Prevalence of BRCA1 and BRCA2 Germline Mutations in Patients of African Descent with Early-Onset and Familial Colombian Breast Cancer.

BACKGROUND: Pathogenic germline mutations in the BRCA1 and BRCA2 (BRCA1/2) genes contribute to hereditary breast/ovarian cancer (OC) in White/mestizo Colombian women. As there is virtually no genetic data on breast cancer (BC) in Colombians of African descent, we conducted a comprehensive BRCA1/2 mutational analysis of 60 Afro-Colombian families affected by breast/OC. MATERIALS AND METHODS: Mutation screening of the complete BRCA1/2 genes for small-scale mutations and large genomic alterations was performed in these families using next-generation sequencing and multiplex ligation-dependent probe amplification analysis. RESULTS: Four pathogenic germline mutations, including one novel mutation, were identified, comprising 3 in BRCA1 and one in BRCA2. The prevalence of BRCA1/2 mutations, including one BRCA1 founder mutation (c.5123C>A) previously identified in this sample set, was 3.9% (2/51) in female BC-affected families and 33.3% (3/9) in those affected by both breast and OC. Haplotype analysis of 2 BRCA2_c.2701delC carriers (one Afro-Colombian and one previously identified White/mestizo Colombian patient with BC) suggested that the mutation arose in a common ancestor. CONCLUSION: Our data showed that 2/5 (40%) mutations (including the one previously identified in this sample set) are shared by White/mestizo Colombian and Afro-Colombian populations. This suggests that these 2 populations are closely related. Nevertheless, variations in the BRCA1/2 mutational spectrum among Afro-Colombian subgroups from different regions of the country were observed, suggesting that specific genetic risk assessment strategies need to be developed.

Low Prevalence of the Four Common Colombian Founder Mutations in BRCA1 and BRCA2 in Early-Onset and Familial Afro-Colombian Patients with Breast Cancer.

BACKGROUND: Inherited mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 (BRCA1/2) confer high risks of breast and ovarian cancer. In Colombian Hispanic families, four common BRCA1/2 founder mutations have previously been identified. Because nothing is known about the contribution of BRCA1/2 germline mutations to early-onset and hereditary breast and/or ovarian cancer in Afro-Colombians, we conducted the first study on 60 patients with early-onset and familial breast cancer in this population. MATERIALS AND METHODS: Screening for the four Colombian founder mutations BRCA1/c.3331_3334delCAAG, BRCA1/c.5123C>A, BRCA2/c.2806_2809delAAAC, and BRCA2/c.1763_1766delATAA was performed using mismatch polymerase chain reaction (PCR) analysis, PCR-based restriction fragment length polymorphism analysis, and qualitative real-time PCR. Mutations were confirmed by direct DNA sequencing. RESULTS: The BRCA1 founder mutation c.5123C>A was identified in one family with breast and ovarian cancer (1/60, 1.7%). Three women were diagnosed with breast cancer, including one with bilateral disease, at the ages of 30, 30/33, and 52 years, and one woman was diagnosed with ovarian cancer at the age of 60 years. CONCLUSION: Our data showed a low prevalence of the BRCA1/2 founder mutations in Colombians of African descent, implying that these mutations should not be recommended for genetic screening programs in the Afro-Colombian population. IMPLICATIONS FOR PRACTICE: Risk reduction intervention programs are needed for women who are found to carry a BRCA1/2 mutation, as is the implementation of prevention programs for patients with inherited breast cancer, to reduce the burden of inherited diseases. With the aim of reducing racial disparities in breast cancer prevention, this study focused on genetic testing and treatment for patients in a minority population with BRCA1/2 mutations.

Ethanol effect on batch and fed-batch Arthrospira platensis growth.

The ability of Arthrospira platensis to use ethanol as a carbon and energy source was investigated by batch process and fed-batch process. A. platensis was cultivated under the effect of a single addition (batch process) and a daily pulse feeding (fed-batch process) of pure ethanol, at different concentrations, to evaluate cell concentration (X) and specific growth rate (µ). A marked increase was observed in the cell concentration of A. platensis in runs with ethanol addition when compared to control cultures without ethanol addition. The fed-batch process using an ethanol concentration of 38 mg L(-1) days(-1) reached the maximum cell concentration of 2,393 ± 241 mg L(-1), about 1.5-fold that obtained in the control culture. In all experiments, the maximum specific growth rate was observed in the early exponential phase of cell growth. In the fed-batch process, µ decreased more slowly than in the batch process and control culture, resulting in the highest final cell concentration. Ethanol can be used as a feasible carbon and energy source for A. platensis growth via a fed-batch process.

