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34 result(s) for "Gutiérrez, Mónica Paola"
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Phenotypic Variation in Disease Severity Among Hospitalized Pediatric Patients With COVID-19: Assessing the Impact of COVID-19 in the EPICO Study
To characterize the clinical phenotypes of SARS-CoV-2 infection in hospitalized children as part of the EPICO multicenter cohort study. We included hospitalized children with confirmed SARS-CoV-2 infection from Colombian and Spanish institutions to assess disease evolution and outcomes. Cluster analysis was performed to identify clinical phenotypes. A total of 2318 patients were included (55% male, 36% infants). Five phenotype clusters emerged: Cluster 1 (26.5%): infants without comorbidities, low PICU admissions and mortality; Cluster 2 (18.5%): respiratory comorbidities, high microorganism co-detection and mortality; Cluster 3 (11.5%): fever, gastrointestinal symptoms, high PICU admissions; Cluster 4 (32%): mild unspecific symptoms, low mortality; Cluster 5 (11.3%): adolescents without comorbidities, low co-detection and hospitalization rates. Findings were consistent across both countries. Identifying clinical phenotypes of SARS-CoV-2 in children may improve risk stratification and guide future management strategies.
Genome-wide Dynamics of Chromatin Maturation Following DNA Replication
All DNA-templated events, including replication and gene transcription, occur in the context of the local chromatin environment. The passage of the replication machinery results in disassembly of chromatin, which must be re-assembled behind the replication fork to re-establish the epigenetic state of the cell. Many of the factors and mechanisms regulating DNA replication and chromatin assembly have been identified from elegant in vitro biochemical experiments, work in model systems like Saccharomyces cerevisiae, or novel proteomic approaches. In spite of current advances in the field, it is still not clear how the chromatin landscape is organized and re-assembled during this process. Current methods, while informative, lack the genome-wide base-pair resolution required to assess the dynamics of chromatin assembly and maturation in a spatial-temporal manner. To overcome the limitations of these studies, I have taken advantage of an epigenome mapping technique based on micrococcal nuclease (MNase) digestion followed by paired-end sequencing. This approach facilitates the analysis of chromatin structure by capturing not only nucleosomes, but also smaller DNA binding protein footprints in a factor-agnostic manner. I have developed a technique based on this approach that generates Nascent Chromatin Occupancy Profiles (NCOPs) to study the dynamics of chromatin assembly following passage of the DNA replication fork at a genome-wide level and at single base-pair resolution in S. cerevisiae. It employs a nucleoside analog to specifically enrich for nascent chromatin, which can be captured following a chase over different periods of time. Thus, NCOPs resolve the structure of nascent and mature chromatin, facilitating the analysis of chromatin maturation across the entire genome. Using NCOPs, I provide a comprehensive description of the maturation process across different genomic regions and the dynamics of small DNA binding factor association with nascent and mature chromatin states. Our results support previous work characterizing the structure of nascent chromatin as being more disorganized and having poorly positioned nucleosomes. Importantly, using positioning and occupancy scores, I provide new details on the structure of nascent and mature chromatin at intergenic regions, including replication origins, and at highly transcribed and poorly transcribed genes. I uncovered that local epigenetic footprints have the potential to shape the dynamics of chromatin assembly, generating a chromatin maturation landscape that is dependent on the parental chromatin. Finally, I resolved patterns of transcription factor occupancy with nascent and mature chromatin, and observed transient factor association in the nascent state. In all, this work provides insight into the dynamics of chromatin assembly, and allows for genome-wide and base-pair resolution investigation of chromatin maturation. The genomic and bioinformatic approaches developed here open the door for further investigation of the dynamics of epigenetic inheritance and the role of known and unknown players in re-establishing the eukaryotic epigenome following passage of the DNA replication fork.
