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The Covid-19 pandemic revealed a complex health problem for people and national health systems. Faced with the initial ignorance of the behavior of the SARS-COV-2 virus in populations, people turned to relief and alternative medicines. In Ecuador, the use of traditional or western medicine and the systematic approach of people to conventional medicine are evident realities. Our work aimed to assess the knowledge, attitudes and practices regarding Covid-19 and the use of formal and traditional medicine to treat the disease or contagion. An open, personal and confidential survey was carried out, with 158 questions on general data, ethnicity, health status, covid-19 tests, use of self-medication, use of medicinal plants or other chemical products, and use of antibiotics or antiparasitics, among other data. In the control of the patients, six months after finishing the survey, they were asked about the acceptance of the vaccine and the decision to be vaccinated or not. The results in 3,000 persons (50% female and 50% male) show frequent use of alternative or traditional medicine, even in health personnel or university studies. The study's conclusions reflect that people choose any of the therapies they have access to and even mix traditional treatments with traditional ones that are unproven or toxic. Keywords: knowledge, attitudes, practices, covid-19, formal medicine, traditional medicine

Se presenta una revisión sobre el estado del conocimiento de la genética y la genómica del cáncer de mama. Se hace referencia a estudios globales sobre genes de predisposición a este tipo de cáncer, así como genes de apoyo al diagnóstico y tratamiento. Adicionalmente se nombran algunos genes útiles en el trabajo clínico y en el manejo del cáncer de mama.

The case of a 4-year-two-month-old female patient is presented, who consulted for a special phenotype: psychomotor retardation, short stature, microcephaly, large and low-set ears, small forehead, prominent brow ridges, labial commissure open, ocular hypertelorism, short neck, mammary hypertelorism and pectus excavatum. The objective of this study is to analyze a patient with unusual phenotypic traits, through physical examination, comparative analysis with other cases, and genetic studies. The cytogenetic study revealed a mosaic karyotype, mos 46,XX,r(15)(q26.3)/46,XX with the presence of the ring in 83%. The genetic mapping array study identified the loss of 3.5 Mb in 15q26.3. Among the genes lost in the terminal region of 15q, an interaction between their protein products was evidenced according to the STRING analysis. This is the second case of a ring chromosome 15 reported in Ecuador. And it would be the 101st in the world since 1966. The special phenotype of these individuals is related to the amount of genetic material lost. The genes involved in the formation of the ring, as well as the proteins that determine these genes and the relationships in different cellular pathways, are analyzed in silico in order to understand the pathophysiology of this disorder. Its diagnosis is mostly postnatal, so the clinical approach differs individually according to the symptoms and signs that appear.

Batrachochytrium dendrobatidis (Bd) infection is one of the principal causes of amphibian declines worldwide. The presence of Bd has been determined in Gastrotheca riobambae tadpoles that inhabit ponds in Quito's Metropolitan Guangüiltagua Park, Ecuador. This study sought to determine whether these tadpoles are infected and to determine the presence of chytridiomycosis in another frog species, Pristimantis unistrigatus, which also inhabits the park and has different reproductive biology and distinct behavioral habits. We used end-point and real-time PCR techniques to detect and quantify Bd infection. At 1 yr, samples were taken from the skin of P. unistrigatus using swabs and were also taken from the mouthparts of G. riobambae tadpoles. It was found that the two species were infected with a Bd prevalence of 39% (53/135) in G. riobambae tadpoles and 15% (57/382) in P. unistrigatus frogs. The two types of samples (tissue and swabs) from mouthparts showed differences in the zoospores per microliter loads (x̄=1,376.7±3,450.2 vs. x̄=285.0±652.3). Moreover, a correlation (r2=0.621) was discovered between the monthly mean maximum temperature of the pond with disease prevalence in G. riobambae tadpoles. Infection levels in the P. unistrigatus population varied significantly over time, and distance to the pond was a determinant factor for infection intensity.

The ethnic group Shuar is located in Ecuador. To identify their genetic composition, 46 ancestry-informative insertion deletion markers (AIM-INDELs) were used. Also, characterization of 15 tandem repeats (STRs) in the AmpFISTR Identifiler Kit were applied. Forensic parameters showed a matching probability of 0.1535, a power of discrimination of 0.8465, a polymorphism information content of 0.6584, probability of exclusion of 0.415 and a typical paternity index of 1.78. The Shuar are not influenced by admixture population events, being a Native American group 98.7%, along with a genetic diversity of 0.699346+/-0.356964.

