Epidemiological studies have shown a dramatic increase in the incidence and the prevalence of allergic diseases over the last several decades. Environmental triggers including risk factors (e.g., pollution), the loss of rural living conditions (e.g., farming conditions), and nutritional status (e.g., maternal, breastfeeding) are considered major contributors to this increase. The influences of these environmental factors are thought to be mediated by epigenetic mechanisms which are heritable, reversible, and biologically relevant biochemical modifications of the chromatin carrying the genetic information without changing the nucleotide sequence of the genome. An important feature characterizing epigenetically-mediated processes is the existence of a time frame where the induced effects are the strongest and therefore most crucial. This period between conception, pregnancy, and the first years of life (e.g., first 1000 days) is considered the optimal time for environmental factors, such as nutrition, to exert their beneficial epigenetic effects. In the current review, we discussed the impact of the exposure to bacteria, viruses, parasites, fungal components, microbiome metabolites, and specific nutritional components (e.g., polyunsaturated fatty acids (PUFA), vitamins, plant- and animal-derived microRNAs, breast milk) on the epigenetic patterns related to allergic manifestations. We gave insight into the epigenetic signature of bioactive milk components and the effects of specific nutrition on neonatal T cell development. Several lines of evidence suggest that atypical metabolic reprogramming induced by extrinsic factors such as allergens, viruses, pollutants, diet, or microbiome might drive cellular metabolic dysfunctions and defective immune responses in allergic disease. Therefore, we described the current knowledge on the relationship between immunometabolism and allergy mediated by epigenetic mechanisms. The knowledge as presented will give insight into epigenetic changes and the potential of maternal and post-natal nutrition on the development of allergic disease.

Long QT syndromes can be either acquired or congenital. Drugs are one of the many etiologies that may induce acquired long QT syndrome. In fact, many drugs frequently used in the clinical setting are a known risk factor for a prolonged QT interval, thus increasing the chances of developing torsade de pointes. The molecular mechanisms involved in the prolongation of the QT interval are common to most medications. However, there is considerable inter-individual variability in drug response, thus making the application of personalized medicine a relevant aspect in long QT syndrome, in order to evaluate the risk of every individual from a pharmacogenetic standpoint.

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Humans have coexisted with helminths and bacteria for the entire existence of our species. Nowadays, helminth infections affect more than 1.9 billion people worldwide, especially in underdeveloped regions that lack optimal sanitary conditions. In addition, commensal microorganisms inhabit several compartments of humans, including the gastrointestinal tract, constituting what we know as the microbiota. Helminths and bacterial microbiota can interact in various ways. In this review, the interactions between helminths and commensal bacteria are analyzed in both animal models and humans. In developing countries, the gut microbiota exhibits high diversity, which could be linked to the high burden of helminthiasis in these areas. In fact, several studies show that helminth infections are associated with an increased gut microbiota diversity and changes in its composition. Interestingly, these changes can modify the risk for some diseases, such as asthma, colitis, viral infections, and metabolic conditions. Besides, the microbiota is necessary for the establishment of some helminth infections and can also influence the evolution of these diseases. Specific bacterial taxa can contribute to the resistance or susceptibility to certain helminths. The mechanisms underlying helminth–microbiota interactions are not completely understood. More research is necessary to address this and other unmet needs, especially considering that available studies are heterogeneous and sometimes yield conflicting results

Purpose of Review Helminth infections modify the natural history of allergic diseases, by either decreasing or increasing their symptoms. Several helminth components are involved in the increasing of the allergic response and symptoms, overcoming the concomitant immunosuppression of helminthiases. However, the role of individual IgE-binding molecules in this process remains to be defined. Recent Findings We updated the list of helminth allergens and IgE-binding molecules, their effects on asthma presentation, and their impact on allergy diagnosis. Data from genetic and epigenetic studies of ascariasis are analyzed. A new species-specific A. lumbricoides allergen has been discovered, with potential use in molecular diagnosis. Summary Most helminth IgE-binding components are not officially classified as allergens in the WHO/IUIS database, although there is evidence of their influence increasing allergic manifestations. Further immunological characterization of these components is needed to better understand their mechanisms of action and evaluate the ways in which they can influence the diagnosis of allergy.

