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2.
BMC Health Serv Res ; 21(1): 926, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488751

RESUMO

BACKGROUND: End-user involvement in developing evidence-based tools for clinical practice may result in increased uptake and improved patient outcomes. Understanding end-user experiences and perceptions about the co-production of knowledge is useful to further the science of integrated knowledge translation (iKT) - a strategy for accelerating the uptake and impact of research. Our study had two main objectives: (1) explore end-user (clinician) experiences of co-producing an evidence-based practice tool; and (2) describe end-user perceptions in knowledge development. METHODS: We used a qualitative study design. We conducted semi-structured interviews with clinicians and used a transcendental phenomenological approach to analyze themes/phenomena. In addition, we explored the interrelated themes between the thematic maps of each objective. RESULTS: Four themes emerged from clinicians' experiences in co-producing the practice tool: ease/convenience of participating, need for support and encouragement, understanding the value of participating, and individual skillsets yield meaningful contributions. Stakeholder roles in knowledge tool development and improving dissemination of evidence and knowledge tools were themes that related to clinician perceptions in knowledge development. The review of interrelated thematic maps depicts an intertwined relationship between stakeholders and dissemination. CONCLUSIONS: End-users provide invaluable insight and perspective into the development of evidence-based clinical tools. Exploring the experiences and perceptions of end-users may support future research endeavours involving iKT, such as the co-production of clinical resources, potentially improving uptake and patient health outcomes.


Assuntos
Terapia Comportamental , Pesquisa Médica Translacional , Humanos , Percepção , Pesquisa Qualitativa
3.
Int J Public Health ; 66: 620425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34408619

RESUMO

Objectives: Over the last 2 decades, the World Health Organization (WHO) has proposed a global strategy and initiatives to establish a Health Research System (HRS) focusing on Health Research Quality and Standardization (HRQS), Health Research Knowledge Transfer and Dissemination (HRKTD), and Health Research Translation and Utilization into Health Care Decisions and Policies (HRTUDP). Despite the increase in health research productivity over the past several decades, HRS Capacity (HRSC) in Palestine and in the Middle East and North Africa (MENA) region has rarely been objectively evaluated. This study aims at eliciting the perceptions of HRS performers in Palestine in order to understand the status of HRSC, identify gaps, and generate policies and solutions capable of strengthening HRSC in Palestine. Methods: Key informants from three sectors, namely government, academia, and local and international organizations, were selected purposively based on different sampling methods: criterion, critical case, snowball, and homogeneous sampling. Fifty-two in-depth interviews with key informants and a total of fifty-two individuals, participating in six focus groups, were conducted by the principal investigator in Palestine. Data were analyzed by using MAXQDA 12. Results: The overall pattern of the Palestinian HRSC is relatively weak. The key findings revealed that while HR productivity in Palestine is improving, HRQS is at an average level and quality guidelines are not followed due to paucity of understanding, policies, and resources. HRKTD is a central challenge with both a dearth of conceptualization of translational science and inadequate implementation. The factors related to inadequate HRKTD include lack of awareness on the part of the researchers, inadequate regulatory frameworks and mechanisms for both communication and collaboration between and among researchers and policy-makers and clinicians, and lack of availability of, and credibility in, systematized and reliable HR data. Despite the limited knowledge translation, in general, HRTUDP is not considered an essential decision-making methodology mainly due to the lack of interface between knowledge producers (researchers) and users (policymakers), understanding level, HR credibility and availability of applied research, and governance, resources, and political fluctuations. Recommendations to strengthen HRS in Palestine include: a consolidated research regulatory framework and an effective capacity strengthening strategy overseen by Palestinian authorities; the promotion of HRQS and concepts and practices of translational science; and, most importantly, the use of findings for evidence-based policies and practice. Conclusion: Strengthening HRSC is both an imperative step and an opportunity to improve the Palestinian health system and ensure it is based on research evidence and knowledge. Building a successful HRS characterized by capacities of high-quality research and well-disseminated and translated knowledge is a prerequisite to effective health systems and services. This can be achieved by political commitment to support such strengthening, a consolidated leadership and governance structure, and a strong operational capacity strengthening strategy.


