Germline mutations of breast cancer susceptibility genes through expanded genetic analysis in unselected Colombian patients.

BACKGROUND: In Colombia and worldwide, breast cancer (BC) is the most frequently diagnosed neoplasia and the leading cause of death from cancer among women. Studies predominantly involve hereditary and familial cases, demonstrating a gap in the literature regarding the identification of germline mutations in unselected patients from Latin-America. Identification of pathogenic/likely pathogenic (P/LP) variants is important for shaping national genetic analysis policies, genetic counseling, and early detection strategies. The present study included 400 women with unselected breast cancer (BC), in whom we analyzed ten genes, using Whole Exome Sequencing (WES), know to confer risk for BC, with the aim of determining the genomic profile of previously unreported P/LP variants in the affected population. Additionally, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to identify Large Genomic Rearrangements (LGRs) in the BRCA1/2 genes. To ascertain the functional impact of a recurrent intronic variant (ATM c.5496 + 2_5496 + 5delTAAG), a minigene assay was conducted. RESULTS: We ascertained the frequency of P/LP germline variants in BRCA2 (2.5%), ATM (1.25%), BRCA1 (0.75%), PALB2 (0.50%), CHEK2 (0.50%), BARD1 (0.25%), and RAD51D (0.25%) genes in the population of study. P/LP variants account for 6% of the total population analyzed. No LGRs were detected in our study. We identified 1.75% of recurrent variants in BRCA2 and ATM genes. One of them corresponds to the ATM c.5496 + 2_5496 + 5delTAAG. Functional validation of this variant demonstrated a splicing alteration probably modifying the Pincer domain and subsequent protein structure. CONCLUSION: This study described for the first time the genomic profile of ten risk genes in Colombian women with unselected BC. Our findings underscore the significance of population-based research, advocating the consideration of molecular testing in all women with cancer.

Use of complementary and alternative medicine by cancer patients in Colombia.

BACKGROUND: The use of complementary and alternative medicines (CAM) among cancer patients varies greatly. The available data suggest an increasing use of CAM over time and a higher prevalence in low- and middle-income countries. However, no reliable data are available from Latin America. Accordingly, we examined the prevalence of CAM use among cancer patients from six Colombian regions. METHODS: We conducted a survey on cancer patients attending comprehensive cancer centres in six capital cities from different regions. The survey was designed based on a literature review and information gathered through focus groups on CAM terminology in Colombia. Independent random samples of patients from two comprehensive cancer centres in every city were obtained. Patients 18 years and older with a histopathological diagnosis of cancer undergoing active treatment were eligible. The prevalence of CAM use is reported as a percentage with the corresponding confidence interval. CAM types are reported by region. The sociodemographic and clinical characteristics of CAM users and non-users were compared using Chi square and t tests. RESULTS: In total, 3117 patients were recruited. The average age 59.6 years old, and 62.8% were female. The prevalence of CAM use was 51.7%, and compared to non-users, CAM users were younger, more frequently women, affiliated with the health insurance plan for low-income populations and non-Catholic. We found no differences regarding the clinical stage or treatment modality, but CAM users reported more treatment-related side effects. The most frequent types of CAM were herbal products, specific foods and vitamins, and individually, soursop was the most frequently used product. Relevant variability between regions was observed regarding the prevalence and type of CAM used (range: 36.6% to 66.7%). The most frequent reason for using CAM was symptom management (30.5%), followed by curative purposes (19.5%). CONCLUSIONS: The prevalence of CAM use among cancer patients in Colombia is high in general, and variations between regions might be related to differences in cultural backgrounds and access to comprehensive cancer care. The most frequently used CAM products and practices have little scientific support, suggesting the need to enhance integrative oncology research in the country.

Prevalence of Neutralizing Antibodies against Adeno-Associated Virus Serotypes 1, 2, and 9 in Non-Injected Latin American Patients with Heart Failure-ANVIAS Study.

Neutralizing antibody (NAb) activity against the viral capsid of adeno-associated viral (AAV) vectors decreases transduction efficiency, thus limiting transgene expression. Several reports have mentioned a variation in NAb prevalence according to age, AAV serotype, and, most importantly, geographic location. There are currently no reports specifically describing the anti-AAV NAb prevalence in Latin America. Here, we describe the prevalence of NAb against different serotypes of AAV vectors (AAV1, AAV2, and AAV9) in Colombian patients with heart failure (HF) (referred to as cases) and healthy individuals (referred to as controls). The levels of NAb were evaluated in serum samples of 60 subjects from each group using an in vitro inhibitory assay. The neutralizing titer was reported as the first dilution inhibiting ≥50% of the transgene signal, and the samples with neutralizing titers at ≥1:50 dilution were considered positive. The prevalence of NAb in the case and control groups were similar (AAV2: 43% and 45%, respectively; AAV1 33.3% in each group; AAV9: 20% and 23.2%, respectively). The presence of NAb for two or more of the serotypes analyzed was observed in 25% of the studied samples, with the largest amount in the positive samples for AAV1 (55-75%) and AAV9 (93%), suggesting serial exposures, cross-reactivity, or coinfection. Moreover, patients in the HF group exhibited more common combined seropositivity for NAb against AAV1 d AAV9 than those in the control group (91.6% vs. 35.7%, respectively; p = 0.003). Finally, exposure to toxins was significantly associated with the presence of NAb in all regression models. These results constitute the first report of the prevalence of NAb against AAV in Latin America, being the first step to implementing therapeutic strategies based on AAV vectors in this population in our region.

