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1.
Aten. prim. (Barc., Ed. impr.) ; 56(5)may. 2024. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-CR-341

RESUMO

Objetivo Analizar mediante el programa de revisión de la medicación, Revisem®, la prevalencia de problemas relacionados con la medicación (PRM) en pacientes de la provincia de Valencia que estaban en tratamiento activo con inhibidores de la bomba de protones (IBP) en 2022. Diseño Estudio observacional descriptivo y retrospectivo. Material y métodos Se analizó el historial farmacoterapéutico (HFT) de 295 pacientes siguiendo los criterios propuestos por la Pharmaceutical Care Network Europe, utilizando la plataforma digital Revisem® del Muy Ilustre Colegio Oficial de Farmacéuticos de Valencia (MICOF). Resultados La edad media de los pacientes fue 81,8 ± 11,1 años y 66,4% fueron mujeres. Se detectó al menos un PRM en 97,3% de los pacientes. De los PRM analizados, 46,9% fueron interacciones, de las cuales 29,7% implicaban un IBP, siendo el omeprazol el de mayor frecuencia. Los PRM con IBP se relacionan de forma significativa con determinadas condiciones del paciente y grupos farmacológicos, como son el sexo femenino, la edad superior a 54 años y la polifarmacia. Conclusiones La plataforma digital Revisem®, permite la detección de una alta prevalencia de PRM a nivel provincial. La aplicación de nuevas herramientas tecnológicas para detectar la prevalencia de PRM es fundamental para optimizar los tratamientos de los pacientes. (AU)


Objective To analyze, using the medication review program, Revisem®, the prevalence of drug-related problems (DRP) in patients in the province of Valencia who were on active treatment with proton pump inhibitors (PPI) in 2022. Design Descriptive and retrospective observational study. Material and methods The pharmacotherapeutic history of 295 patients was analyzed following the criteria proposed by the Pharmaceutical Care Network Europe, using the Revisem® digital platform of the Muy Ilustre Colegio Oficial de Farmacéuticos (MICOF). Results The mean age of the patients was 81.8 ± 11.1 years and 66.4% were women. At least one DRP was detected in 97.3% of patients. 46.9% of the DRP analyzed were interactions, of which 29.7% involved a PPI, with omeprazole being the most frequent. DRPs with PPI are significantly related to certain patient conditions and pharmacological groups, such as female sex, age over 54 years and polypharmacy. Conclusions The application of the Revisem® digital platform allows the detection of a high prevalence of DRP at the provincial level. The application of new technological tools to detect the prevalence of DRP is essential to optimize patient treatments. (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Inibidores da Bomba de Prótons/efeitos adversos , Anormalidades Induzidas por Medicamentos , Epidemiologia Descritiva , Estudos Retrospectivos , Espanha , Serviços Comunitários de Farmácia , Omeprazol
2.
Heliyon ; 10(9): e30043, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38756605

RESUMO

The gender perspective is important for a better diagnosis and treatment of diseases, especially in the field of oncology. This study aimed to analyse the gender approach in scientific articles in the field of oncology by studying the gender composition of the authorship of papers and the gender inclusion in the research carried out. A bibliographic search of articles and reviews signed by at least one Spanish institution published between 2010 and 2019 was carried out using the Science Citation Index Expanded database in the Oncology category. A total of 7523 studies were classified according to the gender composition determined by the author's name and a randomised sample was used to evaluate the inclusion of gender perspectives using a checklist. This study revealed a lack of gender parity in the authorship of oncology publications involving Spanish participation. Papers without author gender parity were eight times higher than papers with parity and showed a greater presence of male than female authorship (58 % versus 31 %). Regarding the introduction of the gender perspective, a negative response of 68 % referring to compliance with the entire checklist was obtained, and only a fifth of the articles presented gender balance in the study sample. Moreover, there is a positive correlation between gender parity in authorship and gender perspective integration in published research. In conclusion, there is a great need to advance the inclusion of gender perspectives in cancer research to overcome gender bias and promote better prevention, detection, and intervention for cancer.