Assuntos
Pesquisa Biomédica , Fortalecimento Institucional , Política de Saúde , Formulação de Políticas , Pesquisa Médica Translacional , Pesquisa Biomédica/organização & administração , Pesquisa Biomédica/normas , Fortalecimento Institucional/métodos , Grupos Focais , Humanos , Oriente Médio
4.
Clin Immunol ; 230: 108815, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34339843

RESUMO

Traumatic Brain Injury (TBI) is the most prevalent of all head injuries. Microglia play an essential role in homeostasis and diseases of the central nervous system. We hypothesize that microglia may play a beneficial or detrimental role in TBI depending on their state of activation and duration. In this study, we evaluated whether TBI results in a spatiotemporal change in microglia phenotype and whether it affects sensory-motor or learning and memory functions in male C57BL/6 mice. We used a panel of neurological and behavioral tests and a multi-color flow cytometry-based data analysis followed by unsupervised clustering to evaluate isolated microglia from injured brain tissue. We characterized several microglial phenotypes and their association with cognitive deficits. TBI results in a spatiotemporal increase in activated microglia that correlated negatively with spatial learning and memory at 35 days post-injury. These observations could define therapeutic windows and accelerate translational research to improve patient outcomes.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Disfunção Cognitiva/etiologia , Microglia/fisiologia , Animais , Encéfalo/patologia , Encéfalo/fisiopatologia , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/psicologia , Disfunção Cognitiva/patologia , Disfunção Cognitiva/psicologia , Modelos Animais de Doenças , Citometria de Fluxo , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Microglia/classificação , Microglia/patologia , Modelos Neurológicos , Modelos Psicológicos , Dinâmica não Linear , Aprendizagem Espacial/fisiologia , Memória Espacial/fisiologia , Análise Espaço-Temporal , Pesquisa Médica Translacional
5.
Int J Equity Health ; 20(1): 187, 2021 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419053

RESUMO

Intersectionality is a widely adopted theoretical orientation in the field of women and gender studies. Intersectionality comes from the work of black feminist scholars and activists. Intersectionality argues identities such as gender, race, sexuality, and other markers of difference intersect and reflect large social structures of oppression and privilege, such as sexism, racism, and heteronormativity. The reach of intersectionality now extends to the fields of public health and knowledge translation. Knowledge translation (KT) is a field of study and practice that aims to synthesize and evaluate research into an evidence base and move that evidence into health care practice. There have been increasing calls to bring gender and other social issues into the field of KT. Yet, as scholars outline, there are few guidelines for incorporating the principles of intersectionality into empirical research. An interdisciplinary, team-based, national health research project in Canada aimed to bring an intersectional lens to the field of knowledge translation. This paper reports on key moments and resulting tensions we experienced through the project, which reflect debates in intersectionality: discomfort with social justice, disciplinary divides, and tokenism. We consider how our project advances intersectionality practice and suggests recommendations for using intersectionality in health research contexts. We argue that while we encountered many challenges, our process and the resulting co-created tools can serve as a valuable starting point and example of how intersectionality can transform fields and practices.


Assuntos
Equidade em Saúde , Colaboração Intersetorial , Racismo , Pesquisa Médica Translacional , Afro-Americanos , Feminino , Feminilidade , Feminismo , Humanos , Pesquisa Interdisciplinar , Justiça Social
6.
Nutrients ; 13(7)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34371855

RESUMO

Aging is a biological process determined by multiple cellular mechanisms, such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication, that ultimately concur in the functional decline of the individual. The evidence that the old population is steadily increasing and will triplicate in the next 50 years, together with the fact the elderlies are more prone to develop pathologies such as cancer, diabetes, and degenerative disorders, stimulates an important effort in finding specific countermeasures. Calorie restriction (CR) has been demonstrated to modulate nutrient sensing mechanisms, inducing a better metabolic profile, enhanced stress resistance, reduced oxidative stress, and improved inflammatory response. Therefore, CR and CR-mimetics have been suggested as powerful means to slow aging and extend healthy life-span in experimental models and humans. Taking into consideration the difficulties and ethical issues in performing aging research and testing anti-aging interventions in humans, researchers initially need to work with experimental models. The present review reports the major experimental models utilized in the study of CR and CR-mimetics, highlighting their application in the laboratory routine, and their translation to human research.


