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The aim of this study was to assess for distinct kidney function trajectories following left ventricular assist device (LVAD) placement. Cohort studies of LVAD recipients demonstrate that kidney function tends to increase early after LVAD placement, followed by decline and limited sustained improvement. Inter-individual differences in kidney function response may be obscured.We identified continuous flow LVAD implantations in US adults (2016-2017) from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). Primary outcomes were estimated glomerular filtration rate (eGFR) trajectories pre-implantation to ∼12 months. Latent class mixed models were applied to primary and validation samples. Clinical differences among trajectory groups were investigated.Among 4,615 LVAD implantations, 5 eGFR trajectory groups were identified. The 2 largest groups (Groups 1 and 2) made up80% of the cohort, and were similar to group average trajectories previously reported, with early eGFR rise followed by decline and stabilization. Three novel trajectory groups were found: worsening followed by sustained low kidney function (Group 3, 10.1%), sustained improvement (Group 4, 3.3%), and worsening followed by variation (Group 5, 1.7%). These groups differed in baseline characteristics and outcomes. Group 4 was younger and had more cardiogenic shock and pre-implantation dialysis; Group 3 had higher rates of pre-existing chronic kidney disease, along with older age.Novel eGFR trajectories were identified in a national cohort, possibly representing distinct cardiorenal processes. Type 1 cardiorenal syndrome may have been predominant in Group 4, and parenchymal kidney disease may have been predominant in Group 3.

We worked on a FePt granular film with a columnar structure, for the purpose of ultrahigh density perpendicular magnetic recording media. In experiments, a Fe53Pt47-SiO230%-C25% (10 nm) film was deposited on a silicon substrate with a MgO (12 nm) interlayer at 510 °C. The perpendicular coercivity of the film is 29 kOe, with a squareness of 1. Bright-field TEM images show that the FePt granular film has small and uniform grains of 8.3 ± 1.9 nm with a columnar structure. More work of high-resolution TEM imaging shows excellent L10 ordering inside the FePt grains. The measurement of remnant coercivity proves that it has an energy barrier of 290kBT at room temperature, meaning excellent thermal stability. We demonstrate FePt granular film to be a qualified candidate for high-density perpendicular magnetic recording media, and both SiO2 and C addition helps form columnar structure.

Traditional informatics in comparative genomics work only with static representations of biomolecules (i.e., sequence and structure), thereby ignoring the molecular dynamics (MD) of proteins that define function in the cell. A comparative approach applied to MD would connect this very short timescale process, defined in femtoseconds, to one of the longest in the universe: molecular evolution measured in millions of years. Here, we leverage advances in graphics-processing-unit-accelerated MD simulation software to develop a comparative method of MD analysis and visualization that can be applied to any two homologous Protein Data Bank structures. Our open-source pipeline, DROIDS (Detecting Relative Outlier Impacts in Dynamic Simulations), works in conjunction with existing molecular modeling software to convert any Linux gaming personal computer into a “comparative computational microscope” for observing the biophysical effects of mutations and other chemical changes in proteins. DROIDS implements structural alignment and Benjamini-Hochberg-corrected Kolmogorov-Smirnov statistics to compare nanosecond-scale atom bond fluctuations on the protein backbone, color mapping the significant differences identified in protein MD with single-amino-acid resolution. DROIDS is simple to use, incorporating graphical user interface control for Amber16 MD simulations, cpptraj analysis, and the final statistical and visual representations in R graphics and UCSF Chimera. We demonstrate that DROIDS can be utilized to visually investigate molecular evolution and disease-related functional changes in MD due to genetic mutation and epigenetic modification. DROIDS can also be used to potentially investigate binding interactions of pharmaceuticals, toxins, or other biomolecules in a functional evolutionary context as well.

