RESUMEN
The primary purpose of this work was to design and implement a compact, battery-powered, fully wearable applicator for delivering therapeutic low-frequency (20-40kHz), low-intensity (100mW/cm2 ISPTP) (LFLI) ultrasound to enable treatment of chronic wounds in home setting. Such a device does not currently exist, and in addition to engineering aspects associated with electromechanical design, its implementation requires a novel approach involving consideration of feedback received not only from healthcare professionals, but also caregivers. One strong motivation for the novel design approach is to enable individuals with chronic wounds to enhance self-care management of wounds in the home setting instead of a hospital or outpatient clinic setting. In the home setting, the device may be exposed to physical maltreatment, requiring precautions with respect to its sturdiness. Although the holistic approach presented have been applied to the design of an applicator for chronic wounds, the design considerations and execution are transferable to any device targeted for home use. The implementation exemplified here examines transformation of an early, relatively fragile design into a robust, time-programmable, safe tool. The modification, which includes comprehensive reconfiguration and redesign of the electronics driving a piezoelectric transducer is presented along with methodology devised with the field feedback obtained from focus groups. This feedback evinced that in addition to electrical engineering, an extensive background in mechanical engineering, material science, biology, and clinical practice is needed to fabricate an end-user friendly, quality-of-life improving, ergonomic device.
RESUMEN
Mitochondrial fatty acid oxidation (FAO) contributes to the proton motive force that drives ATP synthesis in many mammalian tissues. In eutherian (placental) mammals, brown adipose tissue (BAT) can also dissipate this proton gradient through uncoupling protein 1 (UCP1) to generate heat, but the evolutionary events underlying the emergence of BAT are unknown. An essential step in FAO is the transport of cytoplasmic long chain acyl-coenzyme A (acyl-CoA) into the mitochondrial matrix, which requires the action of carnitine palmitoyltransferase 1B (CPT1B) in striated muscle and BAT. In eutherians, the CPT1B gene is closely linked to the choline kinase beta (CHKB) gene, which is transcribed from the same DNA strand and terminates just upstream of CPT1B. CHKB is a rate-limiting enzyme in the synthesis of phosphatidylcholine (PC), a predominant mitochondrial membrane phospholipid, suggesting that the coordinated expression of CHKB and CPT1B may cooperatively enhance mitochondrial FAO. The present findings show that transcription of the eutherian CHKB and CPT1B genes is linked within a unitary epigenetic domain targeted to the CHKB gene, and that that this regulatory linkage appears to have resulted from an intergenic deletion in eutherians that significantly altered the distribution of CHKB and CPT1B expression. Informed by the timing of this event relative to the emergence of BAT, the phylogeny of CHKB-CPT1B synteny, and the insufficiency of UCP1 to account for eutherian BAT, these data support a mechanism for the emergence of BAT based on the acquisition of a novel capacity for adipocyte FAO in a background of extant UCP1.