Prevalence of karyotype alterations in couples with recurrent pregnancy loss in a tertiary center in Brazil.

Objective: To assess the prevalence and type of chromosomal abnormalities in Brazilian couples with recurrent pregnancy loss (RPL) and compare the clinical characteristics of couples with and without chromosome abnormalities. Methods: We assessed the medical records of 127 couples with a history of two or more miscarriages, referred to a tertiary academic hospital in Belo Horizonte, Brazil, from January 2014 to May 2023. Karyotype was generated from peripheral blood lymphocyte cultures, and cytogenetic analysis was performed according to standard protocols by heat-denatured Giemsa (RHG) banding. Results: Abnormal karyotypes were detected in 10 couples (7.8%). The prevalence of chromosomal abnormalities was higher among females (6.3%) compared to males (2.0%), but this difference was not statistically significant (p=0.192). The mean number of miscarriages was. 3.3 ± 1.1 in couples with chromosome abnormalities and 3.1 ± 1.5 in couples without chromosome abnormalities (p=0.681). Numerical chromosomal anomalies (6 cases) were more frequent than structural anomalies. Four women presented low-grade Turner mosaicism. No differences were found between couples with and without karyotype alterations, except for maternal age, which was higher in the group with chromosome alterations. Conclusion: The prevalence of parental chromosomal alterations in our study was higher than in most series described in the literature and was associated with increased maternal age. These findings suggest that karyotyping should be part of the investigation for Brazilian couples with RPL, as identifying the genetic etiology may have implications for subsequent pregnancies.

Characterizing Chemotherapy/Radiotherapy-Induced Genome Chaos in Hodgkin's Lymphoma Patients Using M-FISH.

Hodgkin lymphoma (HL) is one of the most common lymphomas, with an incidence of 3 per 100,000 persons. Current treatment uses a cocktail of genotoxic agents, including adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), along with or without radiotherapy. This treatment regimen has proved to be efficient in killing cancer cells, resulting in HL patients having a survival rate of >90% cancer-free survival at five years. However, this therapy does not have a specific cell target, and it can induce damage in the genome of non-cancerous cells. Previous studies have shown that HL survivors often exhibit karyotypes characterized by complex chromosomal abnormalities that are difficult to analyze by conventional banding. Multicolor fluorescence in situ hybridization (M-FISH) is a powerful tool to analyze complex karyotypes; we used M-FISH to investigate the presence of chromosomal damage in peripheral blood lymphocytes from five healthy individuals and five HL patients before, during, and one year after anti-cancer treatment. Our results show that this anti-cancer treatment-induced genomic chaos that persists in the hematopoietic stem cells from HL patients one year after finishing therapy. This chromosomal instability may play a role in the occurrence of second primary cancers that are observed in 10% of HL survivors. This chapter will describe a protocol for utilizing M-FISH to study treatment-induced genome chaos in Hodgkin's lymphoma (HL) patients, following a brief discussion.

Prevalence of karyotype alterations in couples with recurrent pregnancy loss in a tertiary center in Brazil

Abstract Objective To assess the prevalence and type of chromosomal abnormalities in Brazilian couples with recurrent pregnancy loss (RPL) and compare the clinical characteristics of couples with and without chromosome abnormalities. Methods We assessed the medical records of 127 couples with a history of two or more miscarriages, referred to a tertiary academic hospital in Belo Horizonte, Brazil, from January 2014 to May 2023. Karyotype was generated from peripheral blood lymphocyte cultures, and cytogenetic analysis was performed according to standard protocols by heat-denatured Giemsa (RHG) banding. Results Abnormal karyotypes were detected in 10 couples (7.8%). The prevalence of chromosomal abnormalities was higher among females (6.3%) compared to males (2.0%), but this difference was not statistically significant (p=0.192). The mean number of miscarriages was. 3.3 ± 1.1 in couples with chromosome abnormalities and 3.1 ± 1.5 in couples without chromosome abnormalities (p=0.681). Numerical chromosomal anomalies (6 cases) were more frequent than structural anomalies. Four women presented low-grade Turner mosaicism. No differences were found between couples with and without karyotype alterations, except for maternal age, which was higher in the group with chromosome alterations. Conclusion The prevalence of parental chromosomal alterations in our study was higher than in most series described in the literature and was associated with increased maternal age. These findings suggest that karyotyping should be part of the investigation for Brazilian couples with RPL, as identifying the genetic etiology may have implications for subsequent pregnancies.

Prevalence and Prognosis of Secondary Genetic Aberrations Among Patients With Core Binding Factor Acute Myeloid Leukemia: A Mitelman Database Analysis.

Background: Core binding factor acute myeloid leukemia (CBF-AML) comprises t(8;21) and inv(16) and usually has a favorable prognosis. However, a wide spectrum of secondary genetic aberrations has been shown to be associated with worse outcomes with respect to overall survival (OS) and relapse. We aimed to identify secondary molecular and chromosomal aberrations within each group of CBF-AML, i.e., t(8;21) and inv(16), and to evaluate their prognosis with OS. Methods: Using the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer, we analyzed 193 cases of CBF-AML reported between 2011 and 2021. We conducted a survival analysis to determine the 5-year OS, and we conducted univariate and multivariate Cox regression to identify independent genetic factors related to OS. Results: Among the 193 cases with CBF-AML, structural and numerical chromosome rearrangements were 25.9% and 40.9%, respectively, and secondary genetic mutations were 54.9%. The 5-year OS for the presence of del(7) and trisomy 22 was significantly worse. NRAS mutations had a worse 5-year OS in the t(8;21) group in the univariate analysis but showed no significant difference in the multivariate analysis. Conclusions: CBF-AML has heterogeneous cytogenetic characteristics but no difference in the 5-year OS between the inv(16) and t(8;21) groups. Finally, the presence of del(7), trisomy 22 and NRAS mutations showed a potential prognostic impact in CBF-AML patients. Secondary genetic findings may need to be identified to determine its association to a worse prognosis, and in the future develop better targeted therapies in patients with CBF-AML.

