TXA2 synthesis and COX1-independent platelet reactivity in aspirin-treated patients soon after acute cerebral stroke or transient ischaemic attack

Introduction

The pharmacological target of aspirin is the inhibition of cyclooxygenase-1 (COX1) and thromboxane-A₂ (TX) synthesis. Very few data are available on TX assessment in patients with stroke. We studied platelet TX synthesis, COX1-independent platelet reactivity, the influence of platelet–erythrocyte interactions and the potential association between platelet responses and the severity of stroke, evaluated with a clinical score (NIHSS).

Material and Methods

We examined 157 aspirin-treated patients with acute stroke or TIA, 128 aspirin-free and 15 aspirin-treated healthy subjects (HS). Collagen-induced TX, platelet recruitment in whole blood and platelets ± erythrocytes (haematocrit 40%) were assessed in patients on daily-aspirin within three days from onset. Arachidonic-acid-, ADP-, thrombin-receptor activating peptide TRAP-, and collagen-induced aggregation were also evaluated.

Results

Partial TX inhibition (< 95% inhibition vs aspirin-free controls) was observed in 13% of patients. This was associated with marked increases in COX1-dependent responses (arachidonic-acid- and collagen-induced aggregation and platelet recruitment; P < 0.0001) but not with differences in ADP- or TRAP-induced aggregation. Partial TX inhibition was independently associated with severe stroke (NIHSS ≥ 12) at both admission (P < 0.05) and discharge (P < 0.05). Among patients with fully blocked TX, those with elevated COX1-independent platelet reactivity (mean + 2SD of aspirin-treated HS) were most likely to suffer severe stroke (P < 0.05). Platelet–erythrocyte interactions enhanced platelet reactivity in these patients by COX1-dependent and -independent mechanisms (P < 0.0001).

Conclusions

TX inhibition by aspirin varied across patients. Partial TX inhibition and COX1-independent platelet hyperfunction were associated with more-severe stroke.     

Low molecular weight heparin-induced increase in chylomicron-remnants clearance,is associated with decreased plasma TNF-α level and increased hepatic lipase activity

Objective

The acute effect of heparin on lipoprotein clearance is well characterized. Yet, the effect of prolonged low-molecular-weight-heparin (LMWH) administration on post-prandial lipemia has remained so far unexplored. Recent reports suggest that LMWH could modify lipid and carbohydrate metabolism by diminishing TNFα-mediated inflammatory response. This, together with the known negative effect of TNF-α on insulin sensitivity, prompted us to hypothesize that LMWH would favorably affect post-prandial lipoprotein disposal.

Methods

Twenty four patients were given a vitamin A-fat loading meal at the end of 6-week enoxaparin treatment and after 3-month washout period. Post-prandial lipemia was assessed by measuring retinyl-palmitate (RP) during 8 hours following the meal. Insulin sensitivity index (ISI), plasma lipolytic activity and plasma TNF-α were measured.

Results

Enoxaparin did not impact fasting plasma lipids and lipoproteins levels. Enoxaparin increased RP clearance in the chylomicron remnant (CMR) fraction by 32% (P < 0.01). Additionally, enoxaparin decreased plasma TNF-α by 22% (P < 0.01), increased hepatic lipase (HL) activity by 81% (P < 0.01), along with a 2-fold increase in ISI (P < 0.01). The decrease in CMR correlated with the reduction in TNFα and the increase in ISI and HL activity (R = 0.48, -0.68, - 0.56, respectively, p < 0.05). Significant correlations were also found between the reduction in TNFα and both the increase in ISI and increase in HL activity (R = - 0.43, -0.54, respectively, P < 0.05).

Conclusions

The association of the effect on post-prandial metabolism, plasma TNFα level and HL activity during prolonged enoxaparin treatment may support the hypothesis that the beneficial outcome of enoxaparin may possibly be linked to anti-inflammatory and lipase-potentiating impact.     

Probucol and cilostazol exert a combinatorial anti-atherogenic effect in cholesterol-fed rabbits

Introduction

Probucol (PB) and cilostazol (CZ) both exhibit anti-atherogenic effects. However, their combinatorial effects are unclear. This study was designed to investigate their combinatorial anti-atherogenic effect in cholesterol-fed rabbits.

