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- PublicationEvaluation of DNA damage through cytogenetic approach in smokers and vapers with and without nicotine compared with control group(2024) Paz-y-Miño, César; Ocampo, Ligia; Sánchez, María-Eugenia; Leone, Paola EThe use of tobacco and electronic cigarettes is harmful to health and can cause genetic damage, increasing the risk of cancer and other serious diseases. Although e-cigarettes contain fewer toxic chemicals than conventional tobacco, recent studies have shown that the vapor caused by burning produced by e-cigarettes can also be toxic and carcinogenic. Various studies have found that those exposed to tobacco and vaping have significantly higher levels of damage to their DNA in different types of cells and tissues. Evidence has accumulated that e-cigarette vaping can alter cellular functions and DNA itself, increasing the risk of cancer and aging. The present work evaluates the cytogenetic damage in individuals exposed to conventional cigarette vapors by burning with nicotine and vapors without nicotine, compared with a non-smoking population. The study included participants with an average age of 30 years (+/-10), with a majority of men representing 70% of the sample. The Chi-square test found no significant statistical differences between the men and women exposed (p<0.05). The results of chromosomal fragility found in the four groups studied (control group, conventional smokers, vapers with nicotine and vapers without nicotine) showed breaks and gaps in one or both of the chromatids in all exposed individuals, with highly significant statistical differences (p<0.001) compared to the unexposed control group. No statistically significant differences were found between the group of conventional smokers and the vapers with and without nicotine, nor between the two types of vapers (p>0.05). In conclusion, cytogenetic evidence of DNA damage produced by vaping is shown in the same proportions as a normal cigarette. This will significantly impact public health, which must be considered in preventive actions.
- PublicationVariable patterns of retrotransposition in different HeLa strains provide mechanistic insights into SINE RNA mobilization processes(2024) Moldovan, John B; Kopera, Huira C; Liu, Ying; Garcia-Canadas, Marta; Catalina, Purificacion; Leone, Paola E; Sanchez, Laura; Kitzman, Jacob O; Kidd, Jeffrey M; Garcia-Perez, Jose Luis; Moran, John VAlu elements are non-autonomous Short INterspersed Elements (SINEs) derived from the 7SL RNA gene that are present at over one million copies in human genomic DNA. Alu mobilizes by a mechanism known as retrotransposition, which requires the Long INterspersed Element-1 (LINE-1) ORF2-encoded protein (ORF2p). Here, we demonstrate that HeLa strains differ in their capacity to support Alu retrotransposition. Human Alu elements retrotranspose efficiently in HeLa-HA and HeLa-CCL2 (Alu-permissive) strains, but not in HeLa-JVM or HeLa-H1 (Alu-nonpermissive) strains. A similar pattern of retrotransposition was observed for other 7SL RNA-derived SINEs and tRNA-derived SINEs. In contrast, mammalian LINE-1s, a zebrafish LINE, a human SINE-VNTR-Alu (SVA) element, and an L1 ORF1-containing mRNA can retrotranspose in all four HeLa strains. Using an in vitro reverse transcriptase-based assay, we show that Alu RNAs associate with ORF2p and are converted into cDNAs in both Alu-permissive and Alu-nonpermissive HeLa strains, suggesting that 7SL- and tRNA-derived SINEs use strategies to 'hijack' L1 ORF2p that are distinct from those used by SVA elements and ORF1-containing mRNAs. These data further suggest ORF2p associates with the Alu RNA poly(A) tract in both Alu-permissive and Alu-nonpermissive HeLa strains, but that Alu retrotransposition is blocked after this critical step in Alu-nonpermissive HeLa strains.
