Connecting RNA-Modifying Similarities of TDP-43, FUS, and SOD1 with MicroRNA Dysregulation Amidst A Renewed Network Perspective of Amyotrophic Lateral Sclerosis Proteinopathy.

Beyond traditional approaches in understanding amyotrophic lateral sclerosis (ALS), multiple recent studies in RNA-binding proteins (RBPs)-including transactive response DNA-binding protein (TDP-43) and fused in sarcoma (FUS)-have instigated an interest in their function and prion-like properties. Given their prominence as hallmarks of a highly heterogeneous disease, this prompts a re-examination of the specific functional interrelationships between these proteins, especially as pathological SOD1-a non-RBP commonly associated with familial ALS (fALS)-exhibits similar properties to these RBPs including potential RNA-regulatory capabilities. Moreover, the cytoplasmic mislocalization, aggregation, and co-aggregation of TDP-43, FUS, and SOD1 can be identified as proteinopathies akin to other neurodegenerative diseases (NDs), eliciting strong ties to disrupted RNA splicing, transport, and stability. In recent years, microRNAs (miRNAs) have also been increasingly implicated in the disease, and are of greater significance as they are the master regulators of RNA metabolism in disease pathology. However, little is known about the role of these proteins and how they are regulated by miRNA, which would provide mechanistic insights into ALS pathogenesis. This review seeks to discuss current developments across TDP-43, FUS, and SOD1 to build a detailed snapshot of the network pathophysiology underlying ALS while aiming to highlight possible novel therapeutic targets to guide future research.

Essential Medications for Patients With Suspected or Confirmed Ebola Virus Disease in Resource-Limited Environments.

BACKGROUND: In 2014, the U.S. Public Health Service (USPHS) Commissioned Corps deployed to Monrovia, Liberia, to operate a 25-bed Ebola treatment unit (ETU) constructed by the U.S. Military. The ETU was named the Monrovia Medical Unit (MMU) and was constructed from an U.S. Air Force Expeditionary Medical Support (EMEDS) unit with modifications on the basis of consultation from Médecins Sans Frontières, the World Health Organization, and expert panels from the U.S. Department of Defense and Department of Health and Human Services. From November 12, 2014, to April 30, 2015, 42 patients (18 confirmed Ebola virus disease [EVD] and 24 suspected EVD) from nine countries were treated by USPHS providers at the MMU. The medications used in the MMU were primarily procured from the EMEDS 25-bed pharmacy cache. However, specific formulary additions were made for treatment of EVD. METHODS: Using the MMU pharmacy dispensing data, we compared and contrasted the medications used in the MMU with recommendations in published EVD treatment guidelines for austere settings. FINDINGS: After comparing and contrasting the MMU pharmacy dispensing data with publications with EVD medication recommendations applicable to resource-limited settings, 101 medications were included in the USPHS Essential Medications for the Management of EVD List (EML) for an austere, isolated clinical environment. DISCUSSION/IMPACT/RECOMMENDATIONS: Because Ebola outbreaks often occur in remote areas, proactive planning, improved preparedness, and optimal patient care for EVD are needed, especially in the context of austere environments with a scarcity of resources. We developed the EML to assist in the planning for future Ebola outbreaks in a remote clinical environment and to provide a list of medications that have been used in an ETU. The EML is a comprehensive medication list that builds on the existing publications with EVD treatment recommendations applicable to supply-constrained clinical environments. As well, it is a resource for the provision of medications when evaluating donations, procurement, and may help inform estimates for product inventory requirements for an ETU. We hope the EML will improve readiness and enhance the capabilities of local and regional international responders.

A randomized, controlled study of an educational intervention to improve recall of auxiliary medication labeling and adherence to antibiotics.

PURPOSE: To evaluate whether medication counseling with emphasis on auxiliary labels improves recall of auxiliary label information and adherence to medication schedules. METHODS: A prospective, randomized study of an educational intervention in community pharmacies near Baltimore, Maryland. Fifty literate, English-speaking adults receiving one of the 18 commonly dispensed antibiotics were randomized to receive a counseling session or no counseling. Five to seven days after medication pickup, a structured phone interview was conducted to capture data on recall of auxiliary labels and adherence. RESULTS: A total of 39 subjects completed the phone interview (78%). The rate of correct recall was high: 77% correct recall for all three labels. Among those with incorrect recall, 7 out of 9 subjects received no counseling (p = 0.11). The auxiliary labels incorrectly recalled were all related to dietary restrictions. CONCLUSION: The findings from this study suggest that medication counseling emphasizing auxiliary label information may lead to improved recall and adherence to antibiotics. Additional studies are required to confirm the preliminary findings and determine whether they correspond to improved adherence. Information most commonly misunderstood were related to dietary restrictions. Additional research focusing on counseling related to dietary restrictions is recommended.