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Clinical improvement of DM1 patients reflected by reversal of disease-induced gene expression in blood | BMC Medicine | Full Text
Myotonic dystrophy type 1 (DM1) is an incurable multisystem disease caused by a CTG-repeat expansion in the DM1 protein kinase (DMPK) gene. The OPTIMISTIC clinical trial demonstrated positive and heterogenous effects of cognitive behavioral therapy (CBT) on the capacity for activity and social participations in DM1 patients. Through a process of reverse engineering, this study aims to identify druggable molecular biomarkers associated with the clinical improvement in the OPTIMISTIC cohort. Based on full blood samples collected during OPTIMISTIC, we performed paired mRNA sequencing for 27 patients before and after the CBT intervention. Linear mixed effect models were used to identify biomarkers associated with the disease-causing CTG expansion and the mean clinical improvement across all clinical outcome measures. We identified 608 genes for which their expression was significantly associated with the CTG-repeat expansion, as well as 1176 genes significantly associated with the average clinical response towards the intervention. Remarkably, all 97 genes associated with both returned to more normal levels in patients who benefited the most from CBT. This main finding has been replicated based on an external dataset of mRNA data of DM1 patients and controls, singling these genes out as candidate biomarkers for therapy response. Among these candidate genes were DNAJB12, HDAC5, and TRIM8, each belonging to a protein family that is being studied in the context of neurological disorders or muscular dystrophies. Across the different gene sets, gene pathway enrichment analysis revealed disease-relevant impaired signaling in, among others, insulin-, metabolism-, and immune-related pathways. Furthermore, evidence for shared dysregulations with another neuromuscular disease, Duchenne muscular dystrophy, was found, suggesting a partial overlap in blood-based gene dysregulation. DM1-relevant disease signatures can be identified on a molecular level in peripheral blood, opening new avenues for drug discovery and therapy efficacy assessments.
Flash flooding causes dozens of power outages and impassable roads | News | wrex.com
This morning showers and storms are moving through bring very heavy rain. Our entire area is under a Flood Watch until 10 a.m.
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Power Outage Update: Power has currently been restored to all buildings in the district.
Power Outage FAQs
What is Power Outage?
Power outage (also called a power cut, a power blackout, power failure or a blackout) is a short-term or a long-term loss of the electric power to a particular area.
What Causes Power Outages?
- Severe weather (high winds, lightning, winter storms, heat waves, rain or flooding can cause damage to power lines or equipment);
- Other damage to electric transmission lines (vehicle accidents, trees, and animals can cause damage to power lines or equipment);
- Repairing, maintenance or upgrades on power lines and equipment.
What are the Top Outage Safety Tips?
- Stay away from the downed power lines, park vehicles in protected areas;
- Unplug appliances and electronics, limit cell phone use to conserve battery life;
- Use portable generators outdoors only, well away from open windows and doors;
- Pack perishable foods into a cooler, keep refrigerator and freezer doors shut as much as possible.
Davis Junction, Illinois
| City | Davis Junction |
| County | Ogle |
| State | Illinois (IL) |
| Country | United States |
| Zip Codes | 61020 |