Live birth after single euploid frozen embryo transfer in a 39-year-old woman with high-grade mosaic Turner syndrome.

OBJECTIVE: To describe the reproductive and obstetric outcomes of an intracytoplasmic sperm injection cycle with preimplantation genetic testing for aneuploidy in an advanced reproductive-age woman with high-grade mosaic Turner syndrome. METHODS: Case report of a 39-year-old woman diagnosed with mosaic Turner Syndrome 45,X[90]/46,XX[10] karyotype who underwent in vitro fertilization treatment with blastocyst trophectoderm biopsy for preimplantation genetic testing using next-generation sequencing. RESULT(S): Two of the four blastocysts biopsied were euploid. The patient achieved ongoing pregnancy after the first single euploid frozen embryo transfer, followed by the birth of a healthy child. CONCLUSION: Autologous intracytoplasmic sperm injection cycles can be considered in a select group of advanced reproductive-age women diagnosed with high-grade mosaic Turner syndrome.

Survival analysis of transplant-eligible newly-diagnosed multiple myeloma patients harboring t(4;14), t(14;16), and/or del(17p) in the real-world setting.

Cytogenetic abnormalities (CA) such as t(4;14), t(14;16), and del(17p), are associated with a poor prognosis in Multiple Myeloma (MM) patients. However, there is scarce information regarding the Latin-American population. This study aims to analyze the impact of t(4;14), t(14;16), and del(17p) on the progression-free survival (PFS) and overall survival (OS) of transplant-eligible newly-diagnosed MM (NDMM) patients in Latin America. Retrospective survival analysis based on the Grupo de Estudio Latinoamericano de MM (GELAMM) registry, including all adult patients with NDMM harboring CA t(4;14), t(14;16), and/or del(17p). Fifty-nine patients were included; the median age was 57 years, 55.9% males, 22% ISS-I, 25.4% ISS-II, and 47.5% ISS-III. The majority (89.8%) had one alteration, whereas 10.2% had del(17p) and t(4;14). The frequencies of CA were del(17p) in 61.0%, t(4;14) in 25.4%, and t(14;16) in 3,4%. Autologous stem cell transplantation was performed in 36 cases, 20 patients did not use this consolidative strategy, and this data was missed in three cases. Five-year OS for the entire cohort was 60.8% and 5-year PFS was 28.1%. Bortezomib-based induction regimen (BBR) (p=0.029), consolidation with ASCT (p<0.001), and maintenance therapy (p=0.004) were associated with an improved 5-year OS. In the multivariate analysis, ASCT was the only variable with a positive impact on OS (HR 0.11, 95% CI 0.033 to 0.34, p<0.001). The median PFS presented a non-statistically significant benefit in BBR, ASCT, and maintenance therapy groups. BBR induction, ASCT, and maintenance therapy were associated with improved OS in high-risk NDMM patients.

Phyto-genotoxicity assessment of different associations between sludges from Water and Sewage Treatment Plants, before and after the bioremediation process.

Water Treatment Plants (WTP) and Sewage Treatment Plants (STP) generate residues known as sludge (WS and SS, respectively). SS and WS present some positive characteristics for reuse in agriculture. The aim of the present study was to evaluate, using the Allium cepa test, the effectiveness of the bioremediation process in the detoxification of SS and WS sludges. In this study, the phytotoxic, cytotoxic, genotoxic, and mutagenic potentials of pure sludge samples (WS and SS) were evaluated, as well as the association of these two sludges with soil (S), before and after the bioremediation process. In the T0 period (before undergoing bioremediation), the SS, SS + S, and SS + WS samples totally inhibited the germination of A. cepa, proving the high phytotoxic potential of these samples. For the T1 period (after 6 months of bioremediation), phytotoxicity was observed for the SS, SS + S, SS + WS, and SS + WS + S samples, but there was not a complete inhibition of germination and radicles growth, allowing the evaluation of the other parameters (cytogenotoxic and mutagenic potential). No cytotoxicity was observed for any sample, both in T0 and T1. As for the genotoxicity parameter, a significant result was observed for the pure WS sample in T0 and for all samples in T1, when compared to NC. The genotoxic alteration most found in meristematic cells exposed to treatments was of binucleated cells. Mutagenic potential was also observed for samples of WS and WS + S in T0. From this study, we can conclude that, after six months of bioremediation, despite the SS phytotoxicity being reduced, all samples were genotoxic to the A. cepa organism test.

