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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

Adobe PDF - Supplementary_Data.pdf from Homozygous Deletion Mapping in Myeloma Samples Identifies Genes and an Expression Signature Relevant to Pathogenesis and Outcome

Purpose: Myeloma is a clonal malignancy of plasma cells. Poor-prognosis risk is currently identified by clinical and cytogenetic features. However, these indicators do not capture all prognostic information. Gene expression analysis can be used to identify poor-prognosis patients and this can be improved by combination with information about DNA-level changes.Experimental Design: Using single nucleotide polymorphism–based gene mapping in combination with global gene expression analysis, we have identified homozygous deletions in genes and networks that are relevant to myeloma pathogenesis and outcome.Results: We identified 170 genes with homozygous deletions and corresponding loss of expression. Deletion within the “cell death” network was overrepresented and cases with these deletions had impaired overall survival. From further analysis of these events, we have generated an expression-based signature associated with shorter survival in 258 patients and confirmed this signature in data from two independent groups totaling 800 patients. We defined a gene expression signature of 97 cell death genes that reflects prognosis and confirmed this in two independent data sets.Conclusions: We developed a simple 6-gene expression signature from the 97-gene signature that can be used to identify poor-prognosis myeloma in the clinical environment. This signature could form the basis of future trials aimed at improving the outcome of poor-prognosis myeloma. Clin Cancer Res; 16(6); 1856–64

Supplementary Figure 2 from Deficiency in p53 but not Retinoblastoma Induces the Transformation of Mesenchymal Stem Cells In vitro and Initiates Leiomyosarcoma In vivo

Supplementary Figure 1 from Deficiency in p53 but not Retinoblastoma Induces the Transformation of Mesenchymal Stem Cells In vitro and Initiates Leiomyosarcoma In vivo

Supplementary Figure 3 from Deficiency in p53 but not Retinoblastoma Induces the Transformation of Mesenchymal Stem Cells In vitro and Initiates Leiomyosarcoma In vivo

Sarcomas have been modeled in mice by the expression of specific fusion genes in mesenchymal stem cells (MSC), supporting the concept that MSCs might be the target initiating cell in sarcoma. In this study, we evaluated the potential oncogenic effects of p53 and/or retinoblastoma (Rb) deficiency in MSC transformation and sarcomagenesis. We derived wild-type, p53−/−, Rb−/−, and p53−/−Rb−/− MSC cultures and fully characterized their in vitro growth properties and in vivo tumorigenesis capabilities. In contrast with wild-type MSCs, Rb−/−, p53−/−, and p53−/−Rb−/− MSCs underwent in vitro transformation and showed severe alterations in culture homeostasis. More importantly, p53−/− and p53−/−Rb−/− MSCs, but not Rb−/− MSCs, were capable of tumor development in vivo after injection into immunodeficient mice. p53−/− or p53−/−Rb−/− MSCs originated leiomyosarcoma-like tumors, linking this type of smooth muscle sarcoma to p53 deficiency in fat tissue–derived MSCs. Sca1+ and Sca1 low/− cell populations isolated from ex vivo–established, transformed MSC lines from p53−/−Rb−/− tumors showed identical sarcomagenesis potential, with 100% tumor penetrance and identical latency, tumor weight, and histologic profile. Our findings define the differential roles of p53 and Rb in MSC transformation and offer proof-of-principle that MSCs could provide useful tools to dissect the sarcoma pathogenesis. Cancer Res; 70(10); 4185–94. ©2010 AACR.

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.

Inconsistent access to a healthcare provider (HCP), which can lead to advanced morbidity, is an oft-cited barrier to advancing health. Extensive review of the literature consistently suggests men are far less likely to engage within the healthcare system. This is particularly problematic pertaining to preventive services. As many health conditions are preventable and/or treatable in earlier stages, delay in screening and treatment often leads to long-term negative health outcomes. Lack of early and frequent preventive healthcare (e.g. primordial, primary, and secondary prevention) may even be perceived as “normative” where poorer health outcomes in males are expected.1 In fact, some evidence demonstrates a clear connection that seeking help via healthcare runs contrary to masculinity and dominant masculine principles, such as being strong/sturdy, working through pain, avoiding weakness or anything perceived as feminine, among other psychosocial phenomena.2,3 Changing healthcare “culture” concerning the care of men (i.e. gender-sensitive care) may provide a salient avenue to encourage more consistent and preventive contact or “touch points” in the patient-provider dynamic. There is a need to understand how social norms and practices in healthcare and medical settings can be effectively leveraged to address life-long male health outcomes versus focusing on late(r)-stage palliative care. The purpose of this article is to advance dialogue concerning practical considerations, such as resources (e.g. time, money) and methods (e.g. practitioners considering whether men respond best to immediate efforts to establish rapport versus a traditional power-based dynamic during the medical interaction) so as to inform gender-sensitive touchpoints in the healthcare of men. Location and types of facilities where men are willing to seek care (preventative or palliative) also need to be considered in a holistic, gender-sensitive patient-provider model of healthcare. Implications, policies, and evidence-based practical strategies for leveraging medical education, prevention programming, proper and improper recognition and management, and long-term treatment are presented and discussed with the practitioner in mind.