Assuntos
Envelhecimento/fisiologia , Materiais Biomiméticos/farmacologia , Restrição Calórica , Modelos Teóricos , Pesquisa Médica Translacional/métodos , Envelhecimento/efeitos dos fármacos , Animais , Senescência Celular/efeitos dos fármacos , Senescência Celular/fisiologia , Humanos , Longevidade/efeitos dos fármacos , Longevidade/fisiologia
7.
Pain ; 162(9): 2349-2365, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34448751

RESUMO

ABSTRACT: Endometriosis (ENDO) and interstitial cystitis/bladder pain syndrome (IC/BPS) are chronic pain conditions for which better treatments are urgently needed. Development of new therapies with proven clinical benefit has been slow. We have conducted a review of existing preclinical in vivo models for ENDO and IC/BPS in rodents, discussed to what extent they replicate the phenotype and pain experience of patients, as well as their relevance for translational research. In 1009 publications detailing ENDO models, 41% used autologous, 26% syngeneic, 18% xenograft, and 11% allogeneic tissue in transplantation models. Intraperitoneal injection of endometrial tissue was the subcategory with the highest construct validity score for translational research. From 1055 IC/BPS publications, most interventions were bladder centric (85%), followed by complex mechanisms (8%) and stress-induced models (7%). Within these categories, the most frequently used models were instillation of irritants (92%), autoimmune (43%), and water avoidance stress (39%), respectively. Notably, although pelvic pain is a hallmark of both conditions and a key endpoint for development of novel therapies, only a small proportion of the studies (models of ENDO: 0.5%-12% and models of IC/BPS: 20%-44%) examined endpoints associated with pain. Moreover, only 2% and 3% of publications using models of ENDO and IC/BPS investigated nonevoked pain endpoints. This analysis highlights the wide variety of models used, limiting reproducibility and translation of results. We recommend refining models so that they better reflect clinical reality, sharing protocols, and using standardized endpoints to improve reproducibility. We are addressing this in our project Innovative Medicines Initiative-PainCare/Translational Research in Pelvic Pain.


Assuntos
Cistite Intersticial , Endometriose , Cistite Intersticial/terapia , Feminino , Humanos , Dor Pélvica/terapia , Reprodutibilidade dos Testes , Pesquisa Médica Translacional
8.
BMC Geriatr ; 21(1): 455, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362311

RESUMO

BACKGROUND: Knowledge translation (KT) is challenging to carry out and assess. The content of a program developed to foster KT activities pertaining to the Elder Abuse Suspicion Index (EASI)©, a tool to help identify elder abuse, is described, along with reporting and analysis of some of its outcomes. METHODS: Enquiries about the use of the EASI were encouraged through completion of a structured questionnaire available on an EASI website. These were submitted by email and guided individualized responses. Descriptive data collated anonymously from the questionnaires described in aggregate corresponders' occupations, countries of work, information needs about the tool, and intent of use. The processes that generated this data were evaluated as to whether they conformed to established elements of KT. RESULTS: One hundred thirty-eight queries were received over 6 years coming from enquirers with 12 different professional backgrounds, working in 25 countries. The information sought aimed to facilitate EASI use in clinical, quality improvement, public health, research, teaching, KT, and commercial ventures. CONCLUSIONS: This activity, incorporating recognized elements of a KT undertaking, documents specific global interests in elder abuse detection. It suggests a model for researchers to gauge interest in their findings and to promote exchange around them.


Assuntos
Abuso de Idosos , Idoso , Abuso de Idosos/diagnóstico , Humanos , Inquéritos e Questionários , Pesquisa Médica Translacional
9.
Implement Sci ; 16(1): 76, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344393