Materials and Methods

Rabbits were fed a cholesterol diet with PB or CZ alone or both PB and CZ for 16 weeks. The plasma levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, C-reactive protein, superoxide dismutase, malondialdehyde, and nitric oxide (NO) were measured. The aortic atherosclerotic lesions were grossly and microscopically evaluated. Additionally, in vitro experiments were conducted using human umbilical vein endothelial cells.

Results and Conclusion

We found that the PB group and the PB + CZ group exhibited a reduction in the lesion areas (70% in the PB + CZ group, 56% in the PB group) compared with the vehicle group. However, although PB alone and PB + CZ led to a reduction in the lesion size, the histological analysis revealed that only PB + CZ significantly decreased the macrophage accumulation and smooth muscle cell proliferation in the lesions compared with the vehicle group. The plasma levels of total cholesterol in the PB + CZ group were decreased compared with the vehicle group, Moreover, PB + CZ exerted obvious anti-oxidant and anti-inflammatory effects. Interestingly, the PB + CZ treatment led to a marked increase in the levels of plasma NO. The in vitro experiments showed that the combinatorial treatment up-regulated the levels of NO and protein S-nitrosylation in endothelial cells treated with oxidized LDL. In summary, these results suggest that PB and CZ exert combinatorial anti-atherogenic effects.     

Combination of antithrombin and recombinant thrombomodulin modulates neutrophil cell-death and decreases circulating DAMPs levels in endotoxemic rats

Introduction

The activation of coagulation is recognized as a universal event in severe sepsis. Both antithrombin and thrombomodulin play pivotal roles as suppressors of coagulation. Since the levels of both anticoagulants decrease significantly, we hypothesized that a combination therapy would be beneficial.

Methods

A sepsis model was established using the intravenous infusion of lipopolysaccharide (LPS). Either 125 IU/kg of antithrombin, 0.25 mg/kg of recombinant thrombomodulin, or a combination of both agents was injected immediately after LPS infusion (n = 7 each), while only a physiological saline was injected in the control group (n = 7). Blood samples were obtained at eight hours after LPS infusion, and organ damage markers and the plasma levels of damage-associated molecular patterns (DAMPs), such as histone H3 and cell-free DNA (cf-DNA), were measured. In another series, the leukocytes harvested from normal rats were cultured in plasma obtained from each group (n = 7). Eight hours later, the leukocytes were stained with green fluorescent protein, Annexin V and 7-AAD, and the proportion of alive + apoptic/necrotic cells was calculated.

Results

Organ damage markers such as ALT and BUN were maintained best in the combination group (P < 0.05). The circulating levels of histone H3 and cf-DNA were both significantly lower in the combination therapy group (P < 0.01, 0.05, respectively). The proportion of alive + apoptic/necrotic cells was significantly higher in the combination therapy group (P < 0.05).

Conclusion

The coadministration of antithrombin and recombinant thrombomodulin can modulate cell death and decrease the circulating levels of histone H3 and cf-DNA, leading to protection against organ damage in a rat model of sepsis     

Suppression of angiogenic response in local vein wall is associated with reduced thrombus resolution

Introduction

The formation of new vascular channels within and around venous thrombus contributes to its resolution. Neovascularisation arising from the surrounding vein may facilitate this process. Treatment of cancer patients with anti-angiogenic agents can lead to increased incidence of venous thromboembolic events, but the effect of these agents on the processes that govern thrombus resolution are unclear. The aim of this study was to determine the effect of anti-angiogenic treatment with 2-methoxyestradiol (2ME) on (i) angiogenic response in the thrombosed vein and (ii) venous thrombus resolution.

