von Willebrand factor binding to platelet glycoprotein Ib-IX-V stimulates the assembly of an α-actinin-based signaling complex

Summary. Background: Pathological shear stress induces platelet aggregation that is dependent on von Willebrand factor (VWF) binding to glycoprotein (Gp)Ib‐IX‐V and phosphatidylinositol 3‐kinase activation. We tested the hypothesis that pathological shear stress stimulates phosphatidylinositol 3,4,5‐trisphosphate (PIP₃) synthesis by directing the assembly of a molecular signaling complex that includes class IA phosphatidylinositol 3‐kinase (PI 3‐KIA). Methods: Platelets were subjected to 120 dynes cm^?2 shear stress in a cone‐plate viscometer. Resting and sheared platelets were lyzed, immunoprecipitations of PI 3‐KIA performed, or lipids extracted for PIP₃ measurements. α‐Actinin was incubated with phosphatidylinositol 4,5‐bisphosphate (PIP₂), immunoprecipitated, and used as a substrate for in vitro PI 3‐KIA activity. Results: Pathological shear stress induces biphasic PIP₃ production. In resting platelets, PI 3‐KIA associates with α‐actinin and PIP₂. After exposure to shear stress, α‐actinin and PIP₂ rapidly disassociate from PI 3‐KIA. PI 3‐KIA then gradually re‐associates with PIP₂ and α‐actinin, and this complex becomes linked to GpIbα through the cytoskeleton. PIP₃ production and the observed changes in the association between α‐actinin, PIP₂, and PI 3‐KIA are inhibited when VWF binding to GpIbα is blocked. In a cell‐free system, α‐actinin binds PIP₂ and when the α‐actinin–PIP₂ complex is added to platelet PI 3‐KIA, PIP₃ production is stimulated. Conclusions: These results suggest that pathological shear‐induced VWF binding to GpIb‐IX‐V stimulates PIP₃ production through the assembly of an α‐actinin‐based complex that colocalizes PI 3‐KIA with substrate PIP₂.     

When stress is mental illness: A study of anxiety and depression in employees who use occupational stress counselling schemes

A previous study found that 86 per cent of employees (n = 111) who experience stress in the workplace and sought help from their workplace counselling schemes (Employee Assistance Programmes) had serious mental health problems, but the low participation rate (24 per cent) restricted generalizability and the measure used [General Health Questionnaire (GHQ‐12)] did not allow diagnosis. The present study (n = 58) improved the participation rate to 35 per cent and used a different version of the original measure (GHQ‐28) that allowed diagnostic differentiation as well as validation of the original findings. This new study found almost exactly the same high levels of mental health problems existed (86 per cent) in employees who remained at their work and that participants had higher rates of anxiety than depression. This finding is at variance with the usual co‐morbid presentation of anxiety and depression found in community based mental health services and suggests that depression may be an important differentiating factor between those who can remain at work and use counselling and those who cannot. There are implications for those who provide mental health services. The results of this study further reinforce the suggestion that workplace stress may be yet another name for common mental health problems that require professional help and treatment. Copyright © 2005 John Wiley & Sons, Ltd.     

持续成骨力值对犬骨盆弓状线部骨折愈合的影响

[目的]探讨持续顺应生理力线的压应力对犬骨盆弓状线部骨折愈合的影响.[方法]选用10只成年杂种家犬,双侧髋臼臼顶上方1.5 cm处横形截骨,分别采用ATMFS（骨盆髋臼三维记忆内固定系统）前柱固定器和5孔重建钢板内固定,于术后2、4、6、8、12周处死动物取材,行HE染色、Masson三色法染色组织学检查,图像分析新骨形成积分光密度值,研究不同应力作用模式下的骨盆骨折愈合情况.[结果]ATMFS侧软骨组织形成,骨皮质、骨小梁及胶原纤维成熟时间明显早于钢板侧,术后6、8、12周,两侧骨折端新骨生成面积之间存在显著性差异（P＜0.05）.[结论]ATMFS固定后于骨折端产生的持续顺应生理力线的压应力能够刺激骨折端成骨细胞的形成及骨胶原的合成与分泌,促进骨折早期愈合.     

Evaluating anxiety in patients attending optometric practice

Although anxiety is a well-established obstacle to the delivery of effective health care, there have been no attempts to measure it in the optometric consulting room. In this paper, we introduce physiological and psychological techniques that may be used to evaluate anxiety and arousal in the consulting room and present data from a small group of patients attending for a routine eye examination. Specifically, arousal was assessed before, during, and after the examination by measuring skin conductance in five patients. Anxiety was evaluated using the State-Trait Anxiety Inventory. Our data confirm the ability of these techniques to quantify arousal and anxiety in the optometric consulting room and reveal a previously unknown but important facet of the eye examination. We conclude that these techniques are suitable for use in further experimental work and may be used to identify factors capable of reducing anxiety in the optometric consulting room.     

Differential etiology of posttraumatic stress disorder with conduct disorder and major depression in male veterans.