Frecuencia de discapacidad intelectual de etiología genética debida a rearreglos cromosómicos crípticos / Frequency of intellectual disability of genetic etiology due to cryptic chromosome arrangements

Introducción: la discapacidad intelectual se considera un problema de salud pública global, la prevalencia oscila entre el 1% al 3% de la población mundial, cifra de la que se estima el origen genético estaría representado por el 5-7% de síndromes subteloméricos. El objetivo de la presente investigación fue determinar la frecuencia de discapacidad intelectual de etiología genética debida a rearreglos cromosómicos crípticos en 69 pacientes del IDAI. Material y Métodos. El estudio descriptivo de corte transversal se realizó en el Instituto de Genética en 69 pacientes con discapacidad intelectual de 5 a 18 años del Instituto de Adaptación Infantil (IDAI). El estudio fue dividido en tres etapas, la primera consistió en la elaboración de la historia clínica genética, seguidamente, se realizó el estudio de cariotipo en sangre periférica a todos los pacientes, finalmente, con la sospecha diagnóstica se realizó citogenética molecular a nueve de ellos, empleando una sonda locus específica. Resultados. Se encontró 43.48% de rearreglos cromosómicos, 24.67% correspondió a síndromes crípticos, de estos el 7.25% respondió a síndromes subteloméricos. Se observó mayor afectación en la población masculina: 45 hombres (65%) y 24 mujeres (35%), obteniendo una razón de sexo de 1.88 a favor del sexo masculino. Conclusiones. Se debe considerar la causa genética en toda discapacidad intelectual idiopática, sobre todo la debida a rearreglos cromosómicos crípticos . Para confirmar la sospecha diagnóstica se emplean técnicas de citogenética clásica y de hibridación fluorescente in situ , de esta manera se llega a un diagnóstico más preciso para coadyuvar en el asesoramiento genético del paciente.

Introduction. Intellectual disability is considered a global public health problem, the prevalence ranges from 1% to 3% of the world population, a figure whose genetic origin is estimated to be represented by 5-7% of subtelomeric syndromes. The objective of this research was to determine the frequency of intellectual disability of genetic etiology due to cryptic chromosomal rearrangements in 69 patients of IDAI. Material and methods. The descriptive cross-sectional study was carried out at the Institute of Genetics in 69 patients with intellectual disabilities from 5 to 18 years of age from the Institute for Child Adaptation (IDAI). The study was divided into three stages, the first consisted of preparing the genetic clinical history, then peripheral blood karyotyping was performed on all patients, finally, with suspected diagnosis, molecular cytogenetics was performed on nine of them, using a locus-specific probe. Results. 43.48% of chromosomal rearrangements were found, 24.67% corresponded to cryptic syndromes, of these 7.25% responded to subtelomeric syndromes. Greater involvement was observed in the male population: 45 men (65%) and 24 women (35%), obtaining a sex ratio of 1.88 in favor of the male sex. Conclusions. The genetic cause must be considered in all idiopathic intellectual disability, especially that due to cryptic chromosomal rearrangements. To confirm the diagnostic suspicion, classical cytogenetics and fluorescent in situ hybridization techniques are used, thus reaching a more precise diagnosis to assist in the genetic counseling of the patient.

Estudios citogenéticos en pacientes con fallas reproductivas. Pinar del Río, 2015-2020 / Cytogenetic studies in patients with reproductive failure. Pinar del Río, 2015-2020

RESUMEN Introducción: el estudio citogenético en linfocitos de sangre periférica es una herramienta muy utilizada para el diagnóstico de diferentes cromosomopatías de origen genético en pacientes con fallas reproductivas. Objetivo: describir los resultados del diagnóstico citogenético postnatal realizado a los pacientes con fallas reproductivas. Métodos: se efectuó un estudio descriptivo, retrospectivo en la provincia de Pinar del Río de enero del año 2015 hasta diciembre del 2020, a partir de los resultados del diagnóstico cromosómico en sangre periférica en pacientes que fueron remitidos al centro provincial de genética médica por fallas reproductivas, los cuales se clasificaron en tres grupos de acuerdo con el criterio de indicación. Resultados: en el período analizado, se diagnosticaron 12 casos con anomalías cromosómicas, de los cuales el 58,3 % correspondieron a aneuploidías cromosómicas numéricas, el 25 % a mosaicos cromosómicos y el 17 % con aberraciones cromosómicas estructurales. Resaltar que el 9 % de los casos diagnosticados presentaban variantes polimórficas, sobre todo del cromosoma 9. El aborto espontáneo fue el motivo de indicación más frecuente para el estudio citogenético. Conclusiones: es relevante la importancia del estudio citogenético en sangre periférica a las personas con fallas reproductivas, con el fin de establecer un diagnóstico certero, oportuno y brindar en el asesoramiento genético los elementos etiológicos para las opciones reproductivas futuras de estas parejas.

ABSTRACT Introduction: cytogenetic study in peripheral blood lymphocytes is a widely used tool for the diagnosis of different chromosomal pathologies of genetic origin in patients with reproductive failure. Objective: to describe the results of postnatal cytogenetic diagnosis in patients with reproductive failure. Methods: a descriptive, retrospective study was carried out in Pinar del Río province from January 2015 to December 2020, based on the results of chromosomal diagnosis in peripheral blood in patients who were referred to the provincial center of medical genetics for reproductive failures, which were classified into 3 groups according to the indication criteria. Results: in the analyzed period, 12 cases with chromosomal anomalies were diagnosed, where 58,3 % corresponded to numerical chromosomal aneuploidies, 25 % to chromosomal mosaics and 17 % to structural chromosomal aberrations. It should be pointed out that 9 % of the diagnosed cases presented polymorphic variants, especially of chromosome-9. Spontaneous abortion was the most frequent reason for indication for cytogenetic study. Conclusions: the importance of cytogenetic study in peripheral blood is relevant in people with reproductive failure, in order to establish an accurate and timely diagnosis and to provide genetic counseling with etiological elements for the future reproductive options of these couples.