Allele frequencies, and genetic data for 12 autosomal Short Tandem Repeat (STRs) loci (D2S1360, D3S1744, D4S2366, D5S2500, D6S474, D7S1517, D8S1132, D10S2325, D12S391, D18S51, D21S2055, and SE33 [ACTBP2]) using the Investigator® HDplex kit (QIAGEN) were obtained from 200 non-related individuals from the Ecuadorian mestizo population. Subjects included 100 men and 100 women, from the 24 provinces of Ecuador. Heterozygosity (Ho), power of discrimination (PD), power of exclusion (PE) and polymorphism information content (PIC) were estimated for the population sample. Locus SE33 had the highest values for power of discrimination (0.9372), polymorphism information content (0.9338), and power of exclusion (0.7852). The most informative STRs for the Ecuadorian population were SE33, D7S1517, D10S2325 and the least informative were D2S1360, D3S1744 and D6S474. The Investigator® HDplex makers have shown to be highly informative in the Ecuadorian population and are suitable as a powerful complementary tool in forensic analysis and complex kinship cases.

The perception of taste is determined by several factors, including genetics, which at the same time is related with the diet and diseases in different populations. We aimed to identify the frequency of six single nucleotide polymorphisms (rs307355, rs35744813, rs713598, rs1726866, rs10246939 and rs11091046) involved in the perception of sweet, bitter and salty flavor in Ecuadorian mestizo population. It was found that the presence of the T allele of rs307355 and rs35744813 is associated with decreased ability of subjects to carry out specific discrimination of sweetness, this is particularly interesting given the correlation found (p = 0.0022) between sucrose perception and family history of cancer and diabetes. Furthermore, rs713598, rs1726866 and rs10246939 do not influence the ability to perceive the bitter taste. Concerning the perception of the salty taste, rs11091046 does influence the capacity of detecting it more easily. This theoretical knowledge of the genetic influence on taste perception can contribute to the understanding of eating habits and their impact on human health.

Fifteen autosomal STRs were analyze in order to elucidate the differences between low and high land Ecuadorian population. Seven Ecuadorian geographic areas (Tisaleo-Mocha, Canar, Quito, Rocafuerte, Santa Rosa, Guayaquil and Lago Agrio) from different altitude were selected for the study. After the analysis, little genetic distances were observed between all cities, the more distant cities (FST = 0.02354) were Rocafuerte at an elevation of 17 m.a.s.l. and Quito at 2850 m.a.s.l. and the similar cities (FST = 0.00033) were Rocafuerte (17 m.a.s.l.) and Santa Rosa (10 m.a.s.l). In conclusion, there is not a great genetic distance in the 15 STRs reported in high and low land Ecuadorian population, therefore previously reported frequencies could been used in identification and paternity cases under analysis.

Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder characterized by self-mutilating behavior, unexplained fever, inability to sweat and intellectual disability. CIPA pathogenesis is associated with genetic loss-of-function mutations of the NTRK1 gene, which is auto phosphorylated activating intracellular signaling transduction such as cell survival, growth and differentiation. CIPA occurs with an incidence of 1 in 125 million newborns, and only some hundreds of cases have been reported worldwide. Most of cases have been reported in Asian countries. Here, we estimate the ancestral proportions of a family with consanguinity background affected with CIPA, who carries the missense pathogenic mutations rs80356677 (Asp674Tyr) in the kinase domain of NTRK1 and rs324420 (Pro129Thr) in the FAAH gene. The ancestral proportion was calculated through 45 ancestry informative markers (AIMs) and the comparison was done through the Human Genome Diversity Project panel. The resulting allele frequencies in CIPA family indicate a prevalence of the Native American ancestral component with 87.9%, and minor proportion for the European (8.9%) and African (3%) components. In conclusion, the genetic variations expressing CIPA in a Native American Ecuadorian family could have been caused by the insertion of certain genetic characteristics, which have been passed down from common ancestors as consequence of migration towards South America.

The X-STR markers represent a powerful tool to complement the information provided by the autosomal and Y chromosome markers, particularly, in cases involving at least one woman. In the present study, allele frequencies, power of exclusion (PE), power of discrimination (PD) and polymorphism information content (PIC) were analyzed for 12 X chromosome loci. A total of 200 unrelated Ecuadorian individuals were selected for the population analysis. The data showed that DXS10135 locus had the highest power of discrimination value (PD = 0.9351), and polymorphism information content (PIC = 0.9313). The heterozygosity observed ranged from 0.9300 to 0.6400. The power of exclusion varied between 0.3417 to 0.8570 for DXS10135 and DXS8378 respectively. No significant departure from Hardy Weinberg equilibrium (HWE) was detected for any of the analyzed markers. The X-STR markers have demonstrated their potential to efficiently complement the analysis to solve complex kinship and forensic cases.

