HMGA1, Moonlighting Protein Function, and Cellular Real Estate: Location, Location, Location!

HMGA1; Secretome; Unconventional protein secretionHMGA1; Secretoma; Secreción de proteínas no convencionalesHMGA1; Secretoma; Secreció de proteïnes no convencionalsThe gene encoding the High Mobility Group A1 (HMGA1) chromatin remodeling protein is upregulated in diverse cancers where high levels portend adverse clinical outcomes. Until recently, HMGA1 was assumed to be a nuclear protein exerting its role in cancer by transcriptionally modulating gene expression and downstream signaling pathways. However, the discovery of an extracellular HMGA1-RAGE autocrine loop in invasive triple-negative breast cancer (TNBC) cell lines implicates HMGA1 as a “moonlighting protein” with different functions depending upon cellular location. Here, we review the role of HMGA1, not only as a chromatin regulator in cancer and stem cells, but also as a potential secreted factor that drives tumor progression. Prior work found that HMGA1 is secreted from TNBC cell lines where it signals through the receptor for advanced glycation end products (RAGE) to foster phenotypes involved in tumor invasion and metastatic progression. Studies in primary TNBC tumors also suggest that HMGA1 secretion associates with distant metastasis in TNBC. Given the therapeutic potential to target extracellular proteins, further work to confirm this role in other contexts is warranted. Indeed, crosstalk between nuclear and secreted HMGA1 could change our understanding of tumor development and reveal novel therapeutic opportunities relevant to diverse human cancers overexpressing HMGA1.This research was supported by a grant from Instituto de Salud Carlos III through the project “PI19/01292” (Co-funded by European Regional Development Fund/European Social Fund “A way to make Europe”/“Investing in your future”)

Calidad de vida laboral en trabajadores obreros de la gerencia de servicios públicos y medio ambiente municipalidad distrital de Sayan, 2021

Objetivo: Identificar como se presenta la calidad de vida en el trabajo de los colaboradores obreros de la gerencia de servicios públicos de la Municipalidad Distrital de Sayán, 2021. Métodos: Investigación básica, descriptiva, no experimental y cuantitativa. La población y muestra se conformó de 78 trabajadores quienes respondieron el cuestionario CVT-Gohisalo, cuyos autores son Gonzáles, Hidalgo, Salazar & Preciado ( 2010 ) y adaptado por Aranda, Elizalde, Pando y Gonzáles ( 2017 ).Resultados: El 56% de los trabajadores, presenta nivel moderado de calidad de vida laboral, 24% nivel alto y 19% nivel bajo. En la dimensión Soporte Institucional 53% presenta nivel medio; en Seguridad 46% nivel moderado; en Integración 45% nivel moderado; en Satisfacción 47% nivel medio; en Bienestar 59% nivel moderado; en Desarrollo personal del colaborador 56% medio y en Administración del tiempo libre 59% nivel moderado. Conclusión: Los hallazgos que tuvo la población demostraron que en la Municipalidad analizada se presenta calidad laboral en un nivel moderad

A multicenter evaluation of the efficacy and duration of action of alcaftadine 0.25% and olopatadine 0.2% in the conjunctival allergen challenge model

Background: The purpose of this study was to evaluate the efficacy and duration of action of once-daily dosing with alcaftadine 0.25% ophthalmic solution and olopatadine 0.2% ophthalmic solution as compared with placebo in the prevention of ocular itching, and to directly compare the efficacy of alcaftadine 0.25% with olopatadine 0.2% in the prevention of ocular itching associated with allergic conjunctivitis using the conjunctival allergen challenge model. Methods: Subjects with allergic conjunctivitis (n = 127) were enrolled in a multicenter, double-masked, randomized, active-controlled and placebo-controlled clinical trial. Using the conjunctival allergen challenge model, this study was conducted over the course of approximately 5 weeks. Subjects were randomized into one of three treatment arms: alcaftadine 0.25% ophthalmic solution, olopatadine 0.2% ophthalmic solution, or placebo. Study medications were administered twice over the course of the trial. The primary efficacy measure for the study was ocular itching evaluated by the subject at 3, 5, and 7 minutes post challenge. Secondary endpoints, measured at 7, 15, and 20 minutes post challenge, included conjunctival, ciliary, and episcleral redness, lid swelling, chemosis, and tearing. Duration of action was measured at 16 and 24 hours post-instillation of the study medication at visits 3 and 4, respectively. Results: For the primary measure of ocular itching, both actives, alcaftadine 0.25% and olopatadine 0.2%, were statistically superior to placebo at all three measured time points for both the 16-hour and 24-hour measures (P < 0.0001). Eyes treated with alcaftadine 0.25% had numerically lower mean ocular itching scores than eyes treated with olopatadine 0.2% at every time point, and this difference was statistically significant at the 3-minute time point 16 hours post instillation (P = 0.026). Eyes treated with alcaftadine 0.25% and with olopatadine 0.2% displayed significantly less lid swelling relative to placebo at every time point for the 16-hour and 24-hour post-instillation visits (P < 0.005). Alcaftadine 0.25% was the only active treatment that provided statistically significant relief of chemosis at every time point of the 24-hour post-instillation visit. Conclusion: Both the alcaftadine 0.25% and olopatadine 0.2% ophthalmic solutions provided highly effective relief of ocular itching at both 16 and 24 hours post-instillation. Treatment differences between the actives were most pronounced at the earliest time point (3 minutes post-challenge) following conjunctival allergen challenge (16 hours), when alcaftadine 0.25% ophthalmic solution was statistically superior to olopatadine 0.2% ophthalmic solution. Alcaftadine 0.25% was the only treatment to provide significant relief from chemosis at both 16 and 24 hours post-instillation. Both active treatments and placebo were generally safe and well tolerated