In recent years, piezoelectric fans and their feasibility for use in cooling electronic devices have been widely studied. However, there are few studies that address using a single piezoelectric actuator to generate radial air flow. In this study, a radial-flow multiple fan system (RMFS) was developed for the thermal management of high power LEDs. This system only used one piezoelectric actuator and a magnetic repulsive force to activate up to 20 fans, which featured low power consumption and a large cooling area. The RMFS was mounted in a circular heat sink to evaluate its thermal performance. To find the optimal design for the RMFS, the influence of some geometric parameters was investigated. The performance of different designs was compared with a commercially available axial fan. The results showed that design E had the best thermal performance among the designs because of its relatively large frequency and amplitude. The thermal resistance and percentage improvement under a 35 W heat flux were 0.86 K/W and 36.9%, respectively. In addition, a coefficient of performance (COP) was defined. The COP of design E was approximately 3.7 times that of the rotary fan. For the power consumption aspect, the RMFS is more efficient than the rotary fan.

Undoped GaSb is p-type with the residual acceptor concentration of about 1e17 cm−3 due to the gallium vacancies and gallium in antimony site. Counter-doping of GaSb with low level of Te can reduce the net carrier concentration resulting in higher optical transparency in a broad IR spectral range. In this work, the carrier concentration, mobility and sheet resistance of n-type and p-type Te-doped GaSb substrates were measured using Hall method at 300 K and 77 K. The Hall carrier concentration data at 300 K were correlated with the absorption coefficients of GaSb in the IR spectral range. An empirical relationship between these values was established. Based on this correlation, we discuss application of FTIR spectroscopy for non-destructive optical screening of the substrates that allows construction of the carrier concentration distribution map across GaSb wafers. Investigations of the electronic properties of the low-doped p-type and n-type GaSb substrates upon cooling down to 77 K indicate the reduction of the hole carrier concentration background for both GaSb types. This is evident from the decrease in the Hall-measured carrier concentration for p-type GaSb. For n-type GaSb, an increase in the carrier concentration is observed due to the reduction of the hole carrier concentration background.

Numerous studies have shown that multiple fans with a piezoelectric actuator (MFPA) system can provide better cooling ability than a single piezoelectric fan with low power consumption and low noise. In this study, five MFPA models were designed and developed to be applied inside a pico projector, and the resonant frequency, the vibrational amplitude and the power consumption of these models were measured. Moreover, the Nusselt number, Richardson number, and thermal resistance were used to evaluate the thermal performance of the MFPA. The results reveal that the MFPA model with a combination of 35-mm long carbon fiber plates and 5-mm long Mylar plates achieves the optimal thermal performance. The thermal resistance, Nusselt number, and Richardson number of the MFPA model were, respectively, 4.13 K/W, 81.25, and 0.018 under 8-W heater power. Further experiments were performed with the optimal model set in different orientations. The results show that the Nusselt number dropped from 81.25 to 59.10 when the orientation changed from the normal case to the upside-down case at 8-W heater power.

Aims The endothelium plays an important role during vascular inflammation. Previous data have demonstrated a high expression level of manganese-superoxide dismutase (MnSOD) in endothelial cells and suggested an important role of MnSOD in several cardiovascular diseases. Manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) has been shown to mimic some of the effects of MnSOD and prevented the development of diabetes and obesity. However, its effect on vascular inflammation and the underlying mechanism is still unknown. Methods and results Leukocyte adhesion was evaluated in-vivo and in-vitro using dynamic flow chamber and intravital microscopy in mice. Expression of adhesion molecules induced by TNFα and adhesion of leukocytes to the vessel wall were inhibited by MnTBAP. The anti-inflammatory effect of MnTBAP was partly mediated by up-regulation of the BMPR-II and Smad dependent pathway. Additionally, MnTBAP decelerated the turn-over of endogenous BMPR-II. Conclusion Our data demonstrate that MnTBAP activates Smad signaling, preserves the turn-over of BMPR-II and elicits anti-inflammatory effects in endothelial cells, partly mediated by BMPR-II. This finding suggests a potential therapeutic impact of MnTBAP in the treatment of vascular inflammation.

