Epigenetic alterations are already being incorporated as robust biomarkers for prediction of cancer risk. Despite this success, validation in specific populations with different genetic backgrounds ...and variable lifestyle and environmental exposures is necessary. In this paper, we investigate the potential of blood DNA methylation as a non‐invasive test for detection of sporadic breast cancer biomarker in the Latin American population.
Human diversity is one of the main pitfalls in the development of robust worldwide biomarkers in oncology. Epigenetic variability across human populations is associated with different genetic backgrounds, as well as variable lifestyles and environmental exposures, each of which should be investigated. To identify potential non‐invasive biomarkers of sporadic breast cancer in the Uruguayan population, we studied genome‐wide DNA methylation using Illumina methylation arrays in leukocytes of 22 women with sporadic breast cancer and 10 healthy women in a case–control study. We described a panel of 38 differentially methylated CpG positions that was able to cluster breast cancer patients (BCP) and controls, and that also recapitulated methylation differences in 12 primary breast tumors and their matched normal breast tissue. Moving forward, we simplified the detection method to improve its applicability in a clinical setting and used an independent well‐characterized cohort of 80 leukocyte DNA samples from BCP and 80 healthy controls to validate methylation results at specific cancer‐related genes. Our investigations identified methylation at CYFIP1 as a novel epigenetic biomarker candidate for sporadic breast cancer in the Uruguayan population. These results provide a proof‐of‐concept for the design of larger studies aimed at validating biomarker panels for the Latin American population.
Research suggests there may be a genetic influence on the likelihood of becoming tanning dependent (TD). The way in which mothers regulate their children's sun exposure may be affected by being TD. ...We investigated the associations between single nucleotide polymorphisms (SNPs) related to being TD and early sun exposure.
Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used. Associations between 17 TD related SNPs in children and their mothers and 10 sun exposure variables in children (assessed via questionnaire at age 8) were analyzed in logistic and ordinal logistic regressions. Analyses were adjusted for principal components of population structure and age (at time of questionnaire response). Models with additional adjustment for maternal or offspring genotypes were also tested. Secondary analyses included adjustment for sex and skin pigmentation.
Among ALSPAC children, the rs29132 SNP in the Vesicle-associated membrane protein-associated protein A (VAPA) gene was associated with five sun exposure variables whilst the rs650662 SNP in the Opioid Receptor Mu 1 (OPRM1) gene was associated with three. The remaining SNPs did not show associations beyond what was expected by chance. After Bonferroni correction one SNP in the children was associated with an increased likelihood of using sun cream whilst in the sun at 8 years old (rs60050811 in the Spermatogenesis and Centriole Associated 1 (SPATC1) gene, OR per C allele = 1.34, 95% CI 1.11-1.62, p = .003). In the mothers, rs650662 in OPRM1 was associated with the use of a lower factor of sun cream in their children, (OR per A allele = 0.89, 95% CI 0.82-0.96, p = .002). Whilst rs2073478 in the Aldehyde Dehydrogenase 1 Family Member B1 (ALDH1B1) gene was associated with a reduced odds of their child using a sun block or cream with a 4 star rating (OR per T allele = 0.68, 95% CI 0.53-0.88, p = .003). Similar but weaker associations were observed for the main findings in the secondary analyses.
We found weak evidence to suggest that genes previously associated with TD are associated with sun exposure in children of European ancestry from southwest England.
Prostate cancer is a common complex disease that disproportionately affects men of African descent. Recently, several different common variants on chromosome 8q24 have been shown to be associated ...with prostate cancer in multiple studies and ethnic groups. The objective of this study was to confirm the association of 8q24 markers with prostate cancer in African Americans. We genotyped 24 markers along 8q24 and 80 unlinked ancestry informative markers in a hospital-based case-control sample of 1057 African American men (490 prostate cancer cases and 567 controls). Association analyses of 8q24 markers with prostate cancer risk were adjusted for both global and local 8q24 admixture stratification using estimates from ancestry informative markers. We report that rs7008482, which maps to the 8q24.13 region, is an additional independent prostate cancer risk variant (P = 5 x 10(-4)), and we also replicate the association of rs16901979 with prostate cancer (P = 0.002). Other published risk variants in the region such as rs1447295 and rs6983267 showed a similar direction and magnitude of effect, but were not significant in our population. Both rs7008482 and rs16901979 independently predicted risk and remained significant (P < 0.001) after controlling for each other. Our data combined with additional replications of 8q24 markers provide compelling support for multiple regions of risk for prostate cancer on 8q24.
Hypercalcemia is a rare metabolic disorder in the pediatric population, with several differential diagnoses that resemble hematologic malignancies. In cases of severe hypercalcemia, therapeutic ...strategies other than hyperhydration, such as the use of bisphosphonates, have been described.
