Manganese Distribution across the Blood-Brain Barrier. IV. Evidence for Brain Influx through Store-Operated Calcium Channels

Manganese (Mn) is a required co-factor for many ubiquitous enzymes; however, chronic Mn overexposure can cause manganism, a parkinsonian-like syndrome. Previous studies showed Mn influx into brain is carrier-mediated, though the putative carrier(s) were not established. Studies conducted with cultured bovine brain microvascular endothelial cells (bBMECs), which comprise the blood–brain barrier, revealed 54Mn (II) uptake positively correlated with pH, was temperature-dependent, and was sodium- and energy-independent. Brain 54Mn uptake correlated inversely with calcium (Ca) concentration, but 45Ca uptake was unaltered by high Mn concentration. Lanthanum (La), a non-selective inhibitor of several Ca channel types, as well as verapamil and amiloride, inhibitors of voltage-operated Ca channels, failed to inhibit Mn uptake into cells. Nickel (Ni), another non-selective inhibitor of several Ca channel types, inhibited Mn and Ca uptake into cells by 88 and 85%, respectively. Cyclopiazonic acid (CPA) and thapsigargin, which activate store-operated calcium channels (SOCCs), increased 54Mn and 45Ca uptake into cultured bBMECs. In situ brain perfusion studies were conducted in adult, male Sprague–Dawley rats to verify the cell culture results. Both nickel and verapamil produced a non-significant decrease in Mn and Ca influx. Lanthanum significantly increased Mn influx to 675 and 450% of control in parietal cortex and caudate, respectively, while producing no significant effect on Ca influx. Vanadate, which inhibits Ca-ATPase, inhibited Mn uptake into cultured blood–brain barrier cells, but not into perfused rat brain. Overall these results suggest that both Ca-dependent and Ca-independent mechanisms play a role in brain Mn influx. This work provides evidence that store-operated Ca channels, as well as another mechanism at the blood–brain barrier, likely play a role in carrier-mediated Mn influx into the brain

Manganese Toxicokinetics at the Blood-Brain Barrier

Increased manganese (Mn) use in manufacturing and in gasoline has raised concern about Mn-induced parkinsonism. Previous research indicated carrier-mediated brain entry but did not assess brain efflux. Using in situ rat brain perfusion, we studied influx across the blood-brain barrier (BBB) of three predominant plasma Mn species available to enter the brain: Mn2+, Mn citrate, and Mn transferrin. Our results suggested transporter-mediated uptake of these species. The uptake rate was greatest for Mn citrate. Our results using the brain efflux index method suggested that diffusion mediates distribution from rat brain to blood. To characterize the carriers mediating brain Mn uptake, we used rat erythrocytes, an immortalized murine BBB cell line (b.End5), primary bovine brain endothelial cells (bBMECs), and Sprague Dawley and Belgrade rats. Studies with bBMECs and b.End5 cells suggested concentrative brain Mn2+ and Mn citrate uptake, respectively, consistent with carrier-mediated uptake. Mn2+ uptake positively correlated with pH, suggesting mediation by an electromotive force. Mn2+ uptake was not inhibited by iron or the absence of divalent metal transporter 1 (DMT-1) expression, suggesting an iron-transporter-independent mechanism. Mn2+ uptake inversely correlated with calcium and was affected by calcium channel modulators, suggesting a role for calcium channels. Rat erythrocyte results suggested monocarboxylate transporter 1 (MCT1) and anion exchange transporters do not mediate Mn citrate brain uptake. Considering carrier-mediated brain influx (but not efflux), repeated excessive Mn exposure should produce brain accumulation. Further work is necessary to identify the specific transporter or transporters mediating Mn distribution across the BBB

Idaho Literacy Intervention Program Evaluation 2021

In 2020, the Idaho Legislature authorized an independent, external evaluation of the state’s literacy intervention program (Program) that will consider: (a) program design, (b) use of funds, including funding utilized for all-day kindergarten, (c) program effectiveness; and (d) an analysis of key performance indicators of student achievement, as well as any other relevant matters. For the third year, Idaho Policy Institute (IPI) was contracted to conduct the evaluation. Performance data traditionally used in this evaluation is unavailable because of the COVID-19 pandemic. As a result, IPI administered online surveys to teachers (n=494) and administrators (n=101) and conducted in-depth interviews with teachers (n=11) to understand the function and perceptions of the Program across the state. This report also includes data from the 2019/20 (LEA) literacy plans, budgets, and expenditure data

