Digenic Inheritance of Mutations in Homologous Recombination Genes in Cancer Patients.

BACKGROUND/OBJECTIVES: BRCA1, BRCA2, ATM, and CHEK2 are known cancer predisposition genes (CPGs), but tumor risk in patients with simultaneous pathogenic variants (PVs) in CPGs remains largely unknown. In this study, we describe six patients from five families with multiple cancers who coinherited a combination of PVs in these genes. METHODS: PVs were identified using NGS DNA sequencing and were confirmed by Sanger. RESULTS: Families 1, 2, and 3 presented PVs in BRCA2 and ATM, family 4 in BRCA2 and BRCA1, and family 5 in BRCA2 and CHEK2. PVs were identified using NGS DNA sequencing and were confirmed by Sanger. The first family included patients with kidney, prostate, and breast cancer, in addition to pancreatic adenocarcinomas. In the second family, a female had breast cancer, while a male from the third family had prostate, gastric, and pancreatic cancer. The fourth family included a male with pancreatic cancer, and the fifth family a female with breast cancer. CONCLUSIONS: The early age of diagnosis and the development of multiple cancers in the reported patients indicate a very high risk of cancer in double-heterozygous patients associated with PVs in HR-related CPGs. Therefore, in families with patients who differ from other family members in terms of phenotype, age of diagnosis, or type of cancer, the cascade testing needs to include the study of other CPGs.

The pharmacoepigenetic paradigm in cancer treatment.

Epigenetic modifications, characterized by changes in gene expression without altering the DNA sequence, play a crucial role in the development and progression of cancer by significantly influencing gene activity and cellular function. This insight has led to the development of a novel class of therapeutic agents, known as epigenetic drugs. These drugs, including histone deacetylase inhibitors, histone acetyltransferase inhibitors, histone methyltransferase inhibitors, and DNA methyltransferase inhibitors, aim to modulate gene expression to curb cancer growth by uniquely altering the epigenetic landscape of cancer cells. Ongoing research and clinical trials are rigorously evaluating the efficacy of these drugs, particularly their ability to improve therapeutic outcomes when used in combination with other treatments. Such combination therapies may more effectively target cancer and potentially overcome the challenge of drug resistance, a significant hurdle in cancer therapy. Additionally, the importance of nutrition, inflammation control, and circadian rhythm regulation in modulating drug responses has been increasingly recognized, highlighting their role as critical modifiers of the epigenetic landscape and thereby influencing the effectiveness of pharmacological interventions and patient outcomes. Epigenetic drugs represent a paradigm shift in cancer treatment, offering targeted therapies that promise a more precise approach to treating a wide spectrum of tumors, potentially with fewer side effects compared to traditional chemotherapy. This progress marks a step towards more personalized and precise interventions, leveraging the unique epigenetic profiles of individual tumors to optimize treatment strategies.

Gastric cancer actionable genomic alterations across diverse populations worldwide and pharmacogenomics strategies based on precision oncology.

Introduction: Gastric cancer is one of the most prevalent types of cancer worldwide. The World Health Organization (WHO), the International Agency for Research on Cancer (IARC), and the Global Cancer Statistics (GLOBOCAN) reported an age standardized global incidence rate of 9.2 per 100,000 individuals for gastric cancer in 2022, with a mortality rate of 6.1. Despite considerable progress in precision oncology through the efforts of international consortia, understanding the genomic features and their influence on the effectiveness of anti-cancer treatments across diverse ethnic groups remains essential. Methods: Our study aimed to address this need by conducting integrated in silico analyses to identify actionable genomic alterations in gastric cancer driver genes, assess their impact using deleteriousness scores, and determine allele frequencies across nine global populations: European Finnish, European non-Finnish, Latino, East Asian, South Asian, African, Middle Eastern, Ashkenazi Jewish, and Amish. Furthermore, our goal was to prioritize targeted therapeutic strategies based on pharmacogenomics clinical guidelines, in silico drug prescriptions, and clinical trial data. Results: Our comprehensive analysis examined 275,634 variants within 60 gastric cancer driver genes from 730,947 exome sequences and 76,215 whole-genome sequences from unrelated individuals, identifying 13,542 annotated and predicted oncogenic variants. We prioritized the most prevalent and deleterious oncogenic variants for subsequent pharmacogenomics testing. Additionally, we discovered actionable genomic alterations in the ARID1A, ATM, BCOR, ERBB2, ERBB3, CDKN2A, KIT, PIK3CA, PTEN, NTRK3, TP53, and CDKN2A genes that could enhance the efficacy of anti-cancer therapies, as suggested by in silico drug prescription analyses, reviews of current pharmacogenomics clinical guidelines, and evaluations of phase III and IV clinical trials targeting gastric cancer driver proteins. Discussion: These findings underline the urgency of consolidating efforts to devise effective prevention measures, invest in genomic profiling for underrepresented populations, and ensure the inclusion of ethnic minorities in future clinical trials and cancer research in developed countries.

