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71.
ABSTRACT: BACKGROUND: Walking in neighborhood environments is undertaken for different purposes including for transportation and leisure. We examined whether sidewalk availability was associated with participation in, and minutes of neighborhood-based walking for transportation (NWT) and recreation (NWR) after controlling for neighborhood self-selection. METHOD: Baseline survey data from respondents (n=1813) who participated in the RESIDential Environment (RESIDE) project (Perth, Western Australia) were used. Respondents were recruited based on their plans to move to another neighborhood in the following year. Usual weekly neighborhood-based walking, residential preferences, walking attitudes, and demographics were measured. Characteristics of the respondent's baseline neighborhood were measured including transportation-related walkability and sidewalk length. A Heckman two-stage modeling approach (multivariate Probit regression for walking participation, followed by a sample selection-bias corrected OLS regression for walking minutes) estimated the relative contribution of sidewalk length to NWT and NWR. RESULTS: After adjustment, neighborhood sidewalk length and walkability were positively associated with a 2.97 and 2.16 percentage point increase in the probability of NWT participation, respectively. For each 10km increase in sidewalk length, NWT increased by 5.38 min/wk and overall neighborhood-based walking increased by 5.26 min/wk. Neighborhood walkability was not associated with NWT or NWR minutes. Moreover, sidewalk length was not associated with NWR minutes. CONCLUSION: Sidewalk availability in established neighborhoods may be differentially associated with walking for different purposes. Our findings suggest that large investments in sidewalk construction alone would yield small increases in walking.  相似文献   
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The development of total biliary casts is very unusual, especially in patients who have not undergone liver transplantation. The aetiology of these casts is uncertain but several factors are believed to play a role, including periods of fasting, haemolysis, cholangitis and recent surgery. Resultant bile stasis and/or gallbladder hypocontractility promote sludge and subsequent stone formation. Here we present the case of a previously well 66-year-old woman who developed a total biliary cast several weeks after being involved in a road traffic accident during which she sustained head injuries but no obvious liver insult. This cast was removed at laparotomy but the patient had resultant diffuse biliary tree abnormalities and persistent cholestasis and subsequently required a liver transplant. The possible aetiologies of biliary cast formation and subsequently cholangiopathy necessitating transplantation in this patient are described.  相似文献   
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BACKGROUND: To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension, we extended the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial by an open-label follow-up study lasting 4 years. METHODS: The Syst-Eur trial included 4695 randomized patients with minimum age of 60 years and an untreated blood pressure of 160-219 mmHg systolic and below 95 mmHg diastolic. The double-blind trial ended after a median follow-up of 2.0 years (range 1-97 months). Of 4409 patients still alive, 3517 received open-label treatment consisting of nitrendipine (10-40 mg daily) with the possible addition of enalapril (5-20 mg daily), hydrochlorothiazide (12.5-25 mg daily), or both add-on drugs. Non-participants (n = 892) were also followed up. RESULTS: Median follow-up increased to 6.1 years. Systolic pressure decreased to below 150 mmHg (target level) in 2628 participants (75.0%). During the 4-year open-label follow-up, stroke and cardiovascular complications occurred at similar frequencies in patients formerly randomized to placebo and those continuing active treatment. These rates were similar to those previously observed in the active-treatment group during the double-blind trial. Considering the total follow-up of 4695 randomized patients, immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28% (P = 0.01) and 15% (P = 0.03), respectively, with a similar tendency for total mortality (13%, P = 0.09). In 492 diabetic patients, the corresponding estimates of long-term benefit (P < 0.02) were 60, 51 and 38%, respectively. CONCLUSIONS: Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension. Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years. These findings underscore the necessity of early treatment of isolated systolic hypertension.  相似文献   
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Essentials

  • Endothelial activation initiates multiple processes, including hemostasis and inflammation.
  • The molecules that contribute to these processes are co‐stored in secretory granules.
  • How can the cells control release of granule content to allow differentiated responses?
  • Selected agonists recruit an exocytosis‐linked actin ring to boost release of a subset of cargo.

Summary

Background

Endothelial cells harbor specialized storage organelles, Weibel‐Palade bodies (WPBs). Exocytosis of WPB content into the vascular lumen initiates primary hemostasis, mediated by von Willebrand factor (VWF), and inflammation, mediated by several proteins including P‐selectin. During full fusion, secretion of this large hemostatic protein and smaller pro‐inflammatory proteins are thought to be inextricably linked.

Objective

To determine if secretagogue‐dependent differential release of WPB cargo occurs, and whether this is mediated by the formation of an actomyosin ring during exocytosis.

Methods

We used VWF string analysis, leukocyte rolling assays, ELISA, spinning disk confocal microscopy, high‐throughput confocal microscopy and inhibitor and siRNA treatments to demonstrate the existence of cellular machinery that allows differential release of WPB cargo proteins.

Results

Inhibition of the actomyosin ring differentially effects two processes regulated by WPB exocytosis; it perturbs VWF string formation but has no effect on leukocyte rolling. The efficiency of ring recruitment correlates with VWF release; the ratio of release of VWF to small cargoes decreases when ring recruitment is inhibited. The recruitment of the actin ring is time dependent (fusion events occurring directly after stimulation are less likely to initiate hemostasis than later events) and is activated by protein kinase C (PKC) isoforms.

Conclusions

Secretagogues differentially recruit the actomyosin ring, thus demonstrating one mechanism by which the prothrombotic effect of endothelial activation can be modulated. This potentially limits thrombosis whilst permitting a normal inflammatory response. These results have implications for the assessment of WPB fusion, cargo‐content release and the treatment of patients with von Willebrand disease.
  相似文献   
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ObjectiveTo identify factors associated with patients’ overall rating of inpatient hospital care.ConclusionsOur results are novel in the Canadian population. Several questions for future research have been generated, in addition to opportunities for quality improvement within our own organization.  相似文献   
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