Materials and methods

Venous thrombus was induced in the inferior vena cava (IVC) of 36 adult male BALB/C mice. Thrombosed mice received either the anti-angiogenic agent, 2ME (150 mg/kg/day, i/p), or vehicle control (n = 18/group). In the thrombosed IVC of both groups: hypoxia-inducible factor (HIF) 1α, and its angiogenic targets, vascular endothelial growth factor (VEGF) and placental growth factor (PLGF), were quantified using enzyme-linked immunosorbent assays at days 1 and 10 post-thrombus induction (n = 6/group); and inflammatory cell content, cell proliferation, and vein recanalisation were quantified using immunostaining and image analysis at day 10 (n = 6/group).

Results

In the IVC of mice treated with 2ME compared with control: HIF1α (P < 0.005 and P < 0.02), VEGF (P < 0.005 and P < 0.02), and PLGF levels (P < 0.01 and P < 0.001) were reduced at days 1 and 10 post-thrombus induction respectively, and macrophage content (P < 0.005), neutrophil content (P < 0.01), vein recanalistion (P < 0.05), and thrombus resolution (P < 0.001) were also reduced at day 10.

Conclusions

Anti-angiogenic treatment with 2ME supressed the HIF1-mediated angiogenic drive in local vein wall and attenuated venous thrombus resolution. The potential pro-thrombotic effect of anti-angiogenic agents should be carefully considered when managing venous thromboembolic events in cancer patients.     

Residual perfusion defects in patients with pulmonary embolism are related to impaired fibrinolytic capacity

Background

Few studies investigated the relationship between fibrinolysis abnormalities and residual pulmonary perfusion defects after acute pulmonary embolism (PE).

Objective

To assess the fibrinolytic profile in patients with prior PE in relation to the extent of scintigraphically detectable residual perfusion abnormalities.

Patients and methods

We studied 71 consecutive patients with a prior episode of PE, who were examined after one year of the incident embolic event, and at least one month after anticoagulation withdrawal. They underwent lung scintigraphy to assess the recovery of pulmonary perfusion, echocardiography and chest radiography to look for signs of pulmonary hypertension. Clot formation and lysis were evaluated by two turbidimetric methods: Clot and Lysis Assay and Clot Lysis Time. We also measured the in vitro plasmin-mediated lysis of fibrin from purified fibrinogen, and the circulating levels of fibrinolytic inhibitors. The sample was split in two categories based on the extent of residual perfusion defects: < 10% (n = 53), ≥ 10% (n = 18).

Results

Patients with perfusion defects > 10% had significantly longer lysis time (p < 0.05), and higher levels of plasminogen activator inhibitor-1 (p < 0.01) than those with perfusion defects < 10%. The time interval between symptoms onset and PE diagnosis (time-to-diagnosis) was significantly longer in patients with perfusion defects > 10% than in the others (p = 0.005). In multivariate logistic regression, both lysis time and time-to-diagnosis were independently associated with perfusion defects > 10% (p < 0.001). None of the sampled patients had echocardiographic or radiologic signs of pulmonary hypertension.

Conclusion

Prolonged time-to-diagnosis and fibrinolysis imbalance are independent predictors of incomplete perfusion recovery after acute PE.     

Who are at risk for thromboembolism after arthroplasty? A systematic review and meta-analysis

Background

Thromboembolism, including deep venous thrombosis and pulmonary embolism, is a grave threat to patients undergoing total joint replacement. Using a systematic review and meta-analysis we asked whether gene mutations or polymorphisms could be risk factors for thrombosis after arthroplasty.

Methods

We performed a comprehensive search of Medline, PubMed, Embase, Cochrane databases, China National Knowledge Infrastructure (CNKI), and Google Scholar, and identified 19 studies detailing genetic investigations of patients with thromboembolism following joint replacement.

Results

Our meta-analyses included 5149 patients who underwent arthroplasty surgery. Significant associations with venous thromboembolism were identified for factor G1691A (odds ratio (OR) 1.41, 95% confidence interval (CI) 1.03 - 1.94, p = 0.03), prothrombin G20210A (OR 2.16, 95% CI, 1.27- 3.69, p = 0.005), and MTHFR/C677T/TT (OR 2.36, 95% CI 1.03 - 5.42, p = 0.04) in Caucasian populations. No significant gene mutation was identified in Asian populations.