X chromosome STR markers are a useful tool in population genetics, they provide supplementary information for forensic and kinship analysis where autosomal and Y chromosome information is not enough. A total of 100 unrelated individuals from Imbabura-Ecuador were genotyped using the X-STR Decaplex system (DXS8378, DXS9902, DXS7132, DXS9898, DXS6809, DXS6789, DXS7133, GATA172D05, GATA31E08, and DXS7423). Allele frequencies and population parameters were calculated for each STR. The most informative marker was DXS6809 and the least informative was DXS7133. High discrimination power values were obtained (greater than 99.99%), as well as high mean exclusion chance in trios (mother / daughter / father) 0.9999948011 and duos (father/daughter) 0.9992880836. The genetic distance (FST) obtained comparing the Ecuadorian population and the Pichincha province population show low genetic distances. The data analyzed confirmed the potential of these 10 X-STRs.

Colorectal cancer is one of the leading causes of cancer death worldwide. Over the last decades, several studies have shown that tumor-related genomic alterations predict tumor prognosis, drug response, and toxicity. These observations have led to the development of several therapies based on individual genomic profiles. As part of these approaches, pharmacogenomics analyses genomic alterations which may predict an efficient therapeutic response. Studying these mutations as biomarkers for predicting drug response is of a great interest to improve precision medicine. We conduct a comprehensive review of the main pharmacogenomics biomarkers and genomic alterations affecting enzyme activity, transporter capacity, channels, and receptors; and therefore the new advances in CRC precision medicine to select the best therapeutic strategy in populations worldwide, with a focus on Latin America.

Dentro de los defectos congénitos más frecuentes se encuentran las fisuras labio y/o palatinas (FL/P), presentando una prevalencia de alrededor de 1:1.000 nacimientos vivos. El 70% de FL/P son de tipo no sindrómico, lo cual hace referencia a que se encuentran como un defecto aislado sin anomalías adicionales. Poseen una etiología compleja con un componente tanto ambiental como genético. Con el desarrollo de tecnologías de secuenciación del genoma humano se han identificado variantes polimórficas que pueden estar asociadas al fenotipo de FL/P y por tal motivo pueden contribuir a la etiología multifactorial de éstas. En esta revisión se describen las variantes comúnmente asociadas y su papel en la etiología de las FL/P. Los SNPs localizados en los genes IFR6, MSX1, VAX1, PAX9, CHD1, FGF1, GREM1 y WNT3 se han relacionado significativamente con la presencia de FL/P, y las variantes ubicadas en los genes APC, GSK3, DVL2, BMP4, ABCA4, BHMT, NTN1, TBX1, EPHA3, FAM49A, MGMT, MMP3, TIMP2 y NOG aunque se ha reportado su asociación con la presencia de las fisuras orofaciales aún no es clara su relación con dicho fenotipo. Es importante realizar estudios de identificación de variantes genéticas que involucren poblaciones específicas con el fin de poder comprender la etiología de las FL/P no sindrómicas.

Los sistemas de registro y de reporte de datos son de gran interés, puesto que respaldan la reproducibilidad y transparencia científica. La investigación actual genera una gran cantidad de datos que ya no se pueden documentar utilizando cuadernos de laboratorio de papel (CLP). Los cuadernos electrónicos de laboratorio (CEL) podrían ser una solu-ción prometedora para reemplazar los CLP y promover la reproducibilidad científica y su transparencia. Anteriormente analizamos cinco CEL y realizamos dos encuestas para implementar un CEL en un instituto de investigación biomédica. Entre los CEL proba-dos, encontramos que Microsoft OneNote presenta numerosas características relacio-nadas con las mejores funcionalidades del CEL. Además, ambos grupos encuestados prefirieron OneNote sobre un CEL científico (Elements de PerkinElmer). Sin embargo, OneNote es una aplicación general para tomar notas que no ha sido diseñada para fi-nes científicos. Por lo tanto, en este trabajo proporcionamos varias pautas para adaptar OneNote a un flujo de trabajo experimental.

Background Anaplastic astrocytoma is a rare disorder in children from 10 to 14 years of age, with an estimated 0.38 new cases per 100,000 people per year worldwide. Panel-based next-generation sequencing opens new possibilities for diagnosis and therapy of rare diseases such as this one. Because it has never been genetically studied in the Ecuadorian population, we chose to genetically characterize an Ecuadorian pediatric patient with anaplastic astrocytoma for the first time. Doing so allows us to provide new insights into anaplastic astrocytoma diagnosis and treatment. Case presentation Our patient was a 13-year-old Mestizo girl with an extensive family history of cancer who was diagnosed with anaplastic astrocytoma. According to ClinVar, SIFT, and PolyPhen, the patient harbored 354 genomic alterations in 100 genes. These variants were mostly implicated in deoxyribonucleic acid (DNA) repair. The top five most altered genes were FANCD2, NF1, FANCA, FANCI, and WRN. Even though TP53 presented only five mutations, the rs11540652 single-nucleotide polymorphism classified as pathogenic was found in the patient and her relatives; interestingly, several reports have related it to Li-Fraumeni syndrome. Furthermore, in silico analysis using the Open Targets Platform revealed two clinical trials for pediatric anaplastic astrocytoma (studying cabozantinib, ribociclib, and everolimus) and 118 drugs that target the patient’s variants, but the studies were not designed specifically to treat pediatric anaplastic astrocytoma. Conclusions Next-generation sequencing allows genomic characterization of rare diseases; for instance, this study unraveled a pathogenic single-nucleotide polymorphism related to Li-Fraumeni syndrome and identified possible new drugs that specifically target the patient’s variants. Molecular tools should be implemented in routine clinical practice for early detection and effective preemptive intervention delivery and treatment.

