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Pitavastatin is a unique lipophilic statin with moderate efficacy in lowering LDL-C levels by 30% to 50% with a tolerable safety profile. However, the efficacy of adding ezetimibe to pitavastatin in patients with dyslipidemia has not been well investigated. Therefore, the objective of this double-blind, multicenter, randomized, Phase III study was to compare the efficacy and safety of pitavastatin and ezetimibe combination therapy with those of pitavastatin monotherapy in Korean patients with primary hypercholesterolemia.Korean men and women aged19 and80 years with primary hypercholesterolemia requiring medical treatment were included in this study. During the 8-week screening period, all patients were instructed to make therapeutic lifestyle changes. The screening period consisted of a 4-week washout period and a placebo run-in period (4-8 weeks). During treatment period I, patients were randomly assigned to receive 1 of 4 treatments: pitavastatin 2 mg plus ezetimibe 10 mg, pitavastatin 2 mg, pitavastatin 4 mg plus ezetimibe 10 mg, or pitavastatin 4 mg. The 8-week double-blind treatment period then commenced. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients.The percentages in LDL-C from baseline after 8 weeks of double-blind treatment decreased significantly in the pooled pitavastatin/ezetimibe (-52.8% [11.2%]) and pooled pitavastatin (-37.1% [14.1%]) groups. Treatment with pitavastatin/ezetimibe resulted in a significantly greater LDL-C-lowering effect than that with pitavastatin (difference, -15.8 mg/dL; 95% CI, -18.7 to -12.9; P0.001). The precentages of achieving LDL-C goal in pooled pitavastatin/ezetimibe and pooled pitavastatin groups were 94.2% and 69.1%, respectively (P0.001). There were no significant differences in the incidence of overall AEs and adverse drug reactions. Serious AEs were comparable between the groups.Pitavastatin and ezetimibe combinations effectively and safely decreased LDL-C levels by50% in patients with dyslipidemia. The safety and tolerability of pitavastatin and ezetimibe combination therapy were comparable with those of pitavastatin monotherapy.gov identifier: NCT04584736.

PURPOSE Residual cardiovascular risk reduction by fenofibrate in patients with high serum triglyceride (TG) levels despite previous statin monotherapy is not well characterized. The purpose of this study was to evaluate the efficacy and safety of a combination of choline fenofibrate and statin in patients with inadequately controlled TG levels despite previous statin monotherapy. METHODS This prospective, multicenter, randomized, double-blind study was conducted in Korea. A total of 133 patients with controlled LDL-C but elevated TG levels, already receiving statin monotherapy, were enrolled in the study, which was conducted from July 2018 to December 2019. Patients were randomly assigned to receive combination therapy with choline fenofibrate and statin or statin monotherapy in a 1:1 ratio. After 8 weeks of treatment, the lipid profiles and safety parameters of the patients in the 2 groups were compared. FINDINGS The study included 127 patients (64 in the combination group and 63 in the control group) older than 19 years. After 8 weeks of therapy, mean serum TG levels significantly decreased from 269.8 to 145.5 mg/dL (P < 0.0001) in the combination therapy group, whereas no significant changes occurred in the statin monotherapy group (from 271.1 to 280.5 mg/dL). Contrarily, the mean serum HDLC levels significantly increased from 45.0 to 50.4 mg/dL (P = 0.0004) in the combination therapy group, whereas there were no significant changes in the monotherapy group (from 44.3 to 44.7 mg/dL). There were no additional serious adverse events in the combination therapy group compared with the statin monotherapy group. IMPLICATIONS The combination therapy using choline fenofibrate and statin was found to be effective in serum TG control and likely tolerable in patients with high TG levels despite statin monotherapy. A larger study, conducted for a longer duration, is needed to evaluate the effectiveness of this combination in reducing cardiovascular risk. ClinicalTrials.gov identifier: NCT03874260.

Objectives This study evaluated the association between elevated levels of lipoprotein(a) [Lp(a)] and risk of recurrent ischemic events in patients who underwent percutaneous coronary intervention (PCI). Background Elevated levels of Lp(a) have been identified as an independent, possibly causal, risk factor for atherosclerotic cardiovascular disease in a general population study. Methods A prospective single-center registry was used to identify 12,064 patients with baseline Lp(a) measurements who underwent PCI between 2003 and 2013. The primary outcomes were a composite of cardiovascular death, spontaneous myocardial infarction, and ischemic stroke. Results From the registry, 3,747 (31.1%) patients had high Lp(a) (>30 mg/dL) and 8,317 (68.9%) patients had low Lp(a) (≤30 mg/dL). During a median follow-up of 7.4 years, primary outcomes occurred in 1,490 patients, and the incidence rates of primary outcomes were 2.0 per 100 person-years in the high-Lp(a) group and 1.6 per 100 person-years in the low-Lp(a) group (adjusted hazard ratio [aHR]: 1.17; 95% confidence interval [CI]: 1.05-1.30; P = 0.004). Increased risk of recurrent ischemic cardiovascular events in the high-Lp(a) group was consistent in various subgroups including patients receiving statin treatment at discharge (aHR: 1.18; 95% CI: 1.03-1.34; P = 0.011). In addition, the risk of repeated revascularization was significantly higher in the high-Lp(a) group (aHR: 1.13; 95% CI: 1.02-1.25; P = 0.022). Conclusions Elevated levels of Lp(a) were significantly associated with the recurrent ischemic events in patients who underwent PCI. This study provides a rationale for outcome trials to test Lp(a)-lowering therapy for secondary prevention in patients undergoing PCI.

