A synthetic biology-based device prevents liver injury in mice

BACKGROUND & AIMS The liver performs a panoply of complex activities coordinating metabolic, immunologic and detoxification processes. Despite the liver's robustness and unique self-regeneration capacity, viral infection, autoimmune disorders, fatty liver disease, alcohol abuse and drug-induced hepatotoxicity contribute to the increasing prevalence of liver failure. Liver injuries impair the clearance of bile acids from the hepatic portal vein which leads to their spill over into the peripheral circulation where they activate the G-protein-coupled bile acid receptor TGR5 to initiate a variety of hepatoprotective processes. METHODS By functionally linking activation of ectopically expressed TGR5 to an artificial promoter controlling transcription of the hepatocyte growth factor (HGF), we created a closed-loop synthetic signalling network that coordinated liver injury-associated serum bile acid levels to expression of HGF in a self-sufficient, reversible and dose-dependent manner. RESULTS After implantation of genetically engineered human cells inside auto-vascularizing, immunoprotective and clinically validated alginate-poly-(L-lysine)-alginate beads into mice, the liver-protection device detected pathologic serum bile acid levels and produced therapeutic HGF levels that protected the animals from acute drug-induced liver failure. CONCLUSIONS Genetically engineered cells containing theranostic gene circuits that dynamically interface with host metabolism may provide novel opportunities for preventive, acute and chronic healthcare. LAY SUMMARY Liver diseases leading to organ failure may go unnoticed as they do not trigger any symptoms or significant discomfort. We have designed a synthetic gene circuit that senses excessive bile acid levels associated with liver injuries and automatically produces a therapeutic protein in response. When integrated into mammalian cells and implanted into mice, the circuit detects the onset of liver injuries and coordinates the production of a protein pharmaceutical which prevents liver damage.

Short structured feedback training is equivalent to a mechanical feedback device in two-rescuer BLS: a randomised simulation study.

BACKGROUND Resuscitation guidelines encourage the use of cardiopulmonary resuscitation (CPR) feedback devices implying better outcomes after sudden cardiac arrest. Whether effective continuous feedback could also be given verbally by a second rescuer ("human feedback") has not been investigated yet. We, therefore, compared the effect of human feedback to a CPR feedback device. METHODS In an open, prospective, randomised, controlled trial, we compared CPR performance of three groups of medical students in a two-rescuer scenario. Group "sCPR" was taught standard BLS without continuous feedback, serving as control. Group "mfCPR" was taught BLS with mechanical audio-visual feedback (HeartStart MRx with Q-CPR-Technology™). Group "hfCPR" was taught standard BLS with human feedback. Afterwards, 326 medical students performed two-rescuer BLS on a manikin for 8 min. CPR quality parameters, such as "effective compression ratio" (ECR: compressions with correct hand position, depth and complete decompression multiplied by flow-time fraction), and other compression, ventilation and time-related parameters were assessed for all groups. RESULTS ECR was comparable between the hfCPR and the mfCPR group (0.33 vs. 0.35, p = 0.435). The hfCPR group needed less time until starting chest compressions (2 vs. 8 s, p < 0.001) and showed fewer incorrect decompressions (26 vs. 33 %, p = 0.044). On the other hand, absolute hands-off time was higher in the hfCPR group (67 vs. 60 s, p = 0.021). CONCLUSIONS The quality of CPR with human feedback or by using a mechanical audio-visual feedback device was similar. Further studies should investigate whether extended human feedback training could further increase CPR quality at comparable costs for training.

Shoreline plant establishment and use of a wave-stilling device /

"January 1978."

A lightweight pneumatic coring device : design and field test /

"September 1982."

Tools for compliance for the medical device and in vitrol diagnostic product industries.

Mode of access: Internet.

Development of a test methodology for evaluating crash compatibility and aggressiveness. Test report 1: 1975 Honda Civic CVCC-to-NHTSA test device.

National Highway Traffic Safety Administration, Washington, D.C.

Development of a test methodology for evaluating crash compatibility and aggressiveness. Test report 2: 1975 Ford Torino-to-NHTSA test device.

National Highway Traffic Safety Administration, Washington, D.C.

A feasibility study of a wave-powered device for moving sand /

"June, 1967."

CAM-4, a portable warning device for organophosphate hazardous material spills /

Mode of access: Internet.

Development of a test methodology for evaluating crash compatibility and aggressiveness. Test report 3: 1975 Volvo 244DL-to-NHTSA test device.

National Highway Traffic Safety Administration, Washington, D.C.

Development of a test methodology for evaluating crash compatibility and aggressiveness. Test report 4: 1975 Plymouth Fury-to-NHTSA test device.

National Highway Traffic Safety Administration, Washington, D.C.

Calibration of a six-degree-of-freedom acceleration measurement device. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Breath-collection device for delayed breath-alcohol analysis. Part 2. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

The Walker Roughness Device for roughness measurements. Final report.

Texas State Department of Highways and Public Transportation, Austin