The epidemiology of candidaemia varies between hospitals and geographic regions. Although there are many studies from Asia, a large-scale cross-sectional study across Asia has not been performed. We conducted a 12-month, laboratory-based surveillance of candidaemia at 25 hospitals from China, Hong Kong, India, Singapore, Taiwan and Thailand. The incidence and species distribution of candidaemia were determined. There were 1601 episodes of candidaemia among 1.2 million discharges. The overall incidence was 1.22 episodes per 1000 discharges and varied among the hospitals (range 0.16–4.53 per 1000 discharges) and countries (range 0.25–2.93 per 1000 discharges). The number of Candida blood isolates and the total number of fungal isolates were highly correlated among the six countries ( R ² = 0.87) and 25 hospitals ( R ² = 0.77). There was a moderate correlation between incidence of candidaemia and the intensive care unit (ICU)/total bed ratio ( R ² = 0.47), although ICUs contributed to only 23% of candidaemia cases. Of 1910 blood isolates evaluated, Candida albican s was most frequently isolated (41.3%), followed by Candida tropicalis (25.4%), Candida glabrata (13.9%) and Candida parapsilosis (12.1%). The proportion of C. tropicalis among blood isolates was higher in haemato-oncology wards than others wards (33.7% versus 24.5%, p 0.0058) and was more likely to be isolated from tropical countries than other Asian countries (46.2% versus 18.9%, p 0.04). In conclusion, the ICU settings contribute, at least in part, to the incidence variation among hospitals. The species distribution is different from Western countries. Both geographic and healthcare factors contribute to the variation of species distribution.

Aims Angiogenesis is defined as the sprouting of capillaries from pre-existing vasculature. It is a complex process that includes endothelial proliferation, migration, and tube formation. Previous data have demonstrated a high expression level of manganese-superoxide dismutase (MnSOD) in endothelial cells and suggested an important role of MnSOD in several cardiovascular diseases. In addition, manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) has been shown to mimic some of the effects of MnSOD in various tissues. However, its effect on the vasculature remains unknown. Methods and results HUVECs were treated with MnTBAP. Migration, tube formation, and capillary sprouting assays were performed to evaluate the pro-angiogenic effect in vitro . Matrigel plug assay was performed to assess capillary ingrowth in vivo . Compared to control, treatment with MnTBAP revealed increased cell migration, tube formation and capillary sprouting along with more capillary ingrowth in the Matrigel plug assay. This effect was mediated through a mitofusin (Mfn)-1-dependent pathway. Expression of Tie-2, Ang-2 and VEGF mRNA was increased in muscle tissues after ligation in MnTBAP treated mice. However, revascularization in the hindlimb ischemia model was not statistically significant at day 10 in MnTBAP treated mice. Conclusion In summary, our data demonstrate a strong pro-angiogenic, but less pro-arteriogenic effect of MnTBAP in HUVECs mediated by Mfn-1.

Social determinants of health (SDOH) critically impact healthcare access and outcomes. However, few studies have examined spatial relationships between SDOH and disease prevalence at neighborhood scales. In this study, we merged electronic health record (EHR) data from a major Chicago hospital

Hypertension and diabetes are common among poor urban dwellers. We hypothesized that blood pressure and glucose are higher for patients living farther from the pharmacy they typically use. Medical records of adult South Side dwellers who received care at the University of Chicago's outpatient

Despite improvements in treatments for heart failure in the last 30 years, significant barriers exist for underserved populations including access to care, nonadherence to prescribed treatments, and lack of support for self-management. Community health workers (CHW) are specially trained lay-people

Although inhibition of Rho-associated coiled-coil containing protein kinase (ROCK) has been shown to prevent coronary vasospastic angina (CVA), direct evidence linking ROCK activity and CVA is lacking. Accordingly, we investigated whether ROCK activity is an independent marker for CVA and is altered after treatment with antispastic medications.We prospectively studied 31 Taiwanese patients who were diagnosed with CVA and 33 control subjects. Subject demographics were recorded, and blood samples were obtained at baseline in all participants and in CVA patients after 3 months of antispastic treatment. Compared with control subjects, leukocyte ROCK activity was greater in CVA patients (136% versus 91%, P0.001). A cutoff value for leukocyte ROCK activity of 104% predicted the presence of CVA with specificity and sensitivity rates of 88% and 84%, respectively. ROCK activity increased with the severity of CVA (P for trend0.001). Following 3-month treatment of antispastic agents, leukocyte ROCK activity, high-sensitivity C-reactive protein, and interleukin-6 levels were reduced by 43%, 42% and 27%, respectively (P0.05 for all).Increased levels of leukocyte ROCK activity independently predicted the presence of CVA and correlated with CVA severity. Treatment with antispastic agents substantially reduced the level of leukocyte ROCK activity.

