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Background: Adolescence is a stage of transition with multiple changes and transformations. It is a critical phase to potentiate or disrupt the life course of human beings. In Latin America, adolescents and young adults from countries like Colombia have unequal access to socioeconomic resources, education, and the job market. This may generate social disadvantages and vulnerability., Aim: We aimed to identify conditions of social vulnerability and psychosocial resilience in the life course of adolescents and young adults from a community art network in Bogota, Colombia., Methods: We conducted a qualitative study with a multivocal design supported by the ethnic-social life history construction. The data were collected using narrative interviews. The interviews were transcribed, coded, categorized, and triangulated according to the principles of grounded theory as an analytical method. We adhered to the consolidated criteria for reporting qualitative research (COREQ) checklist., Results: Eight adolescents and young adults between the ages of 12 and 24 years participated in the study. Five categories emerged: social vulnerability, social environment, artistic processes, psychosocial resilience, and life course., Conclusions: Social vulnerability and psychosocial resilience coexist during the life course of adolescents and young adults. Social support networks and community art processes have the potential to promote psychosocial resilience in adolescents and young adults., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

N-Nitrosamines are a class of indirect acting mutagens, as their metabolic degradation leads to the formation of the DNA-alkylating diazonium ion. Following up on the in-silico identification of thousands of nitrosamines that can potentially be derived from small molecule drugs and their known impurities described in a previous publication, we have now re-analyzed this dataset to apply EMA's Carcinogenic Potency Categorization Approach (CPCA) introduced with the 16th revision of their Q&A document for Marketing Authorization Holders. We find that the majority of potential nitrosamines from secondary amine precursors belongs to potency categories 4 and 5, corresponding to an acceptable daily intake of 1500 ng, whereas nitrosamines from tertiary amine precursors distribute more evenly among all categories, resulting in a substantial number of structures that are assigned the more challenging acceptable intakes of 18 ng/day and 100 ng/day for potency categories 1 and 2, respectively. However, the nitrosative dealkylation pathway for tertiary amine is generally far slower than the direct nitrosation on secondary amines, with a direct nitrosation mechanism suspected only for structures featuring electron-rich (hetero)aromatic substituents. This allows for greater focus towards those structures that require further review, and we demonstrate that their number is not substantial. In addition, we reflect on the nitrosamine risk posed by secondary amine API impurities and demonstrate that based on the ICH Q3A/B identification threshold unknown impurities may exist that could be transformed to relevant amounts of NA. We also demonstrate that the analytical sensitivity required for the quantification of high potency nitrosamines can be problematic especially for high dose APIs. In summary, the regulatory framework rolled out with the latest Q&A document represents a substantial improvement compared with the previous situation, but further refinement through interaction between manufacturers, regulators, not-for-profit and academic institutions will be required to ensure patient access to vital medicines without compromising safety., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

This article reports the outcome of an in silico analysis of more than 12,000 small molecule drugs and drug impurities, identifying the nitrosatable structures, assessing their potential to form nitrosamines under relevant conditions and the challenges to determine compound-specific AIs based on data available or read-across approaches for these nitrosamines and their acceptance by health authorities. Our data indicate that the presence of nitrosamines in pharmaceuticals is likely more prevalent than originally expected. In total, 40.4 % of the analyzed APIs and 29.6 % of the API impurities are potential nitrosamine precursors. Most structures identified through our workflow could form complex API-related nitrosamines, so-called nitrosamine drug substance related impurities (NDSRIs), although we also found structures that could release the well-known small and potent nitrosamines NDMA, NDEA, and others. Due to common structural motifs including secondary or tertiary amine moieties, whole essential drug classes such as beta blockers and ACE inhibitors are at risk. To avoid the risk of drug shortages or even the complete loss of therapeutic options, it will be essential that the well-established ICH M7 principles remain applicable for nitrosamines and that that the industry and regulatory authorities keep an open communication not only about the science but also to make sure there is a good balance between risk and benefit to patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Repair of DNA damage is essential to the preservation of genomic stability. During repair of double-strand breaks, several helicases function to promote accurate repair and prevent the formation of crossovers through homologous recombination. Among these helicases is the Fanconi anemia group M (FANCM) protein. FANCM is important in the response to various types of DNA damage and has been suggested to prevent mitotic crossovers during double-strand break repair. The helicase activity of FANCM is believed to be important in these functions, but no helicase activity has been detected in vitro We report here a genetic and biochemical study of Drosophila melanogaster Fancm. We show that purified Fancm is a 3' to 5' ATP-dependent helicase that can disassemble recombination intermediates, but only through limited lengths of duplex DNA. Using transgenic flies expressing full-length or truncated Fancm, each with either a wild-type or mutated helicase domain, we found that there are helicase-independent and C-terminal-independent functions in responding to DNA damage and in preventing mitotic crossovers., (Copyright © 2016 by the Genetics Society of America.)

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.

Objective: To present opinions of physicians participating in a pilot certification exam in the specialty of Family Medicine implemented in Venezuela, in December 2004, by the Mexican Board of Certification of Family Medicine A.C., Design: Descriptive, transversal., Methods: Participant physicians (n:37) completed semi-structured questionnaries: one or two weeks before the exam, and immediately after it., Results: 60% of participants were 41-50 years old and 80% women. All of them were practicing physicians; 49% had 5-10 year experience in family medicine. Main motivation to participate in the exam: the need for continuing learning (83%). Results showed their participation motivated continuing education (46%). Books were the most frequently utilized resource when preparing for the exam (54%). 94% were willing to take the exam again in the future, and all would recommend it to their colleagues. 49% said that examination should be taken every 3-4 years and should be voluntary (54%). 86% considered the content of the exam pertinent to their practice while 54% mentioned it was well adapted to their country's reality. Time for the exam was enough according to 71%, and number of questions was considered excessive by 89%. After the exam, 43% estimated to have personal prognosis for excellent or good outcomes. CONCLUSIONS. The international examination was satisfactory, stimulated desires of update, and the participants would repeat and recommend it in the future. The Mexican experience offers an example to put into practice, and the international collaboration would be a valid option to extend the certification processes in Latin America.