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Article: Regulation of the Mammalian SWI/SNF Family of Chromatin Remodeling Enzymes by Phosphorylation during Myogenesis.

Padilla-Benavides, Teresita / Reyes-Gutierrez, Pablo / Imbalzano, Anthony N

2020 Volume 9, Issue 7

Abstract: Myogenesis is the biological process by which skeletal muscle tissue forms. Regulation of myogenesis involves a variety of conventional, epigenetic, and epigenomic mechanisms that control chromatin remodeling, DNA methylation, histone modification, and ... ...

Abstract	Myogenesis is the biological process by which skeletal muscle tissue forms. Regulation of myogenesis involves a variety of conventional, epigenetic, and epigenomic mechanisms that control chromatin remodeling, DNA methylation, histone modification, and activation of transcription factors. Chromatin remodeling enzymes utilize ATP hydrolysis to alter nucleosome structure and/or positioning. The mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) family of chromatin remodeling enzymes is essential for myogenesis. Here we review diverse and novel mechanisms of regulation of mSWI/SNF enzymes by kinases and phosphatases. The integration of classic signaling pathways with chromatin remodeling enzyme function impacts myoblast viability and proliferation as well as differentiation. Regulated processes include the assembly of the mSWI/SNF enzyme complex, choice of subunits to be incorporated into the complex, and sub-nuclear localization of enzyme subunits. Together these processes influence the chromatin remodeling and gene expression events that control myoblast function and the induction of tissue-specific genes during differentiation.
Language	English
Publishing date	2020-07-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology9070152
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Promotion of adipogenesis by JMJD6 requires the AT hook-like domain and is independent of its catalytic function.

Reyes-Gutierrez, Pablo / Carrasquillo-Rodríguez, Jake W / Imbalzano, Anthony N

PloS one

2019 Volume 14, Issue 8, Page(s) e0216015

Abstract: JMJD6 is a member of the Jumonji C domain containing enzymes that demethylate and/or hydroxylate substrate proteins. It is a multi-functional protein that has been implicated in disparate aspects of transcriptional and post-transcriptional control of ... ...

Abstract	JMJD6 is a member of the Jumonji C domain containing enzymes that demethylate and/or hydroxylate substrate proteins. It is a multi-functional protein that has been implicated in disparate aspects of transcriptional and post-transcriptional control of gene expression, including but not limited to enhancer and promoter binding, release of paused RNA polymerase II, control of splicing, and interaction with the translation machinery. JMJD6 contributes to multiple aspects of animal development, including adipogenesis modeled in culture. We mutated proposed or characterized domains in the JMJD6 protein to better understand the requirement for JMJD6 in adipogenic differentiation. Mutation of JMJD6 amino acids that mediate binding of iron and 2-oxogluterate, which are required cofactors for enzymatic activity, had no impact on JMJD6 function, showing that catalytic activity is not required for JMJD6 contributions to adipogenic differentiation. In addition, we documented the formation of JMJD6 oligomers and showed that catalytic activity is not required for oligomerization, as has been reported previously. We also observed no effect of mutations in the sumoylation site and in the poly-serine stretch. In contrast, mutation of the AT hook-like structure, which mediates interaction with DNA and/or RNA, compromised JMJD6 function by blocking its ability to interact with chromatin at genes that express regulators of adipogenesis. The ability of JMJD6 to interact with nucleic acids may be a critical requirement for its function in adipogenic differentiation. The requirement for the AT hook-like domain and the lack of requirement for catalytic activity giving rise to the idea that co-activation of transcription by JMJD6 may be functioning as a scaffold protein that supports the interactions of other critical regulators.
MeSH term(s)	AT-Hook Motifs ; Adipogenesis ; Animals ; Biocatalysis ; Cell Line ; Mice ; Models, Molecular ; Mutation ; Nuclear Proteins/metabolism ; Protein Domains ; Receptors, Cell Surface/chemistry ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/metabolism ; Sumoylation ; Transcription Factors/metabolism
Chemical Substances	Brd4 protein, mouse ; Nuclear Proteins ; Ptdsr protein, mouse ; Receptors, Cell Surface ; Transcription Factors
Language	English
Publishing date	2019-08-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0216015
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Article ; Online: Why didn’t people get vaccinated against COVID-19? Results from a nationwide survey among Mexican adults

