1,632 research outputs found

    The Role of Chromatin Remodeling Protein and Transcriptional Repressor, Ing4, in Hematopoiesis Regulation

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    The hematopoietic compartment is tasked with the establishment and maintenance of the entire blood program. Key to this process are hematopoietic stem cells (HSCs), which possess the unique ability to self-renew and differentiate to replenish blood cells throughout an organism’s lifetime. In a screen for epigenetic regulators of hematopoiesis in zebrafish, we identified chromatin remodeling protein and transcription repressor, Ing4, as a requirement for hematopoietic stem and progenitor cell (HSPC) specification. Ing4, a member of the inhibitor of growth (ING) family, is a subunit of the HB01-JADE-hEAF6 histone acetyltransferase complex responsible for most nucleosomal histone H4 acetylation in eukaryotes. Ing4 is known to form an inhibitory complex with RelA, the large subunit of the NF-kB protein complex, limiting expression of NF-kB target genes. NF-kB is a dimeric complex of Rel proteins that can activate, and sometimes repress transcription of cytokine genes. Thus, loss of Ing4 in mice causes hyper inflammatory responses because there is no inhibition of NF-kB. Ing4 has also been suggested to regulate a wide variety of cellular processes, including DNA repair, apoptosis, cell-cycle regulation, metastasis, angiogenesis, and tumor suppression. The role of Ing4 in hematopoiesis has not been established. Here, we present data that shows Ing4 is critical for HSC gene regulation to direct both stem cell maintenance and differentiation in mice. Utilizing competitive transplantation, flow cytometry analysis of Ing4-deficient mouse bone marrow and peripheral blood, as well as colony-forming unit (CFU) assays, we have revealed that loss of Ing4 in mice resulted in a shift in the endogenous HSC sub-populations towards short term-HSCs (ST-HSCs)/long term-HSCs (LT-HSCs) and skewed HSC differentiation towards granulocyte-macrophage progenitors (GMPs). Furthermore, when sorted LT-HSC, ST-HSC, and MPP cells were transplanted into irradiated mice, Ing4-/- LT HSCs failed to reconstitute recipient BM, while Ing4-/- MPPs were greater contributors to multilineage engraftment compared to WT MPPs. Interestingly, MPPs are a population that have lost the self-renewal capacity of a stem cell, but our data suggests that under stress hematopoiesis, the loss of Ing4 likely results in reprogramming of MPPs to gain stem-like features. Further characterization of this HSC sub-population is underway. Moreover, the inability of Ing4-/- LT HSCs to engraft suggests an evolutionary requirement for Ing4 in normal hematopoiesis and gives us insight into how Ing4 modulates inflammatory pathways to regulate HSC function. Through a number of in situ hybridization studies, we have previously shown that Ing4-deficient zebrafish embryos have decreased expression of HSC specific genes, runx1 and c-myb, in the aorta—gonad—mesonephros (AGM) region, while mRNA based overexpression of human ING4 results in increased expression of these same genes, suggesting that normal expression levels of Ing4 are required for HSC specification. As in mice, Ing4 deficiency in zebrafish results in increased expression of NF-kB target genes. Interestingly, simultaneous inhibition of NF-kB and Ing4 restores HSC formation in embryonic zebrafish. Based on these observed effects and the literature published on our mouse model, we conducted a mini screen of NF-kB inhibitors with known modes of action, to identify those that could compensate for the consequences of Ing4 loss of function. These experiments revealed that NF-kB inhibitors, MRT673007, Senexin, and Parthenolide significantly reduced cytokine expression in Ing4-deficient zebrafish and as expected, rescued HSC specification in this system. Our findings support a novel role for Ing4 in blood development and highlight a potential molecular mechanism by which Ing4 regulates hematopoiesis through the NF-κB pathway. This provides further insight into the characterization of factors and pathways involved in hematopoiesis and the specific genetic defects in these regulators that can be targeted for therapeutic treatment of blood disorders