RESUMO

BACKGROUND: Since Canadian drug regulatory approval of mifepristone for medical abortion in 2015 and its market availability in January 2017, the role of pharmacists in abortion provision has changed rapidly. We sought to identify the factors that influenced the initiation and provision of medical abortion from the perspectives of Canadian pharmacists, bridging two frameworks - Diffusion of Innovation in Health Service Organizations and integrated knowledge translation. METHODS: We conducted one-on-one semi-structured interviews with pharmacists residing in Canada who intended to stock and dispense mifepristone within the first year of availability. Our data collection, analysis, and interpretation were guided by reflexive thematic analysis and supported by an integrated knowledge translation partnership with pharmacy stakeholders. RESULTS: We completed interviews with 24 participants from across Canada: 33% had stocked and 21% had dispensed mifepristone. We found that pharmacists were willing and able to integrate medical abortion care into their practice and that those who had initiated practice were satisfied with their dispensing experience. Our analysis indicated that several key Diffusion of Innovation constructs impacted the uptake of mifepristone, including: innovation (relative advantage, complexity and compatibility, technical support), system readiness (innovation-system fit, dedicated time, resources), diffusion and dissemination (expert opinion, boundary spanners, champions, social networks, peer opinions), implementation (external collaboration), and linkage. Participants' experiences suggest that integrated knowledge translation facilitated evidence-based changes to mifepristone dispensing restrictions, and communication of those changes to front line pharmacists. CONCLUSIONS: We illustrate how Diffusion of Innovation and integrated knowledge translation may work together as complimentary frameworks for implementation science research. Unlike in the USA, UK, and other highly regulated settings globally, pharmacists in Canada are permitted to dispense mifepristone for medical abortion. We contribute to literature that shows that mifepristone dispensed outside of hospitals, clinics, and medical offices is safe and acceptable to both patients and prescribers. This finding is of particular importance to the current COVID-19 pandemic response and calls for continued and equitable access to abortion care in primary practice.


Assuntos
Abortivos Esteroides/administração & dosagem , Aborto Induzido/métodos , Difusão de Inovações , Mifepristona/administração & dosagem , Farmacêuticos/estatística & dados numéricos , Pesquisa Médica Translacional/métodos , Canadá , Humanos , Entrevistas como Assunto
10.
Artigo em Inglês | MEDLINE | ID: mdl-34360176

RESUMO

The population-level implementation of innovative, evidence-based medical recommendations for adopting health-behaviors depends on the last link in the translation chain: the users. "User-friendly" medical interventions aimed at engaging users to adopt recommended health behaviors are best developed in a collaborative bio-medical and social sciences setting. In the 1990s, National Breast and Colorectal Cancer Early Detection Programs were launched at the Israeli Department of Community Medicine and Epidemiology. Operating under the largest HMO (Health Maintenance Organization) in Israel ("Clalit Health Services"), the department had direct access to HMO community primary-care clinics' teams, insured members, and medical records. Academically affiliated, the department engaged in translational research. In a decades-long translational process, this multi-disciplinary unit led a series of interventions built upon basic and applied behavioral/social science phenomena such as framing, "Implementation Intentions," and "Question-Behavior-Effect". A heterogeneous team of disciplinary specialists created an integrated scientific environment. In order to enhance screening, the team focused on the establishment of a systematic mechanism actively inviting programs' "users" (average-risk targeted individuals on the national level), and continuously applied social and health psychology concepts to study individuals' perceptions, expectations, and needs related to cancer screening. The increase in adherence to screening recommendations was slow and incremental. A decrease in late-stage breast and colorectal cancer diagnoses was observed nationally, but participation was lower than expected. This paper positions screening adherence as a unique challenge and proposes new social and network avenues to enhance future participation.


Assuntos
Detecção Precoce de Câncer , Neoplasias , Grupo com Ancestrais do Continente Europeu , Humanos , Israel , Neoplasias/diagnóstico , Pesquisa Médica Translacional
11.
Rev Esc Enferm USP ; 55: e03764, 2021.
Artigo em Português, Inglês | MEDLINE | ID: mdl-34320114

RESUMO

OBJECTIVE: To explore the perception of health care professionals about barriers and facilitators, and coping strategies for the implementation of the Thirst Management Model in the preoperative period of the burned patient. METHOD: This is a qualitative study, anchored in the conceptual framework Knowledge Translation. The focus group technique was chosen for data collection, composed by eight key professionals, to identify barriers and facilitators in evidence implementation and to point out coping strategies for the critical nodes found. Thematic Content Analysis technique was used to evaluate the data. RESULTS: Five categories emerged: Physical structure, environment and supplies; Particularities of the burned patient; Human Resources; Team attitude; Team training and education. Coping strategies were raised for each barrier identified. CONCLUSION: The main barriers identified were found in the Human Resources and Team Attitude categories. The main facilitators were Particularities of the burned patient and Team training and education. The identification allowed planning coping strategies for critical nodes, providing support for scientific evidence in clinical practice.


