Methods for Scarless, Selection-Free Generation of Human Cells and Allele-Specific Functional Analysis of Disease-Associated SNPs and Variants of Uncertain Significance.

With the continued emergence of risk loci from Genome-Wide Association studies and variants of uncertain significance identified from patient sequencing, better methods are required to translate these human genetic findings into improvements in public health. Here we combine CRISPR/Cas9 gene editing with an innovative high-throughput genotyping pipeline utilizing KASP (Kompetitive Allele-Specific PCR) genotyping technology to create scarless isogenic cell models of cancer variants in ~1 month. We successfully modeled two novel variants previously identified by our lab in the PALB2 gene in HEK239 cells, resulting in isogenic cells representing all three genotypes for both variants. We also modeled a known functional risk SNP of colorectal cancer, rs6983267, in HCT-116 cells. Cells with extremely low levels of gene editing could still be identified and isolated using this approach. We also introduce a novel molecular assay, ChIPnQASO (Chromatin Immunoprecipitation and Quantitative Allele-Specific Occupation), which uses the same technology to reveal allele-specific function of these variants at the DNA-protein interaction level. We demonstrated preferential binding of the transcription factor TCF7L2 to the rs6983267 risk allele over the non-risk. Our pipeline provides a platform for functional variant discovery and validation that is accessible and broadly applicable for the progression of efforts towards precision medicine

Estudio de la influencia de gases de protección en el esfuerzo de corte de soldaduras de filete fabricadas por GMAW-SC

En este trabajo se evaluó la influencia sobre el esfuerzo de corte en soldaduras de filete longitudinales y transversales soldadas mediante GMAW-SC, de cuatro gases de protección que actualmente comercializa Indura S.A: Indurmig 20, Indurmig 8, Indurmig O2 y CO2. Para ello se ensayaron en tracción probetas para ensayo de corte fabricadas bajo la Norma AWS B4.0:2007. Se fabricaron, además, probetas de filetes en unión T para realizar pruebas de micrografía, microdureza y macrografía para dar así significado a los resultados del esfuerzo de corte, por medio del análisis de microestructuras, microdureza Vickers y penetración obtenida para cada gas evaluado. El metal base utilizado fue un acero ASTM A36 y el metal de aporte, ER70S-6. Los resultados muestran que el esfuerzo de corte es mayor al utilizar CO2, con 313 MPa de promedio, y menor en las juntas soldadas con Indurmig O2, con un promedio de 244 MPa, lo que se relaciona directamente con las dimensiones de las gargantas efectivas y, en consecuencia, con la penetración obtenida para cada gas, definiendo guarda relación con el esfuerzo de corte y a medida que el oxígeno aumenta en la composición química del gas, aumenta la dureza, ya que se favorece una mayor velocidad de soldeo y, con ello, una mayor velocidad de enfriamiento y un tamaño de cordón más pequeño. Palabras Clave: Soldadura; GMAW; Ensayo de corte; Gases de protección; Esfuerzo de corte

Self-reported hearing difficulty and its association with general, cognitive, and psychosocial health in the state of Arizona, 2015

