Time-dependent effects of BRAF-V600E on cell cycling, metabolism, and function in engineered myocardium.

Candidate cardiomyocyte (CM) mitogens such as those affecting the extracellular signal-regulated kinase (ERK) signaling pathway represent potential targets for functional heart regeneration. We explored whether activating ERK via a constitutively active mutant of B-raf proto-oncogene (BRAF), BRAF-V600E (caBRAF), can induce proproliferative effects in neonatal rat engineered cardiac tissues (ECTs). Sustained CM-specific caBRAF expression induced chronic ERK activation, substantial tissue growth, deficit in sarcomeres and contractile function, and tissue stiffening, all of which persisted for at least 4 weeks of culture. caBRAF-expressing CMs in ECTs exhibited broad transcriptomic changes, shift to glycolytic metabolism, loss of connexin-43, and a promigratory phenotype. Transient, doxycycline-controlled caBRAF expression revealed that the induction of CM cycling is rapid and precedes functional decline, and the effects are reversible only with short-lived ERK activation. Together, direct activation of the BRAF kinase is sufficient to modulate CM cycling and functional phenotype, offering mechanistic insights into roles of ERK signaling in the context of cardiac development and regeneration.

Simulation device for shoulder reductions: overview of prototyping, testing, and design instructions.

BACKGROUND: Shoulder dislocations are common occurrences, yet there are few simulation devices to train medical personnel on how to reduce these dislocations. Reductions require a familiarity with the shoulder and a nuanced motion against strong muscle tension. The goal of this work is to describe the design of an easily replicated, low-cost simulator for training shoulder reductions. MATERIALS AND METHODS: An iterative, stepwise engineering design process was used to design and implement ReducTrain. A needs analysis with clinical experts led to the selection of the traction-countertraction and external rotation methods as educationally relevant techniques to include. A set of design requirements and acceptance criteria was established that considered durability, assembly time, and cost. An iterative prototyping development process was used to meet the acceptance criteria. Testing protocols for each design requirement are also presented. Step-by-step instructions are provided to allow the replication of ReducTrain from easily sourced materials, including plywood, resistance bands, dowels, and various fasteners, as well as a 3D-printed shoulder model, whose printable file is included at a link in the Additional file 1: Appendix. RESULTS: A description of the final model is given. The total cost for all materials for one ReducTrain model is under US $200, and it takes about 3 h and 20 min to assemble. Based on repetitive testing, the device should not see any noticeable changes in durability after 1000 uses but may exhibit some changes in resistance band strength after 2000 uses. DISCUSSION: The ReducTrain device fills a gap in emergency medicine and orthopedic simulation. Its wide variety of uses points to its utility in several instructional formats. With the rise of makerspaces and public workshops, the construction of the device can be easily completed. While the device has some limitations, its robust design allows for simple upkeep and a customizable training experience. CONCLUSION: A simplified anatomical design allows for the ReducTrain model to serve as a viable training device for shoulder reductions.

Bacterial colonization of peripheral intravenous cannulas in a tertiary care hospital: A cross sectional observational study.

BACKGROUND: The use of intravenous (IV) cannulas is an integral part of patient care in hospitals. These intravenous cannulas are a potential route for microorganisms to enter the blood stream resulting in a variety of local or systemic infections. Studies showing the actual prevalence of colonization of peripheral IV cannulas and its role in BSI are lacking. Hence, this study was aimed to estimate the prevalence of colonization of the injection ports of peripheral IV cannulas. METHODS: This cross sectional study was conducted on patients admitted in ICU and wards in an 800 bedded tertiary care hospital. Swabs were taken from lumens of peripheral IV cannulas and cultured. Patient demographic data and practices followed for maintenance of IV line were noted. RESULTS: A total of 196 injection port samples were taken, out of which 11 tested positive for microbial growth (5.61%). Staphylococcus aureus was the predominant organism contributing 64% of the microbial growth. A significant association was seen between presence of local signs, old age and positive cultures. Flushing IV cannula every 6 h was associated with negative cultures. CONCLUSION: Peripheral IV cannulation has significant potential for microbial contamination and is largely ignored. Most of the risk factors associated with growth of microorganisms in the injection ports of peripheral intravenous cannulas (which has a potential to cause catheter-related blood stream infections) can be prevented by improving protocols for management. To prevent infection from occurring, practitioners should be educated and trained about the care and management of IV.