Assessing therapeutic decisions in generalized myasthenia gravis: Study protocol
The therapeutic landscape in generalized myasthenia gravis (gMG) has been continuously evolving in recent years, with over five products approved, each with different efficacy, safety, and administration profiles. With the availability of new targeted treatments, physicians are faced with the challenge of therapeutic decision-making tailored to traditional therapeutic goals, individual preferences, and personal experience, seeking optimal disease control with a positive safety profile. In this context of uncertainty and multiple novel choices, this study aims to provide insights into the preferred treatment choices of neurologists managing gMG and to identify demographic, professional or behavioral factors influencing the decision-making process. This is a non-interventional, cross-sectional, web-based study involving 150 neurologists treating gMG patients in collaboration with the Spanish Society of Neurology. The primary endpoint will be to assess preferences for different gMG treatment attributes using a conjoint analysis to create hypothetical treatment scenarios. Therapeutic inertia, described as the lack of treatment initiation or intensification when therapeutic goals are not met, will be evaluated as a secondary endpoint through 7 case scenarios simulating real gMG clinical practice situations. Neurologists will also answer a survey composed of demographic, professional, and behavioral characteristics (user resistance behavior, care-related regret, burnout, risk attitude, empathy, work fulfilment, and personality traits) to recognize possible factors influencing decisions. The study findings will contribute to better understanding of decision-making in gMG under a changing therapeutic landscape with multiple new targeted options, and will identify which factors have a role in affecting those decisions.
Physical function and symptoms in adult hematopoietic stem cell transplantation patients, by severity of oral mucositis: a prospective study
Hematopoietic cell transplantation (HCT) is a curative treatment for hematological malignancies that aims to restore hematopoietic function. However, it involves significant toxicities, including oral mucositis. Oral mucositis (OM) impairs nutrition, extends hospital stays, and reduces quality of life. Physical function declines post-transplant, but the role of severe oral mucositis in worsening this impairment remains unclear. To compare the differences in physical function and treatment-related symptoms before and after HCT between adult patients with hematologic cancer who did and did not develop severe oral mucositis during their hospitalization. A prospective longitudinal study was conducted at Clínica Dávila, Santiago, Chile, with 31 adult patients undergoing allogeneic or autologous HCT between September 2023 and March 2024. Patients were grouped based on the presence of severe OM, which was assessed using the WHO scale. Physical function was evaluated with the 30-second sit-to-stand test, handgrip strength, and the 2-minute step test, while treatment-related symptoms intensity was measured using the Edmonton Symptom Assessment Scale. OM incidence was 74.2%, with severe OM affecting 29% of patients. Patients with severe OM scored significantly lower on the sit-to-stand test (Mean Difference 1.5 repetitions, p =0.048); showed higher levels of pain, appetite loss, and nausea; and required more days of parenteral nutrition ( p <0.05). OM onset occurred at day 9.3 post-allogeneic HCT and day 13.6 post-autologous HCT, ending at day 17.0 and day 11.3, respectively. Patients who develop severe oral mucositis after undergoing HCT experience greater impairment in lower limb strength, loss of appetite, pain and nausea at discharge than their counterparts.
PADI2 Polymorphisms Are Significantly Associated With Rheumatoid Arthritis, Autoantibodies Serologic Status and Joint Damage in Women from Southern Mexico
The enzymes of the family peptidylarginine deiminases (PADs) have an important role in the pathogenesis of rheumatoid arthritis (RA) due to their association with the anti-citrullinated protein antibodies (ACPA) production. To evaluate the association between single-nucleotide polymorphisms (SNPs) in the PADI2 gene and RA susceptibility, related clinical parameters, and the serologic status of autoantibodies in a women population with RA from southern Mexico, a case-control study was conducted (case n=229; control n=333). Sociodemographic characteristics were evaluated, along with clinical parameters, inflammation markers, the levels of ACPAs as anti-cyclic citrullinated peptides (anti-CCPs), anti-modified citrullinated vimentin (anti-MCV), and rheumatoid factor (RF). Genomic DNA was extracted from peripheral blood, and three SNPs of the PADI2 gene (rs1005753, rs2057094, and rs2235926) were performed by qPCR using TaqMan probes. The data analysis reveals that the carriers of the T allele for rs2057094 and rs2235926 presented an earlier onset of the disease (β= -3.26; p = 0.03 and β = -4.13; p = 0.015, respectively) while the carriers of the T allele for rs1005753 presented higher levels of anti-CCPs (β= 68.3; p = 0.015). Additionally, the T allele of rs2235926 was associated with a positive RF (OR = 2.90; p = 0.04), anti-MCV (OR = 2.92; p = 0.05), and with the serologic status anti-CCP+/anti-MCV+ (OR = 3.02; p = 0.03), and anti-CCP+/anti-MCV+/RF+ (OR = 3.79; p = 0.004). The haplotypes GTT (OR =1.52; p = 0.027) and TTT (OR = 1.32; p = 0.025) were associated with the presence of RA. In addition, in this study the haplotype TTT is linked to the presence of radiographic joint damage defined by a Sharp-van der Heijde score (SHS) ≥2 (OR = 1.97; p = 0.0021) and SHS ≥3 (OR = 1.94; p = 0.011). The haplotype TTT of SNPs rs1005753, rs2057094, and rs2235926 of the PADI2 gene confers genetic susceptibility to RA and radiographic joint damage in women from southern Mexico. The evidence reveals that SNPs of the PADI2 gene favors the presence of a positive serologic status in multiple autoantibodies and the clinical manifestations of RA at an early onset age.