Conclusion

This study suggests a way to identify patients scheduled for arthroplasty who are at higher risk of thrombosis, enabling individualized treatment.     

Serum soluble CD40 Ligand levels are associated with severity and mortality of brain trauma injury patients

Background

Serum soluble CD40 Ligand (sCD40L) levels, which exhibit prothrombotic and proinflammatory properties, have not been studied in patients with traumatic brain injury (TBI). Thus, the objective of this study was to determine whether serum sCD40L levels are associated with severity and mortality in patients with severe TBI.

Methods

This was a prospective, observational and multicenter study carried out in six Spanish Intensive Care Units. Patients with severe TBI defined as Glasgow Coma Scale (GCS) lower than 9 were included, while those with Injury Severity Score (ISS) in non-cranial aspects higher than 9 were excluded. Serum levels of sCD40L were measured on the day of TBI. Endpoint was established in 30-day mortality.

Results

We found higher serum sCD40L levels (P < 0.001) in non-surviving TBI patients (N = 27) than in survivor ones (N = 73). Logistic regression analysis showed that serum sCD40L levels were associated with 30-day mortality (OR = 1.58; 95% CI = 1.12-2.21; P = 0.008) controlling for APACHE-II score and computer tomography findings. The area under the curve (AUC) for serum sCD40L levels as predictor of 30-day mortality was 0.79 (95% CI = 0.70-0.86; P < 0.001). Survival analysis showed that patients with serum sCD40L levels higher than 2.11 ng/mL presented increased 30-day mortality than patients with lower levels (Hazard ratio = 9.0; 95% CI = 4.25-19.27; P < 0.001). We found an association between serum sCD40L levels and APACHE-II (rho = 0.33; P = 0.001), and GCS score (rho = -0.21; P = 0.04).

Conclusions

To our knowledge, this is the first study reporting data on serum sCD40L levels in patients with severe TBI. The most relevant and newer findings of our study are that serum sCD40L levels in non-surviving patients with severe TBI are higher than in surviving ones, and that there are an association between serum sCD40L levels and TBI severity and mortality.     

Increased intracranial pressure is associated with the development of acute lung injury following severe traumatic brain injury

Objective

This study investigated the relationship among intracranial pressure (ICP), the development of acute lung injury (ALI) and systemic inflammatory response syndrome (SIRS) following a severe traumatic brain injury (TBI).

Methods

Post-traumatic ICP was continuously monitored for the first week following injury in a series of consecutive patients with isolated severe TBI. The initial ICP and the duration of intracranial hypertension (ICH) were calculated. The risk factors associated with the development of ALI and SIRS were evaluated.

Results

Of the 86 patients enrolled, 22 patients developed ALI and 52 patients developed SIRS during the observation period. The patients with ALI presented with a significantly higher initial ICP (31.3 ± 7.8 mmHg vs. 23.0 ± 8.8 mmHg, p < 0.001) and a longer duration of ICH (16.8 ± 6.5 h vs. 11.9 ± 6.0 h, p = 0.002) than those without ALI. The incidence of both ALI and SIRS increased with increasing initial ICP, and the presence of SIRS was associated with a fourfold increase in the risk of developing ALI (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.2–13.0).

Conclusions

Increased ICP is associated with increased risks of developing ALI and SIRS following severe TBI. Future studies designed to verify the causative relationship between increased ICP and the systemic responses are warranted.     

A systematic review and meta-analysis of mindfulness-based stress reduction for the fibromyalgia syndrome

Objectives

This paper presents a systematic review and meta-analysis of the effectiveness of mindfulness-based stress reduction (MBSR) for FMS.

Methods

The PubMed/MEDLINE, Cochrane Library, EMBASE, PsychINFO and CAMBASE databases were screened in September 2013 to identify randomized and non-randomized controlled trials comparing MBSR to control interventions. Major outcome measures were quality of life and pain; secondary outcomes included sleep quality, fatigue, depression and safety. Standardized mean differences and 95% confidence intervals were calculated.

