859 research outputs found
How Liaisons Leverage Self-Regulated Learning During Transitions to Online Learning at a Mid-Western Urban School District: A Transcendental Phenomenological Study
The purpose of this transcendental phenomenological study was to discover how homelessness liaisons leverage self-regulated learning to buffer learners’ risk and adversity during transitions to online learning for students experiencing homelessness (SEHs) at a Midwestern urban school district. The theory guiding this study was Zimmerman’s social cognitive theory of self-regulated learning, a protective factor for SEHs. After collecting data using a questionnaire, conducting individual interviews, and a focus group, the study used bracketing or epoché to analyze data collected on 11 homelessness liaisons regarding how they fostered self-regulation in their students during the transition to online learning COVID-19 Closures caused. Results illustrated that life coaches became their students’ bridge to safety, love, support, and stability, which fosters self-regulation. Implications and future research are discussed
Empowering Citizen Deliberation in Direct Democratic Elections: A Field Study of the 2012 Oregon Citizens’ Initiative Review
Initiatives and referenda permit citizens to vote directly on legislation, but voters often lack essential policy information when deciding whether to support the measures on their ballots. Since citizens often do not trust policy experts and political elites to provide trustworthy information, the State of Oregon (USA) created an institution to address that problem. After an initial test in 2010, Oregon’s governor signed into law the Citizens’ Initiative Review Commission, which convened two stratified random samples of twenty-four Oregon voters. The first panel spent a week examining a tax reform measure, and the second reviewed a measure that would establish private casinos. At the end of their deliberations, each panel produced a one-page Citizens’ Statement that was included in a Voters’ Pamphlet, which the Secretary of State mailed to every registered Oregon voter. Using direct observation, panelist interviews, and large-sample, statewide surveys, researchers studied the deliberative quality and statewide impact of this unique process. They discovered that the panels met a high standard for deliberation, both from the researchers’ perspective as observers and from the point of view of the participants themselves. A majority of Oregon voters became aware of the process, which produced relevant and factually accurate statements. Roughly two-thirds of those who read the statements found them to be helpful when deciding how to vote. Finally, an online survey experiment shows that reading the statements increased voter knowledge substantially. Thus, the Citizens’ Initiative Review appears to provide a viable model for using citizen-centered deliberation to inform the judgments of the voting public.DiffĂ©rentes initiatives participatives et les rĂ©fĂ©rendums permettent aux citoyens de voter directement les lois, mais les Ă©lecteurs disposent rarement des informations politiques essentielles pour pouvoir faire leur choix. Face au manque de confiance des citoyens envers la fiabilitĂ© des informations fournies par les spĂ©cialistes et les Ă©lites politiques, l'Etat de l'Oregon (Etats-Unis) a crĂ©Ă© une institution pour remĂ©dier Ă ce problème. Après un test initial en 2010, le gouverneur de l'Oregon a promulguĂ© la crĂ©ation d’une Commission d’examen d’initiative citoyenne (Citizens’ Initiative Review Commission), rĂ©unissant deux Ă©chantillons alĂ©atoires stratifiĂ©s de vingt-quatre Ă©lecteurs de l'Oregon, qui ont passĂ© une semaine entière Ă examiner une mesure de rĂ©forme fiscale et une mesure visant Ă la crĂ©ation de casinos privĂ©s. Au terme de leurs dĂ©libĂ©rations, chaque panel a rĂ©digĂ© une DĂ©claration des citoyens (Citizens’ Statement) d'une page qui a Ă©tĂ© intĂ©grĂ©e dans un document intitulĂ© la« Brochure des Electeurs » ( Voters’ Pamphlet). Celle-ci a Ă©tĂ© envoyĂ©e par le SecrĂ©taire d'Etat Ă chaque Ă©lecteur inscrit de l'Oregon. Sur la base d’observations directes, d'interviews des membres de la Commission et d'enquĂŞtes Ă grande Ă©chelle au niveau de l'Etat, les chercheurs de cette Ă©tude ont Ă©tudiĂ© la qualitĂ© dĂ©libĂ©rative et l'impact de ce processus unique au niveau de l’Etat de l’Oregon. Ils ont conclu que les panels rĂ©pondaient Ă un haut niveau en matière de dĂ©libĂ©ration, Ă la fois du point de vue des chercheurs en tant qu'observateurs et du point de vue des participants eux-mĂŞmes. Une majoritĂ© des Ă©lecteurs de l'Oregon ont eu conscience de ce processus, ce qui a gĂ©nĂ©rĂ© des dĂ©clarations pertinentes et conformes Ă la rĂ©alitĂ©. Environ deux-tiers des personnes qui ont lu les DĂ©clarations les ont trouvĂ©es utiles au moment de leur dĂ©cision de vote. Enfin, une expĂ©rience de sondage en ligne montre que le