Wrzecionkowska, Dagmara / Stephens, Christopher R. / Gutiérrez Reyes, Juan Pablo

medRxiv

Abstract: Objective: To explore the reasons for not getting vaccinated against COVID-19. Material and methods: In October 2021, a nationwide structured telephone survey (disproportionate stratified sampling) was conducted regarding COVID-19 pandemics, including ... ...

Abstract	Objective: To explore the reasons for not getting vaccinated against COVID-19. Material and methods: In October 2021, a nationwide structured telephone survey (disproportionate stratified sampling) was conducted regarding COVID-19 pandemics, including vaccination experience. To examine associations between inoculation and other characteristics, the chi-square test and logistic regression analysis were applied. Results: Out of 3,126 adults, 68% reported complete vaccination and 21% only the first dose, while 11% remained unvaccinated. Non-vaccination was associated with being younger, male, without a partner, low socioeconomic level, and no previous diagnosis of hypertension, obesity or diabetes. Furthermore, the non-vaccinated were less likely to have tested for COVID-19, and more likely to consider COVID-19 as low severity and not real compared with the vaccinated. Using logistic regression models: place of residence, marital status, educational level, age, BMI, testing for COVID-19, and the perception of COVID-19 (severe and real) were significant predictors of non-vaccination, with the model with 89% accuracy. The predominant reasons for not getting vaccinated were: 63% external barriers (e.g., not being able to attend an appointment), and 37% internal motives (e.g., vaccine does not work). Conclusions: The causes of non-vaccination against COVID-19 are related to both social and geographical determinants. Addressing external barriers is necessary in order to promote equity in vaccination. Reviewing the results in the context of earlier studies on the willingness to vaccinate, the gap between intention and vaccination is notable.
Keywords	covid19
Language	English
Publishing date	2024-01-17
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2024.01.17.24301326
Database	COVID19

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Article ; Online: Regulation of the Mammalian SWI/SNF Family of Chromatin Remodeling Enzymes by Phosphorylation during Myogenesis

Teresita Padilla-Benavides / Pablo Reyes-Gutierrez / Anthony N. Imbalzano

Biology, Vol 9, Iss 152, p

2020 Volume 152

Abstract	Myogenesis is the biological process by which skeletal muscle tissue forms. Regulation of myogenesis involves a variety of conventional, epigenetic, and epigenomic mechanisms that control chromatin remodeling, DNA methylation, histone modification, and activation of transcription factors. Chromatin remodeling enzymes utilize ATP hydrolysis to alter nucleosome structure and/or positioning. The mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) family of chromatin remodeling enzymes is essential for myogenesis. Here we review diverse and novel mechanisms of regulation of mSWI/SNF enzymes by kinases and phosphatases. The integration of classic signaling pathways with chromatin remodeling enzyme function impacts myoblast viability and proliferation as well as differentiation. Regulated processes include the assembly of the mSWI/SNF enzyme complex, choice of subunits to be incorporated into the complex, and sub-nuclear localization of enzyme subunits. Together these processes influence the chromatin remodeling and gene expression events that control myoblast function and the induction of tissue-specific genes during differentiation.
Keywords	myogenesis ; chromatin remodeling enzymes ; cell signaling ; SWI/SNF ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Why did people not get vaccinated against COVID-19? Results from a nationwide survey among Mexican adults