B-cell lymphocytosis in relatives of Colombian patients with chronic B-cell lymphoproliferative disorders / Linfocitosis monoclonal de células B en familiares de pacientes colombianos con síndromes linfoproliferativos crónicos B.

Introduction. Monoclonal B-cell lymphocytosis generally precedes chronic lymphocytic leukemia, affecting about 12% of the healthy adult population. This frequency increases in relatives of patients with chronic B-cell lymphoproliferative disorders. Objective. To determine the frequency of monoclonal B-cell lymphocytosis in relatives of patients with chronic B-cell lymphoproliferative disorders, their immunophenotypic/cytogenetic characteristics, a possible relationship with infectious agents, and short-term follow-up in the Colombian population. Materials and methods. Fifty healthy adults with a family history of chronic B-cell lymphoproliferative disorders were studied using multiparametric flow cytometry, cytogenetic/serological testing, lifestyle survey, and 2-year follow-up. Results. The frequency of monoclonal B-cell lymphocytosis found was 8%, with a predominance of female gender and advanced age, increasing to 12.5% for individuals with a family history of chronic lymphocytic leukemia. Three out of four individuals presented chronic lymphocytic leukemia-type immunophenotype, all with low counts. In turn, a significantly higher number of cells/µl is observed in these individuals in T lymphocyte subpopulations, together with a greater predisposition to the disease. The described clonal populations increase over time in a non-significant manner. Conclusions. The frequency and behavior of monoclonal B-cell lymphocytosis in patients with family history of chronic B-cell lymphoproliferative disorders are like those found in related studies, which suggests that there is no involvement of more relevant genes that can trigger uncontrolled clonal proliferation, but that generates immunological deregulation that could justify a greater risk of serious infection in these individuals.

Introducción. La linfocitosis monoclonal de células B, generalmente, precede la leucemia linfocítica crónica y afecta alrededor del 12 % de la población adulta sana. Esta frecuencia se incrementa en familiares de pacientes con síndromes linfoproliferativos crónicos de células B.Objetivo. Determinar la frecuencia de linfocitosis monoclonal B en familiares de pacientes con síndromes linfoproliferativos crónicos B, sus características inmunofenotípicas y citogenéticas, posible relación con agentes infecciosos, y seguimiento a corto plazo de población colombiana.Materiales y métodos. Se estudiaron 50 adultos sanos con antecedentes familiares de síndromes linfoproliferativos crónicos de célula B, empleando citometría de flujo multiparamétrica, pruebas citogenéticas y serológicas, encuesta de hábitos de vida y seguimiento a dos años.Resultados. La frecuencia encontrada de linfocitosis monoclonal B fue del 8 %, con predominio del sexo femenino y edad avanzada, incrementándose al 12,5 % en individuos con antecedentes familiares de leucemia linfocítica crónica. Tres de cuatro individuos presentaron inmunofenotipo de tipo leucemia linfocítica crónica, todas con bajo recuento. A su vez, en estos individuos se observa de manera significativa un mayor número de células/µl en subpoblaciones linfocitarias T, junto con mayor predisposición a la enfermedad. Las poblaciones clonales descritas aumentan a lo largo del tiempo de manera no significativa.Conclusiones. La frecuencia y comportamiento de la linfocitosis monoclonal de célula B en pacientes con antecedentes familiares de síndromes linfoproliferativos crónicos B es similar a lo encontrado en estudios relacionados,lo que sugiere que no existe afectación degenes de mayor relevancia que puedan desencadenar una proliferación clonal descontrolada, pero que generan desregulación inmunológica que podría indicar un mayor riesgo de infección grave en estos individuos.