fait de lire les DĂ©clarations a considĂ©rablement amĂ©liorĂ© les connaissances des Ă©lecteurs. Ainsi, l’Examen d’initiative citoyenne semble constituer un modèle viable d'utilisation de la dĂ©libĂ©ration citoyenne pour permettre aux Ă©lecteurs d'avoir un jugement Ă©clairĂ©.Varias iniciativas de democracia participativa y los referĂ©ndums permiten a los ciudadanos votar directamente sobre la legislaciĂłn, pero los votantes a menudo carecen de informaciĂłn polĂtica esencial cuando tienen que decidir si apoyan las medidas que figuran en sus papeletas de voto. Dado que los ciudadanos normalmente no confĂan en los expertos polĂticos ni en la Ă©lite polĂtica para que les proporcionen informaciĂłn de confianza, el Estado de OregĂłn (EE. UU.) creĂł una instituciĂłn para abordar este problema. Tras un periodo inicial de prueba en 2010, el gobernador de OregĂłn promulgĂł la ComisiĂłn de RevisiĂłn de Iniciativa Ciudadana, que fue constituida por dos muestras aleatorias estratificadas de veinticuatro votantes de OregĂłn. Estos  grupos especiales de ciudadanos dedicaron toda una semana a examinar una medida de reforma fiscal y otra sobre el establecimiento de casinos privados. Al tĂ©rmino de sus deliberaciones, cada grupo elaborĂł una DeclaraciĂłn Ciudadana de una página que se incluyĂł en un panfleto para los votantes que el Secretario de Estado envĂo por correo a todos los votantes registrados en el Estado de OregĂłn. Utilizando una combinaciĂłn de observaciĂłn directa, entrevistas con los miembros de los grupos especiales y estudios a nivel estatal con una amplia muestra, los investigadores estudiaron la calidad deliberativa y el impacto a nivel estatal de este proceso Ăşnico y llegaron a la conclusiĂłn de que los grupos especiales cumplĂan estrictas normas para la deliberaciĂłn, tanto desde la perspectiva de los investigadores como desde el punto de vista de los propios participantes. Una mayorĂa de los votantes de OregĂłn fueron conscientes del proceso, que produjo declaraciones relevantes y objetivamente precisas. Aproximadamente dos tercios de las personas que leyeron las declaraciones las encontraron Ăştiles a la hora de decidir en quĂ© sentido votar.  Finalmente, un experimento de una encuesta en lĂnea ha demostrado que leer las declaraciones aumentĂł sustancialmente los conocimientos de los votantes. Por lo tanto, la RevisiĂłn de Iniciativa Ciudadana parece proporcionar un modelo viable para utilizar la deliberaciĂłn centrada en los ciudadanos para informar los juicios del pĂşblico votante
EGF-induced activation of Akt results in mTOR-dependent p70S6 kinase phosphorylation and inhibition of HC11 cell lactogenic differentiation
BACKGROUND: HC11 mouse mammary epithelial cells differentiate in response to lactogenic hormone resulting in expression of milk proteins including β-casein. Previous studies have shown that epidermal growth factor (EGF) blocks differentiation not only through activation of the Ras/Mek/Erk pathway but also implicated phosphatidylinositol-3-kinase (PI-3-kinase) signaling. The current study analyzes the mechanism of the PI-3-kinase pathway in an EGF-induced block of HC11 lactogenic differentiation. RESULTS: HC11 and HC11-luci cells, which contain luciferase gene under the control of a β-casein promotor, were treated with specific chemical inhibitors of signal transduction pathways or transiently infected/transfected with vectors encoding dominant negative-Akt (DN-Akt) or conditionally active-Akt (CA-Akt). The expression of CA-Akt inhibited lactogenic differentiation of HC11 cells, and the infection with DN-Akt adenovirus enhanced β-casein transcription and rescued β-casein promotor-regulated luciferase activity in the presence of EGF. Treatment of cells with Rapamycin, an inhibitor of mTOR, blocked the effects of EGF on β-casein promotor driven luciferase activity as effectively as PI-3-kinase inhibitors. While expression of CA-Akt caused a constitutive activation of p70S6 kinase (p70S6K) in HC11 cells, the inhibition of either PI-3-kinase or mTOR abolished the activation of p70S6K by EGF. The activation of p70S6K by insulin or EGF resulted in the phosphorylation of ribosomal protein S6 (RPS6), elongation initiation factor 4E (elF4E) and 4E binding protein1 (4E-BP1). But lower levels of PI-3-K and mTOR inhibitors were required to block insulin-induced phosphorylation of RPS6 than EGF-induced phosphorylation, and insulin-induced phosphorylation of elF4E and 4E-BP1 was not completely mTOR dependent suggesting some diversity of signaling for EGF and insulin. In HC11 cells undergoing lactogenic differentiation the phosphorylation of p70S6K completely diminished by 12 hours, and this was partly attributable to dexamethasone, a component of lactogenic hormone mix. However, p70S6K phosphorylation persisted in the presence of lactogenic hormone and EGF, but the activation could be blocked by a PI-3-kinase inhibitor. CONCLUSION: PI-3-kinase signaling contributes to the EGF block of lactogenic differentiation via Akt and p70S6K. The EGF-induced activation of PI-3-kinase-Akt-mTOR regulates phosphorylation of molecules including ribosomal protein S6, eIF4E and 4E-BP1 that influence translational control in HC11 cells undergoing lactogenic differentiation