Results

Six trials were located with a total of 674 FMS patients. Analyses revealed low quality evidence for short-term improvement of quality of life (SMD = − 0.35; 95% CI − 0.57 to − 0.12; P = 0.002) and pain (SMD = − 0.23; 95% CI − 0.46 to − 0.01; P = 0.04) after MBSR, when compared to usual care; and for short-term improvement of quality of life (SMD = − 0.32; 95% CI − 0.59 to − 0.04; P = 0.02) and pain (SMD = − 0.44; 95% CI − 0.73 to − 0.16; P = 0.002) after MBSR, when compared to active control interventions. Effects were not robust against bias. No evidence was further found for secondary outcomes or long-term effects of MBSR. Safety data were not reported in any trial.

Conclusions

This systematic review found that MBSR might be a useful approach for FMS patients. According to the quality of evidence only a weak recommendation for MBSR can be made at this point. Further high quality RCTs are required for a conclusive judgment of its effects.     

The influence of cytochrome oxidase CYP2A6, CYP2B6, and CYP2C9 polymorphisms on the plasma concentrations of valproic acid in epileptic patients

Objectives

To investigate influences of the functional polymorphisms of Cytochrome P450 isozymes 2A6 (CYP2A6), 2B6 (CYP2B6), and 2C9 (CYP2C9) on pharmacokinetics of VPA in vivo.

Patients and methods

In the study, we analyzed the genotypes of CYP2A6, CYP2B6, and CYP2C9 and their contribution to the steady-state standardized plasma VPA concentrations in 179 subjects with epilepsy of a Northern Han Chinese population. The genotypes were detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results

The subjects with one or two variant CYP2A6*4 alleles showed higher mean plasma VPA concentrations compared with non-*4 alleles [(3.4 ± 0.4) μg kg ml⁻¹ mg⁻¹ vs. (3.6 ± 0.4) μg kg ml⁻¹ mg⁻¹, p = 0.0055]. A significant difference [one-way ANOVA (p = 0.0203)] was also found between mean plasma VPA concentrations and the CYP2B6 genotypes. In addition, subjects with the heterozygous genotype CYP2C9*3 had higher mean plasma VPA concentrations than did those subjects with the wild-type genotype [(3.9 ± 0.4) μg kg ml⁻¹ mg⁻¹ vs. (3.4 ± 0.4) μg kg ml⁻¹ mg⁻¹, p = 0.0001].

Conclusion

The presently evaluated variant alleles in the CYP2A6, CYP2B6, and CYP2C9 genes may explain part of the substantial variability in VPA pharmacokinetics between different subjects.     

Relationships between IGF-1, schizophrenia,and treatment of metabolic syndrome

Objectives

The use of atypical antipsychotic drugs in patients with psychiatric illness may result in dyslipidemia, hypertension, glucose intolerance, and abdominal obesity, which are together referred to as metabolic syndrome (MS). To investigate any correlations among insulin-like growth factor-1 (IGF-1), schizophrenia, and MS, we examined the metabolic profiles of patients with schizophrenia taking atypical antipsychotics.

Design

Patients with schizophrenia, their siblings, and controls participated in this study (N = 50 in each group). The Structured Clinical Interview for DSM-IV Axis 1 Disorders (SCID I) and the Brief Psychiatric Rating Scale (BPRS) were administered to patients, and SCID I was administered to patients' siblings. We drew blood to measure IGF-1 levels and to determine the metabolic profiles of all participants; we also conducted anthropometric measurements.

Results

There were no significant differences in IGF-1 levels between groups. By comparing IGF-1 levels with MS-related parameters, we found that IGF-1 levels were negatively correlated with triglyceride levels in the control group, and positively correlated with HDL levels in the patient group (Pearson's correlation: r = −0.291, P = 0.04, and r = 0.328, P = 0.02, respectively). Compared to their siblings, patients with schizophrenia had a significantly different body mass index, waist circumference, and insulin resistance, and showed a trend toward a difference in glucose levels (ANOVA: P = 0.004, P < 0.0001, P = 0.004, P = 0.072, respectively).

