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The objective of our study was to evaluate a single blood collection tube with a novel antithrombotic formulation to measure both hematological, biochemical, and d-dimer analytes.Paired samples of gold standard blood tubes (EDTA, lithium heparin, sodium citrate) and a new antithrombotic formulation blood tube were collected from 187 patients. The new antithrombotic tube is a lithium heparin tube preloaded with a liquid form of prostacyclin analog. The novel tube was tested on seventeen hematological parameters and smears against EDTA, on fourteen biochemical parameters against lithium heparin and on d-dimer against sodium citrate.All correlation coefficients were close to 0.99. The Bland-Altman analyses presented a satisfactory correspondence for all analytes. All the hematological examinations demonstrated comparable results between EDTA and the novel formulation, except for platelet counts analyzed by impedance method, but not by fluorescence. We detected lower mean platelet volume with/without outliers (5.06%)/(5.13%) in the novel formulation and increased mean corpuscular hemoglobin concentration (2.55%). All the biochemistry analytes demonstrated comparable results between lithium heparin and the novel tube. d-dimer showed comparable results between citrated blood and the novel formulation after dilution correction.We describe a novel antithrombotic formulation tube with the potential to be introduced into clinical laboratories for simultaneous analysis of thirty-two blood analytes.

Platelets interact with multiple adhesion proteins during thrombogenesis, yet little is known about their ability to assemble fibronectin matrix. In vitro three-dimensional superresolution microscopy complemented by biophysical and biochemical methods revealed fundamental insights into how platelet contractility drives fibronectin fibrillogenesis. Platelets adhering to thrombus proteins (fibronectin and fibrin) versus basement membrane components (laminin and collagen IV) pull fibronectin fibrils along their apical membrane versus underneath their basal membrane, respectively. In contrast to other cell types, platelets assemble fibronectin nanofibrils using αIIbβ3 rather than α5β1 integrins. Apical fibrillogenesis correlated with a stronger activation of integrin-linked kinase, higher platelet traction forces, and a larger tension in fibrillar-like adhesions compared to basal fibrillogenesis. Our findings have potential implications for how mechanical thrombus integrity might be maintained during remodeling and vascular repair.

Aims: To determine whether there is an excess of cognitive impairment in patients with type 2 diabetes and foot ulceration. Methods: 55 patients with type 2 diabetes and foot ulcers attending Multidisciplinary Diabetes Foot Ulcer clinics (MDFU cohort) were compared with 56 patients with type 2 diabetes attending Complex Diabetes clinics (CDC cohort) using commonly used screening tests for cognitive impairment (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA)), as well as foot self-care, mood and health literacy. MMSE was also compared between the MDFU cohort and a historical community-based cohort of patients with type 2 diabetes (FDS2 cohort). Results: Median MMSE scores were the same in all three groups (28/30). Median MOCA scores did not differ between the MDFU and CDC cohorts (25/30). There were no significant differences in the percentages of patients with MMSE ≤ 24 or MOCA ≤ 25 between MDFU and CDC cohorts (3.6% versus 10.7%, p = 0.27 and 56.4% versus 51.8%, p = 0.71, respectively), findings that did not change after adjustment for age, sex, education, diabetes duration, and random blood glucose. Conclusions: Using conventionally applied instruments, patients with type 2 diabetes and foot ulceration have similar cognition compared with patients without, from either hospital-based clinic or community settings.

BACKGROUND Diabetes distress, self-efficacy and health literacy are associated with diabetes self-management and health outcomes. Measures of coping styles and their impact on diabetes self-management and diabetes-related distress may add value in identifying those at risk of poorer health outcomes. Current evidence of associations between psychological flexibility/inflexibility and diabetes related health outcomes is limited. AIMS To measure associations of psychological flexibility, self-efficacy and health literacy with diabetes distress and HbA1c, in adults with type 1 diabetes. METHODS We surveyed 105 adults with type 1 diabetes attending a tertiary diabetes outpatient clinic (mean age 27±7.1 years, 53% men, duration of diabetes 12.6±8.5 years, HbA1c 72±22 mmol/mol, 8.7± 2.0 %, 34% using insulin pumps). We assessed psychological flexibility, self-efficacy, health literacy and diabetes distress. Regression models explored the relative contributions of different factors to diabetes distress and HbA1c. RESULTS The majority of health literacy scores were in the low risk range. Those with greater psychological flexibility had higher self-efficacy (r=0.34, p

Upon vascular injury, platelets are crucial for thrombus formation and contraction, but do they directly initiate early tissue repair processes? Using 3D super-resolution microscopy, micropost traction force microscopy, and specific integrin or myosin IIa inhibitors, we discovered here that platelets form fibrillar adhesions. They assemble fibronectin nanofibrils using αIIbβ3 (CD41/CD61, GPIIb-IIIa) rather than α5β1 integrins, in contrast to fibroblasts. Highly contractile platelets in contact with thrombus proteins (fibronectin, fibrin) pull fibronectin fibrils along their apical membrane, whereas platelets on basement membrane proteins (collagen IV, laminin) are less contractile generating less stretched planar meshworks beneath themselves. As probed by vinculin-decorated talin unfolding, platelets on fibronectin generate similar traction forces in apical fibrillar adhesions as fibroblasts do. These are novel mechanobiology mechanisms by which platelets spearhead the fibrillogenesis of the first de novo ECM, including its 2D versus 3D network architectures depending on their ECM environment, and thereby pave the way for cell infiltration.