INTRODUCTIONMany stroke survivors do not receive the optimal levels of personalised therapy needed to support their recovery. Rehabilitation technology could offer a means to provide personalised guidance to stroke survivors struggling to access rehabilitation through other means.AIMSThe aim of this study was to explore stroke survivor and therapist experiences of stroke rehabilitation post discharge into the community and their thoughts about the potential use of markerless, 3D motion capture technology which could support rehabilitation, to contribute towards a better understanding of how technology can support stroke rehabilitation.METHODSFocus groups and interviews were conducted with stroke survivors and therapists and the transcripts analysed using thematic analysis.RESULTSSix themes were identified across the data: access and continuity of care for stroke survivors in the community, stroke survivor confusion and lack of education impacting service navigation and ability to access rehabilitation services, stroke survivor access to non-NHS/private facilities, impact of Covid on stroke services, potential use of technology to support post-stroke rehabilitation in the community and, stroke survivors’ willingness to try new technology.CONCLUSIONSStroke survivors and therapists identified problems with stroke survivors accessing rehabilitation services but were positive about the potential for technology to support stroke rehabilitation.

In 2014, the U.S. Departments of Education and Justice (U.S. DOE/DOJ) jointly released the

In patients with liver cirrhosis, minimal hepatic encephalopathy (MHE) is triggered by a shift in peripheral inflammation, promoting lymphocyte infiltration into the brain. Rifaximin improves neurological function in MHE by normalizing peripheral inflammation. Patients who died with steatohepatitis showed T-lymphocyte infiltration and neuroinflammation in the cerebellum, suggesting that MHE may already occur in these patients. The aims of this work were to assess, in a rat model of mild liver damage similar to steatohepatitis, whether: (1) the rats show impaired motor coordination in the early phases of liver damage, (2) this is associated with changes in the immune system and infiltration of immune cells into the brain, and (3) rifaximin improves motor incoordination, associated with improved peripheral inflammation, reduced infiltration of immune cells and neuroinflammation in the cerebellum, and restoration of the alterations in neurotransmission. Liver damage was induced by carbon tetrachloride (CCl4) injection over four weeks. Peripheral inflammation, immune cell infiltration, neuroinflammation, and neurotransmission in the cerebellum and motor coordination were assessed. Mild liver damage induces neuroinflammation and altered neurotransmission in the cerebellum and motor incoordination. These alterations are associated with increased TNFa, CCL20, and CX3CL1 in plasma and cerebellum, IL-17 and IL-15 in plasma, and CCL2 in cerebellum. This promotes T-lymphocyte and macrophage infiltration in the cerebellum. Early treatment with rifaximin prevents the shift in peripheral inflammation, immune cell infiltration, neuroinflammation, and motor incoordination. This report provides new clues regarding the mechanisms of the beneficial effects of rifaximin, suggesting that early rifaximin treatment could prevent neurological impairment in patients with steatohepatitis.

During the second covid-19 pandemic wave in November-December 2021 Prevention Departments had to face a hardly-sustainable workload of contact tracing and taking charge of the sars-cov2 positive case and of his or her close contacts. Also laboratories have been stressed in their ability to process timely the extraordinary load of swabs performed. In this context of hazardous delays, the Prevention Department of Belluno (Italy) tested its resilience: a simple and effective method of taking charge was implemented, by initially phoning to the positive case and imposing the isolation measure on him or her and later on proceeding with the conventional contact tracing.

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.

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.

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.