Background Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder characterized by insensitivity to pain, inability to sweat and intellectual disability. CIPA is caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) that encodes the high-affinity receptor of nerve growth factor (NGF). Case presentation Here, we present clinical and molecular findings in a 9-year-old girl with CIPA. The high-altitude indigenous Ecuadorian patient presented several health problems such as anhidrosis, bone fractures, self-mutilation, osteochondroma, intellectual disability and Riga-Fede disease. After the mutational analysis of NTRK1, the patient showed a clearly autosomal recessive inheritance pattern with the pathogenic mutation rs763758904 (Arg602*) and the second missense mutation rs80356677 (Asp674Tyr). Additionally, the genomic analysis showed 69 pathogenic and/or likely pathogenic variants in 46 genes possibly related to phenotypic heterogeneity, including the rs324420 variant in the FAAH gene. The gene ontology enrichment analysis showed 28 mutated genes involved in several biological processes. As a novel contribution, the protein-protein interaction network analysis showed that NTRK1, SPTBN2 and GRM6 interact with several proteins of the pain matrix involved in the response to stimulus and nervous system development. Conclusions This is the first study that associates clinical, genomics and networking analyses in a Native American patient with consanguinity background in order to better understand CIPA pathogenesis.

Many studies, comparing the health associated risks of electronic cigarettes with conventional cigarettes, focus mainly on the common chemical compounds found between them. We therefore reviewed chemical compounds found exclusively in electronic cigarettes and describe their genotoxic and carcinogenic effects. The eligibility criteria included articles related exclusively to conventional and electronic cigarettes chemical composition. Articles which reported to be financed from cigarettes industries were excluded. Chemical compounds reported in the selected studies from conventional and electronic cigarettes were tabulated using the Chemical Abstracts Service registry number for chemical substances information. A total of 57 chemical compounds were exclusively reported to be present in electronic cigarettes. To further analyze e-cigarette carcinogenic effects, a gene set, previously reported to be deregulated in the oral epithelium of e-cigarettes users, was genomically analyzed in 32 PanCancer Atlas Studies. The crucial health risks identified were: eye, skin and respiratory tract irritation, with almost 50% of incidence. The main cancer risks associated with e-cigarettes were: ovarian, uterine, bladder, lung, esophageal and stomach carcinomas and adenocarcinomas. Despite being considered as less harmful for human health, the use of these devices is not recommended for first time users and it is considered hazardous for dual users.

[Abstract] Breast cancer (BC) is a heterogeneous disease where genomic alterations, protein expression deregulation, signaling pathway alterations, hormone disruption, ethnicity and environmental determinants are involved. Due to the complexity of BC, the prediction of proteins involved in this disease is a trending topic in drug design. This work is proposing accurate prediction classifer for BC proteins using six sets of protein sequence descriptors and 13 machine-learning methods. After using a univariate feature selection for the mix of fve descriptor families, the best classifer was obtained using multilayer perceptron method (artifcial neural network) and 300 features. The performance of the model is demonstrated by the area under the receiver operating characteristics (AUROC) of 0.980±0.0037, and accuracy of 0.936±0.0056 (3-fold cross-validation). Regarding the prediction of 4,504 cancer-associated proteins using this model, the best ranked cancer immunotherapy proteins related to BC were RPS27, SUPT4H1, CLPSL2, POLR2K, RPL38, AKT3, CDK3, RPS20, RASL11A and UBTD1; the best ranked metastasis driver proteins related to BC were S100A9, DDA1, TXN, PRNP, RPS27, S100A14, S100A7, MAPK1, AGR3 and NDUFA13; and the best ranked RNA-binding proteins related to BC were S100A9, TXN, RPS27L, RPS27, RPS27A, RPL38, MRPL54, PPAN, RPS20 and CSRP1. This powerful model predicts several BC-related proteins that should be deeply studied to fnd new biomarkers and better therapeutic targets. Scripts can be downloaded at https://github.com/muntisa/ neural-networks-for-breast-cancer-proteins. This work was supported by a) Universidad UTE (Ecuador), b) the Collaborative Project in Genomic Data Integration (CICLOGEN) PI17/01826 funded by the Carlos III Health Institute from the Spanish National plan for Scientific and Technical Research and Innovation 2013-2016 and the European Regional Development Funds (FEDER) - “A way to build Europe”; c) the General Directorate of Culture, Education and University Management of Xunta de Galicia ED431D 2017/16 and “Drug Discovery Galician Network” Ref. ED431G/01 and the “Galician Network for Colorectal Cancer Research” (Ref. ED431D 2017/23); d) the Spanish Ministry of Economy and Competitiveness for its support through the funding of the unique installation BIOCAI (UNLC08-1E-002, UNLC13-13-3503) and the European Regional Development Funds (FEDER) by the European Union; e) the Consolidation and Structuring of Competitive Research Units - Competitive Reference Groups (ED431C 2018/49), funded by the Ministry of Education, University and Vocational Training of the Xunta de Galicia endowed with EU FEDER funds; f) research grants from Ministry of Economy and Competitiveness, MINECO, Spain (FEDER CTQ2016-74881-P), Basque government (IT1045-16), and kind support of Ikerbasque, Basque Foundation for Science; and, g) Sociedad Latinoamericana de Farmacogenómica y Medicina Personalizada (SOLFAGEM) Xunta de Galicia; ED431D 2017/16 Xunta de Galicia; ED431G/01 Xunta de Galicia; ED431D 2017/23 Xunta de Galicia; ED431C 2018/49 Gobierno Vasco; IT1045-16