3.
Clin Transl Oncol ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635076

RESUMO

PURPOSE: This study has been focused on assessing the Open Science scenario of cancer research during the period 2011-2021, in terms of the derived scientific publications and raw data dissemination. METHODS: A cancer search equation was executed in the Science Citation Index-Expanded, collecting the papers signed by at least one Spanish institution. The same search strategy was performed in the Data Citation Index to describe dataset diffusion. RESULTS: 50,822 papers were recovered, 71% of which belong to first and second quartile journals. 59% of the articles were published in Open Access (OA) journals. The Open Access model and international collaboration positively conditioned the number of citations received. Among the most productive journals stood out Plos One, Cancers, and Clinical and Translational Oncology. 2693 genomics, proteomics and metabolomics datasets were retrieved, being Gene Expression Omnibus the favoured repository. CONCLUSIONS: There has been an increase in oncology publications in Open Access. Most were published in first quartile journals and received higher citations than non-Open Access articles, as well as when oncological investigation was performed between international research teams, being relevant in the context of Open Science. Genetic repositories have been the preferred for sharing oncology datasets. Further investigation of research and data sharing in oncology is needed, supported by stronger Open Science policies, to achieve better data sharing practices among three scientific main pillars: researchers, publishers, and scientific organizations.

4.
Pharm. pract. (Granada, Internet) ; 22(1): 1-9, Ene-Mar, 2024. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-231363

RESUMO

Objective: Pharmacotherapeutic Follow-up is the Professional Pharmaceutical Care Service aimed at detecting Drug-Related Problems for the prevention and resolution of negative medicine outcomes. The Dader Method is considered a clear and simple tool to develop Pharmacotherapeutic Follow-up. This research aims to analyze the evolution of the international scientific production related to Pharmacotherapeutic Follow-up and the Dader Method to show the current situation of this Professional Pharmacy Assistance Service. In addition, from the data obtained, we give a critical perspective on the implementation of the Dader Method in Community Pharmacy, considering its advantages and disadvantages based on the published scientific literature. Methods: Using bibliometrics tools, indicators were obtained to analyze the international production of scientific articles on Pharmacotherapeutic Followup and the Dader Method during the period (1999-2022) through the Scopus database. Results: The results showed a growth in the international scientific production of publications on Pharmacotherapeutic Follow-up, obtaining 30,287 papers, placing the United States, the United Kingdom, Australia, Canada and Spain as the five most productive countries. The publication of 83 papers on the Dader Method places Spain with the highest number of publications, followed by other Spanish or Portuguese speaking countries, among which Brazil and Colombia have the most prominent number of published papers in Latin America. The most frequent international journal covering the topic of Pharmacotherapeutic Follow-up was the American Journal of Health- Pharmacy (12.4%), while on the Dader Method, the journal Pharmaceutical Care Spain (21.7%) is in the first position, followed by Farmacia Hospitalaria (8.4%). Conclusion: The publications on the Dader method highlighs the greater productivity of the University of Granada and the author María José Faus Dáder. The inclusion of patients in the PTF service using the Dader Method, is more frequent in the hospital context, and is based on the presence of defined chronic pathologies (mainly diabetes), polymedication or specialized care follow-up, with elderly population being the most represented in all cases.(AU)


Assuntos
Humanos , Masculino , Feminino , Serviços Comunitários de Farmácia , Bibliometria , Pesquisa sobre Serviços de Saúde , Planejamento em Saúde , Assistência Farmacêutica
5.
Aten Primaria ; 56(5): 102836, 2024 May.
Artigo em Espanhol | MEDLINE | ID: mdl-38150850

RESUMO

OBJECTIVE: To analyze, using the medication review program, Revisem®, the prevalence of drug-related problems (DRP) in patients in the province of Valencia who were on active treatment with proton pump inhibitors (PPI) in 2022. DESIGN: Descriptive and retrospective observational study. MATERIAL AND METHODS: The pharmacotherapeutic history of 295 patients was analyzed following the criteria proposed by the Pharmaceutical Care Network Europe, using the Revisem® digital platform of the Muy Ilustre Colegio Oficial de Farmacéuticos (MICOF). RESULTS: The mean age of the patients was 81.8 ± 11.1 years and 66.4% were women. At least one DRP was detected in 97.3% of patients. 46.9% of the DRP analyzed were interactions, of which 29.7% involved a PPI, with omeprazole being the most frequent. DRPs with PPI are significantly related to certain patient conditions and pharmacological groups, such as female sex, age over 54 years and polypharmacy. CONCLUSIONS: The application of the Revisem® digital platform allows the detection of a high prevalence of DRP at the provincial level. The application of new technological tools to detect the prevalence of DRP is essential to optimize patient treatments.