Purpose Although the role of high-intensity lipid-lowering therapy in cardiovascular protection has broadened, concerns still exist about new-onset diabetes mellitus (NODM), especially in vulnerable patients. This study aimed to compare the effect of high-dose (4 mg/d) and usual dose (2 mg/d) pitavastatin on glucose metabolism in patients with hyperlipidemia and impaired fasting glucose (IFG). Methods In this 12-month study, glucose tolerance and lipid-lowering efficacy of high-dose pitavastatin (4 mg [study group]) was compared with that of usual dose pitavastatin (2 mg [control group]) in patients with hyperlipidemia and IFG. The primary end point was the change of glycosylated hemoglobin (HbA1c) after 24 weeks of treatment. The secondary end points were as follows: (1) NODM within 1 year after treatment, (2) change of lipid parameters, (3) changes of adiponectin, and (4) change of blood glucose and insulin levels. Findings Of the total 417 patients screened, 313 patients with hypercholesterolemia and IFG were randomly assigned into groups. The mean (SD) change in HbA1c was 0.06% (0.20%) in the study group and 0.03% (0.22%) in the control group (P = 0.27). Within 1 year, 27 patients (12.3%) developed NODM, including 12 (10.6%) of 113 patients in the study group and 15 (14.2%) of 106 in the control group (P = 0.43). The study group had a significantly higher reduction of total cholesterol and LDL-C levels and a higher increase in apolipoprotein A1/apolipoprotein B ratio (0.68 [0.40] vs 0.51 [0.35], P Implications The high-dose pitavastatin therapy did not aggravate glucose metabolism compared with the usual dose therapy. Moreover, it had a better effect on cholesterol-lowering and apolipoprotein distribution in the patients with hyperlipidemia and IFG.

Single risk factors, such as hypertension and dyslipidemia, can combine to exacerbate the development and severity of cardiovascular disease. Treatment goals may be more effectively achieved if multiple disease factors are targeted with combination treatment. We enrolled 202 patients who were randomly divided into the following three groups: telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg, telmisartan 80 mg + rosuvastatin 20 mg, and telmisartan/amlodipine 80/5 mg. The primary efficacy variables were changes from baseline in mean sitting systolic blood pressure (MSSBP) between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg at 8 weeks, and the percent changes from baseline in low‐density lipoprotein (LDL) cholesterol between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg at 8 weeks. The secondary efficacy variables were changes in MSSBP, mean sitting diastolic blood pressure (MSDBP), LDL cholesterol and other lipid levels at 4 weeks and 8 weeks, as well as observed adverse events during follow‐up. There were no significant differences between the three groups in demographic characteristics and no significant difference among the three groups in terms of baseline characteristics for the validity evaluation variables. The mean overall treatment compliance in the three groups was, respectively, 98.42%, 96.68%, and 98.12%, indicating strong compliance for all patients. The Least‐Square (LS) mean (SE) for changes in MSSBP in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg) groups were −19.3 (2.68) mm Hg and −6.69 (2.76) mm Hg. The difference between the two groups was significant (−12.60 (2.77) mm Hg, 95% CI −18.06 to −7.14, P

High LDL-cholesterol (LDL-C) is an established risk factor for cardiovascular disease and is considered an important therapeutic target. It can be measured directly or calculated from the results of other lipid tests. The Friedewald formula is the most widely used formula for calculating LDL-C. We modified the Friedewald formula for a more accurate and practical estimation of LDL-C.Datasets, including measured triglyceride, total cholesterol, HDL-cholesterol, and LDL-C concentrations were collected and assigned to derivation and validation sets. The datasets were further divided into five groups based on triglyceride concentrations. In the modified formula, LDL-C was defined as total cholesterol - HDL-cholesterol - (triglyceride/adjustment factor). For each group, the adjustment factor that minimized the difference between measured LDL-C and calculated LDL-C using modified formula was obtained. For validation, measured LDL-C and LDL-C calculated using the modified formula (LDL-CM), Friedewald formula (LDL-CF), Martin-Hopkins formula (LDL-CMa), and Sampson formula (LDL-CS) were compared.In the derivation set, the adjustment factors were 4.7, 5.9, 6.3, and 6.4 for the groups with triglyceride concentrations100, 101-200, 201-300, and300 mg/dL, respectively. In the validation set, the coefficient of determination (RWe proposed a practical, improved LDL-C calculation formula by applying different factors depending on the triglyceride concentration.

The golfer's body (trunk/arms/club) can be modeled as an inclined axle-chain system and the rotations of its parts observed on the functional swing plane (FSP) can represent the actual angular motions closely. The purpose of this study was to investigate the effects of pelvis-shoulders torsional separation style on the kinematic sequences employed by the axle-chain system in golf driving. Seventy-four male skilled golfers (handicap ≤ 3) were assigned to five groups based on their shoulder girdle motion and X-factor stretch characteristics: Late Shoulder Acceleration, Large Downswing Stretch, Large Backswing Stretch, Medium Total Stretch, and Small Total Stretch. Swing trials were captured by an optical system and the hip-line, thorax, shoulder-line, upper-lever, club, and wrist angular positions/velocities were calculated on the FSP. Kinematic sequences were established based on the timings of the peak angular velocities (backswing and downswing sequences) and the backswing-to-downswing transition time points (transition sequence). The backswing and transition sequences were somewhat consistent across the groups, showing full or partial proximal-to-distal sequences with minor variations. The downswing sequence was inconsistent across the groups and the angular velocity peaks of the body segments were not significantly separated. Various swing characteristics associated with the separation styles influenced the motion sequences.

BACKGROUND The effect of foot orthoses in terms of kinematics and kinetics during walking could be affected on different geometrical designs. Therefore, the purpose of this study was to compare the biomechanical and clinical effects of 3 different insoles on rearfoot motion (RFM) and ankle joint moment parameters. MATERIAL AND METHODS Twenty eight university students with flexible flatfoot were recruited for this study, and each participant was asked to wear 3 different insoles: normal insole without arch support function, type A insole with only arch support function, and type B insole with both arch support and cushion pads for shock absorbing functions. Three-dimensional motion analysis was performed to compute the ranges and peak orientation angles of RFM and ankle joint moment parameters. RESULTS The type A and type B insoles exhibited significantly smaller peak everted position and evertor moment than the normal insole. Also, the type A insole showed significantly smaller range of rearfoot motion in the longitudinal axis and the length of MA (moment arm) in the mediolateral axis than the normal insole. CONCLUSIONS The use of the type A insole using arch support function was induced to promote a cautious gait pattern associated with a relatively lower potential risk compared to the normal insole. The type A and type B insoles could be important to positively reduce the possibility of injury. Also, the smaller length of MA in the type A insole might have a contribution to the decrease of ankle joint evertor moment.