Conclusion

A correlation between IGF-1 and MS may significantly influence future therapeutic strategies for MS. In order to determine the role of IGF-1 in schizophrenia, comprehensive longitudinal studies with first-episode drug-naive patients are needed.     

Prevalence of depressive symptoms and predictors of treatment among U.S. adults from 2005 to 2010

Objectives

To determine nationally representative estimates of the prevalence of depressive symptoms and factors associated with treatment among those with moderate to severe symptoms.

Methods

A cross-sectional, retrospective analysis of adults age ≥ 18 years in the 2005–2010 National Health and Nutrition Examination Survey data who responded to the Patient Health Questionnaire (PHQ-9) was conducted (n= 13,320). Depressive symptoms and severity were defined by PHQ-9 scores. Depression treatment was defined as either receiving antidepressants or seeing a mental health professional. Multivariable logistic regression analyses using population weights identified factors associated with having depressive symptoms and receipt of any treatment.

Results

The prevalence of depressive symptoms increased from 20.92% to 25.66% over 6 years. Among patients with moderate to severe depression, 38.66% received treatment. Multivariable analyses found that being female, other Hispanic, younger age, having certain chronic comorbidities or previous hospitalization, no health insurance and in poverty status were associated with having depressive symptoms (P< .05). Among patients with moderate to severe depression, being female, white, younger age, having comorbidities (arthritis and hypertension) or previous hospitalization were associated with receipt of treatment (P< .05).

Conclusions

The prevalence of depressive symptoms is high, and only a small portion of patients with moderate to severe depression received treatments. Treatment disparities exist and need improvement.     

Procoagulant tissue factor activity on microparticles is associated with disease severity and bacteremia in febrile urinary tract infections

Introduction

Inhibition of tissue factor, the primary initiator of coagulation in sepsis, attenuates morbidity in primates infused with Escherichia coli. In a human endotoxemia model, microparticles expressing procoagulant TF (MP-TF) are released in blood concurrently with markers of inflammation and coagulation. We investigated whether the release of MP-TF into blood is accompanied by procoagulant and inflammatory changes in patients with E. coli urinary tract infection.

Materials and methods

In a multicenter cohort study, we determined clinical disease severity using APACHE II scores and measured plasma MP-TF activity, TAT, sE-selectin, sVCAM-1, procalcitonin and monocyte count in blood of 215 patients with community-acquired febrile E. coli urinary tract infections.

Results

Plasma MP-TF activity on admission corresponded with clinical disease severity (APACHE II score; P = 0.006) and correlated significantly but weakly with plasma markers of disease severity (sE-selectin, sVCAM-1, procalcitonin). Additionally, median plasma MP-TF activity was higher in patients than in healthy controls (197 vs. 79 fM Xa/min; P < 0.0001), and highest in bacteremic patients (325 fM Xa/min). MP-TF activity showed a weak inverse correlation with monocyte count (r_s -0.22; P = 0.016) and a weak correlation with TAT (r_s 0.23, P = 0.017). After 3 days of antibiotic treatment, upon resolution of the infection, plasma MP-TF activity and TAT concentrations declined.

Conclusions

Microparticle-associated procoagulant tissue factor activity is related to disease severity and bacteremia in febrile E. coli UTI patients and may contribute to the prothrombotic state in gram-negative sepsis.     

Direct microscopic monitoring of initial and dynamic clot lysis using plasmin or rt-PA in an in vitro flow system

Introduction

Plasmin is a direct-acting thrombolytic agent with a favorable safety profile upon intra-arterial delivery in pre-clinical and phase I studies. However, the thrombolytic efficacy of plasmin, relative to that of rt-PA, remains to be established. We have compared the dynamics of clot lysis with plasmin or rt-PA in an in vitro perfusion system, in which thrombolytic agent is administered locally, allowed to induce lysis for short intervals, then washed with plasma in a re-circulation circuit.

Materials and Methods

Whole blood human clots were prepared in observation chambers, exposed to plasmin or rt-PA at equimolar concentrations (1.2/1.0, 1.8/1.5 and 2.4/2.0 mg/ml) for measured intervals of time, followed by perfusion with human plasma. Clot size was monitored by digital analysis of sequential photographs obtained through an optical microscope.