BackgroundHearing loss is among the leading causes of disability in persons 65years and older worldwide and is known to have an impact on quality of life as well as social, cognitive, and physical functioning. Our objective was to assess statewide prevalence of self-reported hearing ability in Arizona adults and its association with general health, cognitive decline, diabetes and poor psychosocial health.MethodsA self-report question on hearing was added to the 2015 Behavioral Risk Factor Surveillance System (BRFSS), a telephone-based survey among community-dwelling adults aged >18years (n=6462). Logistic and linear regression were used to estimate the associations between self-reported hearing loss and health outcomes.ResultsApproximately 1 in 4 adults reported trouble hearing (23.2, 95% confidence interval: 21.8, 24.5%), with responses ranging from a little trouble hearing to being deaf. Adults reporting any trouble hearing were at nearly four times higher odds of reporting increased confusion and memory loss (OR 3.92, 95% CI: 2.94, 5.24) and decreased odds of reporting good general health (OR=0.50, 95% CI: 0.40, 0.64) as compared to participants reporting no hearing difficulty. Those reporting any trouble hearing also reported an average 2.5 more days of poor psychosocial health per month (beta=2.52, 95% CI: 1.64, 3.41). After adjusting for sex, age, questionnaire language, race/ethnicity, and income category the association between diabetes and hearing loss was no longer significant.ConclusionsSelf-reported hearing difficulty was associated with report of increased confusion and memory lossand poorer general and psychosocial health among Arizona adults. These findings support the feasibility and utility of assessing self-reported hearing ability on the BRFSS. Results highlight the need for greater inclusion of the full range of hearing disability in the planning process for public health surveillance, programs, and services at state and local levels.National Institute on Deafness and Other Communication Disorders of the National Institutes of Health [R21/R33 DC013681]; James S. and Dyan Pignatelli/UniSource Clinical Chair in Audiologic Rehabilitation for AdultsOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

“Desarrollo de un aplicativo web para el agendamiento de citas médicas dirigido al "Patronato de Amparo Social" del cantón La Maná”.

In the research project, the development of a web application for the scheduling of medical appointments aimed at the "Patronato de Amparo Social" of the La Maná canton was proposed, as it identified a great demand for its medical services, it is required that the information generated by the patients is managed in a technological tool. With the application of research techniques such as: interviews and surveys, the functional and non-functional requirements of the system are established: allowing to know the problems they have in the process of scheduling medical appointments, and the technological tools for their development are defined: Bootstrap as a framework, the programming language PHP, JavaScript, CSS, HTML for the design and development of the application; with its respective MySQL database management system, the same one that was used locally through the XAMPP software and in the cloud through a web server. However, the development of the project was carried out under the agile Scrum methodology through the execution of four Sprints that allowed the development in the management processes of patients, health professionals, statistical assistant and PASGADMLM. Therefore, the web system implemented for appointment scheduling went through black box and white box tests to approve that the functionality is in accordance with the requirements established by the client.En el proyecto de investigación se planteó el desarrollo de un aplicativo web para el agendamiento de citas médicas dirigido al "Patronato de Amparo Social" del cantón La Maná, al identificar una gran demanda en sus servicios médicos, se requiere que la información generada por los pacientes se maneje en una herramienta tecnológica. Con la aplicación de las técnicas de investigación como: entrevista y encuestas, se establecen los requerimientos funcionales y no funcionales del sistema: permitiendo conocer las problemáticas que tienen en el proceso de agendamiento de citas médicas, y se definen las herramientas tecnológicas para su desarrollo: Bootstrap como framework, el lenguaje de programación PHP, JavaScript, CSS, HTML para el diseño y desarrollo del aplicativo; con su respectivo sistema gestor de base de datos MySQL, el mismo que se usó de forma local mediante el software XAMPP y en la nube mediante un servidor web. No obstante, el desarrollo del proyecto se realizó bajo la metodología ágil Scrum mediante la ejecución de cuatro Sprints que permitieron el desarrollo en los procesos de gestión de los pacientes, profesionales de la salud, auxiliar de estadística y PASGADMLM. Por lo tanto, el sistema web implementado para el agendamiento de cita paso por las pruebas de caja negra y caja blanca para aprobar que la funcionalidad esté acorde a los requisitos establecidos por el cliente

Obesidad como factor desencadenante de comorbilidad.