The purposes of this study were to characterise the golfer-ground interactions during the swing and to identify meaningful associations between the golfer-ground interaction force/moment parameters and the maximum clubhead speed in 63 highly skilled male golfers (handicap ≤ 3). Golfers performed shots in 3 club conditions (driver, 5-iron and pitching wedge) which were captured by an optical motion capture system and 2 force plates. In addition to the ground reaction forces (GRFs), 3 different golfer-ground interaction moments (GRF moments, pivoting moments and foot contact moments) were computed. The GRF moment about the forward/backward (F/B) axis and the pivoting moment about the vertical axis were identified as the primary moments. Significant (p < 0.05) correlations of peak force parameters (all components in the lead foot and F/B component in the trail foot) and peak moment parameters (lead-foot GRF moment and trail-foot pivoting moment) to clubhead speed were found. The lead-foot was responsible for generating the GRF moment, while the trail foot contributed to the pivoting moment more. The instant the lead arm becomes parallel to the ground was identified as the point of maximum angular effort, and the loading onto the lead-foot near this point was critical in generating both peak moments.

Background How statins alter the natural course of coronary atherosclerosis with compositional changes remains unclear. Objectives This study aimed to determine the effect of statin therapy on modifying plaque composition. Methods The STABLE (Statin and Atheroma Vulnerability Evaluation) prospective, single-center, double-blind, randomized study evaluated the effect of statins on functionally insignificant coronary stenoses. We randomly assigned 312 patients with a virtual histology (VH) intravascular ultrasound–defined fibroatheroma-containing index lesion to rosuvastatin 40 mg versus 10 mg (2:1 ratio). In 225 (72%) patients, grayscale- and VH-intravascular ultrasound were completed at baseline and 12 months. The primary endpoint was the change in VH-defined percent compositional volume within the target segment from baseline to follow-up in the per-protocol analysis set. Results Percent necrotic core (NC) volume within the target segment significantly decreased from 21.3 ± 6.8% to 18.0 ± 7.5% during 1-year follow-up, whereas the percent fibrofatty volume increased (11.7 ± 5.8% vs. 14.8 ± 9.3%; all p 3 vs. 188.5 ± 67.8 mm 3 ; p = 0.001) and percent (51.4 ± 8.3% vs. 50.4 ± 8.8%; p = 0.018) atheroma volumes decreased. Independent predictors of percent NC volume change were body mass index (β = 0.37; 95% confidence interval [CI]: 0.05 to 0.70), high sensitivity C-reactive protein (β = −3.16; 95% CI: −5.64 to −0.69), and baseline percent NC volume (β = −0.44; 95% CI: −0.68 to −0.19; all p Conclusions Rosuvastatin reduced NC and plaque volume and decreased thin-cap fibroatheroma rate. There were no significant differences between high- versus moderate-intensity rosuvastatin. (Statin and Atheroma Vulnerability Evaluation [STABLE]; NCT00997880 )

HMG-CoA reductase inhibitors, i.e. statins, are effective in reducing cardiovascular disease events but also in cardiac-related and overall mortality. Statins are in general well-tolerated, but currently the concerns are raised if statins may increase the risk of new-onset diabetes mellitus (NOD). In this review, the possible effects of statins on organs/tissues being involved in glucose metabolism, i.e. liver, pancreas, adipose tissue, and muscles, had been discussed. The net outcome seems to be inconsistent and often contradictory, which may be largely affected by in vitro experimental settings or/and in vivo animal conditions. The majority of studies point out statin-induced changes of regulations of isoprenoid metabolites and cell-associated cholesterol contents as predisposing factors related to the statin-induced NOD. On the other hand, it should be considered that dysfunctions of isoprenoid pathway and mitochondrial ATP production and the cholesterol homeostasis are already developed under (pre)diabetic and hypercholesterolemic conditions. In order to connect the basic findings with the clinical manifestation more clearly, further research efforts are needed.

The purpose of this study was to investigate the relationships among release factors (speed, height, and angle) and distance thrown in Paralympic seated shot put. Fortyeight trials performed by 11 men and 5 women during the 2012 US Paralympic trials in track and field were analyzed. With both genders combined, release speed (r = .95, p < .01) and angle (r = .51, p < .01) showed significant correlations to distance thrown. Release speed (r = .94, p < .01) in men and all release factors (r = .60–.98, p < .02) in women showed significant correlations to distance. Release speed and angle were identified as important predictors of the distance, explaining over 89–96% of the variance in distance thrown. Unlike athletes without disability, seated shotputters exhibited significant positive speed–angle correlations (combined: r = .37, p < .01; women: r = .57, p = .03). Application of these results should address a focus in training on generating speed through the release point with a consistent release angle.

Background Apolipoprotein B (apoB) is known to be a more powerful predictor of cardiovascular disease than conventional lipids. We aimed to determine the clinical relevance of a newly developed equation to estimate serum apoB levels based on total cholesterol, HDL cholesterol, and triglycerides in patients with high cardiovascular risk. Methods The occurrence of a major cardiovascular event (MCVE) was assessed using the data from the Treating to New Targets (TNT) and Incremental Decrease in End points through Aggressive Lipid lowering (IDEAL) trials. Results Pooled analysis of these two data sets showed that both directly-measured apoB (HR per 1-SD (95% CI): 1.16 (1.11–1.21), P

Hypertension and dyslipidemia are 2 risk factors of cardiovascular disease that often present simultaneously. Traditionally, treatment of these multiple conditions required separate medications for each disease, which may result in poor compliance and thus lead to possible treatment failure. Fixed-dose combination (FDC) therapy with a single pill may be a solution in these situations.This multicenter, 8-week, randomized, double-blind, Phase III study evaluated the efficacy and safety of FDC treatment with telmisartan (80 mg) and rosuvastatin calcium (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. Patients were randomly assigned to 4 groups: (1) FDC drug (80 mg of telmisartan and 20 mg of rosuvastatin); (2) 80 mg of telmisartan; (3) 20 mg of rosuvastatin; or (4) placebo. After 8 weeks of treatment, the change in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) between the FDC group and the rosuvastatin group, and the percent change in LDL-C between the FDC group and the telmisartan group, were compared.A total of 210 patients were enrolled in the study (84 in the FDC group, 42 in the rosuvastatin group, 43 in the telmisartan group, and 41 in the placebo group). The reduction in blood pressure was significantly greater in the FDC group than in the rosuvastatin group after 8 weeks of treatment (least squares mean change from baseline, -16.1 [1.6] mm Hg vs -1.7 [2.2] mm Hg [P0.001] for MSSBP; -8.8 [1.0] mm Hg vs -1.6 [1.4] mm Hg [P0.001] for MSDBP). Least squares mean percent change in LDL-C from baseline was also significantly greater in the FDC group compared with the telmisartan group (-49.3% [2.2%] vs 1.5% [3.0%]; P0.001). FDC therapy also had a higher rate of achieving the treatment goal in both blood pressure (60% vs 45%; P = 0.024) and LDL-C (88.8% vs 16.3%; P0.001) compared with rosuvastatin or telmisartan alone, respectively. In regression analysis, higher baseline MSSBP, female sex, and lower body mass index were associated with increased reductions in MSSBP, whereas higher baseline LDL-C level and lower body mass index were associated with greater reductions in LDL-C. There were 48 adverse events in 36 patients (17.3% [36 of 208]), and 17 adverse drug reactions in 12 patients (5.8% [12 of 208]), indicating no significant differences in short-term safety among study groups.Treatment with an FDC drug containing telmisartan and rosuvastatin showed similar efficacy in lowering blood pressure and LDL-C levels compared with that of each single drug. ClinicalTrials.gov identifier: NCT01914432.