Results

Plasma perfusion after incubation with thrombolytic agent rapidly removed superficial clot fragments. This initial decrease in clot size was greater with plasmin than with rt-PA when tested at the highest concentrations of agent (0.63 ± 0.11 vs. 0.30 ± 0.11, p = 0.001 for clots with non-cross-linked fibrin and 0.53 ± 0.15 vs. 0.14 ± 0.15, p = 0.02, for clots with cross-linked-fibrin). Subsequent clot lysis during plasma flow was greater after prior incubation with rt-PA. Longer incubation times of plasmin resulted in larger portions of the clot being washed free. Repeated plasmin incubations and plasma perfusions of a clot successfully induced stepwise reductions in clot size.

Conclusions

Initial clot lysis is greater with direct exposure using plasmin than rt-PA. During washout and circulation with plasma, rt-PA induced continued clot lysis, while plasmin lysis was curtailed, presumably because of plasmin inhibition.     

Distinctive correlations of sociotropy and autonomy with working models of the self and other

Background

Beck's cognitive theory of depression postulates personality vulnerability factors termed sociotropy and autonomy, which are accompanied by characteristic interpersonal styles. Meanwhile, Bartholomew contends that negative working models of the self and other built through insecure attachment relationships are externalized as distinctive interpersonal styles. The present study examined the relationships of sociotropy and autonomy with the self- and other-models, and attempted to promote understanding of the two personality traits from an attachment perspective.

Methods

The subjects were 510 healthy Japanese medical students or hospital staffs. Sociotropy and autonomy were assessed by the Sociotropy–Autonomy Scale, and working models of the self and other were evaluated by the Relationship Scales Questionnaire.

Results

The sociotropy score was correlated negatively with the self-model score (β = −0.52, p < 0.001) and positively with the other-model score (β = 0.11, p < 0.01). The autonomy score was correlated positively with the self-model score (β = 0.10, p < 0.05) and negatively with the other-model score (β = −0.33, p < 0.001).

Limitations

It may be risky to generalize the present results to general populations or other ethnic groups.

Conclusions

The present study suggests that both sociotropy and autonomy are associated with attachment insecurity, but the marked difference in their correlation patterns with the self- and other-models leads to the distinctive interpersonal styles of the two personality orientations.     

Safety and Efficacy of Edoxaban,an Oral Factor Xa Inhibitor,Versus Enoxaparin for Thromboprophylaxis After Total Knee Arthroplasty: The STARS E-3 Trial

Introduction

This phase 3 trial compared the safety and efficacy of edoxaban, an oral direct factor Xa inhibitor, with enoxaparin sodium (enoxaparin) for thromboprophylaxis after total knee arthroplasty (TKA) in patients in Japan and Taiwan.

Materials and methods

In this randomized, double-blind, double-dummy study, patients received oral edoxaban 30 mg once daily beginning 6 to 24 hours postsurgery or enoxaparin 2000 IU (equivalent to 20 mg) subcutaneously twice daily beginning 24 to 36 hours postsurgery for 11 to 14 days. The primary efficacy endpoint was the composite of symptomatic pulmonary embolism and symptomatic and asymptomatic deep vein thrombosis. Safety endpoints included the incidence of major bleeding, clinically relevant non-major (CRNM) bleeding, major bleeding or CRNM bleeding, all bleeding events, adverse events, and adverse drug reactions.

Results

Of 716 patients enrolled, 360 and 356 were randomized to receive edoxaban or enoxaparin, respectively. The primary efficacy outcome occurred in 22/299 (7.4%) and 41/295 (13.9%) patients in the edoxaban and enoxaparin groups, respectively (relative risk reduction = 46.8%), indicating non-inferiority (P < 0.001) and superiority (P = 0.010) of edoxaban versus enoxaparin. In the edoxaban and enoxaparin groups, major bleeding occurred in 4/354 (1.1%) versus 1/349 (0.3%) patients (P = 0.373); major or CRNM bleeding occurred in 22/354 (6.2%) versus 13/349 (3.7%) patients (P = 0.129), respectively.