Descripción de polimorfismos genéticos en CYP3A5 y MDR-1 y su impacto en el rechazo agudo clínico de pacientes trasplantados de hígado del Hospital San Vicente Fundación Rionegro / Description of genetic polymorphisms in CYP3A5 and MDR-1 and their impact on clinical acute rejection in liver transplant patients at Hospital San Vicente Fundación Rionegro

Introducción. El tacrolimus es un medicamento inmunosupresor ampliamente usado en trasplante hepático, que presenta una gran variabilidad interindividual la cual se considera asociada a la frecuencia de polimorfismos de CYP3A5 y MDR-1. El objetivo de este estudio fue evaluar la frecuencia de los polimorfismos rs776746, rs2032582 y rs1045642 y su asociación con rechazo clínico y toxicidad farmacológica. Métodos. Se incluyeron pacientes inmunosuprimidos con tacrolimus a quienes se les realizó trasplante hepático en el Hospital San Vicente Fundación Rionegro entre 2020 y 2022, con supervivencia mayor a un mes. Se evaluaron las variables clínicas, rechazo agudo y toxicidad farmacológica. Se secuenciaron los genes de estudio mediante PCR, comparando la expresión o no en cada uno de los pacientes. Resultados. Se identificaron 17 pacientes. El 43 % de los pacientes se clasificaron como CYP3A5*1/*1 y CYP3A5*1/*3, entre los cuales se encontró asociación con aumento en la tasa de rechazo agudo clínico, al comparar con los pacientes no expresivos (100 % vs. 44 %, p=0,05); no hubo diferencias en cuanto a la toxicidad farmacológica u otros desenlaces. Se encontró el polimorfismo rs2032582 en un 50 % y el rs1045642 en un 23,5 % de los pacientes, sin embargo, no se identificó asociación con rechazo u otros eventos clínicos. Conclusiones. Se encontró una asociación entre el genotipo CYP3A5*1/*1 y CYP3A5*1/*3 y la tasa de rechazo clínico. Sin embargo, se requiere una muestra más amplia para validar estos datos y plantear modelos de medicina personalizada.

Introduction. Tacrolimus is an immunosuppressive drug widely used in liver transplantation, which presents great interindividual variability which is considered associated with the frequency of CYP3A5 and MDR-1 polymorphisms. The objective of this study was to evaluate the frequency of the rs776746, rs2032582 and rs1045642 polymorphisms and their association with clinical rejection and drug toxicity. Methods. Immunosuppressed patients with tacrolimus who underwent a liver transplant at the Hospital San Vicente Fundación Rionegro between 2020 and 2022 were included, with survival of more than one month. Clinical variables, acute rejection and pharmacological toxicity were evaluated. The study genes were sequenced by PCR, comparing their expression or not in each of the patients. Results. Seventeen patients were identified. 43% of the patients were classified as CYP3A5*1/*1 and CYP3A5*1/*3, among which an association was found with increased rates of clinical acute rejection when compared with non-expressive patients (100% vs. 44%, p=0.05). There were no differences in drug toxicity or other outcomes. The rs2032582 polymorphism was found in 50% and rs1045642 in 23.5% of patients; however, no association with rejection or other clinical events was identified. Conclusions. An association was found between the CYP3A5*1/*1 and CYP3A5*1/*3 genotype and the clinical rejection rate. However, a larger sample is required to validate these data and propose models of personalized medicine.

Potential of Microalgae Carotenoids for Industrial Application.

Microalgae cultivation, when compared to the growth of higher plants, presents many advantages such as faster growth, higher biomass productivity, and smaller land area requirement for cultivation. For this reason, microalgae are an alternative platform for carotenoid production when compared to the traditional sources. Currently, commercial microalgae production is not well developed but, fortunately, there are several studies aiming to make the large-scale production feasible by, for example, employing different cultivation systems. This review focuses on the main carotenoids from microalgae, comparing them to the traditional sources, as well as a critical analysis about different microalgae cultivation regimes that are currently available and applicable for carotenoid accumulation. Throughout this review paper, we present relevant information about the main commercial microalgae carotenoid producers; the comparison between carotenoid content from food, vegetables, fruits, and microalgae; and the great importance and impact of these molecule applications, such as in food (nutraceuticals and functional foods), cosmetics and pharmaceutical industries, feed (colorants and additives), and healthcare area. Lastly, the different operating systems applied to these photosynthetic cultivations are critically discussed, and conclusions and perspectives are made concerning the best operating system for acquiring high cell densities and, consequently, high carotenoid accumulation.