The purpose of this study was to examine the efficacy and safety of adding ω-3 fatty acids to rosuvastatin in patients with residual hypertriglyceridemia despite statin treatment.This study was a multicenter, randomized, double-blind, placebo-controlled study. After a 4-week run-in period of rosuvastatin treatment, the patients who had residual hypertriglyceridemia were randomized to receive rosuvastatin 20 mg/d plus ω-3 fatty acids 4 g/d (ROSUMEGA group) or rosuvastatin 20 mg/d (rosuvastatin group) with a 1:1 ratio and were prescribed each medication for 8 weeks.A total of 201 patients were analyzed (mean [SD] age, 58.1 [10.7] years; 62.7% male). After 8 weeks of treatment, the percentage change from baseline in triglycerides (TGs) and non-HDL-C was significantly greater in the ROSUMEGA group than in the rosuvastatin group (TGs: -26.3% vs -11.4%, P0.001; non-HDL-C: -10.7% vs -2.2%, P = 0.001). In the linear regression analysis, the lipid-lowering effect of ω-3 fatty acids was greater when baseline TG or non-HDL-C levels were high and body mass index was low. The incidence of adverse events was not significantly different between the 2 groups.In patients with residual hypertriglyceridemia despite statin treatment, a combination of ω-3 fatty acids and rosuvastatin produced a greater reduction of TGs and non-HDL-C than rosuvastatin alone. Further study is needed to determine whether the advantages of this lipid profile of ω-3 fatty acids actually leads to the prevention of cardiovascular event. ClinicalTrials.gov identifier: NCT03026933.

Background— The mechanism of statin for atheroma stabilization remains unclear. We aimed to assess the relationship between on-treatment changes in serum inflammatory biomarker levels and plaque composition in differed nonculprit coronary lesions. Methods and Results— The changes in serum biochemical values, and intravascular ultrasound data were evaluated in 218 patients with virtual histology (VH)-intravascular ultrasound—defined fibroatheroma-containing segments after 12-month rosuvastatin treatment. When stratifying patients into quartiles according to the change in high-sensitivity C-reactive protein (hsCRP), there was a significant positive linear relationship for the changes in %necrotic core (coefficient, 1.31; standard error, 0.54) and %dense calcium volumes (coefficient, 0.80; standard error, 0.27), but a negative linear relationship for the changes in %fibrous (coefficient, −0.94; standard error, 0.45) and %fibrofatty volumes (coefficient, −1.17; standard error, 0.56; all P P =0.02) was greater in those without VH-defined thin-cap fibroatheroma (TCFA, defined as >30° of necrotic core abutting the lumen in 3 consecutive slices) than those with VH-TCFA at follow-up. Diabetes mellitus, a larger normalized total atheroma volume, and the presence of VH-TCFA at baseline predicted the presence of VH-TCFA at follow-up (odds ratio, 4.01, 1.18, and 9.21, respectively; all P P =0.07). The change in low-density lipoprotein-cholesterol had no relationship with the changes in hsCRP or plaque compositions. Conclusions— With 12-month rosuvastatin therapy, a greater hsCRP reduction (not low-density lipoprotein-cholesterol) was associated with a greater decrease in %necrotic core volume and the absence of VH-TCFA, indicating a link between the anti-inflammatory action of statin and plaque stabilization by reducing NC and reinforcing fibrous cap. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00997880.

Objective To investigate whether fenofibrate as add-on to statin treatment reduce persistent cardiovascular risk in adults with metabolic syndrome in a real world setting. Design Propensity matched cohort study. Setting Population based cohort in Korea. Participants 29 771 adults with metabolic syndrome (≥40 years) receiving statin treatment. 2156 participants receiving combined treatment (statin plus fenofibrate) were weighted based on propensity score in a 1:5 ratio with 8549 participants using statin only treatment. Main outcome measure Primary outcome was composite cardiovascular events including incident coronary heart disease, ischaemic stroke, and death from cardiovascular causes. Results The incidence rate per 1000 person years of composite cardiovascular events was 17.7 (95% confidence interval 14.4 to 21.8) in the combined treatment group and 22.0 (20.1 to 24.1) in the statin group. The risk of composite cardiovascular events was significantly reduced in the combined treatment group compared with statin group (adjusted hazard ratio 0.74, 95% confidence interval 0.58 to 0.93; P=0.01). The significance was maintained in the on-treatment analysis (hazard ratio 0.63, 95% confidence interval 0.44 to 0.92; P=0.02). The risk of incident coronary heart disease, ischaemic stroke, and cardiovascular death was lower in the combined treatment group than statin group but was not significant. Participant characteristics did not appear to be associated with the low risk of composite cardiovascular events with combined treatment. Conclusion In this propensity weighted cohort study of adults with metabolic syndrome, the risk of major cardiovascular events was significantly lower with fenofibrate as add-on to statin treatment than with statin treatment alone.