Linfocitosis monoclonal de células B en familiares de pacientes colombianos con síndromes linfoproliferativos crónicos B

Introducción. La linfocitosis monoclonal de células B, generalmente, precede la leucemia linfocítica crónica y afecta alrededor del 12 % de la población adulta sana. Esta frecuencia se incrementa en familiares de pacientes con síndromes linfoproliferativos crónicos de células B. Objetivo. Determinar la frecuencia de linfocitosis monoclonal B en familiares de pacientes con síndromes linfoproliferativos crónicos B, sus características inmunofenotípicas y citogenéticas, posible relación con agentes infecciosos, y seguimiento a corto plazo de población colombiana. Materiales y métodos. Se estudiaron 50 adultos sanos con antecedentes familiares de síndromes linfoproliferativos crónicos de célula B, empleando citometría de flujo multiparamétrica, pruebas citogenéticas y serológicas, encuesta de hábitos de vida y seguimiento a dos años. Resultados. La frecuencia encontrada de linfocitosis monoclonal B fue del 8 %, con predominio del sexo femenino y edad avanzada, incrementándose al 12,5 % en individuos con antecedentes familiares de leucemia linfocítica crónica. Tres de cuatro individuos presentaron inmunofenotipo de tipo leucemia linfocítica crónica, todas con bajo recuento. A su vez, en estos individuos se observa de manera significativa un mayor número de células/ µl en subpoblaciones linfocitarias T, junto con mayor predisposición a la enfermedad. Las poblaciones clonales descritas aumentan a lo largo del tiempo de manera no significativa. Conclusiones. La frecuencia y comportamiento de la linfocitosis monoclonal de célula B en pacientes con antecedentes familiares de síndromes linfoproliferativos crónicos B es similar a lo encontrado en estudios relacionados, lo que sugiere que no existe afectación de genes de mayor relevancia que puedan desencadenar una proliferación clonal descontrolada, pero que generan desregulación inmunológica que podría indicar un mayor riesgo de infección grave en estos individuos.

Introduction. Monoclonal B-cell lymphocytosis generally precedes chronic lymphocytic leukemia, affecting about 12% of the healthy adult population. This frequency increases in relatives of patients with chronic B-cell lymphoproliferative disorders. Objective. To determine the frequency of monoclonal B-cell lymphocytosis in relatives of patients with chronic B-cell lymphoproliferative disorders, their immunophenotypic/ cytogenetic characteristics, a possible relationship with infectious agents, and short-term follow-up in the Colombian population. Materials and methods. Fifty healthy adults with a family history of chronic B-cell lymphoproliferative disorders were studied using multiparametric flow cytometry, cytogenetic/serological testing, lifestyle survey, and 2-year follow-up. Results. The frequency of monoclonal B-cell lymphocytosis found was 8%, with a predominance of female gender and advanced age, increasing to 12.5% for individuals with a family history of chronic lymphocytic leukemia. Three out of four individuals presented chronic lymphocytic leukemia-type immunophenotype, all with low counts. In turn, a significantly higher number of cells/µΙ is observed in these individuals in T lymphocyte subpopulations, together with a greater predisposition to the disease. The described clonal populations increase over time in a non-significant manner. Conclusions. The frequency and behavior of monoclonal B-cell lymphocytosis in patients with family history of chronic B-cell lymphoproliferative disorders are like those found in related studies, which suggests that there is no involvement of more relevant genes that can trigger uncontrolled clonal proliferation, but that generates immunological deregulation that could justify a greater risk of serious infection in these individuals.

Effect of Antioxidants in the Treatment of COPD Patients: Scoping Review.

Chronic obstructive pulmonary disease (COPD) is a common, preventable, treatable lung disease characterized by persistent respiratory symptoms and airflow limitation and multiorgan impact. This affects the nutritional status of patients and requires multidimensional interventions including nutritional interventions according to individual metabolic needs. Our scoping review determined the effects of antioxidants in the treatment of COPD patients and their role in the decrease in the probability of exacerbations, hospital readmissions, and changes in lung function. The sources MEDLINE, LILACS, and Google Scholar were consulted and 19 studies were selected. The most indicated antioxidants are N-Acetylcysteine, vitamins E and D, and Zinc. Other antioxidants from plants or fruits extracts are also being investigated. The beneficial effect of antioxidants in stable or exacerbated patients is not clear, but theoretical and biological arguments of benefit justify lines of research that specify the impact on reducing oxidative stress and negative effects in COPD.

Efficacy of oral Vitamin D supplementation in reducing body mass index and lipid profile in adolescents and young adults in Colombia: A pilot clinical trial protocol nested in the SIMBA cohort.

BACKGROUND: In recent years, the role of vitamin D (VD) as a protective factor in cardiovascular disease has been recognized. Thus, there is a need to study the effect of vitamin D supplementation in the control of different cardiovascular risk factors and metabolic syndrome, especially in young populations where few studies have been conducted. METHODS: Pilot study of a randomized, parallel two-arm, triple-blind clinical controlled trial in 150 adolescents and young adults in the city of Bucaramanga-Colombia. The intervention group will receive 1000 IU of VD and the control group 200 IU of VD daily for 15 weeks. The main outcomes are: serum calcifediol levels (25(OH) D), body mass index and lipid profile; secondary outcomes are complementary to the previous ones (skin folds, waist-hip ratio). Other variables will be analyzed such as assessment of dietary intake, physical activity, sun exposure, cigarette and tobacco consumption and compliance with VD supplementation. DISCUSSION: This study is innovative since there is little evidence from clinical trials in adolescents and young adults; similar studies are not known in our context. The results of this study may facilitate the recommendation of oral vitamin D supplementation in the population of interest. In addition, it is a low-cost and easy-to-apply intervention that could contribute to the formulation and implementation of health policies. TRIAL REGISTRATION: NCT04377386.