Escisión meso-rectal total por vía trans anal (TaTME). Experiencia institucional / Trans anal total meso-rectal excision (TaTME). Institutional experience

Introducción. La cirugía es la base del tratamiento curativo del cáncer de recto. La escisión meso-rectal total ha permitido mejorar los desenlaces oncológicos, disminuyendo las tasas de recurrencia locorregional e impactando en la supervivencia global. El empleo de esta técnica en los tumores de recto medio o distal es un reto quirúrgico, en el que la vía trans anal, permite superar las dificultades técnicas. Método. Se realizó un estudio observacional retrospectivo, recolectando la información de los pacientes con cáncer de recto medio y distal llevados a cirugía con esta técnica, en dos instituciones de cuarto nivel en Medellín, Colombia, entre enero de 2017 y marzo de 2022. Se analizaron sus características demográficas, la morbilidad perioperatoria y la pieza quirúrgica. Resultados. Se incluyeron 28 pacientes sometidos al procedimiento trans anal y laparoscópico de forma simultánea; al 57 % se les realizó una ileostomía de protección. Hubo complicaciones en el 60,7 % de los pacientes; ocurrieron cuatro casos de fuga anastomótica. No se presentó ninguna mortalidad perioperatoria. Conclusiones. La tasa de morbilidad perioperatoria es acorde con lo reportado en la literatura. Se resalta la importancia de la curva de aprendizaje quirúrgica y de incluir la calificación de la integridad meso-rectal dentro del informe patológico. Se requiere seguimiento a largo plazo para determinar el impacto en desenlaces oncológicos, calidad de vida y morbilidad

Introduction. Surgery is the pillar of curative treatment for rectal cancer. Total meso-rectal excision has improved oncological outcomes, decreasing locoregional recurrence rates and impacting overall survival. The use of this technique in tumors of the middle or distal rectum is a surgical challenge, in which the trans anal route allows overcoming technical difficulties. Method. A retrospective observational study was carried out, collecting information from patients with middle and distal rectal cancer undergoing surgery with this technique, in two level 4 institutions in Medellín, Colombia, between January 2017 and March 2022. Results. Twenty-eight patients were included; their demographic characteristics, perioperative morbidity, and surgical specimen were analyzed. All patients underwent the trans anal and laparoscopic procedures simultaneously; 57% underwent a protective ileostomy. There was no perioperative mortality. Complications occurred in 60.7% of the patients. Only four cases of anastomotic leak occurred. Conclusions. The perioperative morbidity rate is consistent with that reported in the literature; the importance of the surgical curve and to include the qualification of the meso-rectal integrity within the pathological report is highlighted. Long-term follow-up is required to determine the impact on oncological outcomes, quality of life, and morbidity

Mosaic trisomy 8 detected by fibroblasts cultured of skin.

INTRODUCTION: Mosaic trisomy 8 or "Warkany's Syndrome" is a chromosomopathy with an estimated prevalance of 1:25,000 to 1:50,000, whose clinical presentation has a wide phenotypic variability. CASE DESCRIPTION: Patient aged 14 years old with antecedents of global retardation of development, moderate cognitive deficit and hypothyroidism of possible congenital origin. CLINICAL FINDINGS: Physical examination revealed palpebral ptosis, small corneas and corectopia, hypoplasia of the upper maxilla and prognathism, dental crowding, high-arched palate, anomalies of the extremities such as digitalization of the thumbs, clinodactyly and bilateral shortening of the fifth finger, shortening of the right femur, columnar deviation and linear brown blotches that followed Blaschko's lines. Cerebral nuclear magnetic resonance revealed type 1 Chiari's malformation and ventriculomegaly. Although the karyotype was normal in peripheral blood (46,XY), based on the finding of cutaneous mosaicism the lesions were biopsied and cytogenetic analysis demonstrated mosaic trisomy 8: mos 47,XY,+8[7]/46,XY[93]. CLINICAL RELEVANCE: Trisomy 8 is clinically presented as a mosaic, universal cases being unfailingly lethal. In this particular case, cutaneous lesions identified the mosaic in tissue, although the karyotype was normal in peripheral blood. The cutaneous mosaicism represented by brown linear blotches which follow Blaschko's lines is a clinical finding that has not previously been described in Warkany's syndrome.