BACKGROUND: Epidemiologic studies reveal that posttraumatic stress disorder (PTSD) is highly comorbid with both conduct disorder and major depression in men. The genetic and environmental etiology of this comorbidity has not been examined. METHODS: Data were analyzed from 6744 middle-aged male-male monozygotic and dizygotic twins from the Vietnam Era Twin Registry. Conduct disorder, major depression, and PTSD were assessed via telephone interview using the Diagnostic Interview Schedule for the DSM-III-R in 1992. Structural equation modeling was used to estimate additive genetic, shared environmental, and individual-specific environmental effects common and specific to conduct disorder, major depression, and PTSD. RESULTS: The association between conduct disorder and PTSD was explained primarily by common shared environmental influences; these explained 10% (95% confidence interval: 6%-17%) of the variance in PTSD. The association between major depression and PTSD was largely explained by common genetic influences; these explained 19% (95% confidence interval: 11%-26%) of the variance in PTSD. CONCLUSIONS: Our findings suggest that different etiologic mechanisms explain the association of conduct disorder and major depression with PTSD in male veterans. If replicated in other populations, results suggest research aimed at identifying specific genetic and environmental factors that influence PTSD may benefit from starting with those that have been more consistently and strongly associated with major depression and conduct disorder.     

Sex,stress, and health: Does stress predict health symptoms differently for the two sexes?

Objectives: Previous studies have been inconsistent with regard to the extent to which stress perception, rather than stressor exposure, predicts negative health symptoms. Because sex differences have been observed in all three of these variables, in this study the possibility that sex differences also exist in the relationships between them is investigated. Methods: Self‐report inventories of perceived stress, stressor exposure, and negative health symptoms were given to 107 young‐adult participants (65 females, 42 males). Results: Sex differences were observed in the associations among perceived stress, stressor exposure, and negative health symptom rates. Specifically, while higher perceived stress and higher stressor exposure rates independently predicted higher negative health symptoms rates in females, only higher stressor exposure rates independently predicted higher negative health symptoms in males. Indeed, unexpectedly, after controlling for exposure to stressors there was a trend towards higher perceived stress predicting lower negative health symptoms in males. Conclusions: While exposure to stress was a significant negative predictor of health for both sexes, perception of stress was predictive only for females. One implication of this finding is that different psychological models are needed to predict health symptoms in the two sexes. Copyright © 2005 John Wiley & Sons, Ltd.     

Looking for resilience: Understanding the longitudinal trajectories of responses to stress

Taking advantage of two large, population-based, and longitudinal datasets collected after the 1999 floods in Mexico (n = 561) and the September 11, 2001 terrorist attacks in New York (n = 1267), we examined the notion that resilience may be best understood and measured as one member of a set of trajectories that may follow exposure to trauma or severe stress. We hypothesized that resistance, resilience, recovery, relapsing/remitting, delayed dysfunction, and chronic dysfunction trajectories were all possible in the aftermath of major disasters. Semi-parametric group-based modeling yielded the strongest evidence for resistance (no or mild and stable symptoms), resilience (initially moderate or severe symptoms followed by a sharp decrease), recovery (initially moderate or severe symptoms followed by a gradual decrease), and chronic dysfunction (moderate or severe and stable symptoms), as these trajectories were prevalent in both samples. Neither Mexico nor New York showed a relapsing/remitting trajectory, and only New York showed a delayed dysfunction trajectory. Understanding patterns of psychological distress over time may present opportunities for interventions that aim to increase resilience, and decrease more adverse trajectories, after mass traumatic events.     

Increase in levels of total free fatty acids in rat brain regions following 3-nitropropionic acid administration

Acute exposure to a neurotoxin, 3-nitropropionic acid (3-NPA), in rats results in an increase in total free fatty acid (FFA) concentration in selective brain regions. We investigated the effect of 3-NPA administration on the cerebral concentrations of FFA used as a marker of oxidative stress. Rats (n=3/group) were dosed subcutaneously (s.c.) either with a vehicle (phosphate buffer) or 3-NPA in phosphate buffer at 30 mg/kg body weight. Animals were sacrificed after 1, 2, 3, and 6 h of injection. Brains were then dissected into frontal cortex (FC), caudate nucleus (CN), and hippocampus (HIP). The concentration of total FFA increased from 130 to 300% within 1–2 h after 3-NPA injection in all brain regions when compared with the baseline level obtained from the control rats and taken as 100%. In CN, FFA returned to the baseline level within 3 h of treatment. However, in FC and HIP the concentration of FFA remained significantly elevated above the baseline until 6 h. The released FFA provide a substrate for free radicals formation. The results of this study suggest a role of oxidative stress in the mechanism of 3-NPA toxicity.     

The heat shock/oxidative stress connection

Involvement of free-radical oxidations in the aging process has been a topic of interest since Harman's original contribution. Because of the close association between aging and Alzheimer disease (AD) and the qualitative similarity in the neuropathology of both conditions, it has been proposed by many investigators that oxidative stress may be important in AD. If such modality of injury was indeed involved, one should expect to find markers of oxidation and heat shock (since free radicals are key mediators of heat-shock induction) in brains of patients with AD. In fact, several studies documented abnormal expression of antioxidant enzymes and heat-shock proteins (HSP) along with other markers of oxidation in AD brains. We showed that abnormally expressed antioxidant enzymes are topographically associated with senile plaques and neurofibrillary tangles, and that the activity of these enzymes is (contrary to what one would expect) markedly reduced. These findings have recently been confirmed by other investigators. Despite a large amount of evidence that suggests an association between oxidative stress and the pathogenesis of AD, it is not yet known whether oxidative stress is a cause or consequence of the disorder. Future research efforts regarding the oxidative stress hypothesis of AD should include attempts, at generating AD pathology by oxidative means in laboratory animals, determining the role and integrity of the heat-shock response in AD, as well as that of various antioxidant systems, growth factors, and hormones with antioxidant and neuroprotective properties.