Screening of variables affecting the selective leaching of valuable metals from waste motherboards' PCBs.

The presence of valuable and hazardous metals in waste printed circuit boards, especially, motherboards, makes their recovery necessary as implies great economic and environmental advantages and develops urban mining processes. Hence, this research is focused on the selective leaching of Cu, Pb, and Sn as base metals using nitric acid and hydrochloric acid and Au, Ag, and Pd as precious metals using thiourea and sodium thiosulfate from waste motherboards' PCBs in a sequential eco-friendly two-stage process. Previously, thiourea and sodium thiosulfate were used as leaching agents to investigate their applicability for the leaching of metals from PCBs in a single-stage process. Screening experimental design was applied to screen the variables affecting the leaching process in order to evaluate their impact on the recovery of metals and select the significant factors. The results demonstrated that base and precious metals can be leached appropriately in two consecutive stages compared to a single-stage process. Nitric acid was found to be a much more efficient agent to leach Cu and Pb in comparison with hydrochloric acid which was more suitable for the leaching of Sn. In the case of precious metals, higher amounts of Au were leached using thiourea, whereas sodium thiosulfate was able to leach more Pd. Roughly similar results were obtained for the leaching of Ag using these leaching agents. Nitric acid concentration, average particle size, temperature, and leaching time were found to be significant to maximize the leaching of Cu and Pb and minimize that for Au, Ag, and Pd in the first stage. Initial pH was the only variable influencing the second stage, in particular, Au leaching by thiourea.

Knowledge of the workers of the construction industry about acquired immunodeficiency syndrome and associated factors.

BACKGROUND: Sexually Transmitted Infections (STIs), such as Human Immunodeficiency Virus (HIV) transmitted by biological, socioeconomic and cultural factors that increase the vulnerability of certain population groups such as civil construction workers. OBJECTIVE: To evaluate the knowledge of workers in the construction industry about infection by HIV and associated factors. METHODS: A cross-sectional, analytical study was conducted, including 381 construction workers, in the cities of João Pessoa, Cabedelo, and Santa Rita, in the State of Paraíba, Brazil, performed through interviews, using a data collection instrument with social demographic variables and the HIV Knowledge Questionnaire. Data were analyzed using descriptive measures, and for comparison between the categories the Kruskal-Wallis test was used, with margin of error of 5% . RESULTS: A predominance of male workers was observed (97.4%) among 381 workers; aged 30-39 (34.1%); married (81.4%); with up to eight years of education (66.6%); family income of up to 2x the minimum wage (52.8%) and coming from the country (43.8%). The average of correct responses was 63.3%, with higher indices (70.0%) related to transmission and forms of prevention. There were higher percentages of hits among those who had studied for 12 years or more. Workers from the capital of Paraíba presented a higher number of correct responses (67.44%). CONCLUSIONS: There is a low index of knowledge of construction workers about HIV, highlighting their consequent vulnerability to acquiring this infection.

Sexual behavior of university students in the context of the COVID-19 pandemic: a mixed-methods study.

OBJECTIVE: To analyze the sexual behaviors of university students during the COVID-19 pandemic. METHOD: Mixed study, carried out on four campuses of a public university in Paraíba, Brazil, between March 2021 and April 2022. The research followed ethical precepts. RESULTS: 404 university students were included, with an average age of 23.7 years, predominantly female, brown and single. The prevalence of self-reported sexually transmitted infections was 7.9%. Male students were more likely to engage in risky sexual behavior. Multiple logistic regression indicated that university students aged 25 or over who had engaged in casual sex in the last 12 months and had received or paid for sex were more likely to have sexually transmitted infections. The content analysis showed that social isolation was reflected in reduced consumption of alcohol and other substances, reduced sexual practices, increased use of social networks, as well as low adherence to condoms. CONCLUSION: Physical distancing has an impact on the sexual behavior of university students, as well as on the consumption of alcohol and other substances.