Wrzecionkowska, Dagmara / Stephens, Christopher R. / Gutierrez Reyes, Juan Pablo

medRxiv

Abstract	Objective: To explore the reasons for not getting vaccinated against COVID-19. Material and methods: In October 2021, a nationwide structured telephone survey (disproportionate stratified sampling) was conducted regarding COVID-19 pandemics, including vaccination experience. To examine associations between inoculation and other characteristics, the chi-square test and logistic regression analysis were applied. Results: Out of 3,126 adults, 68% reported complete vaccination and 21% only the first dose, while 11% remained unvaccinated. Non-vaccination was associated with being younger, male, without a partner, low socioeconomic level, and no previous diagnosis of hypertension, obesity or diabetes. Furthermore, the non-vaccinated were less likely to have tested for COVID-19, and more likely to consider COVID-19 as low severity and not real compared with the vaccinated. Using logistic regression models: place of residence, marital status, educational level, age, BMI, testing for COVID-19, and the perception of COVID-19 (severe and real) were significant predictors of non-vaccination, with the model with 89% accuracy. The predominant reasons for not getting vaccinated were: 63% external barriers (e.g., not being able to attend an appointment), and 37% internal motives (e.g., vaccine does not work). Conclusions: The causes of non-vaccination against COVID-19 are related to both social and geographical determinants. Addressing external barriers is necessary in order to promote equity in vaccination. Reviewing the results in the context of earlier studies on the willingness to vaccinate, the gap between intention and vaccination is notable.
Keywords	covid19
Language	English
Publishing date	2024-01-17
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2024.01.17.24301326
Database	COVID19

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Article ; Online: CETP-derived Peptide Seq-1, the Key Component of HB-ATV-8 Vaccine Prevents Stress Responses, and Promotes Downregulation of Pro-Fibrotic Genes in Hepatocytes and Stellate Cells.

Calixto-Tlacomulco, Sandra / Luna-Reyes, Ismael / Delgado-Coello, Blanca / Gutiérrez-Vidal, Roxana / Reyes-Grajeda, Juan Pablo / Mas-Oliva, Jaime

Archives of medical research

2024 Volume 55, Issue 2, Page(s) 102937

Abstract: Background: The nasal vaccine HB-ATV-8 has emerged as a promising approach for NAFLD (non-alcoholic fatty liver disease) and atherosclerosis prevention. HB-ATV-8 contains peptide seq-1 derived from the carboxy-end of the Cholesteryl Ester Transfer ... ...