Survival and recovery modeling of acute kidney injury in critically ill adults
Objectives: Acute kidney injury is common among the critically ill. However, the incidence, medication use, and outcomes of acute kidney injury have been variably described. We conducted a single-center, retrospective cohort study to examine the risk factors and correlates associated with acute kidney injury in critically ill adults with a particular focus on medication class usage.
Methods: We reviewed the electronic medical records of all adult patients admitted to an intensive care unit between 1 February and 30 August 2020. Acute kidney injury was defined by the 2012 Kidney Disease: Improving Global Outcomes guidelines. Data included were demographics, comorbidities, symptoms, laboratory parameters, interventions, and outcomes. The primary outcome was acute kidney injury incidence. A Least Absolute Shrinkage and Selection Operator regression model was used to determine risk factors associated with acute kidney injury. Secondary outcomes including acute kidney injury recovery and intensive care unit mortality were analyzed using a Cox regression model.
Results: Among 226 admitted patients, 108 (47.8%) experienced acute kidney injury. 37 (34.3%), 39 (36.1%), and 32 patients (29.6%) were classified as acute kidney injury stages I–III, respectively. Among the recovery and mortality cohorts, analgesics/sedatives, anti-infectives, and intravenous fluids were significant (p-value \u3c 0.05). The medication classes IV-fluid electrolytes nutrition (96.7%), gastrointestinal (90.2%), and anti-infectives (81.5%) were associated with an increased odds of developing acute kidney injury, odd ratios: 1.27, 1.71, and 1.70, respectively. Cox regression analyses revealed a significantly increased time-varying mortality risk for acute kidney injury-stage III, hazard ratio: 4.72 (95% confidence interval: 1–22.33). In the recovery cohort, time to acute kidney injury recovery was significantly faster in stage I, hazard ratio: 9.14 (95% confidence interval: 2.14–39.06) cohort when compared to the stage III cohort.
Conclusion: Evaluation of vital signs, laboratory, and medication use data may be useful to determine acute kidney injury risk stratification. The influence of particular medication classes further impacts the risk of developing acute kidney injury, necessitating the importance of examining pharmacotherapeutic regimens for early recognition of renal impairment and prevention
Egg-derived anti-SARS-CoV-2 Immunoglobulin Y (IgY) with broad variant activity as intranasal prophylaxis against COVID-19
UNLABELLED: COVID-19 emergency use authorizations and approvals for vaccines were achieved in record time. However, there remains a need to develop additional safe, effective, easy-to-produce, and inexpensive prevention to reduce the risk of acquiring SARS-CoV-2 infection. This need is due to difficulties in vaccine manufacturing and distribution, vaccine hesitancy, and, critically, the increased prevalence of SARS-CoV-2 variants with greater contagiousness or reduced sensitivity to immunity. Antibodies from eggs of hens (immunoglobulin Y; IgY) that were administered the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were developed for use as nasal drops to capture the virus on the nasal mucosa. Although initially raised against the 2019 novel coronavirus index strain (2019-nCoV), these anti-SARS-CoV-2 RBD IgY surprisingly had indistinguishable enzyme-linked immunosorbent assay binding against variants of concern that have emerged, including Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529). This is different from sera of immunized or convalescent patients. Culture neutralization titers against available Alpha, Beta, and Delta were also indistinguishable from the index SARS-CoV-2 strain. Efforts to develop these IgY for clinical use demonstrated that the intranasal anti-SARS-CoV-2 RBD IgY preparation showed no binding (cross-reactivity) to a variety of human tissues and had an excellent safety profile in rats following 28-day intranasal delivery of the formulated IgY. A double-blind, randomized, placebo-controlled phase 1 study evaluating single-ascending and multiple doses of anti-SARS-CoV-2 RBD IgY administered intranasally for 14 days in 48 healthy adults also demonstrated an excellent safety and tolerability profile, and no evidence of systemic absorption. As these antiviral IgY have broad selectivity against many variants of concern, are fast to produce, and are a low-cost product, their use as prophylaxis to reduce SARS-CoV-2 viral transmission warrants further evaluation.
CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov/ct2/show/NCT04567810, identifier NCT04567810
Getting the message straight: effects of a brief hepatitis prevention intervention among injection drug users
To redress gaps in injection drug users' (IDUs) knowledge about hepatitis risk and prevention, we developed a brief intervention to be delivered to IDUs at syringe exchange programs (SEPs) in three US cities. Following a month-long campaign in which intervention packets containing novel injection hygiene supplies and written materials were distributed to every client at each visit, intervention effectiveness was evaluated by comparing exposed and unexposed participants' self-reported injection practices. Over one-quarter of the exposed group began using the novel hygiene supplies which included an absorbent pad ("Safety Square") to stanch blood flow post-injection. Compared to those unexposed to the intervention, a smaller but still substantial number of exposed participants continued to inappropriately use alcohol pads post-injection despite exposure to written messages to the contrary (22.8% vs. 30.0%). It should also be noted that for those exposed to the intervention, 8% may have misused Safety Squares as part of pre-injection preparation of their injection site; attention should be paid to providing explicit and accurate instruction on the use of any health promotion materials being distributed. While this study indicates that passive introduction of risk reduction materials in injection drug users through syringe exchange programs can be an economical and relatively simple method of changing behaviors, discussions with SEP clients regarding explicit instructions about injection hygiene and appropriate use of novel risk reduction materials is also needed in order to optimize the potential for adoption of health promotion behaviors. The study results suggest that SEP staff should provide their clients with brief, frequent verbal reminders about the appropriate use when distributing risk reduction materials. Issues related to format and language of written materials are discussed
Orienting Patients to Greater Opioid Safety: Models of Community Pharmacy-Based Naloxone
The leading cause of adult injury death in the USA is drug overdose, the majority of which involves prescription opioid medications. Outside of the USA, deaths by drug overdose are also on the rise, and overdose is a leading cause of death for drug users. Reducing overdose risk while maintaining access to prescription opioids when medically indicated requires careful consideration of how opioids are prescribed and dispensed, how patients use them, how they interact with other medications, and how they are safely stored. Pharmacists, highly trained professionals expert at detecting and managing medication errors and drug-drug interactions, safe dispensing, and patient counseling, are an under-utilized asset in addressing overdose in the US and globally. Pharmacies provide a high-yield setting where patient and caregiver customers can access naloxone—an opioid antagonist that reverses opioid overdose—and overdose prevention counseling. This case study briefly describes and provides two US state-specific examples of innovative policy models of pharmacy-based naloxone, implemented to reduce overdose events and improve opioid safety: Collaborative Pharmacy Practice Agreements and Pharmacy Standing Orders
Therapeutic efficacy of favipiravir against Bourbon virus in mice
Bourbon virus (BRBV) is an emerging tick-borne RNA virus in the orthomyxoviridae family that was discovered in 2014. Although fatal human cases of BRBV have been described, little is known about its pathogenesis, and no antiviral therapies or vaccines exist. We obtained serum from a fatal case in 2017 and successfully recovered the second human infectious isolate of BRBV. Next-generation sequencing of the St. Louis isolate of BRBV (BRBV-STL) showed >99% nucleotide identity to the original reference isolate. Using BRBV-STL, we developed a small animal model to study BRBV-STL tropism in vivo and evaluated the prophylactic and therapeutic efficacy of the experimental antiviral drug favipiravir against BRBV-induced disease. Infection of Ifnar1-/- mice lacking the type I interferon receptor, but not congenic wild-type animals, resulted in uniformly fatal disease 6 to 10 days after infection. RNA in situ hybridization and viral yield assays demonstrated a broad tropism of BRBV-STL with highest levels detected in liver and spleen. In vitro replication and polymerase activity of BRBV-STL were inhibited by favipiravir. Moreover, administration of favipiravir as a prophylaxis or as post-exposure therapy three days after infection prevented BRBV-STL-induced mortality in immunocompromised Ifnar1-/- mice. These results suggest that favipiravir may be a candidate treatment for humans who become infected with BRBV
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