S/N/O-Enriched Carbons from Polyacrylonitrile-Based Block Copolymers for Selective Separation of Gas Streams.

A series of polyacrylonitrile (PAN)-based block copolymers with poly(methyl methacrylate) (PMMA) as sacrificial bock were synthesized by atom transfer radical polymerization and used as precursors for the synthesis of porous carbons. The carbons enriched with O- and S-containing groups, introduced by controlled oxidation and sulfuration, respectively, were characterized by Raman spectroscopy, scanning electron microscopy, and X-ray photoelectron spectrometry, and their surface textural properties were measured by a volumetric analyzer. We observed that the presence of sulfur tends to modify the structure of the carbons, from microporous to mesoporous, while the use of copolymers with a range of molar composition PAN/PMMA between 10/90 and 47/53 allows the obtainment of carbons with different degrees of porosity. The amount of sacrificial block only affects the morphology of carbons stabilized in oxygen, inducing their nanostructuration, but has no effect on their chemical composition. We also demonstrated their suitability for separating a typical N2/CO2 post-combustion stream.

Qualidade de vida, funcionalidade e autoestima de pessoas no pós-alta por cura de hanseníase / Quality of life, functionality, and self-concept of people post-discharge from leprosy / Calidad de vida, funcionalidad y autoestima de las personas tras el alta del tratamiento contra la lepra

RESUMO: Objetivo: avaliar a qualidade de vida, funcionalidade e autoestima de pessoas no pós-alta por cura de hanseníase. Métodos: estudo epidemiológico transversal, desenvolvido numa instituição de referência para hanseníase na Paraíba-Brasil, de maio a agosto de 2021. Utilizaram-se quatro instrumentos para caracterização sociodemográfica e clínica, avaliação da qualidade de vida, da funcionalidade e da autoestima. Os dados foram analisados pelos testes qui-quadrado de Pearson, exato de Fisher, Mann-Whitney e Kruskal-Wallis. Resultados: participaram 131 pessoas, dos quais 86 (65,6%) eram do sexo masculino e 72 (55%) com 41 a 60 anos. Houve impacto negativo da qualidade de vida relacionada à saúde em não escolarizados e com baixa renda familiar. Limitação da funcionalidade em quem não pratica atividade física, afetado por neurite e com algum grau de incapacidade física. Contudo, elevada autoestima. Conclusão: torna-se imprescindível capacitar profissionais e organizar medidas assistenciais frente ao cuidado longitudinal e interdisciplinar nessa fase terapêutica.

ABSTRACT Objective: to evaluate the quality of life, functionality, and self-concept of people after discharge from leprosy. Methods: This was a cross-sectional epidemiological study carried out in a reference institution for leprosy in Paraíba, Brazil, from May to August 2021. Four instruments were used for sociodemographic and clinical characterization, assessment of quality of life, functionality, and self-concept. The data was analyzed using Pearson's chi-square, Fisher's exact, Mann-Whitney, and Kruskal-Wallis tests. Results: 131 people took part, of whom 86 (65.6%) were male and 72 (55%) were aged between 41 and 60. There was a negative impact on health-related quality of life among those with no schooling and low family income. Limitation of functionality in those who do not practice physical activity, are affected by neuritis, and have some degree of physical disability. However, high self-concept. Conclusion: It is essential to train professionals and organize assistance measures in the face of longitudinal and interdisciplinary care in this therapeutic phase.

