The Fibrinolytic Effects of Intermittent Pneumatic Compression: Mechanism of Enhanced Fibrinolysis

BACKGROUND AND OBJECTIVES: Intermittent pneumatic compression (IPC) is an effective form of deep vein thrombosis prophylaxis for general surgery patients. The antithrombotic effect of IPC is thought to be the result of increased venous velocity and stimulation of endogenous fibrinolysis. However, the mechanism of enhanced fibrinolytic activity and the relative effects on normal and postthrombotic veins have not been defined. The purposes of this study are 1) to quantify changes in fibrinolytic activity with IPC; 2) to study the mechanism of fibrinolytic enhancement with IPC; and 3) to evaluate whether postthrombotic patients have the same capacity for fibrinolytic enhancement with IPC as do normal subjects. METHODS: Twelve volunteers (6 normal and 6 postthrombotic) had 5 IPC devices applied for 120 minutes in random fashion, 1 per week x 5 weeks. The devices included single-chamber, sequential, foot, calf, and long-leg compression. Subjects had an indwelling antecubital venous cannula placed for blood drawn at baseline, 60, 120, and 180 minutes after IPC devices were applied. Global fibrinolytic activity (euglobulin fraction, fibrin plate assay), tissue plasminogen activator (tPA) antigen (Ag) and activity (Act), plasminogen activator inhibitor-1 (PAI-1) Ag and Act, alpha-2-antiplasmin-plasmin complexes, and von Willebrand factor (vWF) antigen were assayed. RESULTS: A striking elevation in fibrinolytic activity was noted at 180 minutes with all devices in normal subjects and postthrombotic patients (p = 0.01-0.0001); however, baseline and stimulated fibrinolytic activity was attenuated in postthrombotic patients (<0.03). The tPA-Act increased only in normal subjects (3.8 +/- 1.9%) (p = 0.057), despite a decrease in plasma tPA-Ag, which was observed in both normal subjects (-12.4 +/- 3.8%) (p = 0.009) and patients (-17.2 +/- 3.1%) (p = 0.001). PAI-1-Ag decreased in both normal subjects (-13.4 +/- 3.8%) (p = 0.007) and patients (-12.0 +/- 3.1%) (p = 0.013) with a marked reduction in PAI-1-Act in both normal subjects (p = 0.003) and patients (p = 0.004). There were no changes in vWF, and alpha-2-antiplasmin-plasmin complexes increased only in postthrombotic patients (p = 0.021). CONCLUSIONS: Stimulation of endogenous fibrinolytic activity occurs after IPC, both in normal subjects and postthrombotic patients; however, baseline and overall fibrinolytic response in postthrombotic patients is reduced. The mechanism of increased fibrinolytic activity is likely because of a reduction in PAI-1, with a resulting increase of tPA activity

Investigating the potential role of TRPA1 in locomotion and cardiovascular control during hypertension.

Radiotelemetry was used to investigate the in vivo cardiovascular and activity phenotype of both TRPA1 (transient receptor potential ankyrin 1) wild-type (WT) and TRPA1 knockout (KO) mice. After baseline recording, experimental hypertension was induced using angiotensin II infusion (1.1 mg(-1) kg(-1) a day, for 14 days). TRPA1 WT and KO mice showed similar morphological and functional cardiovascular parameters, including similar basal blood pressure (BP), heart rate, size, and function. Similar hypertension was also displayed in response to angiotensin II (156 ± 7 and 165 ± 11 mmHg, systolic BP ± SEM, n = 5-6). TRPA1 KO mice showed increased hypertensive hypertrophy (heart weight:tibia length: 7.3 ± 1.6 mg mm(-1) vs. 8.8 ± 1.7 mg mm(-1)) and presented with blunted interleukin 6 (IL-6) production compared with hypertensive WT mice (151 ± 24 vs. 89 ± 16 pg mL(-1)). TRPA1 expression in dorsal root ganglion (DRG) neurones was upregulated during hypertension (163% of baseline expression). Investigations utilizing the TRPA1 agonist cinnamaldehyde (CA) on mesenteric arterioles isolated from näive mice suggested a lack of TRPA1-dependent vasoreactivity in this vascular bed; a site with notable ability to alter total peripheral resistance. However, mesenteric arterioles isolated from TRPA1 KO hypertensive mice displayed significantly reduced ability to relax in response to nitric oxide (NO) (P < 0.05). Unexpectedly, naïve TRPA1 KO mice also displayed physical hyperactivity traits at baseline, which was exacerbated during hypertension. In conclusion, our study provides a novel cardiovascular characterization of TRPA1 KO mice in a model of hypertension. Results suggest that TRPA1 has a limited role in global cardiovascular control, but we demonstrate an unexpected capacity for TRPA1 to regulate physical activity