    Parental Behaviors of Mothers in Low Socioeconomic Hispanic Families

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    Parental functioning and behaviors in the family impact the outcomes of adolescents; however, few researchers have identified how age-specific parental behaviors and parental stressors impact young children\u27s social-emotional problems in low socioeconomic Hispanic families with children ages 6-11. Based on the family stress model, the purpose of this quantitative correlational study was to examine the relationship between parental behaviors (parental support, involvement, communication, and limit setting) and parental stress on children\u27s social-emotional problems (internalizing and externalizing behavior problems), and the mediating effect of parental behaviors in low socioeconomic Hispanic families with children ages 6-11. A sample of 63 low socioeconomic, Hispanic mothers self-reported their perceived stress, parent-child relationship, and child\u27s behavioral and emotional problems. The data were coded and grouped into 4 path analysis models based on the Pearson r correlation analysis, which indicated a significant relationship between parental behaviors and parental stress on children\u27s externalizing behavior problems. The path analysis indicated that parental behaviors did not mediate the relationship between parental stress and children\u27s externalizing behavior problems. The findings from this study have the potential to benefit low socioeconomic Hispanic families and their young children by improving the quality of parenting and developing and/or improving more targeted and relevant interventions for parent support, potentially leading to an overall community improvement of parent-child relationship and child outcomes

    Diseño de un sistema de drenaje urbano pluvial en las avenidas Víctor Larco, Fátima y húsares de Junín – Trujillo -la libertad

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    Esta investigación tiene como principal objetivo determinar la influencia del caudal generado en épocas de la llegada del niño costero y el diseño del sistema de drenaje urbano pluvial para las avenidas Víctor Larco Herrera, Fátima y Húsares de Junín – Trujillo – La Libertad, para ello se propuso un sistema de drenaje que consiste en 2 subsistemas llamados: sub sistema de la izquierda y sub sistema de la derecha, con 2 descargas: la salida1 y salida2 respectivamente, conteniendo todo el sistema 31 buzones unidos mediante tuberías respetando pendientes mínimas y máximas. Se modeló la propuesta en un software especializado llamado SWMM V.5.1 para comprobar que el sistema propuesto funciona, evitando sobrecargas e inundaciones en los buzones, se utilizó para el cálculo hidrológico el modelo de depósito no lineal y para el cálculo hidráulico se utilizó las fórmulas de la onda dinámica que emulan el flujo no permanente. Para el hietrograma de proyecto se utilizó la precipitación más representativa, la cual fue transformada en intensidad y fue adaptada la forma de la curva sintética IDF generada por el método ILLA SENAMHI UNI para un periodo de retorno de 25 años. Para delimitar la cuenca para la cual se tuvo en cuenta la topografía, dicha cuenca se dividió en 31 sub cuencas urbanas, las cuales se dividieron en 3 áreas: área permeable, área impermeable y área impermeable sin encharcamiento; para el modelo de infiltración se utilizó el número de curva. Como conclusión se obtuvo que, con la implementación del sistema de drenaje urbano pluvial mitigará el caudal generado en las avenidas Víctor Larco, Fátima y Húsares de Junín para épocas de la llegada del niño costero.The main goal of this research is to determine the influence between flow generated at the time of the arrival of the “niño costero” and the design of the urban storm drainage system for the avenues Víctor Larco Herrera, Fátima and Húsares de Junín - Trujillo - La Libertad. He proposed a drainage system consisting of 2 subsystems called: sub left system and sub right system with 2 outputs: salida1 and salida2 respectively, all the system containing 31 “boxes” joined by pipes respecting minimum and maximum slopes. The proposal was modeled in specialized software called SWMM V.5.1 to verify that the proposed system works, avoiding overloads and flooding in the mailboxes, the non-linear tank model was used for the hydrological calculation and the formulas were used for the hydraulic calculation of the dynamic wave that emulate the non-permanent flow which takes into account inertial forces, pressure forces, gravity forces and friction forces. For the project hietrogram, the most representative precipitation was used, which was transformed into intensity and the shape of the synthetic IDF curve generated by the ILLA SENAMHI UNI method was adapted for a return period of 25 years. To delimit the urban basin of 51.58 hectares, the topography was taken into account. This basin was divided into 31 urban sub-basins, so that later each one is divided into 3 areas: permeable area, impervious area and impervious area without puddling; The curve number was used for the infiltration model. As a conclusion, it was obtained that, with the implementation of the urban pluvial drainage system, it will mitigate the flow generated in the avenues Víctor Larco, Fátima and Húsares de Junín for times of the arrival of the “niño costero”.Tesi