Background According to history, in the pre-Hispanic period, during the conquest and Inka expansion in Ecuador, many Andean families of the Cañar region would have been displaced to several places of Tawantinsuyu, including Kañaris, a Quechua-speaking community located at the highlands of the Province of Ferreñafe, Lambayeque (Peru). Other families were probably taken from the Central Andes to a place close to Kañaris, named Inkawasi. Evidence of this migration comes from the presence near the Kañaris–Inkawasi communities of a village, a former Inka camp, which persists until the present day. This scenario could explain these toponyms, but it is still controversial. To clarify this historical question, the study presented here focused on the inference of the genetic relationship between ‘Cañaris’ populations, particularly of Cañar and Ferreñafe, compared to other highland populations. We analysed native patrilineal Y chromosome haplotypes composed of 15 short tandem repeats, a set of SNPs, and maternal mitochondrial DNA haplotypes of control region sequences. Results After the genetic comparisons of local populations—three from Ecuador and seven from Peru—, Y chromosome analyses (n = 376) indicated that individuals from the Cañar region do not share Y haplotypes with the Kañaris, or even with those of the Inkawasi. However, some Y haplotypes of Ecuadorian ‘Cañaris’ were associated with haplotypes of the Peruvian populations of Cajamarca, Chivay (Arequipa), Cusco and Lake Titicaca, an observation that is congruent with colonial records. Within the Kañaris and Inkawasi communities there are at least five clans in which several individuals share haplotypes, indicating that they have recent common ancestors. Despite their relative isolation, most individuals of both communities are related to those of the Cajamarca and Chachapoyas in Peru, consistent with the spoken Quechua and their geographic proximity. With respect to mitochondrial DNA haplotypes (n = 379), with the exception of a shared haplotype of the D1 lineage between the Cañar and Kañaris, there are no genetic affinities. Conclusion Although there is no close genetic relationship between the Peruvian Kañaris (including Inkawasi) and Ecuadorian Cañar populations, our results showed some congruence with historical records.

The incidence of cystic fibrosis (CF) and the frequency of the variants reported for CFTR depend on the population; furthermore, CF symptomatology is characterized by obstructive lung disease and pancreatic insufficiency among other symptoms, which are reliant on the individual's genotype. The Ecuadorian population is a mixture of Native Americans, Europeans, and Africans. That population admixture could be the reason for the new mutations reported in a previous study by Ruiz et al. (2019). A panel of 46 Ancestry Informative Markers was used to estimate the ancestral proportions of each available sample (12 samples in total). As a result, the Native American ancestry proportion was the most prevalent in almost all individuals, except for three patients from Guayaquil with the mutation [c.757G>A:p.Gly253Arg; c.1352G>T:p.Gly451Val] who had the highest European composition.