Introducción: También llamada hiperostosis cortical infantil, caracterizada por la presencia de un episodio en la infancia con neoformación subperióstica en las diáfisis de huesos largos, la mandíbula y las clavículas.; Casos clínicos: se evaluó un recién nacido con hallazgos clínico-radiológicos que comprendieron deformidad angular anterior de antebrazo izquierdo y miembros inferiores. La radiografía simple al nacimiento certificó la hiperostosis cortical con curvatura anterior del radio izquierdo, asociado con importante engrosamiento cortical en la diáfisis de tibias. La radiografía de control a los tres y ocho meses de edad demostró disminución de la hiperostosis cortical; El segundo caso se trata de una paciente de siete años que ha presentado dos exacerbaciones de hiperostosis cortical. Al examen físico presentó, hiperextensibilidad de pabellones auriculares, hipermovilidad de articulaciones pequeñas y manchas de hemosiderina múltiples difusas localizadas en las piernas. El tercer caso correspondió a un lactante menor de un mes tres días de vida, con radiografía que evidenció la hiperostosis cortical de tibias; Conclusión: Concluimos que la familia con neoformación diafisiaria constituyen casos de interés por tratarse de un diagnóstico infrecuente en la edad pediátrica y cuya sospecha clínica puede generarse a partir de un buen examen clínico y estudio del caso índice, complementado con la interpretación de la genealogía asociado con el estudio molecular que lo corrobora.

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.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Epidemiological findings revealed that women with PCOS are prone to develop certain cancer types due to their shared metabolic and endocrine abnormalities. However, the mechanism that relates PCOS and oncogenesis has not been addressed. Herein, in this review article the genomic status, transcriptional and protein profiles of 264 strongly PCOS related genes (PRG) were evaluated in endometrial cancer (EC), ovarian cancer (OV) and breast cancer (BC) exploring oncogenic databases. The genomic alterations of PRG were significantly higher when compared with a set of non-diseases genes in all cancer types. PTEN had the highest number of mutations in EC, TP53, in OC, and FSHR, in BC. Based on clinical data, women older than 50 years and Black or African American females carried the highest ratio of genomic alterations among all cancer types. The most altered signaling pathways were p53 in EC and OC, while Fc epsilon RI in BC. After evaluating PRG in normal and cancer tissue, downregulation of the differentially expressed genes was a common feature. Less than 30 proteins were up and downregulated in all cancer contexts. We identified 36 highly altered genes, among them 10 were shared between the three cancer types analyzed, which are involved in the cell proliferation regulation, response to hormone and to endogenous stimulus. Despite limited PCOS pharmacogenomics studies, 10 SNPs are reported to be associated with drug response. All were missense mutations, except for rs8111699, an intronic variant characterized as a regulatory element and presumably binding site for transcription factors. In conclusion, in silico analysis revealed key genes that might participate in PCOS and oncogenesis, which could aid in early cancer diagnosis. Pharmacogenomics efforts have implicated SNPs in drug response, yet still remain to be found.

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.

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.

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.

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.

A small but growing body of research has investigated the experience of gay male athletes “coming out” in sport, a historically homophobic environment. In this exploratory case study, the experiences of “Mark,” a male volleyball player who came out prior to a championship season, were examined using social identity perspective and athletic identity theory as the frameworks for analysis. Data sources included interviews with Mark, interviews with informants, and Mark’s social-media posts. A narrative of Mark’s coming-out experience was developed and explored in light of the theoretical frameworks, and 2 themes emerged from the data: gay athlete as a (dis)qualifier and “It’s not about the skills, it’s about the attitude,” which explores Mark’s psychological development and its relationship with athletic performance. Implications and strategies for sport psychology consultants working with gay male athletes are discussed.

Resumen 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. Abstract Among the most frequent congenital defects are cleft lip and/or palate (CL/P), with a prevalence of 1:1,000 live births. 70% of CL/P are non-syndromic, which means that they are found as an isolated defect without additional anomalies. They have a complex etiology with both an environmental and genetic component. By the development of human genome sequencing technologies have been identified polymorphic variants that may be associated with the CL/P phenotype and therefore may contribute to the multifactorial etiology of these. This review describes the commonly associated variants and their role in the etiology of CL/P. The SNPs located in the genes IFR6, MSX1, VAX1, PAX9, CHD1, FGF1, GREM1 and WNT3 have been significantly related to the presence of CL/P, and the variants located in the genes APC, GSK3, DVL2, BMP4, ABCA4, BHMT, NTN1, TBX1, EPHA3, FAM49A, MGMT, MMP3, TIMP2 y NOG, although its association with the presence of orofacial fissures has been reported, its relationship with this phenotype is not yet clear. It is important to carry out studies to identify genetic variants that involve specific populations in order to understand the etiology of non-syndromic CL/P.