Accuracy of the mid-trimester ultrasound scan in the detection of fetal congenital anomalies in a reference center in Northeastern Brazil.

OBJECTIVE: To assess the performance of a basic mid-trimester fetal ultrasound scan protocol for the diagnosis of congenital anomalies by calculating its accuracy, sensitivity, and specificity. METHODS: This longitudinal cohort study involved singleton pregnant women recruited at the mid-trimester fetal ultrasound scan through the postnatal evaluation of congenital anomalies. Pregnant women who underwent a routine mid-trimester ultrasound scan for fetal abnormalities at 20-24 weeks of gestation were enrolled in this study. After childbirth, we searched their medical records on gestational outcomes and neonatal examination records, as well as complementary medical examinations, to assess the ultrasound performance in diagnosing congenital malformations. RESULTS: We included 967 pregnant women in the study population, and prenatal ultrasound scans detected congenital abnormalities in 67 fetuses (6.9%). Among newborns, 54 (5.6%) were postnatally diagnosed with malformations. The overall sensitivity and specificity of the mid-trimester ultrasound scan for congenital malformation detection were 61.1% and 96.3%, respectively, with an accuracy of 94.3% (p < .05). CONCLUSION: The mid-trimester ultrasound scan had good accuracy in the detection of congenital malformations, although the overall sensitivity does not support it as the only screening test for anomalies throughout pregnancy.

Cytogenetic risk groups for childhood acute myeloid leukemia based on survival analysis in a cancer referral hospital from Perú / [Grupos de riesgo citogenético de leucemia mieloide aguda pediátrica a partir del análisis de supervivencia en un hospital de referencia para cáncer en Perú].

Introduction: Acute myeloid leukemia is a heterogeneous disorder characterized by immature myeloid cell proliferation. Cytogenetic analysis has revealed the presence of chromosomal aberrations important to patient prognosis. Objective: To determine cytogenetic risk groups of pediatric patients with acute myeloid leukemia according to overall survival. Materials and methods: In this cross-sectional observational study, the clinical records of pediatric patients diagnosed with de novo acute myeloid leukemia admitted to the Instituto Nacional de Enfermedades Neoplásicas between 2001 and 2011 with cytogenetic analysis of bone marrow were included. Cytogenetic risk groups were established according to the criteria of the Medical Research Council. Overall survival curves were generated with the Kaplan-Meier method and compared using the Mantel-Cox test and Cox regression with the software R, version 3.3.2. Results: A total of 130 patients were included, 68 males (52.3%) and 62 females (47.7%), most of them with subtype M2 (33%). The average age was 7.7 years (range: 0-15 years). Chromosomal aberrations were observed in 60.8% of the patients, the most frequent of which was the translocation t(8;21). According to the overall survival analysis, two cytogenetic risk groups were established: favorable and unfavorable. Conclusion: Two groups of cytogenetic risk were determined: high (or unfavorable) and standard (favorable).

Introducción. La leucemia mieloide aguda es una neoplasia heterogénea caracterizada por la proliferación de células mieloides inmaduras. El análisis citogenético ha revelado la presencia de aberraciones cromosómicas de importancia en el pronóstico del paciente. Objetivo. Determinar los grupos de riesgo citogenético de pacientes pediátricos con leucemia mieloide aguda a partir de la supervivencia global. Materiales y métodos. Se hizo un estudio observacional de corte transversal. Se incluyeron los registros clínicos de los pacientes pediátricos con diagnóstico de leucemia mieloide aguda de novo admitidos en el Instituto Nacional de Enfermedades Neoplásicas entre el 2001 y el 2011 y sometidos a análisis citogenético de médula ósea. Los grupos de riesgo citogenético se establecieron según los criterios del Medical Research Council. Las curvas de supervivencia global se elaboraron con el método de Kaplan-Meier y se compararon mediante la prueba de Mantel-Cox y una regresión de Cox, utilizando el programa R, versión 3.3.2. Resultados. Se incluyeron 130 pacientes, 68 varones (52,3 %) y 62 mujeres (47,7 %), mayoritariamente del subtipo M2 (33 %). La edad promedio fue de 7,7 (rango de 0 a 15 años). Se observaron aberraciones cromosómicas en el 60,8 % y la más frecuente fue la traslocación t(8;21). Según el análisis de supervivencia global, se observaron dos grupos de riesgo citogenético: favorable y desfavorable. Conclusión. Se determinaron dos grupos de riesgo citogenético: alto (o desfavorable) y estándar (o favorable).

Structural Chromosome Instability: Types, Origins, Consequences, and Therapeutic Opportunities.