RESUMEN: Objetivo: evaluar la calidad de vida, la funcionalidad y la autoestima de las personas después del alta de la lepra. Métodos: Se trató de un estudio epidemiológico transversal realizado en una institución de referencia para lepra en Paraíba, Brasil, de mayo a agosto de 2021. Se utilizaron cuatro instrumentos para caracterización sociodemográfica y clínica, evaluación de la calidad de vida, funcionalidad y autoestima. Los datos se analizaron mediante las pruebas chi-cuadrado de Pearson, exacta de Fisher, Mann-Whitney y Kruskal-Wallis. Resultados: Participaron 131 personas, de las cuales 86 (65,6%) eran hombres y 72 (55%) tenían entre 41 y 60 años. Se observó un impacto negativo en la calidad de vida relacionada con la salud entre las personas sin estudios y con bajos ingresos familiares. Limitación de la funcionalidad en los que no practican actividad física, afectados por neuritis y con algún grado de discapacidad física. Sin embargo, alta autoestima. Conclusión: Es fundamental formar a los profesionales y organizar medidas asistenciales de cara a la atención longitudinal e interdisciplinar en esta fase terapéutica.

Chemical conjugation of aptamer-sphingomyelin nanosystems and their potential as inhibitors of tumour cell proliferation in breast cancer cells.

Breast cancer is a complex and heterogeneous disease with a high mortality rate due to non-specific cytotoxicity, low intratumoral accumulation and drug resistance associated with the ineffectiveness of chemotherapy. In recent years, all efforts have been focused on finding new markers and therapeutic targets, protein kinase MNK1b being a promising candidate. Recently, an aptamer known as apMNK2F showed a highly specific interaction with this protein kinase, leading to a significant reduction in tumour cell proliferation, migration and colony formation. However, as aptamers are unable to penetrate the cell membrane and reach the target, these small biomolecules need to be conjugated to suitable vectors that can transport and protect them inside the cells. In this work, covalent conjugation between biocompatible and non-harmful nanoemulsions of vitamin E and sphingomyelin and the aptamer was performed to facilitate intracellular delivery of the therapeutic aptamer apMNK2F. All strategies employed were based on 2-step bioconjugation and optimized to get the simplest and most reproducible vehicle with the highest association efficiency (about 70% in all cases). The ability of the nanosystems to successfully deliver the conjugated therapeutic aptamer was demonstrated and compared to other commercial transfection agents such as Lipofectamine 2000, leading to an effective decrease of breast cancer cell proliferation in the MDA-MB-231 cell line. The proliferation inhibition of the aptamer nanoconjugates compared to the non-conjugated aptamer provides evidence that the antitumoral capacity derived from kinase interaction is improved in a dose-dependent manner. Furthermore, various experiments including cell migration and colony formation assays, along with apoptosis induction experiments, emphasize the significant antitumoral potential. Overall, the obtained results indicate that the developed formulation could be a promising therapy for the treatment of breast cancer.

(Dys)functional insights into nucleic acids and RNA-binding proteins modulation of the prion protein and α-synuclein phase separation.

Prion diseases are prototype of infectious diseases transmitted by a protein, the prion protein (PrP), and are still not understandable at the molecular level. Heterogenous species of aggregated PrP can be generated from its monomer. α-synuclein (αSyn), related to Parkinson's disease, has also shown a prion-like pathogenic character, and likewise PrP interacts with nucleic acids (NAs), which in turn modulate their aggregation. Recently, our group and others have characterized that NAs and/or RNA-binding proteins (RBPs) modulate recombinant PrP and/or αSyn condensates formation, and uncontrolled condensation might precede pathological aggregation. Tackling abnormal phase separation of neurodegenerative disease-related proteins has been proposed as a promising therapeutic target. Therefore, understanding the mechanism by which polyanions, like NAs, modulate phase transitions intracellularly, is key to assess their role on toxicity promotion and neuronal death. Herein we discuss data on the nucleic acids binding properties and phase separation ability of PrP and αSyn with a special focus on their modulation by NAs and RBPs. Furthermore, we provide insights into condensation of PrP and/or αSyn in the light of non-trivial subcellular locations such as the nuclear and cytosolic environments.

Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.

Response to Vaccine-Derived Polioviruses Detected through Environmental Surveillance, Guatemala, 2019.