    Quantifying and modelling the ENSO phenomenon and extreme discharge events relation in the La Plata Basin

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    Understanding and monitoring extreme events is essential, particularly in river discharges from the La Plata Basin, where a large percentage of the economic resources and population of the region are concentrated. In this article, we seek to quantify the relationship between extreme events in discharge and the seasonal climatic index NIÑO 3.4. We start by estimating the phase shift between the index and mean seasonal (trimester) discharge values. Based on this result, we align the series and use the copula method to fit a joint distribution. We end up with a model that is particularly useful for quantifying the probability of occurrence of extreme events and monitoring their return periods. As a final step, we generate predictions and validate the model by splitting the series into training and test datasets. We develop a simple effective model for monitoring discharges using the El Niño Southern Oscillation (ENSO) index.Fil: Meis, Melanie. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Llano, Maria Paula. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodriguez, Daniela Andrea. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Calculo. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Calculo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentin

    Medical professionalism: an experimental look at physicians’ Facebook profiles

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    Background: Use of social networking services (SNS) is on the rise. While many users sign in for personal purposes, it is not uncommon for professionals to connect over SNSs with clients, students, and patients. Methods: The present study used an experimental approach to examine how medical doctors’ SNS profiles impacted potential patients’ impressions of professionalism. Participants (N=250 students) were randomly assigned to view one of six Facebook profiles. Profiles were populated with 1) solely professional material, 2) personal material that was strictly healthy, or 3) personal material that included unhealthy behavior. Profiles portrayed a male or female physician resulting in a total of six experimental conditions. Medical professionalism was measured with the First Impressions of Medical Professionalism (FIMP) scale, specifically developed for this study. Results: There was a large and statistically significant main effect for profile type, F(2, 250)=54.77, p\u3c0.001, . Post hoc tests indicated that personal profiles that contained healthy behavior were rated as most professional followed by profiles with strictly professional content. Personal unhealthy profiles were rated as least professional. Additionally, female profiles consistently received higher professionalism ratings across all three profile types [F(1, 250)=5.04, p=0.026, ]. Conclusion: Our results suggest that a physician\u27s SNS profile affects a patient\u27s perception of that physician\u27s medical professionalism. A personal, healthy profile may augment a patient\u27s perception of that physician\u27s character virtues if the profile content upholds the decorum of the medical field

    Baseline Cultural Competence in Physician Assistant Students

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    Purpose Cultural competence is a critical component in health care services. The relationship between health disparities and prejudice and discrimination is well documented. Prejudicial attitudes and discriminatory behavior are modifiable through training yet few programs have evidence-based training. No published data has reported on baseline levels of cultural competencies in medical trainees which is necessary for tailoring programs appropriate to the audience. This manuscript fills that gap by reporting on data from three cohorts of first-year Physician Assistant (PA) students (N = 216). We examined students’ baseline levels with special attention to differences in cultural competence constructs across age, gender, and ethnicity. Methods Students completed self-report measures for ethnic identity, ethno-cultural empathy, multicultural orientation, attitudes about diversity, health beliefs attitudes, colorblind racial attitudes, and burnout at the beginning of their first year. They completed the measures online (Qualtrics) during class time, prior to a lecture on cultural competence. Results Data indicate a correlation between cultural competence constructs supporting the validity of the battery of tests as a cohesive unit to measure cultural competence. There were statistically significant differences between age, gender identity, and ethnic groups across cultural competence variables. Conclusions Data provide baseline data that may be used to tailor educational programs. Findings suggest that our measures show promise for future educational research measuring effectiveness of cultural competence training