The purpose of this research is to publicize obesity as a triggering factor for comorbidity, being one of the most common pathological conditions in humans and present since ancient times that persists and increases for centuries due to genetic and environmental factors. to the point of becoming a disease with disastrous consequences for health. Thus also the important association with comorbidity, which ranges from clinical, metabolic, hormonal, respiratory, neoplasm, orthopedic and even psychological alterations. The objective of the study is "Determine obesity factors as a trigger for comorbidity". Due to the importance of multifactorial etiology, and the result of the interaction between the genotype and the environment, in addition to psychological, social and cultural factors, poor eating habits and heterogeneous factors that influence overweight leading to obese patients. A search was carried out in the digital journals Scielo, Redalyc, PubMed, Medline, Reaciamuc, Google Scholar, Elsevier, Medigraphic, Dialnet and Science Direct. The research was systematic with a scientific documentary design using literature observation instruments. In this study, the influence of comorbidities was analyzed, such as cardiovascular diseases, arterial hypertension, diabetes mellitus, among others, these problems are related to obesity, affecting the child population due to the genetic factor of both parents who present some comorbidities. It is important to know the trends in the prevalence of obesity to monitor the health status of a population by applying prevention strategies by the competent authority.La presente investigación tiene la finalidad de dar a conocer sobre la obesidad como factor desencadenante de comorbilidad, siendo una de las condiciones patológicas más comunes en el ser humano y se presente desde la antigüedad que persiste y se incrementa durante siglos por factores genéticos y ambientales, hasta convertirse actualmente en una enfermedad con consecuencias nefastas para la salud. Así también la asociación importante con la comorbilidad, que abarca desde alteraciones clínicas, metabólicas, hormonales, respiratorias, neoplasias, ortopédicas y hasta psicológicas. El objetivo de estudio es “Determinar factores de obesidad como desencadenante de comorbilidad”. Por la importancia de la etiología multifactorial, y el resultado de la interacción entre el genotipo y el entorno, además de factores psicológicos, sociales y culturales, malos hábitos alimenticios y heterogéneos que influyen en el sobrepeso llevando a pacientes obeso.  Se realizó una búsqueda en las revistas digitales Scielo, Redalyc, PubMed, Medline, Reaciamuc, Google Scholar, Elsevier, Medigraphic, Dialnet y Science Direct. La investigación fue sistemática con diseño documental científico mediante instrumentos de observación de literatura. En este estudio se analizó la influencia de las comorbilidades, tales como enfermedades cardiovasculares, hipertensión arterial, diabetes mellitus entre otros, estos problemas se relacionan con la obesidad afectando a la población infantil por el factor genético de ambos padres que presentan algunas comorbilidades. Es importante conocer las tendencias en la prevalencia de obesidad para monitorizar el estado de salud de una población aplicando estrategias de prevención por la autoridad competente

Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs

Development of nontoxic, tumor-targetable, and potent in vivo RNA delivery systems remains an arduous challenge for clinical application of RNAi therapeutics. Herein, we report a versatile RNAi nanoplatform based on tumor-targeted and pH-responsive nanoformulas (NFs). The NF was engineered by combination of an artificial RNA receptor, Zn(II)-DPA, with a tumor-targetable and drug-loadable hyaluronic acid nanoparticle, which was further modified with a calcium phosphate (CaP) coating by in situ mineralization. The NF can encapsulate small-molecule drugs within its hydrophobic inner core and strongly secure various RNA molecules (siRNAs, miRNAs, and oligonucleotides) by utilizing Zn(II)-DPA and a robust CaP coating. We substantiated the versatility of the RNAi nanoplatform by demonstrating effective delivery of siRNA and miRNA for gene silencing or miRNA replacement into different human types of cancer cells in vitro and into tumor-bearing mice in vivo by intravenous administration. The therapeutic potential of NFs coloaded with an anticancer drug doxorubicin (Dox) and multidrug resistance 1 gene target siRNA (siMDR) was also demonstrated in this study. NFs loaded with Dox and siMDR could successfully sensitize drug-resistant OVCAR8/ADR cells to Dox and suppress OVCAR8/ADR tumor cell proliferation in vitro and tumor growth in vivo. This gene/drug delivery system appears to be a highly effective nonviral method to deliver chemo- and RNAi therapeutics into host cells.National Institute for Biomedical Imaging and Bioengineering (U.S.)National Institutes of Health (U.S.)AXA Research Fund (Postdoctoral Fellowship)National Research Foundation of Korea (Postdoctoral Fellowship 2013R1A6A3A03)National Research Foundation of Korea (Grant 2009-0080734