Assuntos
Sede , Pesquisa Médica Translacional , Grupos Focais , Pessoal de Saúde , Humanos , Pesquisa Qualitativa
12.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299099

RESUMO

The present editorial aims to summarise the six scientific papers that have contributed to this Special Issue, focusing on different aspects of molecular and translational research on colorectal cancer. We believe that the present Special Issue might contribute to the expansion of the current knowledge concerning potential molecular predictive and/or prognostic biomarkers in CRC, as well as new targets for anticancer treatment. This may help in identifying new strategies to improve diagnostic and therapeutic approaches.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Pesquisa Médica Translacional , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Humanos
13.
BMC Res Notes ; 14(1): 282, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301328

RESUMO

OBJECTIVE: In order to assess the applicability of a direct-to-consumer (DTC) genetic testing to translational research for obtaining new knowledge on relationships between drug target genes and diseases, we examined possibility of these data by associating SNPs and disease related phenotype information collected from healthy individuals. RESULTS: A total of 12,598 saliva samples were collected from the customers of commercial service for SNPs analysis and web survey were conducted to collect phenotype information. The collected dataset revealed similarity to the Japanese data but distinguished differences to other populations of all dataset of the 1000 Genomes Project. After confirmation of a well-known relationship between ALDH2 and alcohol-sensitivity, Phenome-Wide Association Study (PheWAS) was performed to find association between pre-selected drug target genes and all the phenotypes. Association was found between GRIN2B and multiple phenotypes related to depression, which is considered reliable based on previous reports on the biological function of GRIN2B protein and its relationship with depression. These results suggest possibility of using SNPs and phenotype information collected from healthy individuals as a translational research tool for drug discovery to find relationship between a gene and a disease if it is possible to extract individuals in pre-disease states by properly designed questionnaire.


Assuntos
Triagem e Testes Direto ao Consumidor , Testes Genéticos , Estudo de Associação Genômica Ampla , Pesquisa Médica Translacional , Aldeído-Desidrogenase Mitocondrial , Humanos , Japão , Fenótipo , Polimorfismo de Nucleotídeo Único , Receptores de N-Metil-D-Aspartato
14.
Artigo em Inglês | MEDLINE | ID: mdl-34280983

RESUMO

BACKGROUND: Physical activity (PA) messages have demonstrated success in targeting parent support for PA. However, little research exists to inform the development and dissemination of optimally effective PA messages targeting parents. A synthesis of existing literature is necessary to inform message development and dissemination strategies. Unique considerations for parents of children with disabilities (CWD) should be identified given a need for inclusive PA messaging that consider the needs of CWD and their families. METHODS: Systematic scoping methodologies included a peer-reviewed literature search and expert consultation to identify literature regarding PA messages targeting parents, and considerations for parents of CWD. RESULTS: Thirty-four articles that met eligibility criteria were included for examination. Twenty-eight studies were identified regarding the PA messages targeting parents; six themes and 12 subthemes emerged from these articles. Six studies were identified regarding unique considerations for parents of CWD; three themes and four subthemes emerged from these articles. CONCLUSIONS: Through knowledge synthesis, this research can contribute to a knowledge translation process to inform practice guidelines for the development and dissemination of PA messages targeting parents, while also providing unique considerations for PA messages targeting parents of CWD.


Assuntos
Crianças com Deficiência , Exercício Físico , Criança , Humanos , Conhecimento , Pesquisa Médica Translacional
15.
Rev Med Inst Mex Seguro Soc ; 59(2): 106-107, 2021 Jun 14.
Artigo em Espanhol | MEDLINE | ID: mdl-34231979

RESUMO

In this editorial the author presents a study, concerning Prader-Willi syndrome, which is paradigmatic for translational medicine, given that it creates a synergy between genetics and molecular biology, in order to improve the care for patients suffering from this syndrome.