- PublicationRecomendaciones generales e informe de la situación de impacto del SARSCoV2 en niños con cáncer en Latinoamérica(0000) Sociedad Latinoamericana de Cuidados Intensivos Pediátricos (SLACIP)
- PublicationQuality and capacity indicators for hospitalized pediatric oncology patients with critical illness: A modified delphi consensus(2020) Arias, Anita V; Garza, Marcela; Murthy, Srinivas; Cardenas, Adolfo; Diaz, Franco; Montalvo, Erika; Nielsen, Katie R; Kortz, Teresa; Sharara-Chami, Rana; Friedrich, Paola; McArthur, Jennifer; Agulnik, AsyaBackground Hospitalized pediatric hematology‐oncology (PHO) patients are at high risk for critical illness, especially in resource‐limited settings. Unfortunately, there are no established quality indicators to guide institutional improvement for these patients. The objective of this study was to identify quality indicators to include in PROACTIVE (PediatRic Oncology cApaCity assessment Tool for IntensiVe carE), an assessment tool to evaluate the capacity and quality of pediatric critical care services offered to PHO patients. Methods A comprehensive literature review identified relevant indicators in the areas of structure, performance, and outcomes. An international focus group sorted potential indicators using the framework of domains and subdomains. A modified, three‐round Delphi was conducted among 36 international experts with diverse experience in PHO and critical care in high‐resource and resource‐limited settings. Quality indicators were ranked on relevance and actionability via electronically distributed surveys. Results PROACTIVE contains 119 indicators among eight domains and 22 subdomains, with high‐median importance (≥7) in both relevance and actionability, and ≥80% evaluator agreement. The top five indicators were: (a) A designated PICU area; (b) Availability of a pediatric intensivist; (c) A PHO physician as part of the primary team caring for critically ill PHO patients; (d) Trained nursing staff in pediatric critical care; and (e) Timely PICU transfer of hospitalized PHO patients requiring escalation of care. Conclusions PROACTIVE is a consensus‐derived tool to assess the capacity and quality of pediatric onco‐critical care in resource‐limited settings. Future endeavors include validation of PROACTIVE by correlating the proposed indicators to clinical outcomes and its implementation to identify service delivery gaps amenable to improvement. Keywords: clinical cancer research, pediatric cancer, translational research
- PublicationMultilevel impacts of a pediatric early warning system in resource-limited pediatric oncology hospitals(2022) Mirochnick, Emily; Graetz, Dylan E; Ferrara, Gia; Puerto-Torres, Maria; Gillipelli, Srinithya R; Elish, Paul; Muniz-Talavera, Hilmarie; Gonzalez-Ruiz, Alejandra; Armenta, Miriam; Barra, Camila; Diaz-Coronado, Rosdali; Hernandez, Cinthia; Juarez, Susana; Loeza, Jose de Jesus; Mendez, Alejandra; Montalvo, Erika; Penafiel, Eulalia; Pineda, Estuardo; Agulnik, AsyaBackground: Pediatric Early Warning Systems (PEWS) reduce clinical deterioration, improve interdisciplinary communication, and provide cost savings; however, little is known about how these impacts are achieved or related. This study evaluates the multi-level impacts of PEWS in resource-limited pediatric oncology centers. Methods: We conducted 71 semi-structured interviews including physicians (45%), nurses (45%), and administrators (10%) from 5 resource-limited pediatric oncology centers in 4 Latin American countries. Interviews were conducted in Spanish, transcribed, and translated into English. A code book was developed using a priori and inductively derived codes. Transcripts were independently coded by 2 coders, achieving a kappa of 0.8-0.9. Thematic content analysis explored perceived impacts of PEWS at the level of the patient, clinician, healthcare team, and institution. Results: PEWS improved the quality of attention for patients, reducing morbidity and mortality. Clinicians felt more knowledgeable, confident, and empowered providing patient care, resulting in greater job satisfaction. PEWS affected team dynamics by improving interdisciplinary (ward and intensive care unit) and interprofessional (physicians and nurses) relationships and communication. This ultimately led to institutional culture change with emphasis on patient safety, collaboration with other centers, and receipt of institutional awards. Together, these impacts led to hospital-wide support of ongoing PEWS use. Conclusions: In resource-limited hospitals, PEWS use results in multi-level positive impacts on patients, clinicians, teams, and institutions, creating a feedback loop that further supports ongoing PEWS use. These findings can guide advocacy for PEWS to various stakeholders, improve PEWS effectiveness, and inform assessment of other interventions to improve childhood cancer outcomes. Keywords: Latin America; Pediatric Early Warning System (PEWS); global health; pediatric critical care; pediatric oncology; quality improvement; resource-limited. Copyright © 2022 Mirochnick, Graetz, Ferrara, Puerto-Torres, Gillipelli, Elish, Muniz-Talavera, Gonzalez-Ruiz, Armenta, Barra, Diaz-Coronado, Hernandez, Juarez, Loeza, Mendez, Montalvo, Penafiel, Pineda and Agulnik.