Background Since 1969, 49 cases have been presented on ring chromosome 4. All of these cases have been characterized for the loss of genetic material. The genes located in these chromosomal regions are related to the phenotype. Case presentation A 10-year-old Ecuadorian Mestizo girl with ring chromosome 4 was clinically, cytogenetically and molecularly analysed. Clinical examination revealed congenital anomalies, including microcephaly, prominent nose, micrognathia, low set ears, bilateral clinodactyly of the fifth finger, small sacrococcygeal dimple, short stature and mental retardation. Cytogenetic studies showed a mosaic karyotype, mos 46,XX,r(4)(p16.3q35.2)/46,XX, with a ring chromosome 4 from 75 to 79% in three studies conducted over ten years. These results were confirmed by fluorescence in situ hybridization (FISH). Loss of 1.7 Mb and gain of 342 kb in 4p16.3 and loss of 3 Mb in 4q35.2 were identified by high-resolution mapping array. Conclusion Most cases with ring chromosome 4 have deletion of genetic material in terminal regions; however, our case has inv dup del rearrangement in the ring chromosome formation. Heterogeneous clinical features in all cases reviewed are related to the amount of genetic material lost or gained. The application of several techniques can increase our knowledge of ring chromosome 4 and its deviations from typical “ring syndrome.”

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.

Se considera como principal marcador de la Leucemia Mieloide Crónica (LMC) la translocación t(9;22) o cromosoma Ph que ocurre en un 90 -95% de pacientes con LMC. Uno de los tratamientos más efectivos es el Gleevec cuyo blanco son las células Ph positivo. Una ventaja de esta nueva droga es la discriminación entre células normales y anormales, y la inducción de apoptosis. Se estudiaron 31 pacientes: 13 en fase crónica, 12 en fase acelerada y 6 en crisis blástica a lo largo de 1 año. Se obtuvo remisión hematológica en todos los casos de fase crónica, pero en los pacientes en fase acelerada y crisis blástica respondieron aproximadamente el 50%. La remisión cito genética ocurrió en un 79% de fase crónica y varía de un 17 a 32 % en fase acelerada y crisis blástica. No existió remisión molecular en ningún paciente. El análisis genético es una buena herramienta para determinar la efectividad del tratamiento y seguimiento de los casos de leucemia.

This study presents mitochondrial data from 55 unrelated individuals from two Ecuadorian Shuar communities: Kumbatza and Yukateis. Maternal linage was determined by analyzing the two mtDNA hypervariable regions: HRVI and HRVII. It was shown that the Shuar population exhibited the haplogroup B. This demonstrates that Shuar group is a conserved population with no mixing with the European and African diaspora populations.

Ecuador has various regions at different altitudes. It is known that at high altitudes, organisms experience multiple stressors, including exposure to ultraviolet (UV) radiation. The UV radiation exposure increases when getting closer to the Equator line. Consequently, cities in the Ecuadorian inter-Andean region and located at 2,800-3,000 m above sea level (masl) are exposed to UV levels approximately 40% higher than those of the lowlands. UV light is a carcinogen that causes mutations, DNA damage and cellular apoptosis. However, the XPC, XPD and XPG genes encode proteins that repair DNA caused by UV radiation. The aim of this study was to evaluate the distribution of three polymorphisms (rs2228001, rs13181 and rs17655) involved in the response to the damage caused by UV radiation in the Ecuadorian populations of high and low altitudes, and thus, correlate the ancestral proportions of these populations. Results showed that the behavior of both groups located at different altitudes is similar. The ancestry of these groups exhibited that the Native American component prevails, and the European and African component varies.

Trisomy 9p syndrome is the fourth most frequent chromosome aberration seen in infants. Duplication of the critical region 9p22p24 leads to mental retardation, psychomotor delay, and craniofacial and digital anomalies. We report a 2-year-old Ecuadorian girl with Trisomy 9p syndrome. Although her phenotype shares characteristics of Noonan syndrome, Giemsa trypsin banding technique shows there is an extra chromosomal segment on chromosome 14, and array analysis shows that it belongs to a duplication of 38 Mb of 9p13.1p24.3. Fluorescence in situ hybridization analysis detected three signals from 9p chromosome. The duplication is de novo, being another unique case of the few reported in the literature.

