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Background

Guidelines and clinical practice vary considerably with respect to thrombosis prophylaxis during plaster cast immobilization of the lower extremity. Identifying patients at high risk for the development of venous thromboembolism (VTE) would provide a basis for considering individual thromboprophylaxis use and planning treatment studies.The aims of this study were (1) to investigate the predictive value of genetic and environmental risk factors, levels of coagulation factors, and other biomarkers for the occurrence of VTE after cast immobilization of the lower extremity and (2) to develop a clinical prediction tool for the prediction of VTE in plaster cast patients.

Methods and Findings

We used data from a large population-based case–control study (MEGA study, 4,446 cases with VTE, 6,118 controls without) designed to identify risk factors for a first VTE. Cases were recruited from six anticoagulation clinics in the Netherlands between 1999 and 2004; controls were their partners or individuals identified via random digit dialing. Identification of predictor variables to be included in the model was based on reported associations in the literature or on a relative risk (odds ratio) > 1.2 and p ≤ 0.25 in the univariate analysis of all participants. Using multivariate logistic regression, a full prediction model was created. In addition to the full model (all variables), a restricted model (minimum number of predictors with a maximum predictive value) and a clinical model (environmental risk factors only, no blood draw or assays required) were created. To determine the discriminatory power in patients with cast immobilization (n = 230), the area under the curve (AUC) was calculated by means of a receiver operating characteristic. Validation was performed in two other case–control studies of the etiology of VTE: (1) the THE-VTE study, a two-center, population-based case–control study (conducted in Leiden, the Netherlands, and Cambridge, United Kingdom) with 784 cases and 523 controls included between March 2003 and December 2008 and (2) the Milan study, a population-based case–control study with 2,117 cases and 2,088 controls selected between December 1993 and December 2010 at the Thrombosis Center, Fondazione IRCCS Ca’ Granda–Ospedale Maggiore Policlinico, Milan, Italy.The full model consisted of 32 predictors, including three genetic factors and six biomarkers. For this model, an AUC of 0.85 (95% CI 0.77–0.92) was found in individuals with plaster cast immobilization of the lower extremity. The AUC for the restricted model (containing 11 predictors, including two genetic factors and one biomarker) was 0.84 (95% CI 0.77–0.92). The clinical model (consisting of 14 environmental predictors) resulted in an AUC of 0.77 (95% CI 0.66–0.87). The clinical model was converted into a risk score, the L-TRiP(cast) score (Leiden–Thrombosis Risk Prediction for patients with cast immobilization score), which showed an AUC of 0.76 (95% CI 0.66–0.86). Validation in the THE-VTE study data resulted in an AUC of 0.77 (95% CI 0.58–0.96) for the L-TRiP(cast) score. Validation in the Milan study resulted in an AUC of 0.93 (95% CI 0.86–1.00) for the full model, an AUC of 0.92 (95% CI 0.76–0.87) for the restricted model, and an AUC of 0.96 (95% CI 0.92–0.99) for the clinical model. The L-TRiP(cast) score resulted in an AUC of 0.95 (95% CI 0.91–0.99).Major limitations of this study were that information on thromboprophylaxis was not available for patients who had plaster cast immobilization of the lower extremity and that blood was drawn 3 mo after the thrombotic event.