C-reactive protein, interleukin-6 and pre-eclampsia: large-scale evidence from the GenPE case-control study.

Multiple small studies have suggested that women with pre-eclampsia present elevated levels of C-reactive protein (CRP) and interleukin-6 (IL-6). However, little is known regarding the source of this CRP and IL-6 increase. Therefore, the aim of this study was to evaluate the relationship between CRP and IL-6 levels with pre-eclampsia considering different confounding factors. Using data from a large Colombian case-control study (3,590 cases of pre-eclampsia and 4,564 normotensive controls), CRP and IL-6 levels were measured in 914 cases and 1297 controls. The association between maternal serum levels of CRP and IL-6 with pre-eclampsia risk was evaluated using adjusted logistic regression models. Pre-eclampsia was defined as presence of blood pressure ≥140/90 mmHg and proteinuria ≥300mg/24 h (or ≥1 + dipstick). There was no evidence of association between high levels of CRP and IL-6 with pre-eclampsia after adjusting for the following factors: maternal and gestational age, ethnicity, place and year of recruitment, multiple-pregnancy, socio-economic position, smoking, and presence of infections during pregnancy. The adjusted OR for 1SD increase in log-CRP and log-IL-6 was 0.96 (95%CI 0.85, 1.08) and 1.09 (95%CI 0.97, 1.22), respectively. Although previous reports have suggested an association between high CRP and IL-6 levels with pre-eclampsia, sample size may lack the sufficient power to draw robust conclusions, and this association is likely to be explained by unaccounted biases. Our results, the largest case-control study reported up to date, demonstrate that there is not a causal association between elevated levels of CRP and IL-6 and the presence of pre-eclampsia.

Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach.

Purpose: Hereditary Breast and Ovarian Cancer (HBOC) syndrome is responsible for ~5-10% of all diagnosed breast and ovarian cancers. Breast cancer is the most common malignancy and the leading cause of cancer-related mortality among women in Latin America (LA). The main objective of this study was to develop a comprehensive understanding of the genomic epidemiology of HBOC throughout the establishment of The Latin American consortium for HBOC-LACAM, consisting of specialists from 5 countries in LA and the description of the genomic results from the first phase of the study. Methods: We have recruited 403 individuals that fulfilled the criteria for HBOC from 11 health institutions of Argentina, Colombia, Guatemala, Mexico and Peru. A pilot cohort of 222 individuals was analyzed by NGS gene panels. One hundred forty-three genes were selected on the basis of their putative role in susceptibility to different hereditary cancers. Libraries were sequenced in MiSeq (Illumina, Inc.) and PGM (Ion Torrent-Thermo Fisher Scientific) platforms. Results: The overall prevalence of pathogenic variants was 17% (38/222); the distribution spanned 14 genes and varied by country. The highest relative prevalence of pathogenic variants was found in patients from Argentina (25%, 14/57), followed by Mexico (18%, 12/68), Guatemala (16%, 3/19), and Colombia (13%, 10/78). Pathogenic variants were found in BRCA1 (20%) and BRCA2 (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as MSH2, MSH6, MUTYH, and PALB2. Additional pathogenic variants were found in HBOC unrelated genes such as DCLRE1C, WRN, PDE11A, and PDGFB. Conclusion: In this first phase of the project, we recruited 403 individuals and evaluated the germline genetic alterations in an initial cohort of 222 patients among 4 countries. Our data show for the first time in LA the distribution of pathogenic variants in a broad set of cancer susceptibility genes in HBOC. Even though we used extended gene panels, there was still a high proportion of patients without any detectable pathogenic variant, which emphasizes the larger, unexplored genetic nature of the disease in these populations.