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Introduction In Colombia Breast cancer (BC), is the most frequent and has the highest mortality rate among all types of cancer. There are few studies of the genomic profile in unselected affected population by BC in Colombia. Some of these studies have only tested the presence of variants reported as founders named “Colombian Profile”.We conducted a large-scale genomic analysis using Whole Exome Sequencing (WES) to evaluate germline mutations in unselected BC patients. Methods This trial included 299 unselected BC female patients aged over 18 years old, without personal and family history of germline BC risk mutations.The protocol was approved by the IRC and EC of Fundación Cardioinfantil (FCI). All patients signed informed consent before recruitment.Genomic DNA was extracted from peripheral blood samples and was used to WES (Novogene Inc. Beijing, China). The variants were filtered using VarSeq v2.1.1 software, following the criteria: missense, non-sense, frameshift, and intronic variants, we additionally considered a MAF ≤0.01 for ATM, CHEK2, and PALB2 genes.Clinical significance of each variant was annotated according to the ACMG/AMP and ENIGMA guidelines.MLPA was assessed using the commercial kit SALSA MLPA Probemix P002-D1 for BRCA1 and P090-C1 for BRCA2 (MRC-Holland, Amsterdam).This study was financially supported by an unrestricted grant from Pfizer. Results This abstract is the first report from 299 patients. To determine the presence of germline variants in the patients a WES was performed. Here we describe the pathogenic and probably pathogenic mutations in BRCA1, BRCA2, ATM, CHEK2, PALB2. We found BRCA1/2 alterations were found in 3.7% of the patients (11 patients, IC 95% 1.7-5.6%), 5 patients in BRCA1 and 6 patients in BRCA2 (1.7% IC 95% 0.7-4%, and 2% IC 95% 0.9-4.4% respectively). We found 29 patients had mutations unrelated to BRCA1/2 (9.5% IC 95% 5.8-11.7%). The most frequently affected gene was ATM (17 patients, 5.7% IC95% 3.6-9%). Discussion and conclusion We found that 12.2% of the population of the study were carriers of a pathogenic/likely pathogenic variant in the evaluated genes, and interestingly 9.5% of them corresponded to non-BRCA1/2 genes. ATM variants have a prevalence of 5.7% in the whole population and represent 42% of all the variants. Other mutations in genes like BRCA2, ATM and CHEK2 were exclusive in non-TNBC. Meanwhile, BRCA1 and PALB2 mutations had higher frequencies in TNBC. We identified five novel mutations.We demonstrate that LGRs are not an important molecular cause in non-hereditary cases of BC.27% of the carriers of mutations in BRCA1/2 did not fulfilled NCCN criteria and 82% of the mutations are not described in “Colombian Profile”. These findings demonstrate the particular genetic profile in an unselected population with breast cancer, and this highlights the importance of WES as a molecular diagnostic tool. We think that universal germline testing in cancer should be considered. Baseline demographic and clinical characteristics Demographic and clinical characteristics of patients with pathogenic and likely pathogenic mutationsVariableBRCA1 n (%, IC 95%)BRCA2 n (%, IC 95%)ATM n (%, IC 95%)PALB2 n (%, IC 95%)CHEK2 n (%, IC 95%)Median age37.4 (22.4 – 54.3)45.5 (36.2 – 54.7)53.1 (45.4 – 60.7)55.8 (27.9 – 83.5)NA*Age≤ 50 years4 (80, 11.1 – 99.2%)4 (66.7, 14.8 – 95.8%)8 (47.1, 23.5 – 80%)2 (50, 24.7 – 97.5)NA*> 50 years1 (20, 0.7 – 88.9%)2 (33.3, 4 – 85%)9 (52.9, 28 – 76.5%)2 (50, 24.7 – 97.5)OverweightYes4 (80, 11 – 99-2%)(33.3, 4 – 85%)9 (52.9, 28 – 76.5%) 3 (75, 0.4 – 99.5%)NA*No1 (20, 0.8 – 88.9%)(66.7, 14.9 – 94.8%)8 (47, 23.5 – 80%)1 (25, 0.4 – 95.9%)Estrogen receptor(+)2 (0.9%, 0.2 – 3.5%)5 (2.2%, 0.9 – 5.3%)16 (7.1%, 4.4 – 11.3%)3 (1.3%, 0.4 – 4.1%)3 (1.3%, 0.4 – 4.1%)(-)3 (4.3%, 1.4 – 12.6%)1 (1.4%, 0.2 – 9.6%)1 (1.4%, 0,2 – 9.6%)1 (1.4%, 0.2 – 9.6%)1 (1.4%, 0.2 – 9.6%)Progesterone receptor(+)2 (0.9%, 0.2 – 3.5%)5 (2.2%, 0.9 – 5.3%)13 (6%, 3.7 – 10.5%)3 (1.3%, 0.4 – 4.1%)4 (1.9%, 0.7 – 5%)(-)3 (4.3%, 1.4 – 12.6%)1 (1.4%, 0,2 – 9.6%)4 (4%, 1.7 – 11.7%)1 (1.4%, 0.2 – 9.6%)0HER-2 3+Yes1 (1.3%, 0.2 – 8.5%)1 (1.3%, 0.2 – 8.5%)4 (5%, 1.9 – 12.7%)1 (1.3%, 0.2 – 8.5%)2 (2.5%, 0.6 – 9.6%)No4 (1.9%, 0.7 – 4.9%)5 (2.3, 0.1 – 5.5%)13 (6%, 3.5- 10.2%)3 (1.4%, 0.4 – 4.3%)2 (0.9%, 0.2 – 3.7%)ER/Pgr y HER-2 negativeYes2 (5.1, 1.3 – 18.7%)001 (2.5%, 0-3 – 16.5%)0No3 (1.2%, 0.4 – 3.6%)6 (2.3%, 1 – 5.1%)17 (6.6%, 4-2 – 10.4%)3 (1.2%, 0.4 – 3.6%)4 (1.6%, 0.6 – 4.1%)Ki67<20%0 1 (16.7, 0.9 – 81%) 5 (29.4, 11.5 – 57.1)0NA*≥20%5 (100%)5 (83.3, 18.6 – 99%)12 (70.6, 42.8 – 88.5%)4 (100%)Median tumoral size mm (min-max)24 (19.6 – 47.8)21 (12.5 – 29.5)24.9 (19.6 – 30.3)27.6 (0 – 59)NA* Lymph nodes involvementYes1 (0.7%, 0.1 – 4.6%)2 (1.3%, 0.3 – 5.2%)10 (6.7%, 3.6 – 12.1%)3 (2%, 0.6 – 6.1%)4 (2.7%, 1 – 7%)1No4 (2.7%, 1 – 7%)4 (2.7%, 1 – 7%)7 (4.7%, 2.2 – 9.5%)1 (0.7%, 0.1 – 4.6%)0MetastasisYes00001 (9%, 1.1 – 46.6%)2No5 (1.9%, 0.8 – 4.5%)6 (2.3%, 1 – 5%)17 (5.7%, 3.5 – 9.3%)4 (1.5 – 0.5 – 4%)3 (1.1%, 0.4 – 3.5%)Clinical stage (AJCC)I2 (40, 3.7 – 91.9%)1 (16.7, 0.9 – 81.3%)4 (23.5, 81 – 51.8%)0NA*II2(40 3.7 – 91.9%)4 (66.7, 14.8 – 95.8%)7 (41.2, 19.3 – 67.3%)4 (100%)III1 (20, 0.7 – 88.9%)1 (16.7, 0.9 – 81.3%)6 (23-3, 15.2 – 62.3%)0IV0000Family history for cancerYes4 (80, 11.1 – 99.2%)5 (83.3, 9 – 81.4%)13 (76.5 – 48.2 – 91.9%)2 (50, 2- 97.5%)NA*No1 (20, 0.7 – 88-9)1 (16.7, 0.9 – 81.4%)4 (23, 8 – 51.8%)2 (50, 2- 97.5%)NCCN criteriaYes4 (2.4%, 0.9 – 6.3%)4 (2.4%, 0.9 – 6.3%)NA*NA*NA*No1 (0.8%, 0.1 – 5.9%)2 (1.7%, 0.4 – 6.6%)Colombian profileYes1 (50%, 19 – 98%)31(50%, 19 – 98%)3NA*NA*NA*No4 (13.5%, 5 – 35.5%)5 (17%, 7 – 40%) Citation Format: Diana Carolina Sierra-Díaz, Adrien Morel, Dora Janeth Fonseca, Nora Contreras, Mariana Angulo-Aguado, Valentina Balaguera, Kevin Llinás-Caballero, Isabel Munevar, Mariana Borras, Mauricio Lema, Henry Idrobo, Daniela Trujillo, Norma Serrano, Ana Isabel Orduz, Diego Lopera, Jaime Gonzalez, Gustavo Rojas, Paula Londoño, Ray Manneh, Catalina Quintero, Paul Laissue, Rodrigo Cabrera, Carlos M Restrepo, William Mantilla. Genetic profile of germline mutations in unselected women with breast cancer in a Colombian population [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-07-05.

Objetivos: el cáncer de mama (CM) es la neoplasia más frecuente en Colombia. La supervivencia global a 5 años es <80 %, siendo el país latinoamericano con el peor pronóstico. Las estrategias preventivas como la identificación de población con riesgo de síndrome de CM y ovario hereditario (HBOC), tiene el potencial de reducir la incidencia de CM y disminuir los diagnósticos en estadios avanzados. La mayoría de los estudios publicados en población colombiana, han evaluado variantes reportadas como fundadoras, denominadas el “Perfil Colombia” o en población seleccionada con alta probabilidad de presentar HBOC. En este estudio realizamos un análisis genómico a gran escala para evaluar mutaciones germinales en pacientes con CM no seleccionadas, en múltiples regiones del país.