Postsynaptic and spiking activity of pyramidal cells,the principal neurons in the rat hippocampal CA1 region,does not control the resultant BOLD response: a combined electrophysiologic and fMRI approach

The specific role of postsynaptic activity for the generation of a functional magnetic resonance imaging (fMRI) response was determined by a simultaneous measurement of generated field excitatory postsynaptic potentials (fEPSPs) and blood oxygen level-dependent (BOLD) response in the rat hippocampal CA1 region during electrical stimulation of the contralateral CA3 region. The stimulation electrode was placed either in the left CA3a/b or CA3c, causing the preferentially basal or apical dendrites of the pyramidal cells in the right CA1 to be activated. Consecutive stimulations with low-intensity stimulation trains (i.e., 16 pulses for 8 seconds) resulted in clear postsynaptic responses of CA1 pyramidal cells, but in no significant BOLD responses. In contrast, consecutive high-intensity stimulation trains resulted in stronger postsynaptic responses that came along with minor (during stimulation of the left CA3a/b) or substantial (during stimulation of the left CA3c) spiking activity of the CA1 pyramidal cells, and resulted in the generation of significant BOLD responses in the left and right hippocampus. Correlating the electrophysiologic parameters of CA1 pyramidal cell activity (fEPSP and spiking activity) with the resultant BOLD response revealed no positive correlation. Consequently, postsynaptic activity of pyramidal cells, the most abundant neurons in the CA1, is not directly linked to the measured BOLD response.     

The case for a medication first approach to the treatment of opioid use disorder

Background: The opioid addiction and overdose crisis continues to ravage communities across the U.S. Maintenance pharmacotherapy using buprenorphine or methadone is the most effective intervention for Opioid Use Disorder (OUD), yet few have immediate and sustained access to these medications. Objectives: To address lack of medication access for people with OUD, the Missouri Department of Mental Health began implementing a Medication First (Med First) treatment approach in its publicly-funded system of comprehensive substance use disorder treatment programs. Methods: This Perspective describes the four principles of Med First, which are based on evidence-based guidelines. It draws conceptual comparisons between the Housing First approach to chronic homelessness and the Med First approach to pharmacotherapy for OUD, and compares state certification standards for substance use disorder (SUD) treatment (the traditional approach) to Med First guidelines for OUD treatment. Finally, the Perspective details how Med First principles have been practically implemented. Results: Med First principles emphasize timely access to maintenance pharmacotherapy without requiring psychosocial services or discontinuation for any reason other than harm to the client. Early results regarding medication utilization and treatment retention are promising. Feedback from providers has been largely favorable, though clinical- and system-level obstacles to effective OUD treatment remain. Conclusion: Like the Housing First model, Medication First is designed to decrease human suffering and activate the strengths and capacities of people in need. It draws on decades of research and facilitates partnerships between psychosocial and medical treatment providers to offer effective and life-saving care to persons with OUD.     

Demonstration of a modelling-based multi-criteria decision analysis procedure for prioritisation of occupational risks from manufactured nanomaterials

Several tools to facilitate the risk assessment and management of manufactured nanomaterials (MN) have been developed. Most of them require input data on physicochemical properties, toxicity and scenario-specific exposure information. However, such data are yet not readily available, and tools that can handle data gaps in a structured way to ensure transparent risk analysis for industrial and regulatory decision making are needed. This paper proposes such a quantitative risk prioritisation tool, based on a multi-criteria decision analysis algorithm, which combines advanced exposure and dose-response modelling to calculate margins of exposure (MoE) for a number of MN in order to rank their occupational risks. We demonstrated the tool in a number of workplace exposure scenarios (ES) involving the production and handling of nanoscale titanium dioxide, zinc oxide (ZnO), silver and multi-walled carbon nanotubes. The results of this application demonstrated that bag/bin filling, manual un/loading and dumping of large amounts of dry powders led to high emissions, which resulted in high risk associated with these ES. The ZnO MN revealed considerable hazard potential in vivo, which significantly influenced the risk prioritisation results. In order to study how variations in the input data affect our results, we performed probabilistic Monte Carlo sensitivity/uncertainty analysis, which demonstrated that the performance of the proposed model is stable against changes in the exposure and hazard input variables.     

Are Medicare's Nursing Home Compare Ratings Accurate Predictors of 90-Day Complications,Readmission, and Bundle Cost for Patients Undergoing Primary Total Joint Arthroplasty?

Background

Nursing Home Compare (NHC) ratings, created and maintained by Medicare, are used by both hospitals and consumers to aid in the skilled nursing facility (SNF) selection process. To date, no studies have linked NHC ratings to actual episode-based outcomes. The purpose of this study was to evaluate whether NHC ratings are valid predictors of 90-day complications, readmission, and bundle costs for patients discharged to an SNF after primary total joint arthroplasty (TJA).