Idaho Diagnostic Site Visit Protocol 2020

Diagnostic site visits are a common evaluation tool for schools across the United States. The goal of site visits is to provide schools with a comprehensive third-party evaluation of policies and practices that impact school quality beyond test scores and assist in school improvement planning. The following report contains a protocol for conducting diagnostic site visits in the state of Idaho. The report is based on the standards to be evaluated during the site visits: faculty and staff, curriclum and instruction, communication and culture, governance, and finance. Also included are: Methods of standard evaluation Evaluation reporting expectations Evidence of standard indicators Scoring sheets and key Interview question example

Idaho Educational Policy Review

Kestrel West and yes. every kid. partnered with Idaho Policy Institute (IPI) to better understand the implementation of state and local-level education policies in school districts across the state of Idaho. IPI reviewed district policy handbooks and conducted surveys with superintendents and teachers in the state to answer research questions spanning several topics including class sizes, open enrollment, and alternative schools

Idaho Literacy Intervention Program Evaluation 2020

For over 20 years, Idaho leaders have recognized the critical importance of early childhood literacy. In this time, the Idaho State Legislature, State Board of Education and State Department of Education have developed policies, rules and plans as well as implemented programs to support reading proficiency in Idaho’s kindergarten through third grade students. In 2015, the Board of Education published an updated Comprehensive Literacy Plan for the state. The Legislature responded in 2016 by amending statutes related to early literacy development and establishing the current Literacy Intervention Program. In 2018, the Idaho Policy Institute completed an external evaluation of the Literacy Intervention Program requested by the Legislature. In 2019, the Legislature requested an additional, updated external evaluation. This report serves as that evaluation. The report evaluates the Literacy Intervention Program and discusses its design, use of funds and effectiveness during its first three years. The Literacy Intervention Program enables tailored literacy intervention plans at the Local Education Agency-level, allowing for flexibility to account for local needs. The mandated collection of data such as Idaho Reading Indicator scores, program budgets and annual expense reports is necessary for ongoing evaluation. Three years of expense data indicate a trend in which Local Education Agencies are better anticipating costs associated with the Program. This allows them to allocate their resources more efficiently. The testing instrument and procedures were changed (moving from the legacy IRI to the new IRI by Istation) in the Program’s third year in order to more effectively evaluate student literacy achievement. This change in testing limits the ability to compare overall literacy achievement across all Program years. However, early indications of patterns within the data can inform the Program’s implementation and evaluation in the future

COVID-19 Idaho Data Guide

What to consider when observing differences in COVID-19 case reporting: Cases Rates Time Day

Transportation Safety in Boise, Idaho: Reaching Vision Zero

Transportation System Safety is a Public Health Issue Vision Zero is a strategy to eliminate all traffic fatalities and severe injuries, while increasing safe, healthy, equitable mobility for all. Its proactive, preventative approach prioritizes traffic safety as a public health issue in order to prevent traffic injuries and fatalities. However, crashes are often perceived as isolated incidents caused by human errors, rather than being viewed collectively. Examining the dynamics related to crash fatalities and severe injuries through a systems approach can enable identification of overarching safety issues and lead City of Boise to address systemic faults that result in negative outcomes

Idaho Permanent Supportive Housing: Comparative Analysis

Permanent supportive housing (PSH) uses a Housing First approach to house people experiencing homelessness and living with a disabling condition. Idaho Housing and Finance Association (IHFA) partnered with Idaho Policy Institute (IPI) to conduct a statewide evaluation comparing scattered-site and single-site PSH programs at Low-Income Housing Tax Credit (LIHTC) properties in Idaho. Of the 151 PSH units in Idaho, 96 are in service consisting of 30 scattered-site and 66 single-site units. Additionally, 55 scattered-site units are anticipated to open in the next two years. No single-site PSH programs using LIHTC are planned. Future single-site PSH programs will require strong public-private partnerships modeled after successful programming in Ada County. This report includes a description of current LIHTC PSH programming in Idaho, recommendations of data required for future evaluations, and key considerations for resource and activity prioritization

Rural Industry Clusters Needs Assessment: Student Survey Summary

As part of an effort to inform future academic programming, Idaho Policy Institute (IPI) worked with Boise State University’s Offices of the Provost and the President to develop actionable insight into the emerging needs and gaps in the dairy industry in the Magic Valley and the technology, cybersecurity, and energy cluster in Eastern Idaho. In the first phase of the project, IPI surveyed high school students in each region in the spring of 2021. A total of 918 students were surveyed, 750 (82.1%) from the Magic Valley (MV) and 168 (17.9%) from Eastern Idaho (EI). Surveys asked students about their plans after high school, including if they plan to attend university, where they hope to attend university, and what they plan on studying. The following summarizes their responses