Genetic variants of chemical neurotransmission have been associated with the development of schizophrenia. This is a syndromic mental disorder that affects the perception of reality and feelings of those affected. This disease is expressed in 1% of the world’s population; in all cases, antipsychotic drugs are used as treatment. Scientific evidence indicates that symptomatologic characteristics and therapeutic response has a genetic influence. The objective of the current work was to describe the presence or absence of allelic polymorphisms found on the dopamine gene and the therapeutic response of 11 Ecuadorian individuals treated with haloperidol (5mg.), for a period of 14 days. Single Nucleotide Polymorphisms (SNPs) in the DRD2, TH and DTNBP1 genes and evaluations recorded from the PANSS, BPRS and UKU scales were assessed. An association with a significance of P = 0.024 was found between the Taq1-B polymorphism on the DRD2 gene and the BPRS positive symptom scale; furthermore, an association with a significance of P = 0.045 was found with the PANSS negative symptoms scale. The absence of the Ser311Cys polymorphism on the DRD2 gene within the sample was also reported. In conclusion, it is noted that there is a statistically significant difference between the symptomatologic group, individuals with allele A / G SNP Taq1-B, and the group of individuals without the polymorphism. Even though the biological mechanisms behind this result are not understood, his study will serve as a basis for the development of future research related to this topic.

Telomere maintenance mechanisms (TMM) are used by cancer cells to avoid apoptosis, 85&ndash, 90% reactivate telomerase, while 10&ndash, 15% use the alternative lengthening of telomeres (ALT). Due to anti-telomerase-based treatments, some tumors switch from a telomerase-dependent mechanism to ALT, in fact, the co-existence between both mechanisms has been observed in some cancers. Although different elements in the ALT pathway are uncovered, some molecular mechanisms are still poorly understood. Therefore, with the aim to identify potential molecular markers for the study of ALT, we combined in silico approaches in a 411 telomere maintenance gene set. As a consequence, we conducted a genomic analysis of these genes in 31 Pan-Cancer Atlas studies from The Cancer Genome Atlas and found 325,936 genomic alterations, from which, we identified 20 genes highly mutated in the cancer studies. Finally, we made a protein-protein interaction network and enrichment analysis to observe the main pathways of these genes and discuss their role in ALT-related processes, like homologous recombination and homology directed repair. Overall, due to the lack of understanding of the molecular mechanisms of ALT cancers, we proposed a group of genes, which after ex vivo validations, could represent new potential therapeutic markers in the study of ALT.

Breast cancer (BC) is the leading cause of cancer-related death among women and the most commonly diagnosed cancer worldwide. Although in recent years large-scale efforts have focused on identifying new therapeutic targets, a better understanding of BC molecular processes is required. Here we focused on elucidating the molecular hallmarks of BC heterogeneity and the oncogenic mutations involved in precision medicine that remains poorly defined. To fill this gap, we established an OncoOmics strategy that consists of analyzing genomic alterations, signaling pathways, protein-protein interactome network, protein expression, dependency maps in cell lines and patient-derived xenografts in 230 previously prioritized genes to reveal essential genes in breast cancer. As results, the OncoOmics BC essential genes were rationally filtered to 140. mRNA up-regulation was the most prevalent genomic alteration. The most altered signaling pathways were associated with basal-like and Her2-enriched molecular subtypes. RAC1, AKT1, CCND1, PIK3CA, ERBB2, CDH1, MAPK14, TP53, MAPK1, SRC, RAC3, BCL2, CTNNB1, EGFR, CDK2, GRB2, MED1 and GATA3 were essential genes in at least three OncoOmics approaches. Drugs with the highest amount of clinical trials in phases 3 and 4 were paclitaxel, docetaxel, trastuzumab, tamoxifen and doxorubicin. Lastly, we collected ~3,500 somatic and germline oncogenic variants associated with 50 essential genes, which in turn had therapeutic connectivity with 73 drugs. In conclusion, the OncoOmics strategy reveals essential genes capable of accelerating the development of targeted therapies for precision oncology.

Osteosarcoma is the most common subtype of primary bone cancer, affecting mostly adolescents. In recent years, several studies have focused on elucidating the molecular mechanisms of this sarcoma, however, its molecular etiology has still not been determined with precision. Therefore, we applied a consensus strategy with the use of several bioinformatics tools to prioritize genes involved in its pathogenesis. Subsequently, we assessed the physical interactions of the previously selected genes and applied a communality analysis to this protein&ndash, protein interaction network. The consensus strategy prioritized a total list of 553 genes. Our enrichment analysis validates several studies that describe the signaling pathways PI3K/AKT and MAPK/ERK as pathogenic. The gene ontology described TP53 as a principal signal transducer that chiefly mediates processes associated with cell cycle and DNA damage response It is interesting to note that the communality analysis clusters several members involved in metastasis events, such as MMP2 and MMP9, and genes associated with DNA repair complexes, like ATM, ATR, CHEK1, and RAD51. In this study, we have identified well-known pathogenic genes for osteosarcoma and prioritized genes that need to be further explored.