Manifestations of Cognitive Presence in Blended Learning Classes of the Philippine K–12 System

Through an exploratory case study, this research sought to determine the applicability of the Community of Inquiry in the K–12 setting. There are research gaps to leverage support for blended learning and flexible learning options to benefit Filipino youth and school-leavers under the Alternative Delivery Mode of the Philippine K–12 system. This study was driven by the following research questions: How is cognitive presence manifested in the blended learning interactions? In what ways do the interactions of cognitive presence with the other presences characterize learning community building? Three blended learning classes were examined based on data collected through surveys, student focus group discussions, teacher interviews, class observations and archived data. Through constant comparison analysis and descriptive statistics, evidence revealed cognitive presence across its categories in the form of connectedness, collaborative work, trust and reciprocation, and shared views on technology by K–12 teachers and learners. The analysis affirmed 'regulating learning' as the intersection of cognitive presence and teaching presence. Implications for practice and recommendations for further research are discussed through the study's proposed modifications on the cognitive presence categories, indicators, and the survey instrument for the K–12 setting where teacher-directed pedagogies or collaborative inquiry processes have not been thoroughly co-opted

Ocular Itch Relief with Alcaftadine 0.25% Versus Olopatadine 0.2% in Allergic Conjunctivitis: Pooled Analysis of Two Multicenter Randomized Clinical Trials

Introduction: The efficacy and safety of the once-daily topical ophthalmic solutions, alcaftadine 0.25% and olopatadine 0.2%, in preventing ocular itching associated with allergic conjunctivitis were evaluated. Methods: Pooled analysis was conducted of two double-masked, multicenter, active- and placebo-controlled studies using the conjunctival allergen challenge (CAC) model of allergic conjunctivitis. Subjects were randomized 1:1:1 to receive alcaftadine 0.25%, olopatadine 0.2%, or placebo. The primary efficacy measure was subject-evaluated mean ocular itching at 3 min post-CAC and 16 h after treatment instillation. Secondary measures included ocular itching at 5 and 7 min post-CAC. Ocular itch was determined over all time points measured (3, 5, and 7 min) post-CAC and the proportion of subjects with minimal itch (itch score <1) and zero itch (itch score = 0) was also assessed. Results: A total of 284 subjects were enrolled in the two studies. At 3 min post-CAC and 16 h after treatment instillation, alcaftadine 0.25% achieved a significantly lower mean itch score compared with olopatadine 0.2% (0.50 vs. 0.87, respectively; P = 0.0006). Alcaftadine demonstrated a significantly lower mean itch score over all time points compared with olopatadine (0.68 vs. 0.92, respectively; P = 0.0390); both alcaftadine- and olopatadine-treated subjects achieved significantly lower overall mean ocular itching scores compared with placebo (2.10; P < 0.0001 for both actives). Minimal itch over all time points was reported by 76.1% of alcaftadine-treated subjects compared with 58.1% of olopatadine-treated subjects (P = 0.0121). Treatment with alcaftadine 0.25% and olopatadine 0.2% was safe and well tolerated; no serious adverse events were reported. Conclusion: Once-daily alcaftadine 0.25% ophthalmic solution demonstrated greater efficacy in prevention of ocular itching compared with olopatadine 0.2% at 3 min post-CAC (primary endpoint), and over all time points, 16 h post-treatment instillation. Alcaftadine and olopatadine both provided effective relief compared with placebo and were generally well tolerated. Electronic supplementary material The online version of this article (doi:10.1007/s12325-014-0155-3) contains supplementary material, which is available to authorized users

Legalización de la marihuana y cannaturismo: ¿una oportunidad para destinos turísticos mexicanos?