Incompatibilidad ABO. Una revisión bibliográfica

Introduction: blood is a body fluid with a very important function in various biological and metabolic processes. Type A and B antigens determined by genetic inheritance are those found on the outside of erythrocytes, they vary in different populations, so they are the subject of important studies in various branches of medicine, in the area of ​​gynecology and obstetrics , it is important to identify a blood incompatibility early or preventively to favor the reduction of neonatal morbidity and mortality rates, since it can lead to hemolytic disease of the newborn or other complications. Objective: To collect the most important and up-to-date information on ABO incompatibility. Methodology: Systematic review of documents and research in English and Spanish obtained from scientific platforms such as Elsevier, ScIELO, PubMed and from national and international university repositories since 2017, with descriptors such as the ABO System, blood, maternal-fetal incompatibility, complications, among others. Results: Of a total of 112 documents initially, 62 were used to read their summaries, excluding the others due to lack of relevance to the research topic or duplication of information. Conclusions: ABO blood incompatibility is a complication that generates an antigen-antibody reaction and can be fatal. Therefore, all medical branches; or at least the vast majority, initially consider performing blood typing tests to apply the corresponding treatments or determine the etiological cause of an associated pathology, knowing that there are natural processes in gynecology in which ABO incompatibility can generate important complications in the newborn such as hemolytic disease of the newborn, anemia, or severe hyperbilirubinemia, which increase morbidity and mortality rates.Introducción: la sangre es un fluido corporal con una función importantísima dentro de varios procesos biológicos y metabólicos. Los antígenos de tipo A y B determinados por herencia genética son los que se encuentran en la parte externa de los eritrocitos, varían en las diferentes poblaciones, por lo que son sujetos de importantes estudios diversas ramas de la medicina, en el área gineco-obstetricia, es importante identificar de forma temprana o preventiva una incompatibilidad sanguínea para favorecer la disminución de los índices de morbilidad y mortalidad neonatal, ya que puede derivar en una enfermedad hemolítica del recién nacido u otras complicaciones con mayor o menor grado. Objetivo: Recopilar la información más importante y actualizada sobre la incompatibilidad ABO. Metodología: Revisión sistemática documentos e investigaciones en inglés y español obtenidas de plataformas científicas como Elsevier, ScIELO, PubMed y de repositorios universitarios nacionales e internacionales desde el 2017, con descriptores como Sistema ABO, incompatibilidad sanguínea, materno-fetal, complicaciones, entre otras.  Resultados: De un total de 112 documentos inicialmente, 62 fueron utilizados para la lectura de sus resúmenes, excluyéndose los demás por falta de relevancia con el tema de investigación o duplicación de la información. Conclusiones: La incompatibilidad sanguínea ABO es una complicación que genera reacción antígeno- anticuerpo y que puede llegar a ser mortal. Por ello, todas las ramas médicas; o por lo menos la gran mayoría, considera inicialmente realizar pruebas de tipificación sanguínea para aplicar los tratamientos correspondientes o determinar la causa etiológica de una patología asociada, sabiendo que existen procesos naturales en ginecología en los que la incompatibilidad ABO puede generar complicaciones importantes en el neonato como la enfermedad hemolítica del recién nacido, anemias o hiperbilirrubinemia grave, mismos que aumentan los índices de morbimortalidad