We hypothesized that C-reactive protein (CRP) may affect the cell cycle and induce apoptotic changes of monocytes. CRP (∼25μg/ml) significantly increased expressions of B-cell translocation gene 2 (BTG2) mRNA and protein in human monocytes through pathways involving CD32/NADPH oxidase 2/p53, which eventually induced G2/M phase arrest and apoptotic cell death. Such pro-apoptotic effect of CRP was not found in thioglycollate-elicited intraperitoneal monocytes/macrophages harvested from BTG2-knockout male C57BL/6 mice (n=5). Within atheromatous plaques obtained from CRP-transgenic male LDLR−/− C57BL/6 mice (n=5) and human coronary arteries, BTG2 co-localized with CRP, p53 and monocytes/macrophages. Therefore the pro-apoptotic pathway of CRP-CD32-Nox2-p53-BTG2 may contribute to the retardation of the atherogenic process.

The purpose of this study was to assess the validity of the X-factor computation methods and to examine whether direct relationships exist between the X-factor parameters and the clubhead velocity in a group of skilled male golfers (n = 18, handicap = -0.6 +/- 2.1). Five driver trials were captured from each golfer using an optical motion capture system (250 Hz). Two plane-based methods (conventional vs. functional swing plane-based) and one Cardan rotation-based method (relative orientation) were used to compute select X-factor (end of pelvis rotation, top of backswing, ball impact (BI), and maximum), X-factor stretch (stretch and maximum stretch), and X-factor velocity (BI and maximum) parameters. The maximum clubhead velocity was extracted and normalized to golfer's body height to eliminate the effect of body size. A one-way repeated MANOVA revealed that the computation methods generated significantly different X-factor parameter values (p < 0.001). The conventional method provided substantially larger X-factor values than the other methods in the untwisting phase and the meaningfulness of select X-factor parameters generated by this method was deemed questionable. The correlation analysis revealed that the X-factor parameters were not directly related to the maximum clubhead velocity (both unnormalized and normalized).

Familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular diseases, and is inherited as an autosomal dominant trait. The prevalence of heterozygous FH is one in five hundred people. Owing to dysfunctional low density lipoprotein (LDL) receptors due to genetic mutations, serum low density lipoprotein-cholesterol (LDL-C) levels are considerably increased from birth. FH is clinically diagnosed by confirmation of family history and characteristic findings such as tendon xanthoma or xanthelasma. Thus, clinical concern and suspicion are important for early diagnosis of the disease. Current guidelines recommend lowering LDL-C concentration to at least 50% from baseline. Statins are shown to lower LDL-C levels with high safety, and thus, have been the drug of choice. However, it is difficult to achieve an ideal level of LDL-C with a single statin therapy in the majority of FH patients. Alternatively, lipid lowering combination therapy with the recently-introduced ezetimibe has shown more encouraging results.

Background— As a substudy of the large, randomized ZEST (Comparison of the Efficacy and Safety of Zotarolimus-Eluting Stent with Sirolimus-Eluting and PacliTaxel-Eluting Stent for Coronary Lesions) trial comparing first- and second-generation drug-eluting stents, we evaluated intimal hyperplasia (IH) and vascular changes using volumetric intravascular ultrasound analysis. Methods and Results— Complete angiographic and volumetric intravascular ultrasound data immediately after stenting and at 9-month follow-up were available in 162 patients with 183 lesions: 61 sirolimus-eluting stents (SES), 64 paclitaxel-eluting stents (PES), and 58 zotarolimus-eluting stents (ZES). External elastic membrane, stent, lumen, and peristent plaque volumes (external elastic membrane minus stent) were normalized by stent length. Percent IH volumes were calculated as [IH volume/stent volume]×100, %. Reduction of minimal luminal area) was greater in PES than SES (−1.4±1.5 mm 2 versus −0.7±0.9 mm 2 , P =0.003), whereas minimal luminal area change in ZES was not significantly different from SES (−1.2±1.0 mm 2 versus −0.7±0.9 mm 2 , P =0.055). Percent IH volume was less in SES compared with PES (9.8±6.0% versus 17.5±11.2%, P =0.002) or with ZES (9.8±6.0% versus 18.2±7.6%, P =0.005). Comparing ZES versus PES, there were no significant differences in %IH volume (17.5±11.2% versus 18.2±7.6%, P =0.779) or changes in normalized lumen volume (−1.2±1.3 mm 2 versus −1.1±0.8 mm 2 , P =0.452). Late stent malapposition was identified in 8 (13%) SES and 2 (3%) PES but in no ZES ( P =0.050). Angiographic restenosis was detected in 6 lesions (3 PES and 3 ZES). Conclusions— The degree of neointimal growth in ZES was similar to that in PES but less than that in SES. ZES had no late stent malappositions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00418067.

We studied the effect of the preprocedural intravascular ultrasound findings on stent expansion and the pre- and postprocedural findings on the long-term clinical outcomes in patients undergoing drug-eluting stent implantation for unprotected left main (LM) bifurcation disease. Using a left anterior descending (LAD) pullback, we evaluated the ostial LAD artery (3 mm distal to the carina), the polygon of confluence (POC; the confluent zone of the LAD artery and left circumflex artery), and the distal LM artery (3 mm just proximal to the POC). The measurements included the minimum lumen area (MLA) and minimum stent area within each segment. In 168 LM bifurcations, the preprocedural MLA and post-stenting minimum stent area within the LM artery were located within the POC in 41% and 70%, respectively. Independent predictors for the post-stent minimum stent area within the distal portion of LM artery above the LAD carina were the preprocedural lumen area of the LAD carina (β = 0.253, 95% confidence interval [CI] 0.10 to 0.36, p = 0.001) and preprocedural MLA within the POC (β = 0.205, 95% CI 0.04 to 0.23, p = 0.008). During the 41.8 ± 18.0-month follow-up period, 26 patients experienced cardiac events. In the multivariate Cox model, female gender (adjusted hazard ratio 2.56, 95% CI 1.173 to 5.594, p = 0.018) and preprocedural MLA within the POC (adjusted hazard ratio 0.829, 95% CI 0.708 to 0.971, p = 0.020) were independent predictors for the occurrence of events at 3 years of follow-up. In conclusion, as assessed by the LAD pullback, the preprocedural MLA within the POC was a surrogate reflecting the overall severity of LM bifurcation disease, contributed to the post-stent minimum stent area within the distal segment of LM bifurcation, and was a predictor of clinical events during follow-up.