This chapter discusses policies related to education for youth with emotional or behavioral disorders, and describes a policy framework for developing placement options for children with emotional or behavioral disorders. It presents a schema or framework for placement policies that was derived from an investigation of the Center for the Study for Policy Options in Special Education, and discusses policies and practices associated with providing effective services to youth with emotional or behavioral disorders. Since the mid-1980s, mental health professionals, educators, and advocates have struggled with the failure of communities and agencies to meet the needs of children and youth with emotional or behavioral disorders. Policies concerning children with emotional or behavioral disorders devote minimal attention to the contexts of deviant behavior and the culture of the schools. The more formal policies have been pieced together over time in response to specific societal problems and with differing objectives.

Colorectal cancer (CRC) is a major health problem with an estimated 1. 8 million new cases worldwide. To date, most CRC studies have focused on DNA-related aberrations, leaving post-transcriptional processes under-studied. However, post-transcriptional alterations have been shown to play a significant part in the maintenance of cancer features. RNA binding proteins (RBPs) are uprising as critical regulators of every cancer hallmark, yet little is known regarding the underlying mechanisms and key downstream oncogenic targets. Currently, more than a thousand RBPs have been discovered in humans and only a few have been implicated in the carcinogenic process and even much less in CRC. Identification of cancer-related RBPs is of great interest to better understand CRC biology and potentially unveil new targets for cancer therapy and prognostic biomarkers. In this work, we reviewed all RBPs which have a role in CRC, including their control by microRNAs, xenograft studies and their clinical implications.

Background Retinoblastoma is a neoplasia that starts in the retina and may have inheritable or sporadic genetic predisposition. This affects children, mainly those who are under 5 years old. Approximately 9,000 new cases are diagnosed per year worldwide. In Ecuador this disease has an incidence of 1 per each 20,000 live births. The genetic predisposition to develop retinoblastoma is strongly influenced by RB1 gene, and may be influenced by the presence of genetic polymorphisms which intervene in the DNA repair system. Methods This study has analyzed the genotype frequency of ERCC2 (Lys751Gln), MSH2 (gIVS12-6TC), RAD54 (Ala730Ala), XPC (Lys939Gln), XPG (Asp1104Hist), XRCC1 (Arg399Gln), and XRCC3 (Thr241Met) polymorphisms of different repair genes, genotyping 90 individuals affected with retinoblastoma and 80 healthy individuals through polymerase chain reaction / restriction fragments length polymorphism and sequencing analysis. Results The presence of the (C/C) mutant homozygous genotype of XPC (Lys939Gln) polymorphism triggers a significant risk of developing retinoblastoma with an odds ratio (OR) of 3 (CI: 1.22-9.84; p < 0.05). Likewise, the A/G heterozygous genotype and the combination A/G+G/G of XRCC1 (Arg399Gln) polymorphism presented ORs of 9.7 (CI: 4.45-21.08; p < 0.001) and 7.55 (IC: 3.57-16; p < 0.001), respectively. Conclusions The genetic variants XPC (Lys939Gln) and XRCC1 (Arg399Gln) may be associated with the risk of developing retinoblastoma in the Ecuadorian population.

Background Detection of chromosomal abnormalities is crucial in various medical areas; to diagnose birth defects, genetic disorders, and infertility, among other complex phenotypes, in individuals across a wide range of ages. Hence, the present study wants to contribute to the knowledge of type and frequency of chromosomal alterations and polymorphisms in Ecuador. Methods Cytogenetic registers from different Ecuadorian provinces have been merged and analyzed to construct an open‐access national registry of chromosome alterations and polymorphisms. Results Of 28,806 karyotypes analyzed, 6,008 (20.9%) exhibited alterations. Down syndrome was the most frequent autosome alteration (88.28%), followed by Turner syndrome (60.50%), a gonosome aneuploidy. A recurrent high percentage of Down syndrome mosaicism (7.45%) reported here, as well as by previous Ecuadorian preliminary registries, could be associated with geographic location and admixed ancestral composition. Translocations (2.46%) and polymorphisms (7.84%) were not as numerous as autosomopathies (64.33%) and gonosomopathies (25.37%). Complementary to conventional cytogenetics tests, molecular tools have allowed identification of submicroscopic alterations regions or candidate genes which can be possibly implicated in patients' symptoms and phenotypes. Conclusion The Ecuadorian National Registry of Chromosome Alterations and Polymorphisms provides a baseline to better understand chromosomal abnormalities in Ecuador and therefore their clinical management and awareness. This data will guide public policy makers to promote and financially support cytogenetic and genetic testing., Of 28,806 karyotypes analyzed in Ecuador, 6,008 (20.9%) exhibited alterations. Down syndrome was the most frequent autosome alteration (88.28%), followed by Turner syndrome (60.50%). Translocations (2.46%) and polymorphisms (7.84%) were not as numerous as autosomopathies (64.33%) and gonosomopathies (25.37%).