Conclusions

Edoxaban 30 mg once daily was more effective for thromboprophylaxis than subcutaneous enoxaparin 2000 IU twice daily following TKA and demonstrated a similar incidence of bleeding events.     

Effects of vaginal delivery,cesarean section and exposure to labor on endothelial function of pregnant women

Introduction

This study was undertaken to assess the influence of labor and cesarean section on endothelial function.

Materials and Methods

Flow-mediated vasodilatation (FMD) was measured before and after delivery for an assessment of endothelial function in three groups: (1) the Vaginal delivery group (with spontaneous labor or induction of labor, n = 48), (2) the Elective C/S group (with a cesarean planned, n = 20), and (3) the C/S after FP group (scheduled for vaginal delivery but required to have an emergency cesarean section because of failure in progress, n = 11).

Results

There were statistically significant changes between the antepartum and postpartum FMD values in the Vaginal delivery group and the Elective C/S group but not in the C/S after FP group (P < 0.001, P = 0.023 and P = 0.22 respectively).

Conclusions

These observations suggest that labor may enhance endothelial function and that cesarean section may impair endothelial function.     

Electrophysiological intermediate biomarkers for oxidative stress in schizophrenia

Objective

Diverse electrophysiological abnormalities have been associated with schizophrenia, but the underlying causes remain elusive. We tested whether the altered oxidative stress in schizophrenia contributes to the electrophysiological abnormalities.

Methods

We used an auditory oddball task to measure mismatch negativity (MMN) and gamma band response on 29 schizophrenia patients and 25 normal controls. Oxidative stress was assessed by monomeric glutathione (GSH, reduced form) and glutathione disulfide (GSSG, oxidized form).

Results

Patients had reduced MMN (p = 0.015) and reduced power of gamma band responses at 21–40 Hz and 41–85 Hz (all p < 0.001). GSH was significantly lower (p < 0.001) while %GSSG was higher (p = 0.023) in patients compared with controls. MMN was correlated with GSH in controls; while 21–40 Hz responses were correlated with GSH in patients. Lower GSH and higher GSSG levels were associated with low community functioning (p = 0.018). Multivariate mediation modeling showed that gamma band at 21–40 Hz was a significant mediator for GSH effect on community functions.

Conclusions

High beta/low gamma range (21–40 Hz) responses may be an intermediate biomarker indexing oxidative stress and its effect on clinical functions.

Significance

Electrophysiological abnormalities and associated clinical functional changes may in part be associated with heightened oxidative stress in schizophrenia.     

Longitudinal course of insomnia: Age-related differences in subjective sleepiness and vigilance performance in a population-based sample

Objective

The present study utilized a population-based sample investigating the following aims: (1) compare the longitudinal course of insomnia in middle-aged and older adults and (2) examine age-related differences on subjective complaint and objective performance in middle-aged and older adults based on the course of insomnia.

Methods

1657 middle-aged adults (48.16% male, mean age = 55.35 ± 4.03 years) and 405 older adults (48.40% male, mean age = 70.13 ± 3.88 years) from the Korean Genome and Epidemiology Study (KoGES) were classified into 4 groups — no insomnia (NI), single episode insomnia (SEI), remitted persistent insomnia (PI-R), and ongoing persistent insomnia (PI-O) based on their course of insomnia over 5 time points spaced two years apart. Their performance on the psychomotor vigilance task (PVT) and subjective daytime sleepiness were compared across different insomnia groups, and the results were compared between middle-aged adults and older adults.

Results

Analysis of covariance indicated that subjective daytime sleepiness was significantly different across the insomnia groups in middle-aged adults based on insomnia group (P = < .0001), but, did not affect objective vigilance performance. In contrast, older adults displayed significantly different PVT response time, but not daytime sleepiness, based on insomnia group (P = 0.03).

Conclusion

Insomnia impacts psychomotor performance and subjective sleepiness differently, based on age group. There may be underlying processes associated with the aging that amplifies the impact of insomnia on vigilance performance, yet lessens perceived sleepiness in older adults.