Selective induction of a glycoprotein IIIa ligand-induced binding site by fibrinogen and von Willebrand factor

Ligand-induced binding sites (LIBS) are neoantigenic regions of glycoprotein (GP)IIb-IIIa that are exposed upon interaction of the receptor with the ligand fibrinogen or the ligand recognition sequence (RGDS). LIBS have been suggested to contribute to postreceptor occupancy events such as full-scale platelet aggregation, adhesion to collagen, and clot retraction. This study examined the induction requirements of a GPIIIa LIBS with regard to ligand specificity. Through the use of the anti-LIBS D3, we report that this complex- activating antibody induces fibrinogen- and von Willebrand factor- binding to GPIIb-IIIa on intact platelets. Bound ligand was detected by flow cytometric analysis and platelet aggregation assays. These bound ligands increased the number of D3-binding sites and altered the affinity of D3 for GPIIb-IIIa on platelets. In contrast, activation of platelet GPIIb-IIIa by D3 did not increase the binding of another RGD- containing ligand, vitronectin. Furthermore, bound vitronectin on thrombin-stimulated platelets did not cause the expression of the D3 LIBS epitope. We conclude direct activation of GPIIb-IIIa in the absence of platelet activation results in selective ligand interaction and that D3 LIBS induction requires the binding of the multivalent ligands, fibrinogen or von Willebrand factor. Thus, the region of GPIIIa recognized by D3 may be an important regulatory domain in ligand- receptor interactions that directly mediate platelet aggregation.     

Experience of managing open fractures of the lower limb at a major trauma centre

Introduction

In April 2012 the John Radcliffe Hospital in Oxford became a major trauma centre (MTC). The British Orthopaedic Association and British Association of Plastic, Reconstructive and Aesthetic Surgeons joint standards for the management of open fractures of the lower limb (BOAST 4) require system-wide changes in referral practice that may be facilitated by the MTC and its associated major trauma network.

Methods

From 2008 to 2013 a multistep audit of compliance with BOAST 4 was conducted to assess referral patterns, timing of surgery and outcomes (surgical site infection rates), to determine changes following local intervention and the establishment of the MTC.

Results

Over the study period, 50 patients had soft tissue cover for an open lower limb fracture and there was a significant increase in the proportion of patients receiving definitive fixation in our centre (p=0.036). The median time from injury to soft tissue cover fell from 6.0 days to 3.5 days (p=0.051) and the median time from definitive fixation to soft tissue cover fell from 5.0 days to 2.0 days (p=0.003). The deep infection rate fell from 27% to 8% (p=0.247). However, in 2013 many patients still experienced a delay of >72 hours between injury and soft tissue cover, primarily owing to a lack of capacity for providing soft tissue cover.

Conclusions

Our experience may be relevant to other MTCs seeking to identify barriers to optimising the management of patients with these injuries.     

运动障碍疾病与脑内金属铜、铁、钙沉积

在过去的20年,金属及其代谢过程对神经疾病的影响引起了神经科学家的极大兴趣。近年来大量文献报道,铁、铜、锰和锌作为重要的神经化学因子与目的蛋白相互作用导致了与疾病病理生理密切相关的反应。     

Tai chi for psychosocial well‐being in older people

Lee LYK, Lee DTF, Woo J. The psychosocial effect of tai chi on nursing home residents. J Clin Nurs 2010; 19: 927–38.     

The Relative Effect of Household and Workplace Smoking Restriction on Health Status Among Chinese Americans Living in New York City

Households and workplaces are the predominant location for exposure to secondhand smoke. The purpose of this study is to examine the association between health status and smoking restrictions at home and work and to compare the relative effect of household and workplace smoking restrictions on health status. This study uses data from a cross sectional representative probability sample of 2,537 Chinese American adults aged 18–74 living in New York City. The analysis was limited to 1,472 respondents who work indoors for wages. Forty-three percent of respondents reported a total smoking ban at home and the workplace, 20% at work only, 22% home only, and 15% reported no smoking restriction at home or work. Smokers who live under a total household smoking ban only or both a total household and total workplace ban were respectively 1.90 and 2.61 times more likely to report better health status compared with those who reported no smoking ban at work or home. Before the NYC Clean Indoor Air Act second-hand smoke (SHS) exposure among this immigrant Chinese population at home and work was high. This study finds that household smoking restrictions are more strongly associated with better health status than workplace smoking restrictions. However, better health status was most strongly associated with both a ban at work and home. Public health efforts should include a focus on promoting total household smoking bans to reduce the well-documented health risks of SHS exposure. Shelley and Hung are with the Department of Sociomedical Sciences, Columbia University Mailman School of Public Health, New York, NY, USA; Yerneni and Fahs are with the Brookdale Center on Aging, Hunter College, City University of New York, New York, NY, USA. Fahs and Das are with the Economics Program Graduate Center, City University of New York, New York, USA. An erratum to this article can be found at     

Molecular and epidemiologic analysis of a county-wide outbreak caused by <Emphasis Type="Italic">Salmonella enterica</Emphasis> subsp. <Emphasis Type="Italic">enterica</Emphasis> serovar Enteritidis traced to a bakery

Background  

An increase in the number of attendees due to acute gastroenteritis and fever was noted at one hospital emergency room in Taiwan over a seven-day period from July to August, 2001. Molecular and epidemiological surveys were performed to trace the possible source of infection.     

SCHISTOSOMIASIS VACCINATION HISTORICAL DEVELOPMENT, PRESENT STATUS AND FUTURE PROSPECTS*

50 years of research on killed or live vaccine for schistosomiasis without successful produc- tion of a human schistosomiasis vaccine are reviewed.