Guatemala implemented wastewater-based poliovirus surveillance in 2018, and three genetically unrelated vaccine-derived polioviruses (VDPVs) were detected in 2019. The Ministry of Health (MoH) response included event investigation through institutional and community retrospective case searches for acute flaccid paralysis (AFP) during 2018-2020 and a bivalent oral polio/measles, mumps, and rubella vaccination campaign in September 2019. This response was reviewed by an international expert team in July 2021. During the campaign, 93% of children 6 months <7 years of age received a polio-containing vaccine dose. No AFP cases were detected in the community search; institutional retrospective searches found 37% of unreported AFP cases in 2018‒2020. No additional VDPV was isolated from wastewater. No evidence of circulating VDPV was found; the 3 isolated VDPVs were classified as ambiguous VDPVs by the international team of experts. These detections highlight risk for poliomyelitis reemergence in countries with low polio vaccine coverage.

Association Between Sense of Coherence and Tobacco Use Among Brazilian Adolescent Students.

Background: Investigating tobacco use and associated factors is essential to set priorities and health promotion strategies among adolescents. Several studies examined the relationship between this behavior and the psychosocial salutogenic construct Sense of Coherence (SOC), but the evidence is limited to adolescents in high-income countries. This study aimed to analyze the association between tobacco use and SOC among Brazilian adolescent students. Methods: A cross-sectional school-based survey was conducted in 2018. Dependent variables were categorical binary (Yes/No): (1) Smoking experimentation (at least one puff in a lifetime); (2) Current smoking (at least one cigarette smoked in the last 30 days); (3) Daily cigarette smoking; and (4) Experimentation with hookah and/or other tobacco products (at least once in a lifetime). Independent variable SOC was assessed with the SOC-13 item scale. Independent-samples t-Test and Logistic regression were used in the statistical analyses. Potential confounders were identified using a Directed Acyclic Graph. Results: Participants were 3034 adolescents aged 13-19. The mean SOC scores were higher among adolescents who answered no to each of the dependent variables than among those who answered yes (p < .05). In the regression analysis, those with higher SOC scores were less likely to report smoking experimentation, current use, daily use, and experimentation with hookah and/or other tobacco products, than those with lower SOC scores. The associations remained after controlling for sociodemographic and/or social-environmental factors. Conclusion: An inverse relationship between SOC and tobacco use was observed among Brazilian adolescent students.

Intersectoral Collaboration to Promote Child Development: The Contributions of the Actor-Network Theory.

An integrated intersectoral care model promises to meet complex needs to promote early child development and address health determinants and inequities. Nevertheless, there is a lack of understanding of actors' interactions in producing intersectoral collaboration networks. The present study aimed to analyze the intersectoral collaboration in the social protection network involved in promoting early child growth and development in Brazilian municipalities. Underpinned by the tenets of actor-network theory, a case study was conducted with data produced from an educational intervention, entitled "Projeto Nascente." Through document analysis (ecomaps), participant observation (in Projeto Nascente seminars), and interviews (with municipal management representatives), our study explored and captured links among actors; controversies and resolution mechanisms; the presence of mediators and intermediaries; and an alignment of actors, resources, and support. The qualitative analysis of these materials identified three main themes: (1) agency fragility for intersectoral collaboration, (2) attempt to form networks, and (3) incorporation of fields of possibilities. Our findings revealed that intersectoral collaboration for promoting child growth and development is virtually non-existent or fragile, and local potential is missed or underused. These results emphasized the scarcity of action by mediators and intermediaries to promote enrollment processes to intersectoral collaboration. Likewise, existing controversies were not used as a mechanism for triggering changes. Our research supports the need to mobilize actors, resources, management, and communication tools that promote processes of interessement and enrollment in favor of intersectoral collaboration policies and practices for child development.

Immune response to co-administration of measles, mumps, and rubella (MMR), and yellow fever vaccines: a randomized non-inferiority trial among one-year-old children in Argentina.

BACKGROUND: In yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration. METHODS: We conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR1YF1), MMR followed by YF vaccine four weeks later (MMR1YF2), or YF followed by MMR vaccine four weeks later (YF1MMR2). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests. RESULTS: Of 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR1YF1 group versus 96.3% in the MMR1YF2 group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR1YF1 versus 94.7% MMR1YF2, a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR1YF1 versus 97.9% MMR1YF2, a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR1YF1 versus 97.5% YF1MMR2, a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted. CONCLUSION: Effective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration. TRIAL REGISTRATION: The study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017.

Exosome-like systems: Nanotechnology to overcome challenges for targeted cancer therapies.