We previously reported the presence of mesenchymal stem/progenitor cells (MSCs) in inflamed pulp tissue. Here we asked whether MSCs also exist in inflamed periapical tissues resulting from endodontic infection. The objectives of this study were to detect the expression of MSC markers in periapical inflammatory tissues and to characterize isolated cells from these tissues.Human periapical inflammatory tissues were collected and processed to detect MSC marker expression by immunohistochemistry. Cells were isolated and tested for cell surface marker expression by using flow cytometry and examined for multiple differentiation potential into osteogenic and adipogenic pathways. In vivo formation of mineralized tissues was assessed in a mouse model.Immunohistochemistry showed positive staining for MSC markers STRO-1, CD90, and CD146. Isolated cells at passage 0 appeared as typical fibroblastic cells, and a few cells formed colony-forming unit-fibroblasts (CFU-Fs). After passaging, the CFU-F forming ability diminished dramatically, and the population doubling was up to 26. Flow cytometry data showed that these cells at passage 2 expressed low levels of STRO-1 and CD146 and moderate to high levels of CD90, CD73, and CD105. At passage 6, the levels of these markers decreased. When incubated in specific differentiation medium, cells demonstrated a strong osteogenic but weak adipogenic capacity. After in vivo cell transplantation, mineralized tissues formed in immunocompromised mice.Human periapical inflammatory tissues expressed MSC markers, suggesting the presence of MSCs. Isolated cells exhibited typical mesenchymal cell immunophenotype with a capacity to form mineralized matrix in vitro and in vivo.

Notch signaling is reported to regulate angiogenesis, interacting with vascular endothelial growth factor (VEGF) signaling. HMG CoA reductase inhibitors (statins) also alter Notch signaling in vascular cells, but the mechanism and involvement of Notch and VEGF signaling in statin-mediated angiogenesis remain unclear. Here, we examined how statins activate the endothelial Notch1, and promote angiogenesis and arteriogenesis. We examined blood flow recovery after hindlimb ischemia in wild-type (WT) and Notch1 mutant mice treated with or without pitavastatin (3 mg/kg/day, p.o.). Although VEGF induction was not altered in ischemic limbs, pitavastatin promoted blood flow recovery in ischemic limbs in control mice but not in Notch1 mutant mice. Furthermore, pitavastatin induced endothelial ephrinB2 downstream of Notch1 and increased the density of both capillaries and arterioles in the ischemic limbs of WT but not of Notch1 mutant mice. Pitavastatin (100 nmol/l) rapidly activated γ-secretase and Notch1 in human umbilical vein endothelial cells without VEGF induction, which was suppressed by pharmacological inhibition and knockdown of Akt. Pitavastatin also augmented endothelial proliferation and tube formation on Matrigel, which were suppressed by either γ-secretase inhibition or knockdown of Notch1. Pitavastatin-induced microvascular sprouting was also impaired in Notch1 mutant aortic explants. Taken together, pitavastatin activates Notch1 through Akt-dependent stimulation of γ-secretase in endothelial cells, and thereby increases vasculogenesis without VEGF induction.

The Rho/Rho-associated coiled-coil forming kinases (ROCKs) are important regulators of the actin cytoskeleton. Because changes in the actin cytoskeleton underlie vascular contractility and remodeling, inflammatory cell recruitment, and cellular proliferation, it is likely that the Rho/ROCK pathway will play a central role in mediating vascular function. Indeed, increased ROCK activity is observed in cerebral and coronary vasospasm, hypertension, vascular inflammation, arteriosclerosis, and atherosclerosis. Recent experimental and clinical studies suggest that inhibition of ROCK could be a promising target for the treatment of cardiovascular disease. For example, inhibition of ROCK might be the underlying mechanism by which statins or HMG-CoA reductase inhibitors exert their therapeutic benefits beyond cholesterol reduction. In this review, we provide a current understanding of the critical role of RhoA/ROCK pathway in the regulation of vascular function and discuss its therapeutic potential in the treatment of atherosclerosis and vascular disease.

