An Ultrasound Array of Emitter-Receiver Stacks for Microbubble-Based Therapy.

Most therapeutic ultrasound devices place emitters and receivers in separate locations, so that the long therapeutic pulses (>1 ms) can be emitted while receivers monitor the procedure. However, with such placement, emitters and receivers are competing for the same space, producing a trade-off between emission efficiency and reception sensitivity. Taking advantage of recent studies demonstrating that short-pulse ultrasound can be used therapeutically, we aimed to develop a device that overcomes such trade-offs.

Passive Cavitation Detection With a Needle Hydrophone Array.

Therapeutic ultrasound and microbubble technologies seek to drive systemically administered microbubbles into oscillations that safely manipulate tissue or release drugs. Such procedures often detect the unique acoustic emissions from microbubbles with the intention of using this feedback to control the microbubble activity. However, most sensor systems reported introduce distortions to the acoustic signal.

Distal Re-Entry to Treat Lower Limb Chronic Total Occlusions Using a Novel Electrically Guided Re-Entry Catheter.

Introduction: Endovascular treatment of challenging infra-inguinal peripheral vascular disease is increasingly common because of new techniques and improved tools. The use of a novel electrically guided 5 F re-entry catheter is presented. By emitting a minute electrical field, detected by a target wire inserted from an opposing access, the catheter's orientation is accurately displayed to the operator, allowing precise re-entry without the need for fluoroscopic alignment.

A PZT-PVDF Stacked Transducer for Short-Pulse Ultrasound Therapy and Monitoring.

Therapeutic ultrasound technologies using microbubbles require a feedback control system to perform the treatment in a safe and effective manner. Current feedback control technologies utilize the microbubble's acoustic emissions to adjust the treatment acoustic parameters. Typical systems use two separated transducers: one for transmission and the other for reception.

3D synthetic aperture imaging with a therapeutic spherical random phased array for transcostal applications.

Experimental validation of a synthetic aperture imaging technique using a therapeutic random phased array is described, demonstrating the dual nature of imaging and therapy of such an array. The transducer is capable of generating both continuous wave high intensity beams for ablating the tumor and low intensity ultrasound pulses to image the target area. Pulse-echo data is collected from the elements of the phased array to obtain B-mode images of the targets.

Simultaneous Ultrasound Therapy and Monitoring of Microbubble-Seeded Acoustic Cavitation Using a Single-Element Transducer.

Ultrasound-driven microbubble (MB) activity is used in therapeutic applications such as blood clot dissolution and targeted drug delivery. The safety and performance of these technologies are linked to the type and distribution of MB activities produced within the targeted area, but controlling and monitoring these activities in vivo and in real time has proven to be difficult. As therapeutic pulses are often milliseconds long, MB monitoring currently requires a separate transducer used in a passive reception mode.

Distinct docking mechanisms mediate interactions between the Msg5 phosphatase and mating or cell integrity mitogen-activated protein kinases (MAPKs) in Saccharomyces cerevisiae.

MAPK phosphatases (MKPs) are negative regulators of signaling pathways with distinct MAPK substrate specificities. For example, the yeast dual specificity phosphatase Msg5 dephosphorylates the Fus3 and Slt2 MAPKs operating in the mating and cell wall integrity pathways, respectively. Like other MAPK-interacting proteins, most MKPs bind MAPKs through specific docking domains.

Phosphorylation of the kinase interaction motif in mitogen-activated protein (MAP) kinase phosphatase-4 mediates cross-talk between protein kinase A and MAP kinase signaling pathways.

MAP kinase phosphatase 4 (DUSP9/MKP-4) plays an essential role during placental development and is one of a subfamily of three closely related cytoplasmic dual-specificity MAPK phosphatases, which includes the ERK-specific enzymes DUSP6/MKP-3 and DUSP7/MKP-X. However, unlike DUSP6/MKP-3, DUSP9/MKP-4 also inactivates the p38α MAP kinase both in vitro and in vivo. Here we demonstrate that inactivation of both ERK1/2 and p38α by DUSP9/MKP-4 is mediated by a conserved arginine-rich kinase interaction motif located within the amino-terminal non-catalytic domain of the protein.

Evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic influenza and other airborne infections.

Background: Influenza viruses are thought to be spread by droplets, but the role of aerosol dissemination is unclear and has not been assessed by previous studies. Oxygen therapy, nebulised medication and ventilatory support are treatments used in clinical practice to treat influenzal infection are thought to generate droplets or aerosols.

Objectives: Evaluation of the characteristics of droplet/aerosol dispersion around delivery systems during non-invasive ventilation (NIV), oxygen therapy, nebuliser treatment and chest physiotherapy by measuring droplet size, geographical distribution of droplets, decay in droplets over time after the interventions were discontinued.

Bilateral Pneumothorax and Subcutaneous Emphysema following Endoscopic Retrograde Cholangiopancreatography: A Rare Complication.

Endoscopic Retrograde Cholangiopancreatography (ERCP) is a widely used diagnostic and therapeutic modality in the management of biliary and pancreatic disease. Some of the complications of the procedure, although rare, may carry significant morbidity and mortality risks. We describe the case of a 68-year-old female who underwent elective ERCP for ductal stone clearance.

Liver and brain abscess caused by Aggregatibacter paraphrophilus in association with a large patent foramen ovale: a case report.

Introduction: Aggregatibacter paraphrophilus (former name Haemophilus paraphrophilus) is a normal commensal of the oral flora. It is a rare cause of hepatobiliary or intracerebral abscesses.

Case Presentation: We report a case of a 53-year-old Caucasian man with a liver abscess and subsequent brain abscesses caused by Aggregatibacter paraphrophilus.

A random phased array device for delivery of high intensity focused ultrasound.

Randomized phased arrays can offer electronic steering of a single focus and simultaneous multiple foci concomitant with low levels of secondary maxima and are potentially useful as sources of high intensity focused ultrasound (HIFU). This work describes laboratory testing of a 1 MHz random phased array consisting of 254 elements on a spherical shell of radius of curvature 130 mm and diameter 170 mm. Acoustic output power and efficiency are measured for a range of input electrical powers, and field distributions for various single- and multiple-focus conditions are evaluated by a novel technique using an infrared camera to provide rapid imaging of temperature changes on the surface of an absorbing target.

Negative-feedback regulation of FGF signalling by DUSP6/MKP-3 is driven by ERK1/2 and mediated by Ets factor binding to a conserved site within the DUSP6/MKP-3 gene promoter.

DUSP6 (dual-specificity phosphatase 6), also known as MKP-3 [MAPK (mitogen-activated protein kinase) phosphatase-3] specifically inactivates ERK1/2 (extracellular-signal-regulated kinase 1/2) in vitro and in vivo. DUSP6/MKP-3 is inducible by FGF (fibroblast growth factor) signalling and acts as a negative regulator of ERK activity in key and discrete signalling centres that direct outgrowth and patterning in early vertebrate embryos. However, the molecular mechanism by which FGFs induce DUSP6/MKP-3 expression and hence help to set ERK1/2 signalling levels is unknown.

DUSP6/MKP-3 inactivates ERK1/2 but fails to bind and inactivate ERK5.

Extracellular signal-regulated kinase-1 and -2 (ERK1/2) are activated by dual threonine and tyrosine phosphorylation of a TEY motif. The highly related kinase ERK5 is also activated by phosphorylation at a TEY motif. Inactivation of ERK1/2 is achieved by distinct members of the dual-specificity protein phosphatase (DUSP) family, which are responsible for the specific, regulated de-phosphorylation of the TEY motif.

Redox-mediated substrate recognition by Sdp1 defines a new group of tyrosine phosphatases.

Reactive oxygen species trigger cellular responses by activation of stress-responsive mitogen-activated protein kinase (MAPK) signalling pathways. Reversal of MAPK activation requires the transcriptional induction of specialized cysteine-based phosphatases that mediate MAPK dephosphorylation. Paradoxically, oxidative stresses generally inactivate cysteine-based phosphatases by thiol modification and thus could lead to sustained or uncontrolled MAPK activation.