Exosomes are natural extracellular nanovesicles (30-150 nm in diameter) with the ability to interact with and be taken up by specific cells. They are being explored as delivery systems and imaging agents for biomedical purposes owing to their biocompatibility, biostability in extracellular biofluids, and organotropic properties. However, their usefulness, efficacy, and clinical application are limited by certain critical parameters, including the need for more robust and reproducible manufacturing processes, characterization, quality control assessment, and clinical studies. Recently, exosome-like systems have emerged as alternatives for overcoming the limitations of natural exosomes. These systems are based on surface engineering approaches and nanoscale platforms that offer a deeper understanding and allow for more exhaustive standardization compared with natural exosomes. By combining the latest knowledge related to exosome research with the most promising developments in nanotechnology, exosome-like systems can be developed as a competitive approach for innovative targeted anti-cancer therapies. This review aims to provide a critical overview of the latest advances in designing and testing innovative exosome-like systems and the most promising modalities that can be translated into the clinic. Future perspectives and challenges in this field are discussed.

The NIH-led research response to COVID-19.

Investment, collaboration, and coordination have been key.

Intermediate molecular phenotypes to identify genetic markers of anthracycline-induced cardiotoxicity risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex disease whose polygenic component is mainly unidentified. We propose that levels of intermediate molecular phenotypes in the myocardium associated with histopathological damage could explain CDA susceptibility; so that variants of genes encoding these intermediate molecular phenotypes could identify patients susceptible to this complication. A genetically heterogeneous cohort of mice generated by backcrossing (N = 165) was treated with doxorubicin and docetaxel. Cardiac histopathological damage was measured by fibrosis and cardiomyocyte size by an Ariol slide scanner. We determine intramyocardial levels of intermediate molecular phenotypes of CDA associated with histopathological damage and quantitative trait loci (ipQTLs) linked to them. These ipQTLs seem to contribute to the missing heritability of CDA because they improve the heritability explained by QTL directly linked to CDA (cda-QTLs) through genetic models. Genes encoding these molecular subphenotypes were evaluated as genetic markers of CDA in three cancer patient cohorts (N = 517) whose cardiac damage was quantified by echocardiography or Cardiac Magnetic Resonance. Many SNPs associated with CDA were found using genetic models. LASSO multivariate regression identified two risk score models, one for pediatric cancer patients and the other for women with breast cancer. Molecular intermediate phenotypes associated with heart damage can identify genetic markers of CDA risk, thereby allowing a more personalized patient management. A similar strategy could be applied to identify genetic markers of other complex trait diseases.

Prevalence of atherogenic dyslipidemia, related factors and level of lipid control in the general population of Galicia. GALIPEMIAS study. / Prevalencia de dislipemia aterogénica, factores relacionados y grado de control lipídico en la población general de Galicia. Estudio GALIPEMIAS.

OBJECTIVES: GALIPEMIAS is a study designed to establish the prevalence of familial dyslipidemia in the general population of Galicia. The objective of the present study was to assess the prevalence of atherogenic dyslipidemia (AD), its relationship with other cardiovascular risk (CVR) factors, and the degree of lipid control. METHODS: Cross-sectional study carried out in the general population over 18 years of age residing in Galicia and with a health card from the Galician Health Service (N=1,000). Selection of the sample by means of random sampling by conglomerates. The AD prevalence adjusted for age and sex and the related variables were analyzed. RESULTS: The prevalence of AD adjusted for age and sex was 6.6% (95% CI: 5.0-8.3%). Arterial hypertension, altered basal glycemia, type 2 diabetes mellitus and cardiovascular disease were more frequent in subjects with AD than in the rest of the population. 47.5% of the subjects with AD had a high or very high CVR. Lipid-lowering drugs were received by 38.9% (30.5% statins) of the participants with AD (46.1% of those with high and 71.4% of those with very high CVR). 25.4% of the subjects with AD had target LDL-c levels, all of them with low or moderate CVR. CONCLUSIONS: The prevalence of AD in the general adult population of Galicia is not negligible, and it was related to several CVR factors and cardiovascular disease. Despite this, this lipid alteration was underdiagnosed and undertreated.