Abstract	Background: The nasal vaccine HB-ATV-8 has emerged as a promising approach for NAFLD (non-alcoholic fatty liver disease) and atherosclerosis prevention. HB-ATV-8 contains peptide seq-1 derived from the carboxy-end of the Cholesteryl Ester Transfer Protein (CETP), shown to reduce liver fibrosis, inflammation, and atherosclerotic plaque formation in animal models. Beyond the fact that this vaccine induces B-cell lymphocytes to code for antibodies against the seq-1 sequence, inhibiting CETP's cholesterol transfer activity, we have hypothesized that beyond the modulation of CETP activity carried out by neutralizing antibodies, the observed molecular effects may also correspond to the direct action of peptide seq-1 on diverse cellular systems and molecular features involved in the development of liver fibrosis. Methods: The HepG2 hepatoma-derived cell line was employed to establish an in vitro steatosis model. To obtain a conditioned cell medium to be used with hepatic stellate cell (HSC) cultures, HepG2 cells were exposed to fatty acids or fatty acids plus peptide seq-1, and the culture medium was collected. Gene regulation of COL1A1, ACTA2, TGF-β, and the expression of proteins COL1A1, MMP-2, and TIMP-2 were studied. Aim: To establish an in vitro steatosis model employing HepG2 cells that mimics molecular processes observed in vivo during the onset of liver fibrosis. To evaluate the effect of peptide Seq-1 on lipid accumulation and pro-fibrotic responses. To study the effect of Seq-1-treated steatotic HepG2 cell supernatants on lipid accumulation, oxidative stress, and pro-fibrotic responses in HSC. Results and conclusion: Peptide seq-1-treated HepG2 cells show a downregulation of COLIA1, ACTA2, and TGF-β genes, and a decreased expression of proteins such as COL1A1, MMP-2, and TIMP-2, associated with the remodeling of extracellular matrix components. The same results are observed when HSCs are incubated with peptide Seq-1-treated steatotic HepG2 cell supernatants. The present study consolidates the nasal vaccine HB-ATV-8 as a new prospect in the treatment of NASH directly associated with the development of cardiovascular disease.
MeSH term(s)	Animals ; Tissue Inhibitor of Metalloproteinase-2/metabolism ; Tissue Inhibitor of Metalloproteinase-2/pharmacology ; Matrix Metalloproteinase 2 ; Cholesterol Ester Transfer Proteins/metabolism ; Down-Regulation ; Hepatocytes/metabolism ; Fibrosis ; Liver Cirrhosis/pathology ; Non-alcoholic Fatty Liver Disease/genetics ; Non-alcoholic Fatty Liver Disease/prevention & control ; Vaccines ; Transforming Growth Factor beta/metabolism ; Transforming Growth Factor beta/pharmacology ; Fatty Acids/metabolism ; Lipids/pharmacology ; Liver/metabolism
Chemical Substances	Tissue Inhibitor of Metalloproteinase-2 (127497-59-0) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Cholesterol Ester Transfer Proteins ; Vaccines ; Transforming Growth Factor beta ; Fatty Acids ; Lipids
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1156844-6
ISSN	1873-5487 ; 0188-4409 ; 0188-0128
ISSN (online)	1873-5487
ISSN	0188-4409 ; 0188-0128
DOI	10.1016/j.arcmed.2023.102937
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Article ; Online: The cast of clasts: catabolism and vascular invasion during bone growth, repair, and disease by osteoclasts, chondroclasts, and septoclasts.

Odgren, Paul R / Witwicka, Hanna / Reyes-Gutierrez, Pablo

Connective tissue research

2016 Volume 57, Issue 3, Page(s) 161–174

Abstract: Three named cell types degrade and remove skeletal tissues during growth, repair, or disease: osteoclasts, chondroclasts, and septoclasts. A fourth type, unnamed and less understood, removes nonmineralized cartilage during development of secondary ... ...

Abstract	Three named cell types degrade and remove skeletal tissues during growth, repair, or disease: osteoclasts, chondroclasts, and septoclasts. A fourth type, unnamed and less understood, removes nonmineralized cartilage during development of secondary ossification centers. "Osteoclasts," best known and studied, are polykaryons formed by fusion of monocyte precursors under the influence of colony stimulating factor 1 (CSF)-1 (M-CSF) and RANKL. They resorb bone during growth, remodeling, repair, and disease. "Chondroclasts," originally described as highly similar in cytological detail to osteoclasts, reside on and degrade mineralized cartilage. They may be identical to osteoclasts since to date there are no distinguishing markers for them. Because osteoclasts also consume cartilage cores along with bone during growth, the term "chondroclast" might best be reserved for cells attached only to cartilage. "Septoclasts" are less studied and appreciated. They are mononuclear perivascular cells rich in cathepsin B. They extend a cytoplasmic projection with a ruffled membrane and degrade the last transverse septum of hypertrophic cartilage in the growth plate, permitting capillaries to bud into it. To do this, antiangiogenic signals in cartilage must give way to vascular trophic factors, mainly vascular endothelial growth factor (VEGF). The final cell type excavates cartilage canals for vascular invasion of articular cartilage during development of secondary ossification centers. The "clasts" are considered in the context of fracture repair and diseases such as arthritis and tumor metastasis. Many observations support an essential role for hypertrophic chondrocytes in recruiting septoclasts and osteoclasts/chondroclasts by supplying VEGF and RANKL. The intimate relationship between blood vessels and skeletal turnover and repair is also examined.
MeSH term(s)	Animals ; Bone Development ; Chondrocytes/pathology ; Disease ; Humans ; Neovascularization, Pathologic/pathology ; Osteoclasts/pathology ; Wound Healing
Language	English
Publishing date	2016-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	185551-7
ISSN	1607-8438 ; 0091-1690 ; 0300-8207
ISSN (online)	1607-8438
ISSN	0091-1690 ; 0300-8207
DOI	10.3109/03008207.2016.1140752
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Article ; Online: Promotion of adipogenesis by JMJD6 requires the AT hook-like domain and is independent of its catalytic function.