Oximetry feedback flow control simulation for oxygen therapy.

Objectives: For many with Chronic Obstructive Pulmonary Disease (COPD), arterial oxygen saturation while receiving Long-Term Oxygen Therapy (LTOT) falls below an acceptable threshold (SpO(2) < 90%) for extended periods during routine daily activities. Using a closed-loop controller, we have evaluated a simulated method to automatically regulate the oxygen flow-rate in response to the measured oxygen demand.

Methods: The closed-loop control scheme was implemented in a computer simulation on Simulink.

Diverse physiological functions for dual-specificity MAP kinase phosphatases.

A structurally distinct subfamily of ten dual-specificity (Thr/Tyr) protein phosphatases is responsible for the regulated dephosphorylation and inactivation of mitogen-activated protein kinase (MAPK) family members in mammals. These MAPK phosphatases (MKPs) interact specifically with their substrates through a modular kinase-interaction motif (KIM) located within the N-terminal non-catalytic domain of the protein. In addition, MAPK binding is often accompanied by enzymatic activation of the C-terminal catalytic domain, thus ensuring specificity of action.

Hippi is essential for node cilia assembly and Sonic hedgehog signaling.

Hippi functions as an adapter protein that mediates pro-apoptotic signaling from poly-glutamine-expanded huntingtin, an established cause of Huntington disease, to the extrinsic cell death pathway. To explore other functions of Hippi we generated Hippi knock-out mice. This deletion causes randomization of the embryo turning process and heart looping, which are hallmarks of defective left-right (LR) axis patterning.

Removal of calcific deposits of the rotator cuff tendon using an intra-articular ultrasound probe.

Calcific tendonitis is a difficult condition to treat. In this report we describe a new technique for imaging the deposit in complicated cases. Previously the patient had an unsuccessful operation due to difficulty in visualising the deposit.

The dual-specificity protein phosphatase DUSP9/MKP-4 is essential for placental function but is not required for normal embryonic development.

To elucidate the physiological role(s) of DUSP9 (dual-specificity phosphatase 9), also known as MKP-4 (mitogen-activated protein kinase [MAPK] phosphatase 4), the gene was deleted in mice. Crossing male chimeras with wild-type females resulted in heterozygous (DUSP9(+/-)) females. However, when these animals were crossed with wild-type (DUSP9(+/y)) males none of the progeny carried the targeted DUSP9 allele, indicating that both female heterozygous and male null (DUSP9(-/y)) animals die in utero.

Miniature ultrasonic probe construction for minimal access surgery.

The increasing use of minimal access techniques for surgery has produced a need for imaging technologies that can be used during such interventions. Ultrasound imaging has the advantage that the probe itself can be interventional. Interventional ultrasound probes must be sufficiently small to gain access to the surgical site, and any rigid portion must be limited in length to permit adequate flexibility.

Both nuclear-cytoplasmic shuttling of the dual specificity phosphatase MKP-3 and its ability to anchor MAP kinase in the cytoplasm are mediated by a conserved nuclear export signal.

MAP kinase phosphatase (MKP)-3 is a cytoplasmic dual specificity protein phosphatase that specifically binds to and inactivates the ERK1/2 MAP kinases in mammalian cells. However, the molecular basis of the cytoplasmic localization of MKP-3 or its physiological significance is unknown. We have used MKP-3-green fluorescent protein fusions in conjunction with leptomycin B to show that the cytoplasmic localization of MKP-3 is mediated by a chromosome region maintenance-1 (CRM1)-dependent nuclear export pathway.

Negative feedback regulation of FGF signaling levels by Pyst1/MKP3 in chick embryos.

Background: The importance of endogenous antagonists in intracellular signal transduction pathways is becoming increasingly recognized. There is evidence in cultured mammalian cells that Pyst1/MKP3, a dual specificity protein phosphatase, specifically binds to and inactivates ERK1/2 mitogen-activated protein kinases (MAPKs). High-level Pyst1/Mkp3 expression has recently been found at many sites of known FGF signaling in mouse embryos, but the significance of this association and its function are not known.