chemicals on living species based on the literature. Since drugs are peculiar chemicals and side effects are peculiar toxic effects, we aimed at extracting information from CTD that matches drug side effects in the human specie.


Assuntos
Doença/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Substâncias Perigosas/toxicidade , Farmacogenética , Toxicogenética , Bases de Dados Factuais , Doença/genética , Humanos , Pesquisa , Integração de Sistemas
2.
N Engl J Med ; 382(18): 1721-1731, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32348643

RESUMO

BACKGROUND: Persons with mental disorders are at a higher risk than the general population for the subsequent development of certain medical conditions. METHODS: We used a population-based cohort from Danish national registries that included data on more than 5.9 million persons born in Denmark from 1900 through 2015 and followed them from 2000 through 2016, for a total of 83.9 million person-years. We assessed 10 broad types of mental disorders and 9 broad categories of medical conditions (which encompassed 31 specific conditions). We used Cox regression models to calculate overall hazard ratios and time-dependent hazard ratios for pairs of mental disorders and medical conditions, after adjustment for age, sex, calendar time, and previous mental disorders. Absolute risks were estimated with the use of competing-risks survival analyses. RESULTS: A total of 698,874 of 5,940,299 persons (11.8%) were identified as having a mental disorder. The median age of the total population was 32.1 years at entry into the cohort and 48.7 years at the time of the last follow-up. Persons with a mental disorder had a higher risk than those without such disorders with respect to 76 of 90 pairs of mental disorders and medical conditions. The median hazard ratio for an association between a mental disorder and a medical condition was 1.37. The lowest hazard ratio was 0.82 for organic mental disorders and the broad category of cancer (95% confidence interval [CI], 0.80 to 0.84), and the highest was 3.62 for eating disorders and urogenital conditions (95% CI, 3.11 to 4.22). Several specific pairs showed a reduced risk (e.g., schizophrenia and musculoskeletal conditions). Risks varied according to the time since the diagnosis of a mental disorder. The absolute risk of a medical condition within 15 years after a mental disorder was diagnosed varied from 0.6% for a urogenital condition among persons with a developmental disorder to 54.1% for a circulatory disorder among those with an organic mental disorder. CONCLUSIONS: Most mental disorders were associated with an increased risk of a subsequent medical condition; hazard ratios ranged from 0.82 to 3.62 and varied according to the time since the diagnosis of the mental disorder. (Funded by the Danish National Research Foundation and others; COMO-GMC ClinicalTrials.gov number, NCT03847753.).


Assuntos
Doença/etiologia , Transtornos Mentais/complicações , Adulto , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Doenças Urogenitais Femininas/etiologia , Humanos , Masculino , Doenças Urogenitais Masculinas/etiologia , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/etiologia , Neoplasias/etiologia , Risco , Esquizofrenia/complicações , Fatores Sexuais
3.
Med. leg. Costa Rica ; 37(1): 33-38, ene.-mar. 2020.
Artigo em Inglês | LILACS | ID: biblio-1098369

RESUMO

Abstract Background: Air contamination happens when unsafe or inordinate amounts of substances including gases, particles, and organic atoms are brought into Earth's climate. Objective: This review article defines air pollution, describes the types of pollutants, enumerates the various causative factors, enumerates the ways it impacts human health and suggests preventive measures to reduce the impact of air pollution on human health. Methods: Literature was studied extensively and effects of air pollution on human health have been described. Results and Conclusion: Air pollution has tremendous effects on human health in the form of respiratory diseases and aggravations in the form of asthma and lung cancer, cardiovascular dysfunctions, and malignant growth. An affiliation has been found to exist between male infertility and air pollution and a relationship has been established between air contamination and higher danger of immune dysfunction, neuroinflammation, neurobehavioral hyperactivity, crime, age-unseemly behaviours, Alzheimer's and Parkinson's disease. Traffic-related air pollutants have been found to affect skin aging and cause pigmented spots on the face. An association exists between air pollution and irritation of the eyes, dry eye syndrome, risk for retinopathy and adverse ocular outcomes. Chronic exposure to air pollutants during pregnancy has been associated with adverse effects on the developing foetus in the form of low birth weight and still birth. Air contamination has been seen as a significant supporter of the expanded predominance of allergic diseases in children.