Percepción de diversos sectores sociales de Colombia sobre los biobancos con fines de investigación / The perception of different social agents in Colombia regarding biobanks for research purposes

Introducción. Los biobancos con fines de investigación son un bien público que necesita de la participación activa de todas las partes interesadas, por lo cual es importante conocer la percepción que tiene el público general en Colombia sobre su intervención en un biobanco. Objetivo. Indagar en diferentes sectores sociales colombianos sobre su percepción en torno a la donación de material biológico humano para ser almacenado en biobancos con fines de investigación. Materiales y métodos. Se hizo un estudio exploratorio tanto cuantitativo como cualitativo, entre personas sanas de diferentes sectores del país mediante una encuesta anónima sobre su conocimiento y actitudes con respecto a los biobancos. Resultado. La encuesta fue respondida por 368 personas, que incluían investigadores en salud, abogados y miembros de comités de ética de la investigación. El 96 % de los sujetos expresó su voluntad de donar material biológico, aunque el 60 % manifestó tener desconfianza en que sus muestras fueran usadas en algunos tipos de investigación, especialmente en clonación humana. Cerca de la mitad de los participantes refirieron saber qué era un biobanco, sin embargo, menos del 3 % tenía claridad suficiente sobre el concepto. Conclusión. Los participantes expresaron su disposición a donar y almacenar material biológico con fines de investigación, así como su opinión sobre algunos aspectos de la gestión de los biobancos. Las opiniones del público general se deben tener en cuenta en el desarrollo de políticas que regulen la actividad de los biobancos con fines de investigación en Colombia.

Introduction: Biobanks for research purposes are public assets that require active participation from all interested parties; therefore, it is important to discern and investigate the perception that the general public in Colombia has with regards to their participation in a biobank. Objective: To question different healthy Colombian social agents about the perception they have on donating human biological material to be stored in a biobank for future research purposes. Materials and methods: We conducted an exploratory quantitative and qualitative research by means of an anonymous survey on healthy members of the Colombian community in order to evaluate their knowledge and stances related to biobanks. Results: Three hundred sixty-eight (368) individuals completed the survey, including health-care researchers, lawyers and members of research ethics committees. Ninety-six percent (96%) of the subjects stated their willingness to donate biological material to biobanks, although 60% expressed distress about their samples being used for certain research activities, mainly human cloning. Even though about half of the participants reported knowing what a biobank is, less than 3% of the individuals had a clear concept of them. Conclusion: Participants showed their willingness to donate and store their biological material for research purposes. Similarly, they expressed their opinion about issues related to the management of biobanks. It is necessary to take into account the opinions of the general public in the development of policies that regulate biobanks for research purposes in Colombia.

TriBURTER: invención y validación perceptual del dispositivo portátil de vibración de alta frecuencia y entrenamiento muscular para pacientes con enfermedades respiratorias / TriBURTER: invention and perceptual validation of a portable device aimed to induce high- frequency vibration and respiratory muscle training in patients with respiratory diseases

Introducción: los dispositivos respiratorios vibrátiles son útiles como elementos de terapia respiratoria pues facilitan la expectoración de las secreciones bronquiales. Un dispositivo respiratorio de vibración que incorpore válvulas duales representa una innovación relevante respecto a los modelos existentes. El presente estudio describe la invención y evaluación de un nuevo dispositivo médico portátil de vibración de alta frecuencia para uso humano que permite simultáneamente el entrenamiento muscular respiratorio para pacientes con enfermedades respiratorias, al que se ha denominado con el acrónimo TriBURTER. Métodos: se conceptualizaron, diseñaron y construyeron modelos virtuales y prototipos funcionales siguiendo metodología de bioingeniería y evaluación in situ del funcionamiento a través de simuladores electrónicos. Adicionalmente se evaluaron, mediante escalas psicométricas específicas, los aspectos perceptuales de la morfología y funcionamiento del dispositivo tanto en voluntarios sanos como pacientes. Resultados: se creó un dispositivo que logra tres efectos: facilitar la movilización de secreciones bronquiales, inducir efecto de entrenamiento sobre los músculos inspiratorios, e inducir entrenamiento de músculos espiratorios. La evaluación perceptual demostró que el diseño final del dispositivo es seguro, adecuado, suficiente y práctico. Conclusión: TriBURTER es un dispositivo médico innovador de terapia respiratoria vibrátil que facilita el drenaje de secreciones y genera una sobrecarga muscular, tanto inspiratoria como espiratoria, regulable y útil en el tratamiento de las enfermedades respiratorias, y que puede ser aplicado tanto en ámbito ambulatorio como domiciliario u hospitalario. Su evaluación perceptual demostró seguridad clínica y una adecuada aceptación de uso por parte de los voluntarios sanos y pacientes en términos de cualidad y funcionamiento. MÉD.UIS. 2016;29(2):49-57.