Rats exhibit age-related mosaic loss of chromosome Y
Mosaic loss of the Y chromosome (LOY) is the most frequent chromosomal aberration in aging men and is strongly correlated with mortality and disease. To date, studies of LOY have only been performed in humans, and so it is unclear whether LOY is a natural consequence of our relatively long lifespan or due to exposure to human-specific external stressors. Here, we explored whether LOY could be detected in rats. We applied a locus-specific PCR and target sequencing approach that we used as a proxy to estimate LOY in 339 samples covering eleven tissues from young and old individuals. We detected LOY in four tissues of older rats. To confirm the results from the PCR screening, we re-sequenced 60 full genomes from old rats, which revealed that the Y chromosome is the sole chromosome with low copy numbers. Finally, our results suggest that LOY is associated with other structural aberrations on the Y chromosome and possibly linked to the mosaic loss of the X chromosome. This is the first report, to our knowledge, demonstrating that the patterns of LOY observed in aging men are also present in a rodent, and conclude that LOY may be a natural process in placental mammals.Alberto Orta et al. demonstrate that frequent mosaic loss of chromosome Y (LOY) observed in aging men might also be present in rats. They show that, like in humans, LOY in rats is associated with aging, but is not dependent on environmental stressors, and may be a natural process in placental mammals.
Epidemiological behavior of suicide attempt in Colombian adolescents years 2016-2019: An ecological study
Abstract Objective: characterize the behavior of attempted suicide in adolescents in Colombia, and its associated epidemiological factors from 2016 to 2019. Method: quantitative, observational, descriptive, and ecological study. The sample was extracted from the database of the Integrated Social Protection Information System, by identifying cases of attempted suicide for ages in the range from 12 to 17 years old, calculated for a prevalence estimate based on a total population of 32,076. Univariate and bivariate analysis of the variables of interest was performed. Results: suicide attempts occurred more frequently in females (n: 24,619; 76.7%), of subsidized regime (n: 17,960; 56%); and being in psychiatric centers is the most frequent vulnerability condition (n: 676; 2.11%). Living in the capital city is a risk factor for attempted suicide (OR: 1.423; 95% CI: 1.385 to 1.462), while being male is a protective factor (OR: 0.290; 95% CI: 0.283 a 0.298). Conclusion: suicide attempts are a subject of interest in Public Health due to their prevalence and impact on the family and social environment. The Nursing professional is competent in the identification, treatment, and prevention of this phenomenon. Resumen Objetivo: caracterizar el comportamiento del intento de suicidio en adolescentes en Colombia y sus factores epidemiológicos asociados en el período entre 2016 y 2019. Método: estudio cuantitativo, de tipo observacional, descriptivo y ecológico. La muestra se obtuvo en la base de datos del Sistema Integrado de Información de la Protección Social, mediante la identificación de casos de intento de suicidio para edades entre los 12 y 17 años, calculado para una estimación de prevalencia a partir de una población total de 32.076. Se realizó análisis univariado y bivariado de las variables de interés. Resultados: el intento de suicidio se presenta con mayor frecuencia en mujeres (n: 24.619; 76,7%), de régimen subsidiado (n: 17.960; 56%); y la condición de vulnerabilidad más frecuente es estar en centros psiquiátricos (n: 676; 2,11%). El vivir en la cabecera municipal es un factor de riesgo para el intento de suicidio (OR: 1,423; IC95%: 1,385 a 1,462) y ser hombre es factor protector (OR: 0,290; IC 95%: 0,283 a 0,298). Conclusión: el intento suicida significa un tema de interés en Salud Pública por su prevalencia e impacto en el ámbito familiar y social, y el profesional de Enfermería posee competencia para la identificación, tratamiento y prevención de este fenómeno. Resumo Objetivo: caracterizar o comportamento da tentativa de suicídio em adolescentes na Colômbia e seus fatores epidemiológicos relacionados no período entre 2016 e 2019. Método: estudo quantitativo, observacional, descritivo e ecológico. A amostra foi obtida a partir do banco de dados do Sistema Integrado de Informação de Proteção Social, por meio da identificação de casos de tentativa de suicídio entre 12 e 17 anos, calculado para uma estimativa de prevalência de uma população total de 32.076. Foram realizadas análises univariadas e bivariadas das variáveis de interesse. Resultados: a tentativa de suicídio ocorre com maior frequência em mulheres (n: 24.619; 76,7%), de regime subsidiado (n: 17.960; 56%); e a condição de vulnerabilidade mais frequente é estar em centros psiquiátricos (n: 676; 2,11%). Morar na sede municipal é fator de risco para tentativas de suicídio (OR: 1,423; IC95%: 1,385 a 1,462) e ser do sexo masculino é fator de proteção (OR: 0,290; IC95%: 0,283 a 0,298). Conclusão: a tentativa de suicídio é um tema de interesse da Saúde Pública devido à sua prevalência e impacto no meio familiar e social, e o profissional de Enfermagem tem competência para identificar, tratar e prevenir esse fenômeno.