Assuntos
Síndrome de Angelman , Síndrome de Prader-Willi , Síndrome de Angelman/genética , Epigênese Genética , Humanos , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genética , Pesquisa Médica Translacional
16.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204435

RESUMO

The central protein in the oncogenic circuitry is the Ras GTPase that has been under intense scrutiny for the last four decades. From its discovery as a viral oncogene and its non-oncogenic contribution to crucial cellular functioning, an elaborate genetic, structural, and functional map of Ras is being created for its therapeutic targeting. Despite decades of research, there still exist lacunae in our understanding of Ras. The complexity of the Ras functioning is further exemplified by the fact that the three canonical Ras genes encode for four protein isoforms (H-Ras, K-Ras4A, K-Ras4B, and N-Ras). Contrary to the initial assessment that the H-, K-, and N-Ras isoforms are functionally similar, emerging data are uncovering crucial differences between them. These Ras isoforms exhibit not only cell-type and context-dependent functions but also activator and effector specificities on activation by the same receptor. Preferential localization of H-, K-, and N-Ras in different microdomains of the plasma membrane and cellular organelles like Golgi, endoplasmic reticulum, mitochondria, and endosome adds a new dimension to isoform-specific signaling and diverse functions. Herein, we review isoform-specific properties of Ras GTPase and highlight the importance of considering these towards generating effective isoform-specific therapies in the future.


Assuntos
Proteínas Proto-Oncogênicas p21(ras)/genética , Biomarcadores , Biomarcadores Tumorais , Regulação da Expressão Gênica , Humanos , Mutação , Isoformas de Proteínas , Proteínas Proto-Oncogênicas p21(ras)/química , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Pesquisa , Transdução de Sinais , Relação Estrutura-Atividade , Pesquisa Médica Translacional , Proteínas ras/metabolismo
17.
Molecules ; 26(11)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199898

RESUMO

In both humans and animal models, consumption of a high-saturated-fat diet has been linked to vascular dysfunction and cognitive impairments. Laboratory animals provide excellent models for more invasive high-fat-diet-related research. However, the physiological differences between humans and common animal models in terms of how they react metabolically to high-fat diets need to be considered. Here, we review the factors that may affect the translatability of mechanistic research in animal models, paying special attention to the effects of a high-fat diet on vascular outcomes. We draw attention to the dissociation between metabolic syndrome and dyslipidemia in rodents, unlike the state in humans, where the two commonly occur. We also discuss the differential vulnerability between species to the metabolic and vascular effects of macronutrients in the diet. Findings from animal studies are better interpreted as modeling specific aspects of dysfunction. We conclude that the differences between species provide an opportunity to explore why some species are protected from the detrimental aspects of high-fat-diet-induced dysfunction, and to translate these findings into benefits for human health.


Assuntos
Transtornos Cerebrovasculares/patologia , Dieta Hiperlipídica/efeitos adversos , Dislipidemias/patologia , Síndrome Metabólica/patologia , Animais , Transtornos Cerebrovasculares/etiologia , Modelos Animais de Doenças , Dislipidemias/induzido quimicamente , Dislipidemias/complicações , Humanos , Síndrome Metabólica/genética , Roedores , Especificidade da Espécie , Pesquisa Médica Translacional
18.
Int J Mol Sci ; 22(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201152

RESUMO

With advanced technology and its development, bioinformatics is one of the avant-garde fields that has managed to make amazing progress in the pharmaceutical-medical field by modeling the infrastructural dimensions of healthcare and integrating computing tools in drug innovation, facilitating prevention, detection/more accurate diagnosis, and treatment of disorders, while saving time and money. By association, bioinformatics and pharmacovigilance promoted both sample analyzes and interpretation of drug side effects, also focusing on drug discovery and development (DDD), in which systems biology, a personalized approach, and drug repositioning were considered together with translational medicine. The role of bioinformatics has been highlighted in DDD, proteomics, genetics, modeling, miRNA discovery and assessment, and clinical genome sequencing. The authors have collated significant data from the most known online databases and publishers, also narrowing the diversified applications, in order to target four major areas (tetrad): DDD, anti-microbial research, genomic sequencing, and miRNA research and its significance in the management of current pandemic context. Our analysis aims to provide optimal data in the field by stratification of the information related to the published data in key sectors and to capture the attention of researchers interested in bioinformatics, a field that has succeeded in advancing the healthcare paradigm by introducing developing techniques and multiple database platforms, addressed in the manuscript.