Using virtual histology and intravascular ultrasound (VH-IVUS), tissue characterization of restenotic in-stent neointima after drug-eluting stent (DES) and bare metal stent (BMS) implantation was assessed. VH-IVUS was performed in 117 lesions (70 treated with DESs and 47 treated with BMSs) with angiographic in-stent restenosis and intimal hyperplasia (IH)50% of the stent area. The region of interest was placed between the luminal border and the inner border of the struts and tissue composition was reported as percentages of IH area (percent fibrous, percent fibrofatty, percent necrotic core, percent dense calcium) at the 2 sites of maximal percent IH and maximal percent necrotic core. Mean follow-up times between stent implantation and VH-IVUS study were 43.5 ± 33.8 months for BMS-treated lesions and 11.1 ± 7.8 months for DES-treated lesions (p0.001). The 2 groups had greater percent necrotic core and percent dense calcium at maximal percent IH and maximal percent necrotic core sites, especially in stents that had been implanted for longer periods. In conclusion, this VH-IVUS analysis showed that BMS- and DES-treated lesions develop in-stent necrotic core and dense calcium, suggesting the development of in-stent neoatherosclerosis.

Background— The long-term natural history of acquired malapposition continues to be the subject of debate. Methods and Results— Using volumetric intravascular ultrasound analyses, we evaluated serial (poststenting, 6-month, and 2-year follow-up) changes in drug-eluting stent–treated vascular segments with acquired malapposition. External elastic membrane, stent, lumen, malapposition, and peristent plaque+media (P+M=external elastic membrane −stent− malapposition) areas were measured; and volumes were calculated and divided by stent length (normalized volume). Among 250 lesions in which complete serial intravascular ultrasound data were available, stent malapposition was identified in 19 lesions (7.6%) at 6 months, and an additional 13 malapposition lesions were newly detected at 2 years (5.2%). Because no malapposition sites resolved, the malapposition rate at 2 years was 12.8%. Malapposition areas and volumes were correlated to the increases in external elastic membrane (positive remodeling) throughout the study period, from immediately after stenting to 6 months and from 6 months to 2 years, both in the group that developed malapposition at 6 months and in the group that developed malapposition at 2 years. Clinical follow-up beyond the 2 year intravascular ultrasound study was done in all patients. Overall, there were 2 cardiac deaths and 1 noncardiac death. Two patients presented with acute myocardial infarction associated with very late stent thrombosis (1 definite stent thrombosis, 1 probable stent thrombosis). Three patients underwent repeat revascularization owing to in-stent restenosis developed after the 2-year follow-up. Conclusions— Expansive vascular remodeling may play a role in the development and dynamic progression of acquired drug-eluting stent malapposition, not only during the first 6 months after implantation but thereafter.

BACKGROUND/AIMS Metabolic syndrome is an emerging risk factor for cardiovascular disease. This study investigated the prevalence of metabolic syndrome among psychiatric patients in order to identify the dominant factors of metabolic syndrome. METHODS We enrolled 225 patients who had been admitted to a chronic psychiatric hospital from October 2005 to February 2006. The prevalence of metabolic syndrome was assessed based on the Adult Treatment Panel (ATP)-III with the new criterion of waist circumference in the Asia-Pacific Region. RESULTS The study population was relatively young (41.1 +/- 8.8 years) and obese (waist in men, 91.3 +/- 9.2 cm; waist in women, 84.1 +/- 8.8 cm). Sixty percent of patients met the waist criterion of metabolic syndrome and 56% met the low high density lipoprotein (HDL) criterion. The mean serum triglycerides were high (170.0 +/- 119.7 mg/dL) and 46% of patients met the triglyceride criterion. In contrast, less than 10% of patients showed impaired fasting glucose or high blood pressure (5%, 9%, respectively). The overall prevalence of metabolic syndrome was 34.2% by applying ATP-III criteria (40% in men and 20% in women, respectively). No specific anti-psychotic drugs were related to significant increase in the incidence of metabolic syndrome. CONCLUSIONS Abdominal obesity and dyslipidemia (low HDL and high triglycerides) were dominant contributing factors of metabolic syndrome among psychiatric patients, and the affected age groups were relatively young. These findings indicate that active and early screening, including triglycerides, HDL, and waist measurement, are absolutely essential to managing metabolic syndrome in psychiatric patients.

Background The potential benefits and risks of the use of dual antiplatelet therapy beyond a 12-month period in patients receiving drug-eluting stents have not been clearly established. Methods In two trials, we randomly assigned a total of 2701 patients who had received drugeluting stents and had been free of major adverse cardiac or cerebrovascular events and major bleeding for a period of at least 12 months to receive clopidogrel plus aspirin or aspirin alone. The primary end point was a composite of myocardial infarction or death from cardiac causes. Data from the two trials were merged for analysis. Results The median duration of follow-up was 19.2 months. The cumulative risk of the primary outcome at 2 years was 1.8% with dual antiplatelet therapy, as compared with 1.2% with aspirin monotherapy (hazard ratio, 1.65; 95% confidence interval [CI], 0.80 to 3.36; P = 0.17). The individual risks of myocardial infarction, stroke, stent thrombosis, need for repeat revascularization, major bleeding, and death from any cause did not differ significantly between the two groups. However, in the dual-therapy group as compared with the aspirin-alone group, there was a nonsignificant increase in the composite risk of myocardial infarction, stroke, or death from any cause (hazard ratio, 1.73; 95% CI, 0.99 to 3.00; P = 0.051) and in the composite risk of myocardial infarction, stroke, or death from cardiac causes (hazard ratio, 1.84; 95% CI, 0.99 to 3.45; P = 0.06). CONCLUSIONS The use of dual antiplatelet therapy for a period longer than 12 months in patients who had received drug-eluting stents was not significantly more effective than aspirin monotherapy in reducing the rate of myocardial infarction or death from cardiac causes. These findings should be confirmed or refuted through larger, randomized clinical trials with longer-term follow-up. (ClinicalTrials.gov numbers, NCT00484926 and NCT00590174.)