Assuntos
Inibidores da Bomba de Prótons , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Feminino , Masculino , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Idoso , Pessoa de Meia-Idade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia
6.
Adicciones ; 35(3): 249-264, 2023 Sep 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33768261

RESUMO

Addictive disorders are a serious health problem to which large amounts of research resources are devoted. This study aims to analyze the evolution and scientific impact of the publications derived from the funding of research projects by the Spanish National Plan on Drugs (PNSD). The list of grants awarded was provided by the PNSD. Derived publications were obtained by asking the principal investigators of the grants and searching in the Web of Science and Scopus. Bibliometric indicators and evolutive trends of scientific production per project were calculated. On average, the PNSD conferred 15 annual grants to research projects, with an annual amount close to one million euros (€944,200.64) and an average amount per grant of just over €60,000, being higher in basic research and in alcohol. 71,9% of the grants had derived publications and almost half of them produced between one and three publications, with basic research being the most prolific. The international journal in which most articles were published was Psychopharmacology (50) and among Spanish journals, Adicciones stood out (28). A high level of co-authorship and international collaboration was identified. Most of the PNSD-funded projects produced research articles, many of them in journals belonging to the first and second quartiles of the Journal Citation Reports. The results of this study have revealed the scientific impact of the PNSD research projects funding and may contribute to determining future funding priorities.


Los trastornos adictivos son un grave problema de salud al que se destinan gran cantidad de recursos de investigación. El propósito de este trabajo es analizar la evolución e impacto científico de las publicaciones derivadas de las ayudas a proyectos de investigación financiados por el Plan Nacional Sobre Drogas (PNSD). La relación de ayudas concedidas fue proporcionada por el PNSD. Las publicaciones derivadas se obtuvieron preguntando a los investigadores principales de las ayudas y buscando en Web of Science y Scopus. Se calcularon indicadores bibliométricos y tendencias evolutivas de la producción científica por proyecto. Por término medio, el PNSD concedió 15 ayudas anuales a proyectos de investigación, con un importe anual cercano al millón de euros (944.200,64€) y un importe medio por ayuda de algo más de 60.000€, siendo mayor en la investigación básica y en alcohol. El 71,9% de las ayudas tuvieron publicaciones derivadas y casi la mitad produjeron entre una y tres publicaciones, siendo la investigación básica la más prolífica. La revista extranjera en la que más artículos se publicaron fue Psychopharmacology (50) y entre las españolas destacó Adicciones (28). Se identificó un alto índice de coautoría y de colaboración internacional. La mayoría de los proyectos financiados por el PNSD produjeron artículos de investigación y muchos de ellos en revistas del primer y segundo cuartil del Journal Citation Reports. Los resultados de este estudio han permitido conocer la repercusión científica de las ayudas a proyectos de investigación del PNSD y puede contribuir a determinar futuras prioridades de financiación.


Assuntos
Pesquisa Biomédica , Editoração , Humanos , Bibliometria
7.
Adicciones (Palma de Mallorca) ; 35(3): 249-264, 2023. tab, graf, mapas
Artigo em Inglês, Espanhol | IBECS | ID: ibc-226069

RESUMO

Los trastornos adictivos son un grave problema de salud al que se destinan gran cantidad de recursos de investigación. El propósito de este trabajo es analizar la evolución e impacto científico de las publicaciones derivadas de las ayudas a proyectos de investigación financiados por el Plan Nacional Sobre Drogas (PNSD). La relación de ayudas concedidas fue proporcionada por el PNSD. Las publicaciones derivadas se obtuvieron preguntando a los investigadores principales de las ayudas y buscando en Web of Science y Scopus. Se calcularon indicadores bibliométricos y tendencias evolutivas de la producción científica por proyecto. Por término medio, el PNSD concedió 15 ayudas anuales a proyectos de investigación, con un importe anual cercano al millón de euros (944.200,64€) y un importe medio por ayuda de algo más de 60.000€, siendo mayor en la investigación básica y en alcohol. El 71,9% de las ayudas tuvieron publicaciones derivadas y casi la mitad produjeron entre una y tres publicaciones, siendo la investigación básica la más prolífica. La revista extranjera en la que más artículos se publicaron fue Psychopharmacology (50) y entre las españolas destacó Adicciones (28). Se identificó un alto índice de coautoría y de colaboración internacional. La mayoría de los proyectos financiados por el PNSD produjeron artículos de investigación y muchos de ellos en revistas del primer y segundo cuartil del Journal Citation Reports. Los resultados de este estudio han permitido conocer la repercusión científica de las ayudas a proyectos de investigación del PNSD y puede contribuir a determinar futuras prioridades de financiación. (AU)