Marijuana tourism is a recent phenomenon that is emerging as a result of the legalization of marijuana in several states of the United States, and Canada. In Mexico there has been an interest in legalizing marijuana for recreational purposes but there are many concerns about its possible effects on society. Based on a review of the literature and official statistics, this article examines the implications of legalizing this drug for society in general and the tourism industry in particular. The emergence of a marijuanarelated touristic offering was identified, which, if regulated, could diversify the tourist offerings of Mexican destinations. It was also found that the impacts of the legalization of marijuana tend to be mostly positive and can contribute to alleviating economic and social problems in tourist destinations. The possible implications of the legalization of this drug for Mexico are discussed.El cannaturismo es un fenómeno que está emergiendo a raíz de la legalización de la marihuana en varios estados de los Estados Unidos, y en Canadá. En México se aprobó un proyecto de ley para legalizar esta droga para consumo recreativo pero existen muchas preocupaciones sobre sus posibles efectos en la sociedad. Con base en una revisión de literatura y estadísticas oficiales, este artículo examina las implicaciones de la legalización de esta droga para la sociedad, en general, y la industria turística en particular. Se identificó el surgimiento de una variada y dinámica oferta cannaturística, que, de implementarse de manera regulada, puede diversificar la oferta turística de los destinos mexicanos. También se encontró que los impactos de la legalización de la marihuana tienden a ser mayormente positivos y pueden contribuir a aliviar problemáticas económicas y sociales en destinos turísticos. Se discuten las posibles implicaciones de la legalización de esta droga para México

Incidencia del uso de la tecnología y la actividad física en estudiantes de 7 a 17 año

A cross-sectional descriptive study was conducted with 165 students of the District Institute of Educational Experiences in the city of Barranquilla, to assess the level of physical activity. Age, gender, educational level, socioeconomic status, BMI, waist circumference and physical activity using the Physical Activity Questionnaire (IPAQ-C) was evaluated. 64.9% of participants have 8-13 years, 51% male and 49% female, 21.2% belong to grade 5, 88.4% are of socioeconomic 3 and 4, 38.7% are overweight and obesity; and the average rate waist 67. In relation to sedentary comes in a 65.1%; one in five students are obese. It is recommended to promote physical education program with minimum of sixty minutes three times a week.Se realizó un estudio descriptivo transversal con 165 estudiantes del instituto Distrital de Experiencias Pedagógicas de la ciudad de Barranquilla, para valorar el nivel de actividad física. Se evaluó la edad, el género, el nivel académico, estrato socioeconómico, el IMC, perímetro de cintura y la actividad física con el uso del Cuestionario de actividad física (IPAQ-C). El 64.9% de los participantes tiene entre 8-13 años, el 51% son hombres y el 49% son mujeres, el 21.2% pertenecen al grado 5°, el 88.4% son de estrato socioeconómico 3 y 4, el 38.7% presentan sobrepeso y obesidad; y el promedio del índice de cintura de 67. Con relación a la actividad física el sedentarismo se presenta en un 65.1%; uno de cada cinco estudiantes son obesos. El 98% de los estudiantes dedican en promedio seis horas diarias a las actividades tecnológicas, así: videojuegos con un 48%, televisión con un 30% y uso de la computadora en un 20%. Sólo el 2% no realiza ningún tipo de actividad con el uso de la tecnología. Se recomienda promover un programa de educación física con mínimo de sesenta minutos, tres veces a la semana

Insoluble Vascular Amyloid Deposits Trigger Disruption of the Neurovascular Unit in Alzheimer’s Disease Brains

Funding: This work was supported by Fondo Nacional de Ciencia y Tecnologia, FONDOCyT, from the Ministry of Higher Education, Science and Technology, Dominican Republic (2015-3A2-127 to MP-H) and (2018-2019-2A3-208 to J.L.-M. and M.P.-H). Acknowledgments: The authors want to express their gratitude to the following: P. Davies†(Albert Einstein College of Medicine, Bronx, NY, USA) and Lester I. Binder† (North Western, Chicago, IL, USA) for the generous gift of mAbs TG-3 and Alz-50, and Tau-1, Tau-5, and Tau-7, respectively; Tec. Amparo Viramontes Pintos for the handling of the brain tissue; support in the confocal microscopy unit of CIIDIR Durango, Instituto Politécnico Nacional; Union Medica University Clinic, Dominican Republic, for their support and collaboration in the development of this research project. We also want to express our gratitude to the Mexican families who have donated the brain of their loved ones affected by Alzheimer’s disease and made our research possible. This work is dedicated to the memory of José Raúl Mena López† . †Deceased.Peer reviewedPublisher PD