We present the case of a previously healthy 12-year-old boy who was admitted to the emergency department due to fatigue, hypo-responsiveness, and progressively worsening poor appetite for the previous 19 days. Initial laboratory tests revealed severe hypercalcemia (total calcium: 19 mg/dl), hyperphosphatemia, elevated creatinine, and hyperuricemia. Management with hyperhydration and xanthine oxidase inhibitor (allopurinol) was provided. The patient was transferred to the pediatric intensive care unit where treatment with furosemide, systemic corticosteroid, and zoledronic acid was started. Metabolic, infectious, renal, and endocrinological causes were excluded. Follow-up paraclinical studies showed a progressive hematologic involvement with heterogeneous hypochromic microcytic anemia, thrombocytopenia, and elevated lactic dehydrogenase. Bone marrow aspiration and biopsy were performed, which confirmed the diagnosis of B-precursor acute lymphoblastic leukemia. Hypercalcemia was resolved 72 h after the application of bisphosphonates.
Hypercalcemia as an oncological metabolic emergency in the onset of acute lymphoblastic leukemia is uncommon in children. The use of intravenous bisphosphonates is an effective therapy in the early resolution of the condition. We present the case of a 12-year-old patient with malignant hypercalcemia who responded favorably to the use of a single dose of bisphosphonates.
To control for hidden population stratification in genetic-association studies, statistical methods that use marker genotype data to infer population structure have been proposed as a possible ...alternative to family-based designs. In principle, it is possible to infer population structure from associations between marker loci and from associations of markers with the trait, even when no information about the demographic background of the population is available. In a model in which the total population is formed by admixture between two or more subpopulations, confounding can be estimated and controlled. Current implementations of this approach have limitations, the most serious of which is that they do not allow for uncertainty in estimations of individual admixture proportions or for lack of identifiability of subpopulations in the model. We describe methods that overcome these limitations by a combination of Bayesian and classical approaches, and we demonstrate the methods by using data from three admixed populations—African American, African Caribbean, and Hispanic American—in which there is extreme confounding of trait-genotype associations because the trait under study (skin pigmentation) varies with admixture proportions. In these data sets, as many as one-third of marker loci show crude associations with the trait. Control for confounding by population stratification eliminates these associations, except at loci that are linked to candidate genes for the trait. With only 32 markers informative for ancestry, the efficiency of the analysis is ∼70%. These methods can deal with both confounding and selection bias in genetic-association studies, making family-based designs unnecessary.
Objetivo: Explorar la construcción de percepciones sobre la Interrupción Voluntaria del Embarazo en estudiantes de pregrado en Enfermería de la Universidad Surcolombiana. Materiales y métodos: ...Estudio cualitativo, con enfoque fenomenológico, de alcance exploratorio- descriptivo. Se aplicó entrevista semiestructurada a un grupo focal de 10 estudiantes, se transcribió en procesador de palabras y se codificó con ayuda de ATLAS ti versión 6. Resultados: La actual percepción del estudiante sobre la Interrupción Voluntaria del Embarazo está permeado no solo por los conceptos adquiridos sobre el tema durante la formación universitaria sino también por aquellos adquiridos previo al pregrado. Sin embargo, la divergencia de opiniones y poco fundamentadas derivadas del contexto social, familiar, religioso, y académico influyeron en que el enfermero en formación sienta conflicto interno para sentar postura personal frente al tema, haciéndolo muchas veces susceptible a la influencia de ideas y posturas sobre la Interrupción Voluntaria del Embarazo impartidas vehementemente por algunos docentes. Conclusión: La construcción de percepciones en los estudiantes son resultado de la conjugación del contexto en el que viven y se desarrollan previo al ingreso universitario y del contexto académico ligado a la formación de pregrado, en donde los estrechos conocimientos recibidos con diversidad de posturas y de enfoques generan fricción de ideas e influyen negativamente en el desempeño del futuro profesional caracterizado por inseguridad, incertidumbre y preocupación, profundizando las barreras para que la mujer acceda al libre derecho de la Interrupción Voluntaria del Embarazombarazo.
The goal of the present study was to perform a cross-cultural adaptation and clinical validation of the Preschool Confusion Assessment Method for the Intensive Care Unit-Spanish (psCAM-ICU-S) for its ...clinical use in the Colombian Population.