COMPARISON OF THE LEVELS OF DENTAL FLUOROSIS IN STUDENTS OF TWO MUNICIPALITIES FROM SANTANDER

Objective: To compare the levels of dental fluorosis in students between the 6 and 17 years old in two scholar institutions from two municipalities of Santander.Material and methods: An observational descriptive cross sectional study was done; the universe and the sample were integrated by the totality of scholars of two educational institutions for two municipalities of Santander. Sociodemographic variables, systemic conditions, perception of the teeth appearance, dental decay (COP index) and dental flurosis (Dean and Thysltrup & Fejerskov index) were registered. The statistic analysis implied the calculation of summary measures according to the nature of the variables; by bivariate analysis the municipality was considered like exit variable, for the qualitative variables Chi square and Fisher Exact test was applied and by the quantitative variables t student and Wilcoxon ranks test was used.Results: Three hundred forty and two students were evaluated, 249 subjects came from Oiba and 93 from Cepita. In Oiba, 80.7% subjects and 97.8% from Cepita registered dental fluorosis.Conclusions: Although the prevalence of fluorosis observed in Cepita were superior, the results must be look with discretion based on the differences of age between the two populations.Objetivo: Describir los niveles de fluorosis dental en escolares entre los 6 y 17 años de edad vinculados a dos instituciones educativas de dos municipios de Santander.Materiales y métodos: Se realizó un estudio observacional descriptivo de corte transversal; el universo y la muestra estuvo integrada por la totalidad de escolares vinculados a dos concentraciones educativas de dos municipios de Santander. Se recolectaron variables sociodemográficas, condiciones sistémicas, percepción de los menores frente a la apariencia de sus dientes, caries dental (índice COP) y la fluorosis dental (índice de Dean e índice de Thysltrup & Fejerskov). El análisis estadístico implicó el cálculo de medidas de resumen según la naturaleza de las variables; para el bivariado se consideró como variable de salida, municipio de residencia y las otras como explicatorias, para las variables cualitativas se aplicó test de Chi2 y Exacto de Fisher y para las cuantitativas prueba t de Student o test de rangos de Wilcoxon.Resultados: Se evaluaron 342 escolares, 249 sujetos procedían de Oiba y 93 de Cepitá. El 80.7% de las personas del primer municipio y el 97.8% del segundo registraron fluorosis dental.Conclusión: Aunque la prevalencia de fluorosis observada en el municipio de Cepitá fue superior a la de Oiba, los resultados deben mirarse con discreción debido a las diferencias de edad entre las poblaciones.[Blanco H, Durán L, Neira LN, Pourgoshtasbi L, Carvajal LC, Concha SC. Comparación de los niveles de fluorosis dental en escolares de dos municipios de Santander. Ustasalud 2008; 7: 108 - 116

Stratigraphic evidence of two historical tsunamis on the semi-arid coast of north-central Chile

On September 16, 2015, a Mw 8.3 earthquake struck the north-central Chile coast, triggering a tsunami observed along 500 km of coastline, between Huasco (28.5°S) and San Antonio (33.5°S). This tsunami provided a unique opportunity to examine the nature of tsunami deposits in a semi-arid, siliciclastic environment where stratigraphic and sedimentological records of past tsunamis are difficult to distinguish. To improve our ability to identify such evidence, we targeted one of the few low-energy, organic-rich depositional environments in north-central Chile: Pachingo marsh in Tongoy Bay (30.3°S).We found sedimentary evidence of the 2015 and one previous tsunami as tabular sand sheets. Both deposits are composed of poorly to moderately sorted, gray-brown, fine-to medium-grained sand and are distinct from underlying and overlying organic-rich silt. Both sand beds thin (from ∼20 cm to \u3c1 \u3ecm) and fine landward, and show normal grading. The older sand bed is thicker and extends over 125 m further inland than the 2015 tsunami deposit. To model the relative size of the tsunamis that deposited each sand bed, we employed tsunami flow inversion. Our results show that the older sand bed was produced by higher flow speeds and depths than those in 2015. Anthropogenic evidence along with 137Cs and 210Pb dating constrains the age of the older tsunami to the last ∼110 years. We suggest that the older sand bed was deposited by the large tsunami in 1922 CE sourced to the north of our study site. This deposit represents the first geologic evidence of a pre-2015 tsunami along the semi-arid north-central Chile coast and highlights the current and continuing tsunami hazard in the region