Multispecies and Multifluid MHD Approaches for the Study of Ionospheric Escape at Mars

A detailed model‐model comparison between the results provided by a multispecies and a multifluid magnetohydrodynamic (MHD) code for the escape of heavy ions in the Martian‐induced magnetosphere is presented. The results from the simulations are analyzed and compared against a statistical analysis of the outflow of heavy ions obtained by the Mars Atmosphere and Volatile EvolutioN/Suprathermal and Thermal Ion Composition instrument over an extended period of time in order to estimate the influence of magnetic forces in the ion escape. Both MHD models are run with the same chemical reactions and ion species in a steady state mode under idealized solar conditions. Apart from being able to reproduce the asymmetries observed in the ion escape, it is found that the multifluid approach provides results that are closer to those inferred from the ion data. It is also found that the j × B force term is less effective in accelerating the ions in the models when compared with the Mars Atmosphere and Volatile EvolutioN results. Finally, by looking at the contribution of the plume and the ion escape rates at different distances along the tail with the multifluid model, it is also found that the escape of heavy ions has important variabilities along the tail, meaning that the apoapsis of a spacecraft studying atmospheric escape can affect the estimates obtained.Key PointsOverall modeled ion escape and relative contribution of the plume depend on downtail distanceAcceleration from j times B force appears weaker in simulations when compared to MAVEN dataAsymmetries in the escape arise from upstream conditions, crustal fields, and neutral atmospherePeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146439/1/jgra54496_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146439/2/jgra54496.pd

Reconnection in the Martian Magnetotail: Hall‐MHD With Embedded Particle‐in‐Cell Simulations

Mars Atmosphere and Volatile EvolutioN (MAVEN) mission observations show clear evidence of the occurrence of the magnetic reconnection process in the Martian plasma tail. In this study, we use sophisticated numerical models to help us understand the effects of magnetic reconnection in the plasma tail. The numerical models used in this study are (a) a multispecies global Hall‐magnetohydrodynamic (HMHD) model and (b) a global HMHD model two‐way coupled to an embedded fully kinetic particle‐in‐cell code. Comparison with MAVEN observations clearly shows that the general interaction pattern is well reproduced by the global HMHD model. The coupled model takes advantage of both the efficiency of the MHD model and the ability to incorporate kinetic processes of the particle‐in‐cell model, making it feasible to conduct kinetic simulations for Mars under realistic solar wind conditions for the first time. Results from the coupled model show that the Martian magnetotail is highly dynamic due to magnetic reconnection, and the resulting Mars‐ward plasma flow velocities are significantly higher for the lighter ion fluid, which are quantitatively consistent with MAVEN observations. The HMHD with Embedded Particle‐in‐Cell model predicts that the ion loss rates are more variable but with similar mean values as compared with HMHD model results.Key PointsModel results show that the Martian magnetotail is highly dynamic due to magnetic reconnectionThe numerical simulations predict that the Mars‐ward plasma flow, due to magnetic reconnection, is faster for lighter ions, consistent with MAVEN observationsThe HMHD EPIC model simulations predict that the ion loss rates are more variable but with similar mean values as compared with HMHD modelPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144660/1/jgra54262_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144660/2/jgra54262.pd

Dual Use of Veterans Health Administration and Indian Health Service: Healthcare Provider and Patient Perspectives

Many American Indian and Alaska Native veterans are eligible for healthcare from Veterans Health Administration (VHA) and from Indian Health Service (IHS). These organizations executed a Memorandum of Understanding in 2003 to share resources, but little was known about how they collaborated to deliver healthcare. To describe dual use from the stakeholders’ perspectives, including incentives that encourage cross-use, which organization’s primary care is “primary,” and the potential problems and opportunities for care coordination across VHA and IHS. VHA healthcare staff, IHS healthcare staff and American Indian and Alaska Native veterans. Focus groups were conducted using a semi-structured guide. A software-assisted text analysis was performed using grounded theory to develop analytic categories. Dual use was driven by variation in institutional resources, leading patients to actively manage health-seeking behaviors and IHS providers to make ad hoc recommendations for veterans to seek care at VHA. IHS was the “primary” primary care for dual users. There was little coordination between VHA and IHS resulting in delays and treatment conflicts, but all stakeholder groups welcomed future collaboration. Fostering closer alignment between VHA and IHS would reduce care fragmentation and improve accountability for patient care