Assuntos
Dermatopatias/diagnóstico , Poluentes Ambientais/efeitos adversos , Poluição Ambiental/análise , Doença/etiologia , Costa Rica , Doença de Alzheimer/diagnóstico
5.
Am J Pathol ; 190(4): 728-731, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32061726

RESUMO

This Guest Editorial introduces the theme reviews focusing on the glycocalyx in human disease.


Assuntos
Doença/etiologia , Glicocálix/fisiologia , Humanos
6.
Science ; 367(6476): 392-396, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31974245

RESUMO

Despite extensive evidence showing that exposure to specific chemicals can lead to disease, current research approaches and regulatory policies fail to address the chemical complexity of our world. To safeguard current and future generations from the increasing number of chemicals polluting our environment, a systematic and agnostic approach is needed. The "exposome" concept strives to capture the diversity and range of exposures to synthetic chemicals, dietary constituents, psychosocial stressors, and physical factors, as well as their corresponding biological responses. Technological advances such as high-resolution mass spectrometry and network science have allowed us to take the first steps toward a comprehensive assessment of the exposome. Given the increased recognition of the dominant role that nongenetic factors play in disease, an effort to characterize the exposome at a scale comparable to that of the human genome is warranted.


Assuntos
Doença/etiologia , Doença/genética , Expossoma , Saúde , Suplementos Nutricionais/efeitos adversos , Genoma Humano , Humanos , Compostos Orgânicos/efeitos adversos , Fenômenos Físicos , Medição de Risco , Estresse Psicológico/complicações
7.
Cell ; 180(2): 221-232, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31978342

RESUMO

Human diseases are increasingly linked with an altered or "dysbiotic" gut microbiota, but whether such changes are causal, consequential, or bystanders to disease is, for the most part, unresolved. Human microbiota-associated (HMA) rodents have become a cornerstone of microbiome science for addressing causal relationships between altered microbiomes and host pathology. In a systematic review, we found that 95% of published studies (36/38) on HMA rodents reported a transfer of pathological phenotypes to recipient animals, and many extrapolated the findings to make causal inferences to human diseases. We posit that this exceedingly high rate of inter-species transferable pathologies is implausible and overstates the role of the gut microbiome in human disease. We advocate for a more rigorous and critical approach for inferring causality to avoid false concepts and prevent unrealistic expectations that may undermine the credibility of microbiome science and delay its translation.


Assuntos
Disbiose/microbiologia , Microbioma Gastrointestinal/fisiologia , Roedores/microbiologia , Animais , Doença/etiologia , Transplante de Microbiota Fecal/métodos , Humanos , Camundongos , Microbiota/fisiologia , Modelos Animais , Ratos
8.
Annu Rev Pathol ; 15: 371-394, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31977295

RESUMO

Modeling has enabled fundamental advances in our understanding of the mechanisms of health and disease for centuries, since at least the time of William Harvey almost 500 years ago. Recent technological advances in molecular methods, computation, and imaging generate optimism that mathematical modeling will enable the biomedical research community to accelerate its efforts in unraveling the molecular, cellular, tissue-, and organ-level processes that maintain health, predispose to disease, and determine response to treatment. In this review, we discuss some of the roles of mathematical modeling in the study of human physiology and pathophysiology and some challenges and opportunities in general and in two specific areas: in vivo modeling of pulmonary function and in vitro modeling of blood cell populations.