Introduction: vibratory devices are used in respiratory therapy in order to facilitate removal of bronchial secretions. A portable hydraulic system incorporating inspiratory and expiratory valves could provide additional advantages over existing ones. The present study describes the invention and evaluation of a new portable medical device able to induce high frequency vibration and allowing respiratory muscle training for patients with respiratory diseases, which has been named with the acronym TriBURTER. Methods: based on conventional methods of bioengineering, a hydraulic device was conceptualized, designed, built, and validated using electronic simulators. In addition, perceptual evaluations of morphology, final prototype design and function were evaluated in both healthy volunteers and patients through specific psychometric scales. Results: a hydraulic device including two unidirectional valves was finally obtained allowing to induce simultaneously a triple effect: mobilization of bronchial secretions, inspiratory muscle training, and expiratory muscle training. Perceptual evaluations showed that the final design is safe, adequate, sufficient and practical. Conclusion: TriBURTER is an innovative hydraulic medical device for respiratory therapy that facilitates drainage of secretions and generates adjustable inspiratory and expiratory muscle loads. The perceptual evaluations of the device showed proper acceptance of use by healthy volunteers and patients in terms of quality and performance. This device is useful for the treatment of respiratory diseases and can be prescribed for both outpatient and domiciliary or hospital settings. MÉD.UIS. 2016;29(2):49-57.

Determination of Anti-Adeno-Associated Viral Vector Neutralizing Antibodies in Patients With Heart Failure in the Cardiovascular Foundation of Colombia (ANVIAS): Study Protocol.

BACKGROUND: Recent progress in the pathophysiology of heart failure (HF) has led to the development of new therapeutic options such as gene therapy and the use of adeno-associated viral (AAV) vectors. Despite the promising results in early clinical trials of gene therapy for HF, various obstacles have been faced, such as the presence of neutralizing antibodies (NAbs) against the capsid vectors. NAb activity limits vector transduction levels and therefore diminishes the final therapeutic response. Recent studies evaluating the prevalence of NAbs in various populations found considerable geographic variability for each AAV serotype. However, the levels of NAbs in Latin American populations are unknown, becoming a limiting factor to conducting AAV vector therapeutic trials in this population. OBJECTIVE: The goal of this study is to determine for the first time, the prevalence of anti-AAV NAbs for the serotypes 1, 2, and 9 in HF patients from the city of Bucaramanga, Colombia, using the in vitro transduction inhibition assay. METHODS: We will conduct a cross-sectional study with patients who periodically attend the HF clinic of the Cardiovascular Foundation of Colombia and healthy volunteers matched for age and sex. For all participants, we will evaluate the NAb levels against serotypes AAV1, AAV2, and AAV9. We will determine NAb levels using the in vitro transduction inhibition assay. In addition, participants will answer a survey to evaluate their epidemiological and socioeconomic variables. Participation in the study will be voluntary and all participants will sign an informed consent document before any intervention. RESULTS: The project is in the first phase: elaboration of case report forms and the informed consent form, and design of the recruitment strategy. Patient recruitment is expected to begin in the spring of 2016. We expect to have preliminary results, including the titer of the viral vectors, multiplicity of infections that we will use for each serotype, and the general validation of the assay, at the end of 2016. The final results are expected mid-2017. CONCLUSIONS: This project is the first effort to evaluate NAb levels against AAV1, AAV2, and AAV9 serotypes in patients with HF in Latin America. Our results will allow us to check the cross-reactivity response between the serotypes assessed, to describe the epidemiological characteristics of the participant population, and to set up a link with earlier reports of NAb prevalence in the literature.

Analysis of population genetic structure from Bucaramanga (Colombia) based on gene polymorphisms associated with regulation of blood pressure / Análisis de la estructura genética poblacional a partir de polimorfismos de genes asociados con la regulación de la presión arterial en una muestra de Bucaramanga, Colombia

Introduction: In spite nearly 40% of the variability in blood pressure can be explained by genetic factors, the identification of genes associated to essential high blood pressure is difficult in populations where individuals have different genetic precedents; in these circumstances it is necessary to determinate whether the population is sub-structured because this can bias studies associated with this disease.Objectives: To determine the genetic structure of the population in Bucaramanga from genetic polymorphisms associated with the regulation of blood pressure: 448G>T, 679C>T y 1711C>T from the gene kinase 4 of the dopaminergic receptor linked to the protein G and Glu298Asp, -786T>C and the VNTR of the intron 4 of the gene of endothelial nitric oxide.Methodology: A sample of 552 unrelated individuals was studied through analysis of Restriction fragment length polymorphism. The allelic, haplotypic and genotypic frequencies were calculated, the Hardy-Weinberg equilibrium was determined and a molecular analysis of variance was performed to determine the genetic structure.Results: 38 Haplotypes were identified, with GCCTG4b as the most frequent (21.2%). The most diverse polymorphism was 448G>T with a frequency of 49.9% for heterozygous. The six polymorphisms were found in genetic equilibrium and genetic structure of populations was not evidenced (FST = 0,0038).Conclusion: The population studied does not present a genetic sub-structure and the polymorphisms analyzed were found in genetic equilibrium, this indicates that the population mixes randomly and there are no sub-groups capable of affecting the results of the association studies

Complejo de la esclerosis tuberosa, revisión de tema y presentación de caso / The tuberous sclerosis complex, review and case presentation