    Graduate Ethics Education: A Content Analysis of Syllabi

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    Ethical practice of psychology is emphasized by APA accreditation requirements. The current study is a content analysis of 53 ethics courses syllabi from all APA accredited programs listed in the American Psychologist 2011 annual report. This article is a companion to Domenech Rodríguez et al. (2013) and contributes knowledge on the current state of graduate ethics education. Of the parent project respondents (N = 364), 14% returned syllabi for the present study. General information (e.g., objectives, honor code, academic honesty, common policy, and classroom expectations), assignments, APA format, and teaching sources were coded. Coding of objectives were developed from McKeachie and Svinkicki (2011) definition and de las Fuentes (2005) conceptualization of specific objectives (awareness, skill, and knowledge). A little over half (56.6%) of syllabi stated clear objectives, only 52.8% covered academic honesty, and 16 (30.2%) did not include a section to address accommodations for students with disabilities. Most syllabi used APA format to cite sources, however, most sources used were 5 years or older. Overall, syllabi were quite varied in the information they included. Greater consistency in syllabus content would make future evaluations on the state of graduate ethics education more accurate. Recommendations for observational and self-report alternatives are also presented

    Prior Design for Dependent Dirichlet Processes: An Application to Marathon Modeling

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    This paper presents a novel application of Bayesian nonparametrics (BNP) for marathon data modeling. We make use of two well-known BNP priors, the single-p dependent Dirichlet process and the hierarchical Dirichlet process, in order to address two different problems. First, we study the impact of age, gender and environment on the runners’ performance. We derive a fair grading method that allows direct comparison of runners regardless of their age and gender. Unlike current grading systems, our approach is based not only on top world records, but on the performances of all runners. The presented methodology for comparison of densities can be adopted in many other applications straightforwardly, providing an interesting perspective to build dependent Dirichlet processes. Second, we analyze the running patterns of the marathoners in time, obtaining information that can be valuable for training purposes. We also show that these running patterns can be used to predict finishing time given intermediate interval measurements. We apply our models to New York City, Boston and London marathons

    Nivel de sobrecarga y síntomas depresivos en cuidadores de pacientes en hemodiálisis atendidos en el hospital “Daniel Alcides Carrión”-2023

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    Objetivo: Determinar la asociación que existe entre el nivel de sobrecarga y síntomas depresivos en cuidadores primarios de pacientes en terapia de hemodiálisis atendidos en el Hospital “Daniel Alcides Carrión” -2023. Materiales y métodos: método científico; tipo analítico, transversal, observacional, prospectivo; alcance correlacional, diseño no experimental; población y muestra 60 cuidadores primarios, como instrumento el cuestionario sobre la carga del cuidador de Zarit e Inventario de depresión de Beck: (BDI-II). Resultados: Existe asociación significativa (valor = 0,000 9,4877) entre el nivel de sobrecarga y síntomas depresivos en cuidadores primarios. A nivel descriptivo, predominó sexo femenino (70%), la media de edad = 40.47 años, 46.7% casados y 21.7% convivientes, el 80% católicos, 38.3% era pareja sentimental y el 30% hijo (a), 56.7% era cuidador único del paciente, el 78.3% los cuidaba por más de 15 horas al día; finalmente, el 45% tenía ente 1 a 3 años cuidando a su paciente. Finalmente, el 63.3% presentaron sobrecarga intensa y el 75% tienen síntomas depresivos entre los niveles leve y moderado
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