Rho-associated kinases (ROCKs) have been shown to be involved in the pathogenesis of atherosclerosis. It is clinically important to estimate the degree of ROCK activity in humans. The purpose of this study was to confirm the validity of a leukocyte ROCK parameter as an index of ROCK activity in comparison with vascular response to a ROCK inhibitor.We evaluated the ratio of phospho myosin-binding subunit (p-MBS) on myosin light-chain phosphatase to total MBS in peripheral leukocytes by Western blot analysis and forearm blood flow (FBF) response to the ROCK inhibitor fasudil using strain-gauge plethysmography in 36 healthy subjects and 39 patients with cardiovascular diseases. Fasudil (3, 10, 30μg/min) was infused intra-arterially for 5min at each dose. Leukocyte p-MBS/total-MBS was higher in cardiovascular diseases than in healthy subjects (0.97±0.37 vs. 0.51±0.14; P=0.002). Fasudil increased FBF from 4.9±1.2 to 14.5±5.7mL/min/100mL tissue (P0.0001) in patients with cardiovascular diseases, while fasudil did not alter FBF in healthy subjects. There was a significant relationship between leukocyte p-MBS/total-MBS and maximal FBF response to fasudil in all subjects (r=0.72, P0.0001). There was also a significant correlation between p-MBS/total-MBS and maximal FBF response to fasudil in patients with cardiovascular diseases (r=0.59, P0.0001). In healthy subjects, there was no significant correlation between the two parameters.These findings suggest that assessment of leukocyte ROCK activity is minimally invasive and does not require pharmacologic intervention using ROCK inhibitors. Leukocyte p-MBS/total-MBS may be useful for evaluating ROCK activity in a clinical setting.

Through local cell-cell interactions, the Notch signaling pathway controls tissue formation and homeostasis during embryonic and adult life. In the heart, Notch1 is expressed in a variety of cell types, such as cardiomyocytes, smooth muscle cells, and endothelial cells. In cardiomyocytes, Notch1 is activated in proliferating embryonic and immature cardiomyocytes, and it is downregulated in the myocardium during postnatal development. However, Notch signaling in the adult myocardium could be activated transiently in response to myocardial injury, suggesting that Notch signaling may contribute to cardiac repair. Indeed, activation of Notch1 intracellular domain blunts the severity of myocardial injury and improves myocardial hemodynamic function. Conversely, genetic ablation of the Notch1 gene, either systemically or in bone marrow-derived cells, leads to impaired cardiac repair following myocardial infarction. In this review, we discuss the complex mechanisms of Notch signaling and its role in cardiac repair and regeneration after myocardial infarction.

Background Increased sympathetic nervous system activity is commonly observed in heart failure with reduced ejection fraction and is one cause of pathological structural remodeling of the left ventricle. Sacubitril/valsartan reduces mortality and heart failure hospitalizations, but its effect on sympathetic nervous system activity is unknown. Methods Patients enrolled in the prospective, longitudinal REMODEL study underwent 123-meta-iodobenzylguanidine scintigraphy prior to and three months following conversion from angiotensin converting enzyme inhibitor or angiotensin receptor blocker therapy to sacubitril/valsartan. The early heart-to-mediastinum (H/M) ratio, late H/M ratio and washout rate were calculated. Baseline and on-therapy values were compared using a paired t-test analysis. Results 40 patients were enrolled in this study. The mean age was 55 ± 12 years, 25 (63%) were male, and 30 (75%) had a non-ischemic heart failure etiology. Following transition to sacubitril/valsartan therapy, the late H/M ratio increased from 1.39 ± 0.19 to 1.52 ± 0.19 (p Conclusions Addition of sacubitril/valsartan to baseline heart failure therapy resulted in a decrease in cardiac sympathetic activity, as shown by a decrease in both the early and late H/M ratio and an increase in the washout rate on MIBG imaging. The decrease in sympathetic nervous system activity may underlie the improvement in survival seen with sacubitril/valsartan and can serve as a good measure of medication response.