La esclerosis tuberosa fue descrita por primera vez en 1880 y corresponde a un trastorno autosómico dominante, en el que se ha identificado la mutación de dos genes responsables de la enfermedad. Desencadena una enfermedad sistémica que cursa con convulsiones y manifestaciones cutáneas, además de compromiso de riñón, pulmón y corazón. El compromiso del sistema nervioso central genera una gran morbilidad en los pacientes que la padecen, usualmente ante la presencia de tubérculos corticales, y el desarrollo a mediano plazo de las capacidades cognitivas depende su manejo temprano. El diagnóstico se establece por el cuadro clínico a partir de criterios mayores y menores establecidos, además del apoyo de estudios de imágenes y moleculares que permiten identificar las mutaciones de los genes TSC1 y TSC2. El manejo quirúrgico de las lesiones mejora la evolución clínica y el aspecto físico del paciente.

Ausencia de asociación entre síndrome metabólico y síntomas depresivos en adultos colombianos / Lack of association between metabolic syndrome and depressive symptoms in Colombian adults

Background: There is a possible association depressive symptoms (DS) and metabolic syndrome (MS), to the extent that treating one condition improves the other. Aim: To estimate the association between MS and DS among the employees of a medical school. Material and methods: Cross sectional study of 159 people aged 41±11 years (88 men). MS was evaluated according to International Diabetes Federation (IDF), National Cholesterol Education Program (NCEP)ZAdult Treatment Panel III (ATP-III) and ATP-IIIa criteria and the depression questionnaire of the Center for Epidemiológica! Studies (CES-D) was used for DS. A multivariate logistic regression was performed adjusting for age and gender. Results: The prevalence of MS according to ATP-III was 13.2 percent (95 percent CI: 8.4-19.5), to ATP-IIIa was 34.0 percent (95 percent CI: 26.6-41.9) and to IDF was 33.3 percent (95 percent CI: 26.1-41.2). The prevalence of clinically relevant SD was 15.1 percent (95 percent CI: 9.9-21.6). No significant association was found between DS and MS according to the different criteria: ATP-III OR 1.30 (95 percent CI: 0.40-4.24), ATP-IIIa OR 0.94 (95 percent CI: 0.37-2.33), IDF OR 1.20 (95 percent CI: 0.49-2.95). Conclusions: In this series, no association was observed between MS and depression.

Impacto de las nuevas definiciones en la prevalencia del síndrome metabólico en una población adulta de Bucaramanga, Colombia / Impact of the new definitions in the prevalence of the metabolic syndrome in an adult population at Bucaramanga, Colombia

Introducción. La prevalencia de síndrome metabólico depende de los criterios de clasificación empleados, como son los de la International Diabetes Federation y el Adult Treatment Panel o su modificación.Objetivo. Comparar la prevalencia del síndrome metabólico generada por cada una de las tres definiciones en una población de adultos. Materiales y métodos. Se estudiaron 155 personas (54,2 por ciento varones, edad promedio de 40,9 años). Se aplicaron las tres definiciones y se comparó la prevalencia con la prueba de Wilcoxon y la concordancia con kappa de Cohen. Resultados. La prevalencia de síndrome metabólico según el Adult Treatment Panel-III (ATP-III) fue 12,3 por ciento (IC95 por ciento 7,5-18,5), según el Adult Treatment Panel-IIIa (ATP-IIIa), 34,8 por ciento (IC95 por ciento 27,4-42,9) y según la International Diabetes Federation (IDF), 32,9 por ciento (IC95 por ciento 25,6-40,9). La prevalencia por ATP-III es inferior a la vista por ATP-IIIa e IDF (p<0,001), pero entre estas dos últimas es similar (p=0,083). Hay pobre concordancia entre ATP-III y ATP-IIIa (k=0,414, IC95 por ciento 0,409-0,420), y entre ATP-III e IDF (k=0,374, IC95 por ciento 0,368–0,379), pero muy buena entre ATP-IIIa e IDF (k=0,957, IC95 por ciento 0,950–0,963). Conclusión. Las nuevas definiciones para el síndrome metabólico (ATP-IIIa e IDF) aumentan tres veces la prevalencia del diagnóstico, sin encontrar diferencias entre ellas, a pesar de que la última organización incluye la obesidad central como un criterio necesario para el diagnóstico, cuando en la primera no se hace igual ponderación.