Objective— The serum level of tumor necrosis factor-α (TNF-α) is in the picomolar range under inflammatory conditions. We investigated whether these picomolar levels of TNF-α directly modulate the functional activities of circulating monocytes. Methods and Results— In THP-1 monocytes treated with TNF-α (1 to 100 pmol/L/30 minutes), cytosolic RhoA small GTPase rapidly translocated to the plasma membrane via functionally active ezrin/radixin/moesin (ERM) complex, a cytoskeletal linker, and subsequent actin polymerization through NF-κB activation. The threonine phosphorylation of ERM was accomplished by the activation of TNF receptor type I (TNFRI) and signaling pathways involving PI3K and an atypical PKC; ie, PKCζ. The TNF-α-treated monocytes (10 pmol/L) displayed more potent and prolonged generation of GTP-bound RhoA in response to secondary stimulation with RhoA-activating monocyte chemoattractant protein-1 (MCP-1). Clearly, human circulating monocytes preconditioned by 10 pmol/L TNF-α augmented MCP-1–mediated chemotaxis and firm adhesion on VCAM-1 and ICAM-1 in vitro and ex vivo. The elevation of serum TNF-α (>5 pmol/L within 16 hours), which was introduced by intraperitoneal injection of mouse-specific TNF-α to C57/BL6 mice, enhanced the number of CD80+ monocytes transmigrating to the JE/MCP-1–injected intraperitoneal space. Conclusions— Picomolar concentrations of TNF-α in the bloodstream may prime the RhoA-dependent activities of circulating monocytes to enhance recruitment to active inflammatory foci.

Aims We investigated the mechanism by which cannabinoid receptors-1 (CB1) and -2 (CB2) modulate inflammatory activities of macrophages. Methods and results Real-time polymerase chain reaction showed the predominant CB2 expression in freshly isolated human monocytes. PMA, a potent inducer of differentiation, upregulated CB1 and increased CB1:CB2 transcript ratio from 1:17.5 to 1:3 in 5 days of culture. Immunohistochemistry showed that CB1 protein was colocalized in CD68- and CD36-positive macrophages in human atheroma. Through selective expression of CB1 or CB2 to thioglycollate-elicited peritoneal macrophages, we proved that CB1 and CB2 mediate opposing influences on the production of reactive oxygen species (ROS). Flow cytometry showed that cannabinoid-induced ROS production by macrophages was CB1-dependent. Immunoblotting assays confirmed that macrophage CB1, not CB2, induced phosphorylation of p38-mitogen-activated protein kinase, which modulated ROS production and the subsequent synthesis of tumour necrosis factor-α and monocyte chemoattractant protein-1. Pull-down assays showed that the Ras family small G protein, Rap1 was activated by CB2. Dominant-negative Rap1 profoundly enhanced CB1-dependent ROS production by macrophages, suggesting CB2 Rap1-dependently inhibits CB1-stimulated ROS production. Conclusion CB1 promotes pro-inflammatory responses of macrophages through ROS production, which is negatively regulated by CB2 through Rap1 activation. Blocking CB1 together with selective activation of CB2 may suppress pro-inflammatory responses of macrophages.

The purpose of this study was to investigate the muscle activities of pectoralis major, upper serratus, lat dorsi, anterior deltoid, rhomboids, infraspinatus, and posterior deltoid using Noraxon 8 channels EMG system during T-ball swing in children with Down syndrome. Five Down syndrome, one healthy children, and one baseball adult player were participated in the study. Down syndrome`s children showed higher muscle activity than one healthy children and one baseball adult player during address to backswing and backswing to impact swing phase. While Down syndrome`s children showed lower muscle activity than one healthy children and one baseball adult player during impact to follow swing phase. The strength of the pectoralis major and upper serratus muscle may help to improve T-ball swing movement during impact to follow swing phase.

This paper deals with a behavior based decentralized control strategy for UAV swarming utilizing the artificial potential functions and the sliding mode control technique. Individual interactions for swarming behavior are modeled using the artificial potential functions. The motion of individual UAV is directed toward the negative gradient of the combined potential. For tracking the reference trajectory of UAV swarming, a swarming center is considered as the object of control. The sliding-mode control technique is adopted to make the proposed swarm control strategy robust with respect to the system uncertainties and the varying mission environment. Numerical simulation is performed to verify the performance of the proposed controller.

The purpose of this study were to investigate the effects of knee brace on the knee muscular neuro-biomechanical variables during the rebound in female highschool basketball players. Twelve high school female () basketball players rebound jumped for maximal vertical height to sufficiently stress the anterior cruciate ligament with and without knee brace. Kinematic data were collected to estimate the knee flexion, abduction angles and jump height. The EMG data from the biceps femoris and rectus femoris was used to estimate the ratio of quadriceps muscle activity. Female athletes with knee brace showed more reduced the knee abduction angle and the ratio of quadriceps muscle activity at foot contact phase than without knee brace. In conclusion, Female athletes with brace reduced knee anterior cruciate ligament loads.

Objectives We investigated the mechanism by which C-reactive protein (CRP) affects pro-inflammatory activities of vascular smooth muscle cells (VSMCs). Methods and results RT-PCR, flow cytometry, and immunoblotting assays consistently showed the expression of FcγRIIa by cultured VSMCs isolated from human coronary arteries. Immunofluorescence staining of human coronary artery plaque showed the co-localization of FcγRIIa with α-actin(+) VSMCs in atheromatous regions. Confocal microscopic image analysis of H2DCFDA-labeled cells showed that CRP induced intracellular reactive oxygen species (ROS) generation by FcγRIIa(+) HEK293T cells. Moreover, CRP time- and dose-dependently generated ROS in VSMCs through FcγRIIa activation. VSMCs mainly express NADPH oxidase 4 isoform (Nox4), the suppression of which using a specific siRNA completely abolished CRP-induced ROS generation by VSMCs. The downregulation of p22phox, a component of the active Nox4 complex, by transfecting with specific decoy oligomers and functional blocking of FcγRIIa not only inhibited the CRP-induced ROS generation but also reduced the degree of AP-1 and NF-κB activation, the production of MCP-1, IL-6, and ET-1, and the apoptotic changes of VSMCs in response to CRP. Conclusions CRP-induced ROS generation by VSMCs, which requires functional activation of FcγRIIa and NADPH oxidase 4, orchestrates pro-inflammatory activities of VSMCs and may eventually promote atherogenesis and plaque rupture.