Background: In addition to inhibiting cholesterol synthesis, statins (HMG-CoA reductase inhibitors) decrease the formation of isoprenoid intermediates required for the activation of key signaling pathways, including Rho/Rho kinase (ROCK). In experimental settings, statins inhibit ROCK and reverse vascular dysfunctions in atherosclerosis, independent of cholesterol reduction. It is not known whether statins inhibit ROCK activity in humans with atherosclerosis. Methods: We investigated 35 patients with stable atherosclerosis in a randomized, double-blind study comparing treatment with high-dose (80 mg/d) or low-dose (10 mg/d) atorvastatin to placebo for 28 days. Blood samples for leukocyte ROCK activity, fasting lipids, and high-sensitivity C-reactive protein (hs-CRP) were obtained on days 0, 7, 14, and 28 after randomization and change over time with the two statin treatments relative to placebo was examined. Results: Atorvastatin 80 mg/d reduced ROCK activity (p = 0.002 vs. placebo). This decline was rapid and significant within 2 weeks of treatment. The inhibition of ROCK by atorvastatin (80 mg/d) remained significant even after controlling for changes in low-density lipoprotein cholesterol (LDL-C) and triglycerides (p = 0.01). Furthermore, there was no correlation between changes in ROCK activity and changes in LDL-C (r = 0.2, p = 0.25) or triglycerides (r =0 .1,p = 0.55). There was a modest correlation between ROCK inhibition and change in hs-CRP among patients randomized to atorvastatin 80 mg/d (r = 0.6, p = 0.07). Conclusions: These first-in-man findings demonstrate that high-dose atorvastatin rapidly inhibits the proatherogenic Rho/ROCK pathway, independent of cholesterol reduction. This inhibition may contribute to the clinical benefits of statins. Rho/ROCK may provide a useful therapeutic target in patients with

Background Rho-kinase (ROCK) is a downstream effector of Rho GTPase that is known to regulate various pathological processes important to the development of ischemic stroke, such as thrombus formation, inflammation, and vasospasm. Inhibition of ROCK leads to decreased infarct size in animal models of ischemic stroke. This study tests the hypothesis that ROCK activity increases during the acute phase of ischemic stroke. Methods Serial blood samples were drawn from 10 patients with acute ischemic stroke presenting within 24 h of symptom onset and with NIHSS scores ≥ 4. Samples were taken at 24, 48, and 72 h. Leukocyte ROCK activity was determined by immunoblotting leukocyte lysates with antibodies to the phosphorylated form of myosin-binding subunit (P-MBS) of myosin light chain phosphatase (MLCP). MBS and P-MBS contents were normalized to α-tubulin, and ROCK activity was expressed as the ratio of P-MBS to MBS. ROCK activities in these 10 patients were compared to baseline ROCK activities in 10 control subjects without acute illness and matched for sex, age, and number of vascular risk factors using a two-tailed Student's t -test. Results The mean NIHSS score in patients with stroke was 15.4. ROCK activity was significantly increased at 24 and 48 h in patients after acute ischemic stroke when compared to control values, with peak elevations at 48 h after stroke onset. There was no apparent correlation between ROCK activity and stroke severity based on NIHSS. Conclusions Leukocyte ROCK activity is increased in patients after acute ischemic stroke with maximal activity occurring about 48 h after stroke onset. These findings suggest that activation of ROCK may play a role in the pathogenesis of ischemic stroke in humans.