Introduction. The prevalence of metabolic syndrome depends on the criteria used for its classification. Three criteria in common use are those from International Diabetes Federation (IDF), the Adult Treatment Panel (ATP-III) or its update (ATP-IIIa). Objective. The prevalence statistic for generated for metabolic syndrome was compared for on the basis of each of the three criteria. Materials and methods. The sample consisted of 155 teachers and employees in the school of medicine. The average age was 40.9; 54.2% were men. The three criteria were applied and the prevalences were compared with the Wilcoxon test and Cohen’s kappa. Results. Metabolic syndrome prevalence generated by each criterion was as follows: ATP-III was 12.3% (95%CI 7.5-18.5), ATP-IIIa was 34.8% (95%CI 27.4-42.9) and IDF 32.9% (95%CI 25.6--40.9). The prevalence indicated by ATP-III was lower than the ATP-IIIa or IDF prevalances (p < 0,001); however those of ATPIII-a and IDF were similar (p=0,083). Poor agreement was seen between ATP-III and ATP-IIIa (k=0.414, IC95% 0.409-0.420), and between ATP-III and IDF (k=0.374, IC95% 0.368-0.379); however, very good agreement was obtained between ATP-IIIa and IDF (k=0.957, IC95% 0.950-0.963). Conclusion. The new definitions for metabolic syndrome, ATP-IIIa and IDF, increase the prevalence statistic by three times. This occurred despite the inclusion in IDF of an obesity factor in the criteria set.

Non-HLA associations with autoimmune diseases.

Susceptibility to autoimmune diseases (AID) has been associated with multiple combinations of genes and environmental or stochastic factors. The strongest influence on susceptibility to autoimmunity is the major histocompatibility complex (MHC), in particular HLA; however, linkage analyses among multiple affected family members have established that non-MHC chromosomal susceptibility regions also influence the susceptibility towards AID. Besides HLA, three non-HLA genes have been convincingly associated with different AID: Citotoxic T lymphocyte-associated antigen 4 (CTLA4), Protein Tyrosine Phosphatase (PTPN22) and Tumor Necrosis Factor-alpha (TNF), indicating that autoimmune phenotypes could represent pleiotropic outcomes of non-specific diseases' genes that underline similar immunogenetic mechanisms. Identification of genes that generate susceptibility will enhance our understanding of the mechanisms that mediate these complex diseases and will allow us to predict and/or prevent them as well as to discover new therapeutic interventions.

Human CRP gene polymorphism influences CRP levels: implications for the prediction and pathogenesis of coronary heart disease.

OBJECTIVE: C-reactive protein (CRP) concentrations are predictive of cardiovascular disease, and levels are heritable, in part. We identified novel polymorphisms in the CRP gene and assessed their influence on CRP level. METHODS AND RESULTS: CRP was measured in 250 male army recruits before and after strenuous exercise and perioperatively in 193 coronary artery bypass graft (CABG) patients. Two novel polymorphisms were identified in the CRP gene, -717G>A in the promoter and +1444C>T in the 3'UTR. Among army recruits, CRP was higher in +1444TT homozygotes than +1444 C-allele carriers at baseline (1.04+/-0.38 versus 0.55+/-0.06, P=0.014) and at all time points after exercise (2.35+/-0.68 versus 1.07+/-0.12, 2.11+/-0.53 versus 0.88+/-0.09, and 1.77+/-0.44 versus 0.71+/-0.09, P=0.034, P=0.007, and P=0.013, at 2, 48, and 96 hours after exercise, respectively). In the CABG patients, mean CRP (mg/L) rose from 1.97+/-0.36 at baseline to 167.2+/-5.0 72 hours postoperatively. Genotype did not influence CRP at baseline; however, peak post-CABG CRP levels were higher in +1444TT homozygotes compared with +1444C-allele carriers (198+/-17 versus 164+/-5, P=0.03). CONCLUSIONS: The CRP gene +1444C>T variant influences basal and stimulated CRP level. These findings have implications both for the prediction and pathogenesis of coronary heart disease.

Estado actual del diagnóstico de la toxoplasmosis en la mujer embarazada y su feto / Present state of toxoplasmosis diagnosis on pregnant women and in her fetus

La toxoplasmosis adquirida por la mujer embarazada tiene la mayoría de las veces una presentación subclínica, y su diagnóstico se basa en exámenes serológicos sistemáticos, para verificar sí la gestante está inmunizada, o si es susceptible al Toxoplasma. Las gestantes no inmunizadas (seronegativas), conforman un grupo de especial cuidado, en las cuales la repetición de las pruebas serológicas debe permitir un diagnóstico precoz y un manejo apropiado de las primoinfecciones. Por otro lado la infección congénita con Toxoplasma gondii puede producir alteraciones serias del desarrollo fetal; con el fin de reducir las graves secuelas mediante tratamiento antiparasitario oportuno, se hace necesario la implementación de herramientas que permitan realizar un diagnóstico temprano de la infección fetal, con técnicas que sean altamente específicas y de gran sensibilidad y además, que en lo posible sean inocuas para el feto. La presente revisión describe las principales secuencias metodológicas desarrolladas, y actualmente utilizadas en diversos países para la detección serológica de la seroconversión de las madres gestantes, y la manera de descartar la transmisión congénita del parásito