Magnetism, entropy, and the first nano-machines

The efficiency of bio-molecular motors stems from reversible interactions $\sim$ $k_B T$; weak bonds stabilizing intermediate states (enabling $direct$ conversion of chemical into mechanical energy). For their (unknown) origins, we suggest that a magnetically structured phase (MSP) formed via accretion of super-paramagnetic particles (S-PPs) by magnetic rocks on the Hadean Ocean floor had hosted motor-like diffusion of ligand-bound S-PPs through its template-layers; its ramifications range from optical activity to quantum coherence. A gentle flux gradient offers both detailed-balance breaking non-equilibrium and $asymmetry$ to a magnetic dipole, undergoing infinitesimal spin-alignment changes. Periodic perturbation of this background by local H-fields of template-partners can lead to periodic high and low-template affinity states, due to the dipole's magnetic degree of freedom. An accompanying magnetocaloric effect allows interchange between system-entropy and bath temperature. We speculate on a magnetic reproducer in a setting close to the mound-scenario of Russell and coworkers that could evolve bio- ratchets.Comment: 17 pages, 1 figur

The Identification of Factors That Influence the Quality of Bypass Anastomosis and an Evaluation of the Usefulness of an Experimental Practical Scale in This Regard

BACKGROUND: Several factors associated with interrupted and continuous suturing techniques affect the quality of bypass anastomosis. It is difficult to determine the impact of these factors during surgery. The primary objective of this study was to evaluate factors with the potential to influence the quality of bypass anastomosis using either interrupted or continuous suturing. A secondary objective was to evaluate the usefulness of a practical scale when comparing interrupted and continuous suturing techniques to improve bypass anastomosis. METHODS: Interrupted (n = 100) and continuous (n = 100) suturing techniques were used in 200 end-to-side bypasses to a depth of 3 cm and were assessed by 5 neurosurgeons. RESULTS: Vessel closing time (P <0.001), stitch distribution (P <0.001), intima-intima attachment (P <0.001), and size of the orifice (P <0.001) had a significant impact on the quality of the bypass regardless of the suturing technique used. The suturing technique used (interrupted or continuous) and positioning of the recipient vessel (vertical or horizontal) did not significantly influence the quality of anastomosis. Using multivariate analysis, the highest statistical significance with regard to bypass quality was attributed to the large size of the orifice and intimal attachment. CONCLUSIONS: There were advantages and disadvantages to both suturing techniques. The scale was a practical way to measure and improve performance.Peer reviewe

Home based exercise to improve turning and mobility performance among community dwelling older adults: protocol for a randomized controlled trial

Background: Turning is a common activity for older people, and is one of the activities commonly associated with falls during walking. Falls that occur while walking and turning have also been associated with an increased risk of hip fracture in older people. Despite the importance of stability during turning, there has been little focus on identifying this impairment in at risk older people, or in evaluating interventions aiming to improve this outcome. This study will evaluate the effectiveness of a 16 week tailored home based exercise program in older adults aged (50 years and above) who were identified as having unsteadiness during turning.Methods/Design: A single blind randomized controlled trial will be conducted, with assessors blind to group allocation. Study participants will be aged 50 years and above, living in the community and have been identified as having impaired turning ability [outside of age and gender normal limits on the Step Quick Turn (180 degree turn) task on the Neurocom® Balance Master with long plate]. After a comprehensive baseline assessment, those classified as having balance impairment while turning will be randomized to intervention or control group. The intervention group will receive a 16 week individualized balance and strength home exercise program, based on the Otago Exercise Program with additional exercises focused on improving turning ability. Intervention group will attend four visit to the assessment centre over 16 weeks period, for provision, monitoring, modification of the exercise and encourage ongoing participation. Participants in the control group will continue with their usual activities. All participants will be re-assessed on completion of the 16 week program. Primary outcome measures will be the Step Quick Turn Test and Timed-Up and Go test. Secondary outcomes will include other clinical measures of balance, psychological aspects of falls, incidence of falls and falls risk factors. Discussion: Results of this study will provide useful information for clinicians on the types of exercises to improve turning ability in older people with increased falls risk and the effectiveness of these exercises in improving outcomes