Comprometimento da saúde no pós-alta de pacientes tratados por hanseníase e fatores relacionados: revisão de escopo / Post-discharge health impairment of patients treated for leprosy and related factors: scope review / Deterioro de la salud tras el alta en pacientes tratados por lepra y factores re-lacionados: una revisión general

Objetivo: mapear evidências na literatura científica sobre o comprometimento de saúde no pós-alta de pacientes tratados por Hanseníase e fatores relacionados. Materiais e Método: revisão de escopo realizada a partir das bases de dados CINAHL, LILACS, MEDLINE, PUBMED, SCOPUS e Web of Science em março de 2021, norteados pela estratégia mnemônica que auxilia na identificação do Problema, Conceito e Contexto propostos pelo Instituto Joanna Briggs, sistematizados por meio do fluxograma PRISMA-ScR e registrados na Open Science Framework (osf.io/vmdc6). Foram incluídos estudos sobre a temática publicados até fevereiro de 2021 no cenário nacional e internacional. Resultados: dos dez artigos incluídos na amostra final, nove evidenciaram algum grau de comprometimento funcional, demonstrando fragilidades no acompanhamento desde o diagnóstico até o período pós-alta. Conclusões: evidencia-se acometimentos com maior frequência sobretudo de ordem física, que impactam diretamente a funcionalidade nas atividades de vida diária e social dessas pessoas. As fragilidades no monitoramento pós-alta foram relacionadas ao déficit de profissionais capacitados, ao desconhecimento de técnicas de avaliação e classificação do grau de incapacidade, à carência na oferta de educação em saúde, à dificuldade de acesso aos serviços de saúde, ao atraso no tratamento dos episódios reacionais e reabilitação biopsicossocial e à ausência da sistematização do cuidado.(AU)

Objective: to map evidence in the scientific literature on the post-discharge health impairment of patients treated for leprosy and related factors. Materials and Method: scope review carried out from the CINAHL, LILACS, MEDLINE, PUBMED, SCOPUS and Web of Science databases in March 2021, guided by the mnemonic strategy that helps to identify the Problem, Concept and Context proposed by the Joanna Institute Briggs, systematized through the PRISMA-ScR flowchart, and registered in the Open Science Framework (osf.io/vmdc6). Studies on the subject published until February 2021 in the national and international scenario were included. Results: of the ten articles included in the final sample, nine showed some degree of functional impairment, demonstrating weaknesses in follow-up from diagnosis to the post-discharge period. Conclusions: there is evidence of more frequent involvement, especially of a physical nature, which directly impact the functionality of these people's daily and social activities. Weaknesses in post-discharge monitoring were related to the lack of trained professionals, lack of knowledge of assessment techniques and classification of the degree of disability, lack of health education provision, difficulty in accessing health services, delay in treatment of reactional episodes and biopsychosocial rehabilitation and the absence of systematization of care.(AU)

Objetivo: mapear en la literatura científica las evidencias sobre el deterioro de la salud post-alta en pacientes tratados por lepra y factores relacionados. Materiales y Métodos: revisión de alcance realizada a partir de las bases de datos CINAHL, LILACS, MEDLINE, PUBMED, SCOPUS y Web of Science en marzo de 2021, guiada por la estrategia mnemotécnica que ayu-da a identificar el Problema, Concepto y Contexto propuesta por el Instituto Joanna Briggs, sistematizada a través del flujograma PRISMA-ScR y registrada en el Open Science Framework (osf.io/vmdc6). Fueron incluidos estudios sobre el tema, publicados hasta febrero de 2021, en el escenario nacional e internacional. Resultados: de los diez artículos incluidos en la muestra final, nueve mostraron algún grado de deterioro funcional, demostrando debilidades en el seguimiento desde el diagnóstico hasta el período posterior al alta. Conclusiones: se evidencia con mayor frecuencia ataques sobre todo de orden físico que impactan directamente en la funcionalidad en las actividades de la vida diaria y social de las personas. Fragilidades en el seguimiento postoperatorio relacionadas con el déficit de profesionales capacitados, el desco-nocimiento de las técnicas de evaluación y clasificación del grado de incapacidad, la carencia en la oferta de educación en salud, la dificultad de acceso a los servicios de salud, el retraso en el tratamiento de los episodios reaccionarios y la rehabilitación biopsicosocial y la ausencia de...(AU)