ADIPOQ single nucleotide polymorphisms and breast cancer in northeastern Mexican women
Background Adiponectin gene ( ADIPOQ ) polymorphisms have been shown to affect adiponectin serum concentration and some have been associated with breast cancer (BC) risk. The aims of this study were to describe the frequency of single nucleotide polymorphisms (SNPs) of ADIPOQ in Mexican women with BC and to determine if they show an association with it. Methods DNA samples from 397 patients and 355 controls were tested for the ADIPOQ gene SNPs: rs2241766 (GT) and rs1501299 (GT) by TaqMan allelic discrimination assay. Hardy–Weinberg equilibrium (HWE) was tested. Multiple SNP inheritance models adjusted by age and body mass index (BMI) were examined for the SNP rs1501299. Results We found that in the frequency analysis of rs1501299 without adjusting the BMI and age, the genotype distribution had a statistically significant difference ( P  = 0.003). The T allele was associated with a BC risk (OR, 1.99; 95% CI 1.13–3.51, TT vs. GG; OR, 1.53; 95% CI 1.12–2.09, GT vs. GG). The SNP rs2241766 was in HW disequilibrium in controls. In conclusion, the rs1501299 polymorphism is associated with a BC risk. Conclusions Identification of the genotype of these polymorphisms in patients with BC can contribute to integrate the risk profile in both patients and their relatives as part of a comprehensive approach and increasingly more personalized medicine.
Development and evaluation of the psychometric properties of a digital questionnaire for the evaluation of perinatal psychosocial needs
Background If the purpose of maternal education is for women to take control of their own health and that of their family in the process, it is essential to have a simple instrument that allows them to self-assess, globally, how prepared they are to face future childbirth and maternity. As there is nothing similar in our area, the objective of this study was to design a complete, specific measurement questionnaire, with good metric quality and in digital format, for the assessment of perinatal psychosocial needs. Methods A cross-sectional study was carried out, to evaluate the psychometric properties of a digital measurement questionnaire. The questionnaire was developed in 4 steps following the recommendations of the International Test Commission. The participants were 263 pregnant women who were recruited in primary health care appointments in the Basque Healthcare Service (Osakidetza); they completed the newly created questionnaire and all the test selected as gold standard. Their mean age was 33.55 (SD = 4.73). The analysis of the psychometric characteristics was based on mixed expert judgment procedures (focus group of healthcare professionals, item assessment questionnaire and interviews with users) and quantitative procedures (EFA, CFA, association with the gold standard and classification agreement index, ordinal alpha and McDonald's omega). Results The final version of the questionnaire was made up of 55 items that evaluate 8 aspects related to perinatal psychosocial well-being (anxious-depressive symptoms, pregnancy acceptance, partner support, coping, internal locus of control, childbirth self-efficacy, perception of childbirth as a medicalized event, and fear of childbirth). Various tests were made of the validity and reliability of the scores, providing metric guarantees for their use in our context. Conclusions The use of this complete, quick-to-use tool with good psychometric properties will allow pregnant women to take stock of their situation, assess whether they have the necessary resources in the psychological and social sphere, and work together with midwives and other health professionals in the areas that are lacking.