Pablo Reyes-Gutierrez / Jake W Carrasquillo-Rodríguez / Anthony N Imbalzano

PLoS ONE, Vol 14, Iss 8, p e

2019 Volume 0216015

Abstract	JMJD6 is a member of the Jumonji C domain containing enzymes that demethylate and/or hydroxylate substrate proteins. It is a multi-functional protein that has been implicated in disparate aspects of transcriptional and post-transcriptional control of gene expression, including but not limited to enhancer and promoter binding, release of paused RNA polymerase II, control of splicing, and interaction with the translation machinery. JMJD6 contributes to multiple aspects of animal development, including adipogenesis modeled in culture. We mutated proposed or characterized domains in the JMJD6 protein to better understand the requirement for JMJD6 in adipogenic differentiation. Mutation of JMJD6 amino acids that mediate binding of iron and 2-oxogluterate, which are required cofactors for enzymatic activity, had no impact on JMJD6 function, showing that catalytic activity is not required for JMJD6 contributions to adipogenic differentiation. In addition, we documented the formation of JMJD6 oligomers and showed that catalytic activity is not required for oligomerization, as has been reported previously. We also observed no effect of mutations in the sumoylation site and in the poly-serine stretch. In contrast, mutation of the AT hook-like structure, which mediates interaction with DNA and/or RNA, compromised JMJD6 function by blocking its ability to interact with chromatin at genes that express regulators of adipogenesis. The ability of JMJD6 to interact with nucleic acids may be a critical requirement for its function in adipogenic differentiation. The requirement for the AT hook-like domain and the lack of requirement for catalytic activity giving rise to the idea that co-activation of transcription by JMJD6 may be functioning as a scaffold protein that supports the interactions of other critical regulators.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: CK2-Dependent Phosphorylation of the Brg1 Chromatin Remodeling Enzyme Occurs during Mitosis.

Padilla-Benavides, Teresita / Haokip, Dominic T / Yoon, Yeonsoo / Reyes-Gutierrez, Pablo / Rivera-Pérez, Jaime A / Imbalzano, Anthony N

International journal of molecular sciences

2020 Volume 21, Issue 3

Abstract: Brg1 (Brahma-related gene 1) is one of two mutually exclusive ATPases that can act as the catalytic subunit of mammalian SWI/SNF (mSWI/SfigureNF) chromatin remodeling enzymes that facilitate utilization of the DNA in eukaryotic cells. Brg1 is a phospho- ... ...