Chromosomal instability (CIN) refers to an increased rate of acquisition of numerical and structural changes in chromosomes and is considered an enabling characteristic of tumors. Given its role as a facilitator of genomic changes, CIN is increasingly being considered as a possible therapeutic target, raising the question of which variables may convert CIN into an ally instead of an enemy during cancer treatment. This review discusses the origins of structural chromosome abnormalities and the cellular mechanisms that prevent and resolve them, as well as how different CIN phenotypes relate to each other. We discuss the possible fates of cells containing structural CIN, focusing on how a few cell duplication cycles suffice to induce profound CIN-mediated genome alterations. Because such alterations can promote tumor adaptation to treatment, we discuss currently proposed strategies to either avoid CIN or enhance CIN to a level that is no longer compatible with cell survival.

Grupos de riesgo citogenético de leucemia mieloide aguda pediátrica a partir del análisis de supervivencia en un hospital de referencia para cáncer en Perú / Cytogenetic risk groups for childhood acute myeloid leukemia based on survival analysis in a cancer referral hospital from Perú

Resumen | Introducción. La leucemia mieloide aguda es una neoplasia heterogénea caracterizada por la proliferación de células mieloides inmaduras. El análisis citogenético ha revelado la presencia de aberraciones cromosómicas de importancia en el pronóstico del paciente. Objetivo. Determinar los grupos de riesgo citogenético de pacientes pediátricos con leucemia mieloide aguda a partir de la supervivencia global. Materiales y métodos. Se hizo un estudio observacional de corte transversal. Se incluyeron los registros clínicos de los pacientes pediátricos con diagnóstico de leucemia mieloide aguda de novo admitidos en el Instituto Nacional de Enfermedades Neoplásicas entre el 2001 y el 2011 y sometidos a análisis citogenético de médula ósea. Los grupos de riesgo citogenético se establecieron según los criterios del Medical Research Council. Las curvas de supervivencia global se elaboraron con el método de Kaplan-Meier y se compararon mediante la prueba de Mantel-Cox y una regresión de Cox, utilizando el programa R, versión 3.3.2. Resultados. Se incluyeron 130 pacientes, 68 varones (52,3%) y 62 mujeres (47,7%), mayoritariamente del subtipo M2 (33%). La edad promedio fue de 7,7 (rango de 0 a 15 años). Se observaron aberraciones cromosómicas en el 60,8% y la más frecuente fue la traslocación t(8;21). Según el análisis de supervivencia global, se observaron dos grupos de riesgo citogenético: favorable y desfavorable. Conclusión. Se determinaron dos grupos de riesgo citogenético: alto (o desfavorable) y estándar (o favorable).

Abstract | Introduction: Acute myeloid leukemia is a heterogeneous disorder characterized by immature myeloid cell proliferation. Cytogenetic analysis has revealed the presence of chromosomal aberrations important to patient prognosis. Objective: To determine cytogenetic risk groups of pediatric patients with acute myeloid leukemia according to overall survival. Materials and methods: In this cross-sectional observational study, the clinical records of pediatric patients diagnosed with de novo acute myeloid leukemia admitted to the Instituto Nacional de Enfermedades Neoplásicas between 2001 and 2011 with cytogenetic analysis of bone marrow were included. Cytogenetic risk groups were established according to the criteria of the Medical Research Council. Overall survival curves were generated with the Kaplan-Meier method and compared using the Mantel-Cox test and Cox regression with the software R, version 3.3.2. Results: A total of 130 patients were included, 68 males (52.3%) and 62 females (47.7%), most of them with subtype M2 (33%). The average age was 7.7 years (range: 0-15 years). Chromosomal aberrations were observed in 60.8% of the patients, the most frequent of which was the translocation t(8;21). According to the overall survival analysis, two cytogenetic risk groups were established: favorable and unfavorable. Conclusion: Two groups of cytogenetic risk were determined: high (or unfavorable) and standard (favorable).

Caso Clínico: Lipoblastoma en un Lactante / Clinical Case: Lipoblastoma in an Infant

Introducción: El lipoblastoma es una neoplasia benigna de presentación infrecuente originada en el tejido adiposo, de presentación casi exclusiva en pacientes pediátricos antes de los tres años de edad, con predominio en el sexo masculino. Se localiza principalmente en las extremidades y tronco, como una tumoración indolora de crecimiento progresivo. El tratamiento de elección es quirúrgico y tiene pronóstico favorable. Las recidivas se presentan en los casos en los que la resección no pudo ser completa. Caso clínico: Lactante mujer de 7 meses de edad. Desde los tres meses de edadpresentó aumento progresivo del volumen de la extremidad inferior izquierda.Al examen físico se evidenciógran tumoraciónde 12 x 7 centímetrosque compromete la cara posterior del muslo izquierdo: Masa indolora y bien delimitada. Sin compromiso de la movilidad, sin edema de miembro. Taller diagnóstico: La Resonancia Magnética reportó unatumoración sólida de muslo izquierdo hiper-intensa en T1 y T2, hipo-intensa en STIR con septos finos en su interior, se extiende desde el musculo abductor magno del bíceps femoral y mide 11.2 x 7.9 x 8.4 cm en sus ejes longitudinal, anteroposterior y transversal respectivamente, desplazando y comprimiendo a los músculos semitendinoso, semimembranoso y gracilis. La paciente fue sometida a escisión completa y amplia de la masa, mediante abordaje posterolateral. Desenlace:Patología reportóun tumor constituido por tejido adiposo con tejido mixoide,sin atipia nuclear; se evidencia infiltración parcial del musculo esquelético adyacente, sin afectación de piel, sin necrosisy bordes quirúrgicos negativos para neoplasia. Inmunohistoquímica con marcador de proliferación celular KI-67 resultado positivo de 1%, y estudio de MDM2 (inhibidor de la activación transcripcional de p53) negativo; hallazgos compatibles con lipoblastoma. El estudio citogenético no fue realizado. Evolución: La paciente fue dada de alta al cuarto día post-operatorio sin complicaciones. Con una recuperación completa, en el quinto mes de seguimiento se realizónuevo estudio de resonancia magnética en la cual no se visualizan imágenes que sugieran tumor residual ni recidiva tumoral. Conclusión: El lipoblastoma debe ser tomada en cuenta como diagnóstico diferencial en niños con tumores de partes blandas, su tratamiento es eminentemente quirúrgico con un buen pronóstico si la extirpación es completa