Conclusions

These results show that information on environmental risk factors, coagulation factors, and genetic determinants in patients with plaster casts leads to high accuracy in the prediction of VTE risk. In daily practice, the clinical model may be the preferred model as its factors are most easy to determine, while the model still has good predictive performance. These results may provide guidance for thromboprophylaxis and form the basis for a management study.  相似文献   
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In addition to sperm cells, seminal fluid contains various small membranous vesicles. These include prostasomes, membrane vesicles secreted by prostate epithelial cells. Prostasomes have been proposed to perform a variety of functions, including modulation of (immune) cell activity within the female reproductive tract and stimulation of sperm motility and capacitation. How prostasomes mediate such diverse functions, however, remains unclear. In many studies, vesicles from the seminal plasma have been categorized collectively as a single population of prostasomes; in fact, they more likely represent a heterogeneous mixture of vesicles produced by different reproductive glands and secretory mechanisms. We here characterized membranous vesicles from seminal fluid obtained from vasectomized men, thereby excluding material from the testes or epididymides. Two distinct populations of vesicles with characteristic sizes (56 ± 13 nm vs. 105 ± 25 nm) but similar equilibrium buoyant density (~1.15 g/ml) could be separated by using the distinct rates with which they floated into sucrose gradients. Both types of vesicle resembled exosomes in terms of their buoyant density, size, and the presence of the ubiquitous exosome marker CD9. The protein GLIPR2 was found to be specifically enriched in the lumen of the smaller vesicles, while annexin A1 was uniquely associated with the surface of the larger vesicles. Prostate stem-cell antigen (PSCA), a prostate-specific protein, was present on both populations, thereby confirming their origin. PSCA was, however, absent from membrane vesicles in the seminal fluid of some donors, indicating heterogeneity of prostasome characteristics between individuals.  相似文献   
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Transforming growth factor beta (TGF‐β) is a signalling molecule that plays a key role in developmental and immunological processes in mammals. Three TGF‐β isoforms exist in humans, and each isoform has unique therapeutic potential. Plants offer a platform for the production of recombinant proteins, which is cheap and easy to scale up and has a low risk of contamination with human pathogens. TGF‐β3 has been produced in plants before using a chloroplast expression system. However, this strategy requires chemical refolding to obtain a biologically active protein. In this study, we investigated the possibility to transiently express active human TGF‐β1 in Nicotiana benthamiana plants. We successfully expressed mature TGF‐β1 in the absence of the latency‐associated peptide (LAP) using different strategies, but the obtained proteins were inactive. Upon expression of LAP‐TGF‐β1, we were able to show that processing of the latent complex by a furin‐like protease does not occur in planta. The use of a chitinase signal peptide enhanced the expression and secretion of LAP‐TGF‐β1, and co‐expression of human furin enabled the proteolytic processing of latent TGF‐β1. Engineering the plant post‐translational machinery by co‐expressing human furin also enhanced the accumulation of biologically active TGF‐β1. This engineering step is quite remarkable, as furin requires multiple processing steps and correct localization within the secretory pathway to become active. Our data demonstrate that plants can be a suitable platform for the production of complex proteins that rely on specific proteolytic processing.  相似文献   
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There is a wide variety of donor sites available for minor nasal reconstructions involving alar, lobular, and columellar defects. Unfortunately, the problems all these sites have in common are that the color match may be unsatisfactory or that the end result may be marred by conspicuous scarring. If nasal-skin resources could be fully exploited, the elimination of these two important problems could become an obtainable goal.This article discusses the potential of the nasal dorsum as a donor site and describes methods that were used to try to achieve this goal. Skin redistribution, skin expansion, and skin distraction methods were used in 28 patients with alar (n = 13), lobular (n = 8), and columellar (n = 7) malformations and who had been followed up since the early 1980s.  相似文献   
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Orangutans have the longest immature period and inter-birth interval of all ape species. This may be explained by a slow life history, the need to develop skills or by their relatively solitary lifestyle, which prevents a mother from associating with two offspring. This study of wild immature orangutans at the Ketambe Research Station, Indonesia, describes, with partly cross-sectional, partly longitudinal data, their development to independence. The study subjects ranged from 1 to 11 years of age. Data on their activity budget, diet, mother–offspring proximity and maintenance of proximity, association with conspecifics and play behavior were collected. The results indicate that immature orangutans can provide for their own food and transport, and therefore were independent of direct maternal care, at an age of possibly 3 but more clearly 6 years. This is similar to chimpanzees, and refutes the slow life history hypothesis. Immature orangutans remain within their mother’s vicinity until the age of 8 years, indicating a dependence on indirect maternal care, and this coincides with the period during which the mother does not produce another offspring. A female orangutan seems unable to associate with an older immature while caring for a new infant. This is consistent with the solitary-lifestyle hypothesis and corroborates the results obtained with the Sumatran orangutan population at Suaq Balimbing. However, why an immature depends indirectly on its mother for such a long period remains unclear. It is possible that it needs to develop ecological or social skills or needs the protection of its mother. Unfortunately, no data were available to distinguish between these possibilities.  相似文献   
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BackgroundIt is generally unknown to what extent organ transplant recipients can be physically challenged. During an expedition to Mount Kilimanjaro, the tolerance for strenuous physical activity and high-altitude of organ transplant recipients after various types of transplantation was compared to non-transplanted controls.MethodsTwelve organ transplant recipients were selected to participate (2 heart-, 2 lung-, 2 kidney-, 4 liver-, 1 allogeneic stem cell- and 1 small bowel-transplantation). Controls comprised the members of the medical team and accompanying family members (n = 14). During the climb, cardiopulmonary parameters and symptoms of acute mountain sickness were recorded twice daily. Capillary blood analyses were performed three times during the climb and once following return.ResultsEleven of the transplant participants and all controls began the final ascent from 4700 meters and reached over 5000 meters. Eight transplant participants (73%) and thirteen controls (93%) reached the summit (5895m). Cardiopulmonary parameters and altitude sickness scores demonstrated no differences between transplant participants and controls. Signs of hyperventilation were more pronounced in transplant participants and adaptation to high-altitude was less effective, which was related to a decreased renal function. This resulted in reduced metabolic compensation.ConclusionOverall, tolerance to strenuous physical activity and feasibility of a high-altitude expedition in carefully selected organ transplant recipients is comparable to non-transplanted controls.  相似文献   
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Netherlands Heart Journal -  相似文献   
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