INTRODUCCIÓN: La trisomía 8 en mosaico o Síndrome de Warkany, es una cromosomopatía con una prevalencia estimada de 1:25,000 a 1:50,000, que se presenta clínicamente con una amplia variabilidad fenotípica. DESCRIPCIÓN DEL CASO: Paciente de 14 años con antecedente de retardo global del desarrollo, déficit cognitivo moderado e hipotiroidismo de posible origen congénito. HALLAZGOS CLÍNICOS: Al examen físico presenta ptosis palpebral, corneas pequeñas y corectopia, hipoplasia de maxilar superior y prognatismo, apiñamiento dental, paladar alto ojival, anomalías en extremidades como digitalización de pulgares, clinodactilia y acortamiento bilateral del quinto dedo en manos, acortamiento de fémur derecho, desviación de columna y máculas lineales pardas que siguen las líneas de Blaschko. En la resonancia nuclear magnética cerebral se aprecia malformación de Chiari tipo 1 y ventriculomegalia. El cariotipo en sangre periférica fue normal (46,XY) sin embargo, ante el hallazgo de mosaicismo cutáneo, se realizó biopsia de las lesiones y su análisis citogenético demostró trisomía 8 en mosaico: mos47,XY,+8[7] /46,XY[93]. RELEVANCIA CLÍNICA: La trisomía 8 se presenta clínicamente en mosaico, los casos universales son indefectiblemente letales. En este caso particular, las lesiones cutáneas identificaron el mosaico en tejido, frente al cariotipo normal en sangre periférica. El mosaicismo cutáneo representado por las máculas lineales pardas (que siguen las líneas de Blaschko) es un hallazgo clínico que no se había descrito en el síndrome de Warkany.

Mosaic trisomy 8 detected by fibroblasts cultured of skin / Mosaico trisomía 8 detectada por los cultivos de fibroblastos de la piel

Introduction: Mosaic trisomy 8 or "Warkany's Syndrome" is a chromosomopathy with an estimated prevalance of 1:25,000 to 1:50,000, whose clinical presentation has a wide phenotypic variability. Case Description: Patient aged 14 years old with antecedents of global retardation of development, moderate cognitive deficit and hypothyroidism of possible congenital origin. Clinical Findings: Physical examination revealed palpebral ptosis, small corneas and corectopia, hypoplasia of the upper maxilla and prognathism, dental crowding, high-arched palate, anomalies of the extremities such as digitalization of the thumbs, clinodactyly and bilateral shortening of the fifth finger, shortening of the right femur, columnar deviation and linear brown blotches that followed Blaschko's lines. Cerebral nuclear magnetic resonance revealed type 1 Chiari's malformation and ventriculomegaly. Although the karyotype was normal in peripheral blood (46,XY), based on the finding of cutaneous mosaicism the lesions were biopsied and cytogenetic analysis demonstrated mosaic trisomy 8: mos 47,XY,+8[7]/46,XY[93]. Clinical Relevance: Trisomy 8 is clinically presented as a mosaic, universal cases being unfailingly lethal. In this particular case, cutaneous lesions identified the mosaic in tissue, although the karyotype was normal in peripheral blood. The cutaneous mosaicism represented by brown linear blotches which follow Blaschko's lines is a clinical finding that has not previously been described in Warkany's syndrome.

Introducción: La trisomía 8 en mosaico o Síndrome de Warkany, es una cromosomopatía con una prevalencia estimada de 1:25,000 a 1:50,000, que se presenta clínicamente con una amplia variabilidad fenotípica. Descripción del Caso: Paciente de 14 años con antecedente de retardo global del desarrollo, déficit cognitivo moderado e hipotiroidismo de posible origen congénito. Hallazgos Clínicos: Al examen físico presenta ptosis palpebral, corneas pequeñas y corectopia, hipoplasia de maxilar superior y prognatismo, apiñamiento dental, paladar alto ojival, anomalías en extremidades como digitalización de pulgares, clinodactilia y acortamiento bilateral del quinto dedo en manos, acortamiento de fémur derecho, desviación de columna y máculas lineales pardas que siguen las líneas de Blaschko. En la resonancia nuclear magnética cerebral se aprecia malformación de Chiari tipo 1 y ventriculomegalia. El cariotipo en sangre periférica fue normal (46,XY) sin embargo, ante el hallazgo de mosaicismo cutáneo, se realizó biopsia de las lesiones y su análisis citogenético demostró trisomía 8 en mosaico: mos47,XY,+8[7]/46,XY[93]. Relevancia Clínica: La trisomía 8 se presenta clínicamente en mosaico, los casos universales son indefectiblemente letales. En este caso particular, las lesiones cutáneas identificaron el mosaico en tejido, frente al cariotipo normal en sangre periférica. El mosaicismo cutáneo representado por las máculas lineales pardas (que siguen las líneas de Blaschko) es un hallazgo clínico que no se había descrito en el síndrome de Warkany.