Many primary-tumor subregions have low levels of molecular oxygen, termed hypoxia. Hypoxic tumors are at elevated risk for local failure and distant metastasis. Metastatic disease is the leading cause of cancer-related deaths and involves critical interactions between tumor cells and the microenvironment. Here we focused on elucidating the molecular hallmarks of tumor hypoxia that remains poorly defined. To fill this gap, we analyzed the genomic alterations and hypoxia score of 233 hypoxia-related genes of 6,343 individuals across 17 TCGA Pan-Cancer types. In addition, we analyzed a protein-protein interactome (PPi) network and the shortest paths from hypoxic proteins to metastasis. As results, mRNA high alteration was prevalent in all cancer types. Genomic alterations and hypoxia score presented a highest frequency in tumor stage 4 and positive metastasis status in all cancer types. The most significant signaling pathways were HIF-1, ErbB, PI3K-Akt, FoxO, mTOR, Ras and VEGF. The PPi network revealed a strong association among hypoxic proteins, cancer driver proteins and metastasis driver proteins. The analysis of shortest paths revealed 99 ways to spread metastasis signaling from hypoxic proteins. Additionally, we proposed 62 hypoxic genes strongly associated with metastasis and 27 of them with high amount of genomic alterations. Overall, tumor hypoxia may drive aggressive molecular features across cancer types. Hence, we identified potential biomarkers and therapeutic targets regulated by hypoxia that could be incorporated into strategies aimed at improving novel drug development and treating metastasis.

No se han establecido estándares para el tratamiento de cavidades cervicales no cariosas; un biomaterial adecuado permitirá buena adaptación y longevidad de la restauración. Objetivo: Determinar la microfiltración en cavidades clase V no cariosas restauradas con ionómero de vidrio y resina nanoparticulada. Materiales y métodos: Cavidades clase V realizadas en la superficie vestibular de 80 premolares sanos (1,5 mm de profundidad x 3 mm de altura en sentido ocluso- gingival x 2 mm de ancho en sentido mesio-distal) se restauraron aleatoriamente con dos biomateriales (n = 40): 1) ionómero de vidrio y 2) resina de nano relleno. Después, los especímenes fueron aislados con barniz y sumergidos en azul de metileno por 24 horas. Posteriormente, las muestras se sometieron 500 ciclos de termociclado por 8 horas y 45 minutos con cambios térmicos de 37°, 72° y 75°C, cada ciclo con una duración de 17 segundos. Las muestras fueron lavadas con agua destilada y seccionadas longitudinalmente para determinar el grado de microfiltración utilizando un estereoscopio (Leica M60, Biosystems). Los datos categóricos se analizaron con el test Chi2 en SPSS 24®. Resultados: Se pudo apreciar que la filtración es significativamente menor en resina que con ionómeros de vidrio (p < 0,001). Sin embargo, ninguno de los materiales de restauración probados fue capaz de sellar los márgenes o las paredes de los dientes completamente. Conclusión: como resultado del presente experimento se determina que las restauraciones de clase V obturadas con resina de nano relleno presentan menor microfiltración marginal que las restauradas con ionómero de vidrio.

Background Turner syndrome is a genetic disorder that affects women. It is caused by an absent or incomplete X chromosome, which can be presented in mosaicism or not. There are 12 cases of Turner syndrome patients who present structural alterations in autosomal chromosomes. Case presentation The present case report describes a patient with a reciprocal, maternally inherited translocation between chromosomes 2 and 12 with a mosaicism of X monosomy 45,X,t(2;12)(p13;q24)[95]/46,XX,t(2;12)(p13;q24)[5]. Through genetic mapping arrays, altered genes in the patient were determined within the 23 chromosome pairs. These genes were associated with the patient’s clinical features using a bioinformatics tool. Conclusion To our knowledge, this is the first case in which a translocation (2;12) is reported in a patient with Turner syndrome and confirmed by conventional cytogenetics, FISH and molecular genetics. Clinical features of our patient are closely related with the loss of one X chromosome, however mild intellectual disability can be likely explained by autosomal genes. The presence of familial translocations was a common finding, thus emphasizing the need for familiar testing for further genetic counselling.