Metabolic syndrome (MetS) is a cluster of atherosclerotic cardiovascular disease risk factors and is closely associated with insulin resistance and obesity (1,2). The precise diagnosis of MetS, however, is still somewhat controversial, and no serological markers are available for its detection. Nevertheless, according to the criteria of National Cholesterol Educational Program Adult Treatment Panel (ATP)-III (3), the prevalence of MetS in U.S. adults who are older than 20 years of age is approximately 24% (4). Metabolic syndrome is a growing problem worldwide, particularly in the Asian population (5). The World Health Organization Expert Consultation recommended a lower cut-off point for observed risk in Asian populations than that for non-Asian populations, varying from 22 to 25 kg/m2 (6). Some studies on migrants from Asian countries to Western countries also indicated that Asian populations might be more susceptible to the Western diet and lifestyle than white ones in developing the MetS (7,8). Patients with MetS have twice the incidence of developing new-onset diabetes compared with those without MetS (9). Metabolic syndrome, therefore, is associated with increasing risk of developing diabetes and cardiovascular disease. Several inflammatory mediators and adipocytokines, including tumor necrosis factor (TNF)-alpha (10), interleukin (IL)-6 (11), high-sensitivity C-reactive protein (hs-CRP) (12,13), and adiponectin (14) are associated with the development of insulin resistance and MetS (15,16). Despite these associations, the pathogenesis of MetS remains unknown. We recently reported that Rho kinase (ROCK) mediates the expression of plasminogen activator inhibitor-1 under hyperglycemic conditions (17). Furthermore, ROCK is upregulated under inflammatory conditions (18) and may be involved in adipocyte differentiation (19). Thus, growing evidence suggest that ROCK may contribute to the pathogenesis of MetS. However, clinical studies are lacking, which definitively link ROCK activity with MetS. Rho kinase is a serine/threonine kinase that mediates the downstream signaling of the small guanosine triphosphate-binding protein, Rho, on the actin cytoskeleton (20). ROCK consists of 2 isoforms, ROCK1 and ROCK2. In mostly animal models, the inhibition of ROCK ameliorates many cardiovascular conditions, including hypertension (21), atherosclerosis (22), myocardial fibrosis (23), and stroke (24). Furthermore, ROCK also could regulate insulin signaling and glucose metabolism through direct phosphorylation of the insulin receptor substrate (IRS)-1 (25). Thus, it is likely that ROCK plays an important role in the pathogenesis of MetS and diabetes. However, evidence is lacking showing that ROCK activity is increased in human subjects with MetS. In the current study, we measured ROCK activity in Taiwanese population with MetS and determined whether ROCK activity is an independent marker of MetS and whether it correlates with other components and risk markers of MetS.

We aimed to clarify responsiveness to angiotensin (Ang) II in the porcine basilar artery and the role of Ang II receptor subtypes by functional, radioligand binding, and cell culture studies. Ang II induced more potent contractions in the proximal part than in the distal part of isolated porcine basilar arteries. The contraction induced by Ang II was inhibited by the Ang II type 1 (AT1) receptor antagonist losartan, but the Ang II type 2 (AT2) receptor antagonist PD123319 enhanced it. After removal of the endothelium, the effect of losartan remained but the effect of PD123319 was abolished. The specific binding site of [3H]Ang II on the smooth muscle membrane was inhibited by losartan, but not by PD123319. Stimulation of angiotensin II increased nitric oxide (NO) production in cultured basilar arterial endothelial cells. This production was inhibited by PD123319 and the NO synthase inhibitor L–NG-nitroarginine. These results suggest that the contraction induced by Ang II might be mediated via the activation of AT1 receptors on the basilar arterial smooth muscle cells and be modulated via the activation of AT2 receptors on the endothelial cells, followed by NO production.

Centrifuge model tests have been conducted to investigate the effect of negative skin friction on piles installed through soft clay and founded in underlying dense sand. The first test series involved the study of fundamental mechanism of piles subject to negative skin friction only. In these tests, negative skin friction was induced by self-weight consolidation of clay followed by in-flight sand surcharge placement on the clay. The second test series examined the behavior of piles subject to simultaneous negative skin friction and axial load. The effects of axial load on the load-transfer characteristics along a pile experiencing locked-in negative skin friction induced by consolidating clay are investigated in detail in this paper. The effects of pile tip condition (end-bearing or socket pile), pile socket length and magnitude of applied load on the pile are also studied.