The history of Ecuador was marked by the arrival of Europeans with Africans, resulting in the mixture of Native Americans with Africans and Europeans. The present study contributes to the knowledge of the Ecuadorian mestizo population by offering information about ancestry and ethnic heterogeneity. Forty-six AIM-InDels (Ancestry Informative Insertion/Deletion Markers) were used to obtain information on 240 Ecuadorian individuals from three regions (Amazonia, the Highlands, and the Coast). As a result, the population involved a significant contribution from Native Americans (values up to 51%), followed by Europeans (values up to 33%) and Africans (values up to 13%). Furthermore, we compared the data obtained with nine previously reported scientific articles on autosomal, mitochondrial DNA and Y chromosomes. The admixture results correspond to Ecuador’s historical background and vary slightly between regions.

Colorectal cancer (CRC) 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 a number of precision therapies based on individual genomic profiles. As part of these approaches, pharmacogenomics analyses genomic alterations that may predict an efficient therapeutic response. Studying these mutations as biomarkers for predicting drug response is of a great interest to improve precision medicine. Here 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.

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). Patients with CIPA lack the primary afferents and sympathetic postganglionic neurons leading to lack of pain sensation and the presence of anhidrosis, respectively. Herein, we conducted a genomic analysis of 4,811 genes and 18,933 variants, including 54 mutations of NTRK1 in a high-altitude indigenous Ecuadorian patient with CIPA. As results, the patient presented 87.8% of Native American ancestry, 6.6% of African ancestry and 5.6% of European ancestry. The mutational analysis of the kinase domain of NTRK1 showed two pathogenic mutations, rs80356677 (Asp674Tyr) and rs763758904 (Arg602*). The genomic analysis showed 68 pathogenic and/or likely pathogenic variants in 45 genes, and two variants of uncertain significance in CACNA2D1 (rs370103843) and TRPC4 (rs80164537) genes involved in the pain matrix. The GO enrichment analysis showed 28 genes with relevant mutations involved in several biological processes, cellular components and molecular functions. In addition, the protein-protein interaction (PPi) networking analysis showed that NTRK1, SPTBN2 and GRM6 interact with several proteins of the pain matrix. In conclusion, this is the first time that a study associates genomic, ancestral and networking data in a high-altitude Native American Ecuadorian patient with consanguinity background in order to better understand CIPA pathogenesis.

Introducción: La enfermedad de Caffey también se ha denominado hiperostosis cortical infantil, caracterizada por la presencia de un episodio en la infancia con neoformación subperióstica en las diáfisis de huesos largos, el maxilar inferior y las clavículas. Casos clínicos: Se evaluó a un recién nacido con hallazgos clínico-radiológicos que comprendieron deformidad angular anterior del antebrazo izquierdo y miembros inferiores. La radiografía simple del nacimiento certificó la hiperostosis cortical con curvatura anterior del radio izquierdo, asociado con importante engrosamiento cortical en la diáfisis de tibias. La radiografía de control a los tres y ocho meses de edad mostró disminución de la hiperostosis cortical. El segundo caso es el de una niña de siete años que ha presentado dos exacerbaciones de hiperostosis cortical. En el examen físico presentó hiperextensibilidad de pabellones auriculares, hipermovilidad de articulaciones pequeñas y manchas de hemosiderina múltiples difusas localizadas en las piernas. El tercer caso correspondió a un lactante menor de un mes y tres días de vida, con radiografía que evidenció la hiperostosis cortical de tibias. Conclusión: La familia con neoformación diafisiaria constituye casos de interés por tratarse de un diagnóstico infrecuente en la edad pediátrica y cuya sospecha clínica puede generarse a partir de un buen examen clínico y estudio del caso índice, complementado con la interpretación de la genealogía asociado con el estudio molecular que lo corrobora.