Addictive disorders are a serious health problem to which large amounts of research resources are devoted. This study aims to analyze the evolution and scientific impact of the publications derived from the funding of research projects by the Spanish National Plan on Drugs (PNSD). The list of grants awarded was provided by the PNSD. Derived publications were obtained by asking the principal investigators of the grants and searching in the Web of Science and Scopus. Bibliometric indicators and evolutive trends of scientific production per project were calculated. On average, the PNSD conferred 15 annual grants to research projects, with an annual amount close to one million euros (€944,200.64) and an average amount per grant of just over €60,000, being higher in basic research and in alcohol. 71,9% of the grants had derived publications and almost half of them produced between one and three publications, with basic research being the most prolific. The international journal in which most articles were published was Psychopharmacology (50) and among Spanish journals, Adicciones stood out (28). A high level of co-authorship and international collaboration was identified. Most of the PNSD-funded projects produced research articles, many of them in journals belonging to the first and second quartiles of the Journal Citation Reports. The results of this study have revealed the scientific impact of the PNSD research projects funding and may contribute to determining future funding priorities. (AU)


Assuntos
Humanos , Transtornos Relacionados ao Uso de Substâncias , Apoio à Pesquisa como Assunto/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde/estatística & dados numéricos , Bibliometria , Espanha , Indicadores de Produção Científica , Publicações Científicas e Técnicas , Fator de Impacto de Revistas
8.
PLoS One ; 17(5): e0268993, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35639752

RESUMO

BACKGROUND: As part of the Open Science movement, this study aims to analyze the current state of open access and open data policies concerning the availability of articles and raw data of the journals belonging to the category "Medicine, General & Internal" of the Science Citation Index Expanded. METHODS: Journal data sharing policies were evaluated through the following variables: possibility of manuscript storage in repositories; reuse policy; publication on a website; and statement regarding complementary material. Subsequently, an analysis of the supplementary material associated with each article was performed through the PubMed Central repository. The study reported was assessed following the STROBE guidelines for observational studies. RESULTS: This study shows that only one-third of the journals included in the category "Medicine, General & Internal" allow the depositing of their documents in repositories and its reuse, while approximately half of the journals agree to publish the document on a website as well as to deposit supplementary material along with the publication. However, the reality about this last variable is that only 9.5% of the articles analyzed contained supplementary material being the main journals involved, BMJ Open, JAMA Network Open, New England Journal of Medicine, Lancet and Plos Medicine. CONCLUSIONS: The analysis of the opening policies of the journals concerning data availability in medical research reveals the unequal positioning of publishers towards the sharing of open data, the ambiguity regarding government policies about the obligation to deposit data and the need for ethical and standardization requirements in the typology/format of the data deposited without forgetting the important role that the researcher plays. Further studies based on journals indexed in medical databases other than Science Citation Index Expanded are needed.


Assuntos
Pesquisa Biomédica , Publicações Periódicas como Assunto , Indexação e Redação de Resumos , Disseminação de Informação , Medicina Interna
9.
Scientometrics ; 126(6): 4975-4990, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33935332

RESUMO

During the previous Ebola and Zika outbreaks, researchers shared their data, allowing many published epidemiological studies to be produced only from open research data, to speed up investigations and control of these infections. This study aims to evaluate the dissemination of the COVID-19 research data underlying scientific publications. Analysis of COVID-19 publications from December 1, 2019, to April 30, 2020, was conducted through the PubMed Central repository to evaluate the research data available through its publication as supplementary material or deposited in repositories. The PubMed Central search generated 5,905 records, of which 804 papers included complementary research data, especially as supplementary material (77.4%). The most productive journals were The New England Journal of Medicine, The Lancet and The Lancet Infectious Diseases, the most frequent keyword was pneumonia, and the most used repositories were GitHub and GenBank. An expected growth in the number of published articles following the course of the pandemics is confirmed in this work, while the underlying research data are only 13.6%. It can be deduced that data sharing is not a common practice, even in health emergencies, such as the present one. High-impact generalist journals have accounted for a large share of global publishing. The topics most often covered are related to epidemiological and public health concepts, genetics, virology and respiratory diseases, such as pneumonia. However, it is essential to interpret these data with caution following the evolution of publications and their funding in the coming months.