Background We analyzed the long-term (5-year) outcome of patients treated with stenting for unprotected left main coronary artery (LMCA) stenosis. Methods Between January 1995 and September 2001, 187 consecutive patients with unprotected LMCA stenosis and normal left ventricular function underwent elective stenting. Patients were examined or interviewed after 1, 3 and 6 months, and every 4 months thereafter for the occurrence of major adverse cardiac events (MACE), including death, myocardial infarction (MI) and target lesion revascularization (TLR). Results The procedural success rate was 99.5%. During hospitalization, there were no deaths and only one stent thrombosis. Six-month angiography in 162 patients (follow-up rate, 86.6%) showed a restenosis rate of 33.3%. During 5-year follow-up, there were 13 deaths (6 cardiac, 7 noncardiac) and 2 nonfatal MI. TLRs were required in 36 (20.9%) patients and new lesion revascularizations were required in 13 (5.0%) patients. At 1, 3 and 5 years, the cumulative probabilities for freedom from MACE were 79.9±1.8%, 77.5±2.5% and 77.5±2.5%, respectively. Conclusion The initial favorable outcomes of patients with normal left ventricular function after stenting of unprotected LMCA stenosis were sustained for up to 5 years.

Objectives This study used serial angiographic and intravascular ultrasound (IVUS) analysis to evaluate the long-term efficacy of a nonpolymeric, paclitaxel-eluting stent coating on intimal hyperplasia (IH) 2 years after implantation. Background Long-term efficacy of patients treated with nonpolymeric paclitaxel-eluting stents beyond 1 year has not been well determined. Methods Patients were randomized to placebo or 1 of 2 doses of paclitaxel (low dose, 1.28 μg/mm2; high dose, 3.10 μg/mm2). Complete after-procedure, 6-month, and 2-year angiographic and IVUS data were available in 53 patients (17, 17, and 19 patients, respectively). Results Baseline characteristics were similar among the 3 groups. Although 6-month minimal luminal diameter (MLD) was significantly smaller in placebo compared with paclitaxel-eluting stent patients (1.9 ± 0.6 mm in placebo, 2.5 ± 0.6 mm in low-dose, and 2.6 ± 0.5 mm in high-dose patients, p = 0.004), the MLDs at 2 years were similar (2.3 ± 0.6 mm, 2.3 ± 0.7 mm, and 2.0 ± 0.8 mm, respectively, p = 0.4). Despite a stepwise reduction in IH accumulation at 6 months (23 ± 18 mm3in placebo, 14 ± 11 mm3in low-dose, and 10 ± 12 mm3in high-dose, p =0.017), the increase of IH volume from 6 months to 2 years was significantly greater in the high-dose patients (13 ± 14 mm3in high-dose vs. 4 ± 7 mm3in low-dose patients, p =0.074; and vs. 1 ± 13 mm3in placebo, p =0.019). Late target lesion revascularization (beyond 1 year) was performed in 2 high-dose patients. Conclusions Despite the suppression of IH after non-polymeric paclitaxel-eluting stents compared with bare-metal stents at 6 months, a “late catch-up” IH growth was found in the high-dose patients at 2-year follow-up.

Using serial intravascular ultrasound (IVUS), we identified independent predictors of changes in coronary plaque size in relation to serum lipid levels. One hundred three patients with nonstenotic coronary plaques underwent baseline and 12-month follow-up IVUS studies; 54 patients (52%) were treated with statins. Standard IVUS analyses were performed. Baseline IVUS study showed no statistical differences in mean external elastic membrane, lumen, and plaque/media (PM) area between statin-treated and nonstatin-treated patients. Although there was an increase in mean PM cross-sectional area in nonstatin-treated patients, mean PM cross-sectional area decreased in statin-treated patients (0.11 +/- 0.24 vs -0.20 +/- 0.30 mm(2), p0.001). There was a positive relation between changes in mean PM area and follow-up low-density lipoprotein (LDL) cholesterol level (r = 0.430, p0.001), follow-up total cholesterol level (r = 0.365, p0.001), changes in LDL cholesterol level (r = 0.312, p = 0.002), and changes in total cholesterol level (r = 0.252, p = 0.012). In multivariate linear regression analysis, the only independent predictor of changes in mean PM area was follow-up LDL cholesterol level (r = 0.469, p0.001, 95% confidence interval 0.003 to 0.006). The cut-off value of follow-up LDL cholesterol for no change or a decrease in mean PM area was100 mg/dl at regression analysis. In conclusion, the present 12-month follow-up IVUS study showed that follow-up LDL cholesterol level was the only independent predictor of changes in coronary plaque size. When patients achieved a follow-up LDL cholesterol level100 mg/dl, regression or no progression of coronary plaque was expected. Aggressive lipid-lowering treatments with statins to decrease the follow-up LDL cholesterol level to100 mg/dl are recommended.

The membrane-anchored form of CX3CL1 has been proposed as a novel adhesion protein for leukocytes. This functional property of CX3CL1 is mediated through CX3CR1, a chemokine receptor expressed predominantly on circulating white blood cells. Thus far, it is still uncertain at what stage of the trafficking process CX3CR1 becomes importantly involved and how the CX3CR1-dependent adhesion of leukocytes is regulated during inflammation. The objective of this study was to examine the functional effects of chemokine stimulation on CX3CR1-mediated adhesion of human monocytes. Consistent with previous reports, our data indicate that the activity of CX3CR1 on resting monocytes is sufficient to mediate cell adhesion to CX3CL1. However, the basal, nonstimulated adhesion activity is low, and we hypothesized that like the integrins, CX3CR1 may require a preceding activation step to trigger firm leukocyte adhesion. Compatible with this hypothesis, stimulation of monocytes with MCP-1 significantly increased their adhesion to immobilized CX3CL1, under both static and physiological flow conditions. The increase of the adhesion activity was mediated through CCR2-dependent signaling and obligatory activation of the p38 MAPK pathway. Stimulation with MCP-1 also induced a rapid increase of CX3CR1 protein on the cell surface. Inhibition of the p38 MAPK pathway prevented this increase of CX3CR1 surface expression and blunted the effect of MCP-1 on cell adhesion, indicating a causal link between receptor surface density and adhesion activity. Together, our data suggest that a chemokine signal is required for firm CX3CR1-dependent adhesion and demonstrate that CCR2 is an important regulator of CX3CL1-dependent leukocyte adhesion.