Abstract	Brg1 (Brahma-related gene 1) is one of two mutually exclusive ATPases that can act as the catalytic subunit of mammalian SWI/SNF (mSWI/SfigureNF) chromatin remodeling enzymes that facilitate utilization of the DNA in eukaryotic cells. Brg1 is a phospho-protein, and its activity is regulated by specific kinases and phosphatases. Previously, we showed that Brg1 interacts with and is phosphorylated by casein kinase 2 (CK2) in a manner that regulates myoblast proliferation. Here, we use biochemical and cell and molecular biology approaches to demonstrate that the Brg1-CK2 interaction occurred during mitosis in embryonic mouse somites and in primary myoblasts derived from satellite cells isolated from mouse skeletal muscle tissue. The interaction of CK2 with Brg1 and the incorporation of a number of other subunits into the mSWI/SNF enzyme complex were independent of CK2 enzymatic activity. CK2-mediated hyperphosphorylation of Brg1 was observed in mitotic cells derived from multiple cell types and organisms, suggesting functional conservation across tissues and species. The mitotically hyperphosphorylated form of Brg1 was localized with soluble chromatin, demonstrating that CK2-mediated phosphorylation of Brg1 is associated with specific partitioning of Brg1 within subcellular compartments. Thus, CK2 acts as a mitotic kinase that regulates Brg1 phosphorylation and subcellular localization.
MeSH term(s)	Animals ; Breast/cytology ; Breast/metabolism ; Casein Kinase II/metabolism ; Chromatin Assembly and Disassembly ; DNA Helicases/genetics ; DNA Helicases/metabolism ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Female ; Humans ; Mice ; Mitosis ; Myoblasts/cytology ; Myoblasts/metabolism ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Phosphorylation ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Nuclear Proteins ; Transcription Factors ; Casein Kinase II (EC 2.7.11.1) ; SMARCA4 protein, human (EC 3.6.1.-) ; Smarca4 protein, mouse (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-)
Language	English
Publishing date	2020-01-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21030923
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Article ; Online: Costo económico de atención de embarazos atribuibles a la falla de la política de prevención del embarazo adolescente en México.

Aracena-Genao, Belkis / Leyva-Flores, Rene / Gutiérrez-Reyes, Juan Pablo

Cadernos de saude publica

2022 Volume 38, Issue 6, Page(s) e00109721

Abstract: The objective was to estimate the direct medical cost of pregnancy care attributable to the failure of Mexico's teenage pregnancy prevention policy. From the provider's perspective, this economic study estimated the mean cost of prenatal care, childbirth, ...

Title translation	Economic cost of pregnancy care attributable to the failure of Mexico's teenage pregnancy prevention policy.
Abstract	The objective was to estimate the direct medical cost of pregnancy care attributable to the failure of Mexico's teenage pregnancy prevention policy. From the provider's perspective, this economic study estimated the mean cost of prenatal care, childbirth, puerperium, abortion and complications. To quantify the costs attributable to policy failure, three scenarios were constructed: (a) total number of pregnancies; (b) number of pregnancies above the target; (c) number of unwanted pregnancies. The cost of providing contraceptive methods was also estimated and the characteristics of pregnant adolescents were described. Of the adolescents (n = 5,477,027), 30.2% were sexually active; 46.8% used contraception; 44.1% had become pregnant and 9.1% had an abortion. Most pregnant women (65%) attended secondary school or under; 30% dropped out of school; 72.5% lived with a partner; 72.3% had complications. The mean cost of pregnancy care was estimated at USD 2,210.55 and the mean cost of providing contraceptives at USD 64.95. The total cost of policy failure was estimated for each scenario (in millions): (a) USD 1,614.39, (b) USD 876.61 and (c) USD 171.50, respectively; whereas the annual cost of providing contraceptives in each scenario was estimated in: (a) USD 47.43, (b) USD 25.76 and (c) USD 5.04. The failure of the policy is expressed in the high frequency of pregnancy in low-income adolescents and in high costs for the health system. The provision of contraceptives is 34 times cheaper than pregnancy care and could, together with improved living conditions, contribute to reduce the frequency of adolescent pregnancies.
MeSH term(s)	Adolescent ; Brazil ; Contraception/methods ; Contraceptive Agents ; Female ; Humans ; Mexico ; Policy ; Pregnancy ; Pregnancy in Adolescence/prevention & control
Chemical Substances	Contraceptive Agents
Language	Spanish
Publishing date	2022-06-27
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	1115730-6
ISSN	1678-4464 ; 0102-311X
ISSN (online)	1678-4464
ISSN	0102-311X
DOI	10.1590/0102-311XES109721
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