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SILVER SPRING, Md., Feb. 7, 2023 /PRNewswire/ -- Today, the U.S. Food and Drug Administration is providing an at-a-glance summary of news from around the agency: On Monday, the FDA updated its easy step-by-step guide to include information about reporting your over-the-counter (OTC) at-home...
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In vitro studies with the nonspecific MLK inhibitor CEP-1347 had previously demonstrated protection against HIV-1 gp120-mediated neurotoxicity to rodent hippocampal and dorsal root ganglion neurons (Bodner et al., 2002, 2004). We subsequently showed that both HIV-1 Tat and gp120 induced autophosphorylation of MLK3 in rodent neuronal cultures, which could be inhibited by CEP-1347 (Sui et al., 2006). Additionally, CEP-1347 was neuroprotective under these conditions and reversed the proinflammatory phenotype of human monocytes exposed to Tat and gp120 (Sui et al., 2006). Studies with a dominant-negative MLK3 mutant confirmed the specificity of MLK3 signaling in mediating neurotoxicity after exposure to Tat (Sui et al., 2006). Subsequently, we used a murine model of HIV-1 encephalitis to demonstrate that administration of CEP-1347 prevented microgliosis, reversed macrophage production of toxic inflammatory mediators after HIV-1 infection, and restored normal synaptic architecture (Eggert et al., 2010).
We then examined the effect of Tat and URMC-099 treatment on microglial phagocytosis. For our initial studies, we used a basic colored latex bead assay to measure the phagocytic activity of microglia exposed to Tat for various durations. By 4 h of Tat exposure, BV-2 cells significantly increase their level of phagocytic activity in this model system (Fig. 2E,F). For subsequent experiments, we examined the 12 h exposure time point, because this exposure led to the greatest increase in phagocytic activity. Treatment of Tat-exposed microglia with 100 nm URMC-099 significantly decreased the phagocytic activity of the BV-2 cells to saline-treated control levels (Fig. 2G,H).
URMC-099 appeared to have no effect on Tat-mediated immune cell recruitment into the CNS. This could be for a number of reasons. First, although URMC-099 decreased the production of inflammatory and recruitment related cytokines in our in vitro and in vivo models, it did not reduce their production to control levels, most notably in the case of MCP-1, suggesting that remaining cytokine production after Tat exposure in vivo could be large enough to drive monocyte recruitment into the CNS (Weiss et al., 1999; McManus et al., 2000). It is also possible that recruitment depends on endothelial activation and adhesion factor expression, and, although there are data to support roles for MLK3 signaling in both of these processes (Muniyappa and Das, 2008; Li et al., 2012), it does not appear to play a major role in our experimental paradigm. Regardless, although leukocytes still enter the brain parenchyma after exposure to Tat, MLK3 inhibition by URMC-099 treatment alters the ability of these immune effector cells to damage synapses and axons, thus contributing to its efficacious neuroprotective profile.
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Healthcare leaders from around the world joined the Executive Summit 2022 to discuss how we can deliver healthcare that works for everyone, everywhere, while finding solutions to the globally eminent workforce crisis.
Adrienne Boissy and Albert Wu talk about how to begin restoring trust not just with patients but also within the workforce, and how to reconcile a dedication to patient care with the demands of a staff shortage.
Join your classmates from across your campus and across the state from Monday, September 21, 2020 though Sunday, January 3, 2021 as together we show our love for reading and discover new and exciting ideas, authors, and stories through our favorite books.
In accordance with the 40 CFR Part 763 (enacted by Congress in 1986) of the Asbestos Hazard Emergency Response Act (AHERA). Section 763.93 pertaining to the Asbestos in School Identification and Notification Rule, Harmony School of Discovery -Houston hereby notifies all parties of the Asbestos Management Plan availability.
During the school closure last spring and over the summer months, Harmony offered meals to all children ages 18 and under in the community. Meals were distributed at select schools at no charge. The last distribution day will be the week of August 10th and will include meals through August 16th.
Online school begins on August 17th, and with the start of a new school year begins meal service under the National School Lunch Program. Just as if meals were served on site, all students will be charged for meals according to their eligibility of free, reduced, or paid. For students of paid eligibility, breakfast cost $1.75 and lunch is $3.30. For students of reduced price eligibility, breakfast cost $0.30 and lunch is $0.40. Parents are encouraged to submit an application for free or reduced price meals by going to www.schoolcafe.com and setting up a parent account. Paper applications may also be picked up from the school on meal distribution days. Once a student is approved for free or reduced price meals, they will remain that eligibility for the rest of the school year and the first 30 days of the next. Parents are encouraged to reapply whenever there is a loss of income or new participation in SNAP/TANF.
Durante el cierre de la escuela, la primavera pasada y durante los meses de verano, Harmony ofreció comidas a todos los niños menores de 18 años en la comunidad. Las comidas se distribuyeron sin costo, en escuelas seleccionadas. El ultimo día de distribución será durante la semana del 10 de agosto e incluirá comidas hasta el 16 de agosto.
La escuela en línea comienza el 17 de agosto y con el inicio de un nuevo año escolar comienza el servicio de comidas bajo el Programa Nacional de Almuerzos Escolares. Al igual que si las comidas se sirvieran en la escuela, a todos los estudiantes se les cobrará de acuerdo con su elegibilidad, ya sea gratis, precio reducido o pago. Para los estudiantes con elegibilidad pago, el costo del desayuno es $1.75 y el del almuerzo es $3.30. Para estudiantes con elegibilidad de precio reducido, el costo del desayuno es $0.30 y el del almuerzo es $0.40. Se anima a los padres a llenar una solicitud para recibir comidas gratis o a precio reducido en www.schoolcafe.com y configurar una cuenta para padres. Las solicitudes impresas también se pueden recoger en la escuela los días de distribución de comidas. Una vez que se aprueba a un estudiante para recibir comidas gratis o a precio reducido, seguirá siendo elegible durante el resto del año escolar y los primeros 30 días del siguiente. Se le anima a los padres a volver a presenter una solicitud cada vez que haya una pérdida ingresos o una nueva participación en SNAP/TANF (por sus siglas en inglés).
_newsletter%20-%20CopyAugust 13, 2020/by arahmanovic -new/wp-content/uploads/sites/106/2019/10/HS-Discovery-Houston-tr-300x163.png 0 0 arahmanovic -new/wp-content/uploads/sites/106/2019/10/HS-Discovery-Houston-tr-300x163.png arahmanovic2020-08-13 15:44:452020-08-13 15:44:45August Parent and Family EngagementNews Technology NeedsHello HSD families!