Introduction: Lipoblastoma is an infrequent benign neoplasm originating in adipose tissue, presenting almost exclusively in pediatric patients before the age of three years, predominantly in males. It is located mainly on the limbs and trunk, as a painless, progressively growing tumor. The treatment of choice is surgical and has a favorable prognosis. Recurrences occur in cases in which the resection could not be complete. Clinical case: 7-month-old female infant. From the age of three months, he presented a progressive increase in the volume of the left lower limb. Physical examination revealed a large mass measuring 12 x 7 centimeters that involves the posterior aspect of the left thigh: a painless and well-defined mass. No compromise of mobility, no limb edema. Diagnostic workshop: Magnetic resonance imaging reported a hyper-intense solid tumor of the left thigh in T1 and T2, hypo-intense in STIR with fine septa inside it, extending from the abductor magnus muscle of the biceps femoris and measuring 11.2 x 7.9 x 8.4 cm in its longitudinal, anteroposterior and transverse axes respectively, displacing and compressing the semitendinosus, semimembranosus and gracilis muscles. The patient underwent a complete and wide excision of the mass using a posterolateral approach. Outcome: Pathology reported a tumor made up of adipose tissue with myxoid tissue, without nuclear atypia; partial infiltration of the adjacent skeletal muscle is evidenced, without skin involvement, without necrosis and negative surgical margins for neoplasia. Immunohistochemistry with a cell proliferation marker KI-67, a positive result of 1%, and a negative MDM2 study (inhibitor of transcriptional activation of p53); findings consistent with lipoblastoma. The cytogenetic study was not performed. Evolution:The patient was discharged on the fourth postoperative day without complications. With a complete recovery, in the fifth month of follow-up a new magnetic resonance study was performed in which no images that suggest residual tumor or tumor recurrence are visualized Conclusion: Lipoblastoma should be taken into account as a differential diagnosis in children with soft tissue tumors, its treatment is eminently surgicalwith a good prognosis if the removal is complete

The correlation between micronuclei count and smoking behavior: a hospital-based study / Correlación entre recuento de micronúcleos y hábito tabáquico: un estudio hospitalario

Background: Micronucleus is a microscopically visible cyto-plasmic chromatin mass in the extranuclear vicinity, originating from aberrant mitosis, which consists of eccentric chromosomes that have failed to reach spindle poles during mitosis. The present study was designed to evaluate and compare cytogenetic changes in the buccal mucosa of smokers and non-smokers based on the occurrence of micronuclei. The study aimed to determine the correlation between the micronuclei count and the frequency and duration of smoking habit. Materials and Methods: Two groups (smokers and non-smokers) of 34 individuals each were examined. Cytological buccal smears were taken from participants using a moistened wooden spatula and stained with standard Papanicolaou stain. Presence of micronuclei was assessed at 40X magnification using a light microscope and a count per 500 cells was determined. The results of the study were analyzed statistically using Mann-Whitney U test, Spearman's rank correlation coefficient and Student t-test. Result: Smears from smokers showed a significant increase in the total number of micronuclei per 500 cell count compared to non-smokers. There was a strong positive correlation between the occurrence of micronuclei and the frequency and duration of smoking. A age-related increase in older age groups was also observed. Conclusion: The study reveals a strong positive correlation between the occurrence of micronuclei and the frequency and duration of smoking. This observation is vital in the utilization of the micronuclei detection in smears as a prognostic, educational and interventional tool in the management of patients with smoking habits.

Antecedentes: El micronúcleo es una masa de cromatina citoplasmática microscópicamente visible en el área extranuclear, que se origina a partir de la mitosis aberrante, y que consiste en cromosomas excéntricos que no han podido alcanzar los polos del huso durante la mitosis. El presente estudio fue diseñado para evaluar y comparar los cambios citogenéticos en la mucosa bucal de fumadores y no fumadores en función de la aparición de micronúcleos. El estudio tuvo como objetivo determinar la correlación entre el recuento de micronúcleos y la frecuencia y duración del hábito de fumar. Materiales and Métodos: Se examinaron dos grupos (fumadores y no fumadores) de 34 individuos cada uno. Se tomaron frotis bucales citológicos de todos los participantes con una espátula de madera humedecida y se tiñeron con la tinción estándar de Papanicolaou. La presencia de micronúcleos se evaluó al microscopio óptico con un aumento de 40X y se determinó un recuento por 500 células. Los resultados del estudio se analizaron estadísticamente utilizando la prueba U de Mann-Whitney, el coeficiente de correlación de rango de Spearman y la prueba t de Student. Resultados: Los frotis de fumadores mostraron un aumento significativo en el número total de micronúcleos por 500 células en comparación con los no fumadores. Hubo una fuerte correlación positiva entre la aparición de micronúcleos y la frecuencia y duración del tabaquismo. También se observó un aumento relacionado con la edad en los grupos de mayor edad. Conclusión: el estudio revela una fuerte correlación positiva entre la aparición de micronúcleos y la frecuencia y duración del tabaquismo. Esta observación es vital en la utilización de la detección de micronúcleos en frotis como una herramienta pronostica, educativa e intervencionista en el manejo de pacientes con hábitos de fumar.