Assuntos
Pesquisa Biomédica/métodos , Biologia Computacional/métodos , Doença/etiologia , Modelos Teóricos , Animais , Pesquisa Biomédica/tendências , Biologia Celular/tendências , Biologia Computacional/tendências , Simulação por Computador , Humanos , Fenômenos Fisiológicos
9.
Annu Rev Pathol ; 15: 179-209, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31977298

RESUMO

The human eosinophil has long been thought to favorably influence innate mucosal immunity but at times has also been incriminated in disease pathophysiology. Research into eosinophil biology has uncovered a number of interesting contributions by eosinophils to health and disease. However, it appears that not all eosinophils from all species are created equal. It remains unclear, for example, exactly how having eosinophils benefits the human host when helminth infections in the developed world have become scarce. This review focuses on our current state of knowledge as it relates to human eosinophils. When information is lacking, we discuss lessons learned from mouse studies that may or may not directly apply to human biology and disease. It is an exciting time to be an "eosinophilosopher" because the use of biologic agents that selectively target eosinophils provides an unprecedented opportunity to define the contribution of this cell to eosinophil-associated human diseases.


Assuntos
Doença/etiologia , Eosinófilos/fisiologia , Imunidade Inata/fisiologia , Animais , Helmintíase/imunologia , Humanos , Contagem de Leucócitos , Camundongos
10.
Am J Pathol ; 190(2): 272-285, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31783008

RESUMO

Over the past 15 years, elegant studies have demonstrated that in certain conditions, programed cell death resembles necrosis and depends on a unique molecular pathway with no overlap with apoptosis. This form of regulated necrosis is represented by necroptosis, in which the receptor-interacting protein kinase-3 and its substrate mixed-lineage kinase domain-like protein play a crucial role. With the development of knockout mouse models and molecular inhibitors unique to necroptotic proteins, this cell death has been found to occur in virtually all tissues and diseases evaluated. There are different immunologic consequences depending on whether cells die through apoptosis or necroptosis. Therefore, distinguishing between these two forms of cell death may be crucial during pathologic evaluations. In this review, we provide an understanding of necroptotic cell-death and highlight diseases in which necroptosis has been found to play a role. We also discuss the inhibitors of necroptosis and the ways these inhibitors have been used in preclinical models of diseases. These two discussions offer an understanding of the role of necroptosis in diseases and will foster efforts to pharmacologically target this unique yet pervasive form of programed cell death in the clinic.


Assuntos
Doença Crônica/epidemiologia , Doença/etiologia , Inflamação/fisiopatologia , Necroptose , Animais , Doença Crônica/terapia , Humanos
11.
Artigo em Inglês | MEDLINE | ID: mdl-31795378

RESUMO

Augustini studied Roma and published reports in 1775-1776 on their illnesses and death. Our intention was to compare the features of these two topics described by him in the late 18th century with those in the present time. We studied Augustini's work on illnesses and death in the past. The present qualitative study was conducted in 2012-2013 in the same geographical area in which Augustini lived and worked more than two hundred years ago, i.e., the Tatra Region in Slovakia; our findings were evaluated in 2017-2018. We carried out semi-structured interviews with more than 70 informants and organised two sessions of focus groups. Data were analysed using content analysis (Augustini) and an open coding process. Our findings suggest that illnesses in Roma are treated differently nowadays compared with 1775-1776. For example, the traditional forms of healing have completely disappeared in the area of investigation. We did not observe any differences in dying and death perceptions between the past and nowadays. Although data and knowledge on health disparities and related mechanisms exist, and much more about perceptions of Roma regarding illnesses is now known compared with 1775-1776, so far, this knowledge has not helped to design effective interventions to overcome them. Substandard living conditions in marginalised Roma communities have not significantly improved since 1775-1776, which may contribute to their higher morbidity and mortality also nowadays. Political and social consensus should lead to a comprehensive vision for enhancing the social situation and living conditions in segregated settlements, especially providing housing for the poorest classes and overcoming health disparities.