10.
Head Face Med ; 15(1): 24, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31639009

RESUMO

Following publication of the original article [1], the author informed.

11.
Head Face Med ; 15(1): 23, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31493796

RESUMO

BACKGROUND: Due to the lack of bibliometric studies in the field of lingual orthodontics in dentistry, the aim of this study was to assess the evolution and current status of activity in this field during the period 1978-2017. METHODS: A bibliometric analysis of the scientific articles indexed in the Science Citation Index-Expanded of the Web of Science and in the Scopus® database was performed using the truncated terms "ling* apppli*" or "ling* orthod*" or "ling* bracket*". The types of texts included for analysis were limited to "articles" and "reviews". The following information was extracted from each article identified: title, authors' name(s), institutional affiliation(s), country of origin, journal title, year of publication, type of publication, and number of citations. RESULTS: A total of 341 articles were identified by 646 different authors, 6.2% were reviews and 93.8% were other types of journal articles. Bibliometric indicators showed a tremendous increase in the rate of publication over time with two peaks in productivity in 1989 and 2013. Fourteen authors and 15 institutional collaboration networks were identified in which European institutions were the most productive. Methodological articles were the most frequent types of research articles (28.1%), followed by case reports/series (17.1%), and narrative reviews (4.7%). Articles providing the highest quality evidence were interventional clinical trials (1.8%) and systematic reviews (0.9%). The remaining articles were non-research papers and were for information purposes only. CONCLUSIONS: Bibliometric indicators point to an irregular increase in the numbers of published works in lingual orthodontics over time. Research output is dominated by methodological articles as a technique-driven subspecialty. Although articles on lingual orthodontics are published mainly in North American journals, lingual orthodontics is largely a European domain.


Assuntos
Bibliometria , Ortodontia , Assistência Odontológica , Humanos , Língua
12.
Clin Implant Dent Relat Res ; 21(4): 708-714, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31237062

RESUMO

BACKGROUND: Implant dentistry is subject to major economic pressures as a result of the growth in the manufacturing and commercialization of dental implants. PURPOSE: To examine research funding in implant dentistry by means of a bibliometric analysis of articles indexed in Web of Science (WoS) published during the period 2008-2017. MATERIALS AND METHODS: The search was conducted applying the truncated term "implant*" in the WoS dentistry area. Only items labeled as "article" or "review" were selected. Records were manually refined and normalized to unify terms and to remove typographical, transcription, and/or indexing errors. RESULTS: A total of 14 255 records were identified for analysis. About 5002 of the 14 255 published works received funding. Of these, 85.9% of funded research articles received at least one citation. Of the 7733 funding entities mentioned, 29.8% were government entities, 25% NGOs and Foundations, 23.7% private companies, 19.6% academic entities, and 1.9% hospitals and research centers. Clinical Oral Implants Research and the International Journal of Oral & Maxillofacial Implants published the highest numbers of funded articles. CONCLUSIONS: This study revealed an overall increase in the funding of research in implant dentistry in recent years. Funded articles were cited more frequently and published in journals with higher impact factors.


Assuntos
Bibliometria , Implantes Dentários , Odontologia
13.
Angle Orthod ; 88(6): 785-796, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30102086

RESUMO

OBJECTIVES:: To identify and analyze the 100 most-cited articles in orthodontics indexed in the Web of Science Category of "Dental, Oral Surgery and Medicine" from 1946 to 2016. MATERIALS AND METHODS:: On hundred articles were identified in a search of the database of the ISI Web of Science and Journal Citation Reports, applying the truncated search term "orthodon*." Records were manually refined and normalized to unify terms and to remove typographical, transcription, and/or indexing errors. RESULTS:: The 100 most-cited articles were published between 1946 and 2012, with numbers of citations ranging from 115 to 881. Of the 251 authors participating, 87.65% published a single work, while three authors published four works. Most of the authors with several citations were from the United States, although the University of Oslo produced the highest number of frequently cited works. Most of the articles were clinical studies, and the most frequently cited topic was mini-implants. It was noted that self-citation could be a potential cause of bias in bibliometric analysis. CONCLUSIONS:: This bibliometric citation analysis reveals new, useful, and interesting information about scientific progress in the field of orthodontics.