Análisis citogenético en linfocitos de trabajadores expuestos a radiación ionizante en una unidad de cardiología intervencional de Chile: estudio piloto y revisión de la literatura / Citogenetic effects upon lymphocyes in subjects exposed to ionizing radiadion in an interventional laboratory cardiology: pilot study and literature review

ANTECEDENTES: Un número creciente de artículos está llamando la atención en forma consistente sobre la eventual asociación que existe entre los denominados trabajadores ocupacionalmente expuestos a bajos niveles de radiación ionizante (POEs) y una mayor frecuencia de aberraciones cromosómicas, a nivel Sudamericano estos estudios son escasos. OBJETIVO: Evaluar la frecuencia de aberraciones cromosómicas en linfocitos de sangre periférica de POEs de un hospital y de sujetos sanos. Adicionalmente, se realizó una revisión exhaustiva de los artículos que a la fecha abordaron este tema. MATERIAL Y MÉTODO: Se condujo un análisis citogenético destinado a cuantificar las aberraciones cromosómicas en sangre periférica de linfocitos de 6 POEs de la unidad de Cardiología Intervencional y, como controles, 6 muestras de sujetos de la población general fueron analizadas. RESULTADOS: Se observó un importante contraste en el número de aberraciones cromosómicas presentadas en los POEs versus la población general no expuesta a radiaciones ionizantes, siendo esta de una relación de 6:1, respectivamente. CONCLUSIÓN: Los resultados preliminares indican una mayor frecuencia de aberraciones cromosómicas en los POEs versus la población general, sin embargo, se deberá esperar los resultados de la segunda fase de investigación, donde al ampliar la muestra en análisis se podrán obtener conclusiones estadísticamente significativas.

BACKGROUND: There is growing evidence of an increased number of chromosomes aberrations in subjects exposed to low levels of ionizing radiation (POEs). There are few studies on this subject in Latin America AIM: To evaluate the frequency of chromosome aberrations in lymphocytes obtained from peripheral blood in subjects working in laboratories where low levels of ionizing radiation are present and to compare these findings to those of unexposed subjects. METHODS: A cytogenic analysis to quantify chromosome aberrations was performed in 6 POs subjects from a cardiology invasive laboratory and 6 controls from a general unexposed population. RESULTS: Compared to controls, an approximately 6-fold increase in the number of chromosome aberrations was observed.in subjects exposed to ionizing radiation CONCLUSION: These preliminary results indicate that there is an increased number of chromosome aberrations in subjects exposed to low levels of ionizing radiation, as occurs in people working in a cardiology interventional laboratory. Studies in large numbers of subjects and preferably followed prospectively are needed to evaluate more precisely this effect.

Autism associated with 12q (12q24. 31-q24. 33) deletion: further report of an exceedingly rare disorder / Autismo associado à síndrome de deleção do cromossomo 12q24. 31-q24. 33: relato adicional de um distúrbio extremamente raro

ABSTRACT Chromosomal abnormalities are responsible for several congenital malformations in the world, some of these are associated to telomeric/subtelomeric deletions. The abnormalities involving the telomere of chromosome 12 are rare, with few reports of deletions involving 12q24.31 region in the literature, and, to our knowledge, only four of them in the 12q24.31-q24.33 region. We report a further case of interstitial deletion of bands 12q24.31-q24.33 associated with autism spectrum disorder. A 2-year-old boy with global developmental delay associated with multiple congenital anomalies. The Human Genome CGH Microarray 60K confirmed the diagnosis of 12q deletion syndrome. This study made a review of the current literature comparing our patient with previously reported cases. These detailed analyses contribute to the development of genotype/phenotype correlations for 12q deletions that will aid in better diagnosis and prognosis of this deletion.

RESUMO Anomalias cromossômicas são responsáveis por inúmeras malformações congênitas no mundo, algumas delas associadas a deleções teloméricas/subteloméricas. As anomalias que envolvem o telômero do cromossomo 12 são raras, com poucos relatos na literatura sobre deleções relacionados à região 12q24.31 e, até onde sabemos, apenas quatro deles na região 12q24.31-q24.33. Relatamos um outro caso de deleção intersticial das bandas 12q24.31-q24.33 associada ao transtorno do espectro do autismo. Trata-se de um menino de 2 anos de idade com atraso global no desenvolvimento associado a múltiplas anomalias congênitas. A utilização do Human Genome CGH Microarray 60K confirmou o diagnóstico da síndrome de deleção 12q. Este estudo fez uma revisão da literatura atual, comparando nosso paciente com casos previamente relatados. Estas análises detalhadas contribuem para o desenvolvimento de correlações genótipo/fenótipo para deleções 12q, que ajudam aos melhores diagnóstico e prognóstico desta deleção.