Assuntos
Biologia Computacional , Desenvolvimento de Medicamentos , Descoberta de Drogas , MicroRNAs , Técnicas Microbiológicas/métodos , Sequenciamento Completo do Genoma , Animais , COVID-19 , Indústria Farmacêutica , Estudo de Associação Genômica Ampla , Humanos , Farmacovigilância , Saúde Pública , Pesquisa Médica Translacional
19.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298969

RESUMO

Cancer is a complex disease involving alterations of multiple processes, with both genetic and epigenetic features contributing as core factors to the disease. In recent years, it has become evident that non-coding RNAs (ncRNAs), an epigenetic factor, play a key role in the initiation and progression of cancer. MicroRNAs, the most studied non-coding RNAs subtype, are key controllers in a myriad of cellular processes, including proliferation, differentiation, and apoptosis. Furthermore, the expression of miRNAs is controlled, concomitantly, by other epigenetic factors, such as DNA methylation and histone modifications, resulting in aberrant patterns of expression upon the occurrence of cancer. In this sense, aberrant miRNA landscape evaluation has emerged as a promising strategy for cancer management. In this review, we have focused on the regulation (biogenesis, processing, and dysregulation) of miRNAs and their role as modulators of the epigenetic machinery. We have also highlighted their potential clinical value, such as validated diagnostic and prognostic biomarkers, and their relevant role as chromatin modifiers in cancer therapy.


Assuntos
Epigênese Genética , MicroRNAs/genética , Neoplasias/genética , RNA Neoplásico/genética , Pesquisa Médica Translacional , Biomarcadores Tumorais , Neoplasias da Mama/genética , Metilação de DNA , DNA de Neoplasias/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Terapia Genética , Código das Histonas , Humanos , Neoplasias Pulmonares/genética , MicroRNAs/biossíntese , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Neoplasias/terapia , Neoplasias Ovarianas/genética , Prognóstico , Processamento Pós-Transcricional do RNA , RNA Neoplásico/biossíntese , Neoplasias Gástricas/genética
20.
Int J Mol Sci ; 22(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34281267

RESUMO

BACKGROUND: Parkinson's disease (PD) is the second most frequent neurodegenerative disease, which creates a significant public health burden. There is a challenge for the optimization of therapies since patients not only respond differently to current treatment options but also develop different side effects to the treatment. Genetic variability in the human genome can serve as a biomarker for the metabolism, availability of drugs and stratification of patients for suitable therapies. The goal of this systematic review is to assess the current evidence for the clinical translation of pharmacogenomics in the personalization of treatment for Parkinson's disease. METHODS: We performed a systematic search of Medline database for publications covering the topic of pharmacogenomics and genotype specific mutations in Parkinson's disease treatment, along with a manual search, and finally included a total of 116 publications in the review. RESULTS: We analyzed 75 studies and 41 reviews published up to December of 2020. Most research is focused on levodopa pharmacogenomic properties and catechol-O-methyltransferase (COMT) enzymatic pathway polymorphisms, which have potential for clinical implementation due to changes in treatment response and side-effects. Likewise, there is some consistent evidence in the heritability of impulse control disorder via Opioid Receptor Kappa 1 (OPRK1), 5-Hydroxytryptamine Receptor 2A (HTR2a) and Dopa decarboxylase (DDC) genotypes, and hyperhomocysteinemia via the Methylenetetrahydrofolate reductase (MTHFR) gene. On the other hand, many available studies vary in design and methodology and lack in sample size, leading to inconsistent findings. CONCLUSIONS: This systematic review demonstrated that the evidence for implementation of pharmacogenomics in clinical practice is still lacking and that further research needs to be done to enable a more personalized approach to therapy for each patient.


Assuntos
Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/metabolismo , Antiparkinsonianos/farmacologia , Catecol O-Metiltransferase/genética , Catecol O-Metiltransferase/metabolismo , Inibidores de Catecol O-Metiltransferase/metabolismo , Inibidores de Catecol O-Metiltransferase/farmacologia , Agonistas de Dopamina/metabolismo , Agonistas de Dopamina/farmacologia , Genótipo , Humanos , Levodopa/efeitos adversos , Levodopa/metabolismo , Levodopa/farmacologia , Inibidores da Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Doença de Parkinson/metabolismo , Farmacogenética/métodos , Farmacogenética/tendências , Variantes Farmacogenômicos , Pesquisa Médica Translacional
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