Assuntos
Doença/etiologia , Mortalidade , Feminino , Humanos , Masculino , Pesquisa Qualitativa , Roma , Eslováquia
14.
PLoS Biol ; 17(11): e3000526, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31730640

RESUMO

The Amazon is Brazil's greatest natural resource and invaluable to the rest of the world as a buffer against climate change. The recent election of Brazil's president brought disputes over development plans for the region back into the spotlight. Historically, the development model for the Amazon has focused on exploitation of natural resources, resulting in environmental degradation, particularly deforestation. Although considerable attention has focused on the long-term global cost of "losing the Amazon," too little attention has focused on the emergence and reemergence of vector-borne diseases that directly impact the local population, with spillover effects to other neighboring areas. We discuss the impact of Amazon development models on human health, with a focus on vector-borne disease risk. We outline policy actions that could mitigate these negative impacts while creating opportunities for environmentally sensitive economic activities.


Assuntos
Agricultura/métodos , Conservação dos Recursos Naturais/métodos , Doenças Transmitidas por Vetores/epidemiologia , Agricultura/legislação & jurisprudência , Brasil , Mudança Climática , Conservação dos Recursos Naturais/legislação & jurisprudência , Doença/etiologia , Ecossistema , Florestas , Humanos , Doenças Transmitidas por Vetores/transmissão
15.
Genome Biol ; 20(1): 233, 2019 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694669

RESUMO

The driver tissues or cell types in which susceptibility genes initiate diseases remain elusive. We develop a unified framework to detect the causal tissues of complex diseases or traits according to selective expression of disease-associated genes in genome-wide association studies (GWASs). This framework consists of three components which run iteratively to produce a converged prioritization list of driver tissues. Additionally, this framework also outputs a list of prioritized genes as a byproduct. We apply the framework to six representative complex diseases or traits with GWAS summary statistics, which leads to the estimation of the lung as an associated tissue of rheumatoid arthritis.


Assuntos
Doença/etiologia , Expressão Gênica , Predisposição Genética para Doença , Genômica/métodos , Algoritmos , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Transtorno Bipolar/genética , Transtorno Bipolar/metabolismo , Estatura/genética , Encéfalo/metabolismo , Colesterol/genética , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Estudo de Associação Genômica Ampla , Humanos , Esquizofrenia/genética , Esquizofrenia/metabolismo
19.
Metabolism ; 100S: 153941, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31610853

RESUMO

Modern biomedical scientists are often trapped in silos of knowledge and practice, such as those who study brain structure, function and behavior, on the one hand, and body systems and disorders, on the other. Scientists and physicians in each of those silos have not often paid attention to the brain-body communication that leads to multi-morbidity of systemic and brain-related disorders [eg. depression with diabetes or cardiovascular disease]. Outside of biomedicine, social scientists have long recognized the impact of the social and physical environment on individuals and populations but have not usually connected these effects with changes in underlying biology. However, with the rise of epigenetics, science and the public understanding of science is leaving an era in which the DNA sequence was thought to be "destiny" and entering an era where the environment shapes the biology and behavior of individuals and groups through its interactive effects on brain and body. It does so, at least in part, by shaping epigenetically the structure and function of brain and body systems that show a considerable amount of adaptive plasticity throughout development and adult life. This results in substantial individual differences even between identical twins. These individual differences are produced epigenetically by the two-way interaction between the brain and hormones, immune system mediators and the autonomic nervous system. Disorders, then, are often multimorbid involving both brain and body, such as depression with diabetes and cardiovascular disease. It is therefore imperative to incorporate into "precision medicine" a better understanding of how these differences affect the efficacy of pharmacological, behavioral and psychosocial interventions. This article presents an overview of this new synthesis, using as an example emerging evidence about the linkages between systemic inflammation, insulin resistance and mental health and neurodegenerative diseases.


Assuntos
Encéfalo/fisiologia , Doença/etiologia , Epigenômica , Medicina de Precisão/métodos , Encéfalo/fisiopatologia , Doença/genética , Meio Ambiente , Interação Gene-Ambiente , Humanos , Meio Social
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