Increase of binucleated cells in the oral mucosa: a study on the use of psychotropics by students of a Brazilian institution

SUMMARY This study aimed to assess the prevalence of medical and nonmedical use of psychiatric medication among undergraduate students of health sciences from a public university in Brasil. Another objective was to determine the frequency of nuclear morphological abnormalities in the buccal mucosa of students using psychiatric drugs. A cross-sectional study based on a Web survey was carried out with 375 health sciences undergraduate students from schools of Pharmacy, Physical Education, Nutrition, and Medicine. Additionally, spontaneous genetic damages in exfoliated cells of the buccal mucosa of 41 individuals by counting micronucleus (MN) and binucleated (BN) cells frequencies were evaluated. The results showed 76 (20.3%) of students reported the use of psychotropic drugs after enrolling in university. The majority of these students were from Pharmacy and Medicine programs, females, aged between 18-25 years old, nonsmokers, alcohol addicts, and with a family history of mental illness. In addition, Medical students, individuals with high-income, who live alone and are in the last period of the program are more likely to use psychotropic drugs. Moreover, exposure to psychiatric medication was able to increase the number of binucleated cells. These results provide evidence that the use of psychoactive drugs is increased in the academic context and may be related to the failure of the cell cycle.

RESUMO O objetivo deste estudo foi avaliar a prevalência de uso médico e não médico de medicação psiquiátrica entre estudantes de graduação em Ciências da Saúde de uma universidade pública do Brasil. Outro objetivo foi determinar a frequência de anormalidades nucleares morfológicas na mucosa bucal desses estudantes. Realizou-se um estudo transversal baseado na Web com 375 estudantes de graduação em Ciências da Saúde das escolas de Farmácia, Educação Física, Nutrição e Medicina. Adicionalmente, danos genéticos espontâneos em células esfoliadas da mucosa bucal de 41 indivíduos foram analisados para estudo da frequência de micronúcleos e células binucleadas. Os resultados mostraram que 76 (20,8%) dos estudantes relataram que usaram drogas psicotrópicas após se matricularem na universidade. O uso desses medicamentos foi maior entre estudantes de cursos de Farmácia e Medicina, sexo feminino, idade entre 18 e 25 anos, não tabagistas, alcoolistas e histórico familiar de doença mental. Além disso, estudantes de Medicina, indivíduos com alta renda, que moram sozinhos e estão no último período do curso são mais propensos a usar drogas psicotrópicas. Ademais, a exposição à medicação psiquiátrica foi capaz de aumentar o número de células binucleadas. Esses resultados fornecem evidências de que o uso de drogas psicotrópicas aumenta no contexto acadêmico e pode estar relacionado à falha do ciclo celular.

Efecto antigenotóxico de las semillas de Salvia hispanica "chia" utilizando la prueba de Allium cepa / Antigenotoxic effect of Salvia hispanica "chia" seeds using the Allium cepa test

Objetivo: El objetivo fue evaluar el efecto antigenotóxico de las semillas de Salvia hispanica expuestas al efecto genotóxico de la azida de sodio utilizando la prueba de Allium cepa. Materiales y métodos: Estudio experimental, las unidades de análisis fueron células meristemáticas de 40 bulbos de Allium cepa. Se dispuso 5 grupos de trabajo: control negativo, control positivo, pretratamiento, simultáneo y postratamiento, además de dos concentraciones (10% y 20%). Las raíces se expusieron a los tratamientos por un total de 48 horas. Resultados: Se observó una disminución significativa del índice mitótico (IM) del control negativo (23,7) respecto al control positivo (3,4) confirmando la acción genotóxica de la azida de sodio. En el grupo pretratamiento, la reducción de daño (RD%) fue de -151,2% y -59,2% señalando su nulo papel desmutagénico. En el grupo postratamiento y simultáneo, la RD% fue de 37,6%, 67,2% y 59,2%, 64,8% respectivamente para ambas concentraciones indicando su actividad bioantimutagénica dependiente de la concentración. Sin embargo, a las concentraciones evaluadas no se halló significancia estadística. Conclusión: Las semillas de Salvia hispanica expuestas al efecto genotóxico de la azida de sodio utilizando la prueba de Allium cepa no tienen un efecto antigenotóxico a las concentraciones de 10% y 20%.

Objective: The objective was to assess the antigenotoxic effect of Salvia hispanica seeds exposed to the genotoxic effect of sodium azide using the Allium cepa test. Materials and Methods: This is an experimental study. The analyzed units were meristem cells from forty Allium cepa bulbs Five working groups were available: negative controls, positive controls, pre-treatment, simultaneous, and post-treatment, and two concentrations (10% and 20%) were used. Bulbs were exposed to treatment for a total 48-hour time. Results: A significant reduction in the mitotic index (MI) of negative controls (23.7) was observed, compared to positive controls (3.4), confirming the genotoxic action of sodium azide. In the pre-treatment group, damage reduction values (DR%) were -151.2% and -59.2%, indicating their absent demutagenic role. In both posttreatment and simultaneous groups, DR% values were 37.6 %, 67.2 %, 59.2 %, and 64.8 % for both concentrations, respectively, indicating their concentration-dependent bioantimutagenic activity. However, no statistically significant differences were found between the concentrations tested. Conclusion: Salvia hispanica seeds exposed to the genotoxic effect of sodium azide using the Allium cepa test have no antigenotoxic effect at 10% and 20% concentrations.