Assuntos
Bibliometria , Ortodontia/estatística & dados numéricos , Humanos , Publicações Periódicas como Assunto/estatística & dados numéricos
14.
Stem Cells Dev ; 27(11): 717-722, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29635977

RESUMO

The availability of research data sets is an important milestone because it can enhance the dynamics of research. This study aims to analyze the PubMed Central repository to determine the availability and type of raw data sets in Cell & Tissue Engineering journals indexed in Journal Citation Reports. The number and types of files were registered. The main finding of this study is that, beyond the mandatory deposit of data in specific repositories that some journals require, the exchange of data as supplementary material in the Cell & Tissue Engineering journals is not a common practice since researchers are still reticent to do so.


Assuntos
Disseminação de Informação/métodos , Publicações Periódicas como Assunto/normas , Relatório de Pesquisa/normas , Pesquisa com Células-Tronco , Engenharia Tecidual/estatística & dados numéricos , Humanos , Armazenamento e Recuperação da Informação/normas , Armazenamento e Recuperação da Informação/estatística & dados numéricos , Publicações Periódicas como Assunto/estatística & dados numéricos
15.
Clin Ther ; 38(12): 2684-2689.e1, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27842713

RESUMO

PURPOSE: The purpose of this study to investigate the evolution and current status of peer-reviewed publications concerning generic drugs during the past few decades. METHODS: Scientific articles about generic drugs published until 2012 were retrieved through the PubMed/MEDLINE database, and a content analysis was performed. FINDINGS: Our study revealed an increasing number of publications on generics since 1984. Statins, antiretroviral therapies, and antiepileptics, followed by immunosuppressants and antithrombotic agents, were the most common therapeutic drug categories. IMPLICATIONS: Almost 60% of the generics detailed in studies indexed in MEDLINE were acting on the cardiovascular system as anti-infectives and on the nervous system, which is not surprising considering the leading causes of death and disability worldwide.


Assuntos
Medicamentos Genéricos , Pesquisa/tendências , Humanos , Revisão da Pesquisa por Pares , Publicações Periódicas como Assunto
16.
Stem Cells ; 26(8): 2052-62, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18511603

RESUMO

The DNA mismatch repair (MMR) system maintains genomic integrity by correcting replication errors: its malfunction causes genomic instability in several tumor types. Hypoxia-inducible factor-1alpha (HIF1alpha), the major regulator of the processes that occur in hypoxia and certain epigenetic events downregulate the expression of MMR genes in cancer cells. However, there is a lack of information regarding MMR regulation and the genetic stability of stem cells under hypoxic conditions. The expression of the MMR system is downregulated in murine and human stem cells cultured in hypoxia, which correlates with lower DNA repair activity in neural stem cells. We observed, through the use of short hairpin loop RNAi expression constructs, that HIF1alpha positively regulated MLH1 and MSH6 when the C17.2 neural stem cells were exposed to short-term hypoxia. However, in prolonged exposure to oxygen depletion, the reduced transcriptional activation of MMR genes was directed by specific epigenetic events. Chromatin immunoprecipitation experiments showed a hypoacetylated/hypermethylated histone H3 and lower SP1 binding within MLH1 and MSH6 adjacent promoter regions. Treatment with the histone deacetylase inhibitor trichostatin A increased histone H3 acetylation and SP1 occupancy and enhanced MMR expression. Sequencing of microsatellite markers revealed genomic instability in the murine and human stem cells grown under hypoxia. Thus, the present article reports, for the first time in the stem cell field, experimental data that indicate that hypoxic niches are an environment in which stem cells might undergo genomic instability, which could lie at the origin of subpopulations with cancer stem cell properties. Disclosure of potential conflicts of interest is found at the end of this article.


Assuntos
Reparo de Erro de Pareamento de DNA , Regulação para Baixo , Instabilidade Genômica , Hipóxia , Células-Tronco/citologia , Animais , Células Cultivadas , Reparo do DNA , Epigênese Genética , Genoma , Histonas/metabolismo , Humanos , Mesoderma/citologia , Camundongos , Interferência de RNA
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