Background In the context of the current drug discovery efforts to find disease modifying therapies for Parkinson's disease (PD) the current single target strategy has proved inefficient. Consequently, the search for multi-potent agents is attracting more and more attention due to the multiple pathogenetic factors implicated in PD. Multiple evidences points to the dual inhibition of the monoamine oxidase B (MAO-B), as well as adenosine A2A receptor (A2AAR) blockade, as a promising approach to prevent the neurodegeneration involved in PD. Currently, only two chemical scaffolds has been proposed as potential dual MAO-B inhibitors/A2AAR antagonists (caffeine derivatives and benzothiazinones). Methods In this study, we conduct a series of chemoinformatics analysis in order to evaluate and advance the potential of the chromone nucleus as a MAO-B/A2AAR dual binding scaffold. Results The information provided by SAR data mining analysis based on network similarity graphs and molecular docking studies support the suitability of the chromone nucleus as a potential MAOB/ A2AAR dual binding scaffold. Additionally, a virtual screening tool based on a group fusion similarity search approach was developed for the prioritization of potential MAO-B/A2AAR dual binder candidates. Among several data fusion schemes evaluated, the MEAN-SIM and MIN-RANK GFSS approaches demonstrated to be efficient virtual screening tools. Then, a combinatorial library potentially enriched with MAO-B/A2AAR dual binding chromone derivatives was assembled and sorted by using the MIN-RANK and then the MEAN-SIM GFSS VS approaches. Conclusion The information and tools provided in this work represent valuable decision making elements in the search of novel chromone derivatives with a favorable dual binding profile as MAOB inhibitors and A2AAR antagonists with the potential to act as a disease-modifying therapeutic for Parkinson's disease.

El cáncer de ovario es la neoplasia maligna ginecológica más letal debido a su asintomatología y etapa avanzada de diagnóstico. La tasa de incidencia a nivel mundial es de 6,3 por cada 100.000 mujeres, presentando las tasas más altas en zonas geográficas industrializadas como Europa (10,1), América del Norte (8,7) y Oceanía (7,6). Entre los factores de riesgo asociados con el desarrollo de este cáncer se encuentran: edad avanzada, niveles descontrolados de carga hormonal, obesidad, antecedentes familiares de cáncer, exposición a agentes carcinogénicos, presencia de agentes patógenos y mutaciones genéticas. Con respecto al perfil genético, la presencia de mutaciones en los diferentes biomarcadores moleculares (supresores de tumores, oncogenes, genes de apoptosis y reparadores del ADN) aumenta el riesgo de desarrollar cáncer de ovario. Entre los genes más representativos están: BRCA1, BRCA2, TP53, RAD51 y VDR. Además, el correcto tratamiento de esta enfermedad dependerá del estadio tumoral, edad, capacidad de absorción de fármacos, histopatología, carga hormonal y perfil genético. Entre los tratamientos más aplicados se encuentra la cirugía, los medicamentos homeopáticos; la aplicación de fármacos, la aplicación de micro ARNs y de inhibidores multicinasas. En conclusión, el desarrollo del cáncer (ovario) dependerá de la interacción de cuatro variables relevantes: (1) el tiempo y (2) la dosis de exposición a los carcinógenos, (3) la edad avanzada, y (4) la predisposición genética. Es decir, los factores ambientales asociados con los factores genéticos predisponen al desarrollo de cáncer.

El cáncer es un grupo de enfermedades causadas por factores externos e internos, y caracterizadas por el crecimiento y la dispersión de células anormales. El cáncer de piel ha incrementado el número de casos en los últimos años mientras que el cáncer pulmonar presenta el mayor índice de mortalidad en países industrializados. En Quito, los tipos más frecuentes de cáncer en hombres son próstata, piel y estómago mientras que en mujeres son piel, mama y cérvix invasor. La determinación de las distribuciones genotípicas y las frecuencias alélicas de polimorfismos en los genes SRD5A2 en cáncer de próstata, GPX-1 y MnSOD en cáncer de vejiga y EGFR en cáncer pulmonar, se realizó a través de la técnica bialélica PCR-RFLP, y sus datos fueron analizados mediante chi-cuadrado (χ2) y odds ratio (OR). Como resultados, las variantes genéticas V89L (SRD5A2) (OR 3.7, p < 0.001), P198L (GPX-1) (OR 3.8; p < 0.001) y L858R (EGFR) (OR 5.9; p < 0.001), presentaron diferencias significativas y son factores de riesgo para el desarrollo del cáncer. En conclusión, la predisposición de una persona para desarrollar cáncer dependerá de la exposición a agentes cancerígenos y de su perfil genético, el cual influirá en la síntesis proteica y en el mal funcionamiento de los mecanismos celulares

Este estudio analiza las consecuencias de las asperciones aéreas con glifosato y surfactantes en la parte norte del Ecuador. Los tests de aberraciones cromosómicas y el ensayo cometa fueron utilizados para el biomonitoreo humano. Un total de 24 individuos expuestos y 21 individuos controles fueron incluidos en el estudio. Los resultados muestran niveles significativamente altos de aberraciones cromosómicas en las muestras de los individuos expuestos (22.42%) comparados con los controles (1.38%). De igual manera, el ensayo cometa mostró un alto grado de daño al ADN en el grupo expuesto (35.5Ilm) comparado con el grupo control (25.94Ilm). Estos resultados sugieren que el glifosato, en la formulación utilizada durante las asperciones aéreas, podría tener un efecto genotóxico sobre los individuos expuestos.