We designed a Cross-cultural adaptation study followed by a cross-sectional validation study at a Single-center Pediatric Intensive Care Unit (PICU) at a University Hospital in Bogotá, Colombia. The study population was children aged from 6 months to 5 years and 11 months who had been treated in the PICU with a Richmond sedation-agitation scale score of-3 or higher. A three-phase study was carried out. The first phase comprised the application of psychometric tests on the tool. In the second phase, the psCAM-ICU-S was applied to the target population. Patients were evaluated by a nurse and a pediatric intensivist using the psCAM-ICU-S; additionally, a child psychiatrist evaluated each patient using the
criteria; the psychiatrist evaluation was chosen as the gold standard for the diagnosis of delirium. In the third phase, an evaluation of the tool's effectiveness was carried out by using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios. Interrater agreement was also assessed by using the Fleiss' kappa.
Psychometric tests established the instrument's reliability and consistency as well as the clarity of its items. A total of 31 patients were evaluated. On average, the instrument presented a sensitivity of 93.3%, specificity of 94.8%, PPV 78%, NPV 99%, a positive likelihood ratio of 19.93, and a negative ratio of 0.07. The prevalence of delirium was 16.1% by the child psychiatrist and 25.8% using de psCAM-ICU-S. We confirmed high Interrater agreement, Kappa index (0.672-0.902).
The psCAM-ICU-S was a valid and reliable instrument for the diagnosis of delirium in critically ill pediatric patients.
Introduction
Upper limb movements are affected frequently by brain ischemia (BI). Mechanisms involved in recovery and compensatory movements have developed several studies. However, less attention is ...given to skeletal muscles, where neuromuscular junction (NMJ) has an important role on muscle tropism and functional performance.
Methods
Animals were divided into two groups: control (C) and BI. Then, animals were skilled to perform single‐pellet retrieval task, following these procedures: habituation, shaping, and single‐pellet retrieval task. BI was induced using stereotaxic surgery in order to apply endothelin‐1 in motor cortex, representative of movements of dominant paw. Reaching task performance was evaluated by single‐pellet retrieval task 1 day before BI induction, 4 and 15 days after BI induction. After that, biceps, triceps, fingers flexor, and extensor muscles were extracted. NMJ was assessed in morphometric characteristics (total area, total perimeter, and feret). Muscle fiber cross‐sectional area and connective tissue percentage were also evaluated for characterization. Student's t test was used for comparisons between C and BI groups. Tau Kendall's correlation was applied among variables from BI group.
Results
An increase in all NMJ morphometric parameters, as well as increase of atrophy and fibrosis in BI group compared with C. There was a high level of direct correlation between mean values of NMJ morphometry with percentage of success in reaching task in BI group.
Conclusion
Brain ischemia‐induced NMJ compensatory expansion, muscle atrophy, and fibrosis in forelimb muscles that are related to reaching performance.
Reaching task performance. Brain ischemia and his effects in Reaching task.
Among Latin American women, breast cancer incidences vary across populations. Uruguay and Argentina have the highest rates in South America, which are mainly attributed to strong, genetic European ...contributions. Most genetic variants associated with breast cancer were described in European populations. However, the vast majority of genetic contributors to breast cancer risk remain unknown. Here, we report the results of a candidate gene association study of sporadic breast cancer in 176 cases and 183 controls in the Uruguayan population. We analyzed 141 variants from 98 loci that have been associated with overall breast cancer risk in European populations. We found weak evidence for the association of risk variants rs294174 (ESR1), rs16886165 (MAP3K1), rs2214681 (CNTNAP2), rs4237855 (VDR), rs9594579 (RANKL), rs8183919 (PTGIS), rs2981582 (FGFR2), and rs1799950 (BRCA1) with sporadic breast cancer. These results provide useful insight into the genetic susceptibility to sporadic breast cancer in the Uruguayan population and support the use of genetic risk scores for individualized screening and prevention.
The relationship between mitochondrial DNA (mtDNA) and breast cancer has been frequently examined, particularly in European populations. However, studies reporting associations between mtDNA ...haplogroups and breast cancer risk have had a few shortcomings including small sample sizes, failure to account for population stratification and performing inadequate statistical tests. In this study we investigated the association of mtDNA haplogroups of European origin with several breast cancer risk factors in mothers and children of the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort that enrolled over 14,000 pregnant women in the Southwest region of the UK. Risk factor data were obtained from questionnaires, clinic visits and blood measurements. Information on over 40 independent breast cancer risk factor-related variables was available for up to 7781 mothers and children with mtDNA haplogroup data in ALSPAC. Linear and logistic regression models adjusted for age, sex and population stratification principal components were evaluated. After correction for multiple testing we found no evidence of association of European mtDNA haplogroups with any of the breast cancer risk factors analysed. Mitochondrial DNA haplogroups are unlikely to underlie susceptibility to breast cancer that occurs via the risk factors examined in this study of a population of European ancestry.
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