Blood clots stop bleeding and provide cell-instructive microenvironments. Still, in vitro models used to study implant performance typically neglect any possible interactions of recruited cells with surface-adhering blood clots. Here we study the interaction and synergies of bone marrow derived human mesenchymal stem cells (hMSCs) with surface-induced blood clots in an in vitro model by fluorescence microscopy, scanning and correlative light and electron microscopy, ELISA assays and zymography. The clinically used alkali-treated rough titanium (Ti) surfaces investigated here are known to enhance blood clotting compared to native Ti and to improve the healing response, but the underlying mechanisms remain elusive. Here we show that the presence of blood clots synergistically increased hMSC proliferation, extracellular matrix (ECM) remodelling and the release of matrix fragments and angiogenic VEGF, but did not increase the osteogenic differentiation of hMSCs. While many biomaterials are nowadays engineered to release pro-angiogenic factors, we show here that clot-entrapped blood cells on conventional materials in synergy with hMSCs are potent producers of pro-angiogenic factors. Our data might thus not only explain why alkali-treatment is beneficial for Ti implant integration, but they suggest that the physiological importance of blood clots to create pro-angiogenic environments on implants has been greatly underestimated. The importance of blood clots might have been missed because the pro-angiogenic functions get activated only upon stimulation by synergistic interactions with the invading cells.

Low correlations of cell culture data with clinical outcomes pose major medical challenges with costly consequences. While the majority of biomaterials are tested using in vitro cell monocultures, the importance of synergistic interactions between different cell types on paracrine signalling has recently been highlighted. In this proof-of-concept study, we asked whether the first contact of surfaces with whole human blood could steer the tissue healing response. This hypothesis was tested using alkali-treatment of rough titanium (Ti) surfaces since they have clinically been shown to improve early implant integration and stability, yet blood-free in vitro cell cultures poorly correlated with in vivo tissue healing. We show that alkali-treatment, compared to native Ti surfaces, increased blood clot thickness, including platelet adhesion. Strikingly, blood clots with entrapped blood cells in synergistic interactions with fibroblasts, but not fibroblasts alone, upregulated the secretion of major factors associated with fast healing. This includes matrix metalloproteinases (MMPs) to break down extracellular matrix and the growth factor VEGF, known for its angiogenic potential. Consequently, in vitro test platforms, which consider whole blood-implant interactions, might be superior in predicting wound healing in response to biomaterial properties.

A straightforward strategy is presented for the site-specific incorporation of fluorophores or reactive probes into the extracellular matrix (ECM) protein fibronectin (Fn) by using the enzyme-catalyzed transamidation by activated factor XIII. Characterization by SDS-PAGE, western blotting, absorption measurements, mass spectrometry, and stepwise photobleaching for labeling quantification at the single-molecule level showed that the labeling was efficient and restricted to the N-terminal tails. The introduction of labels did not interfere with Fn fibrillogenesis, as verified by the incorporation of fluorescently labeled Fn into ECM and manually pulled Fn fibers. Site-specific incorporation of an azide was used to create a template for bioorthogonal click chemistry reactions in a second bioconjugation step, thus offering versatile modification and application possibilities in the context of matrix biology and tissue engineering.

Background: In an innovative event that challenged traditional orientation programs, the Curtin University School of Nursing and Midwifery brought together nursing students, academic and student support staff, and health industry representatives. This unique whole-of-school convention consisted of sessions tailored to each student year group and aimed to promote nursing identity, highlight leadership opportunities, and showcase employer pathways. Method: To evaluate the event, a survey approach was used to collect quantitative data via questionnaire and qualitative data via open-ended questions from first-year students ( n = 113), staff ( n = 24), and industry representatives ( n = 14). Results: Students, staff, and industry evaluations indicated a successful event that achieved its goals, including student engagement and motivation and community building. Conclusion: This orientation model could be used as a basis for institution-wide engagement activities. [ J Nurs Educ. 2015;54(12):712–715.]

Reduced testosterone levels have been implicated as a potential causative factor in cognitive decline with older age. Men who possess the apolipoprotein E (APOE) epsilon4 allele have an increased risk of developing Alzheimer's disease; however, no studies have examined whether the influence of testosterone on cognition in healthy older men may be modulated by this genetic predisposition.The objective of the study was to investigate the association between serum testosterone concentrations and cognitive performance in healthy older men, taking into account APOE epsilon4 status.This was a cross-sectional study conducted from 2003 to 2004.The study population consisted of community-dwelling males residing in Perth, Western Australia.Healthy men over 55 yr, free of cognitive impairment and dementia (n = 45), were included in the study.Participants had fasting early morning blood samples for testosterone and SHBG and were assessed for mood as well as indices of general cognition, verbal and visual memory, executive functioning, working memory, and attention.There was a significant interaction between calculated free testosterone (FT) and APOE epsilon4 on general cognition (P = 0.01) and executive functioning, working memory, and attention (P0.01). Higher levels of FT were associated with better general cognition in non-epsilon4 carriers (P = 0.01). By contrast, in epsilon4 carriers higher FT levels were associated with lower scores on tests of executive functioning, working memory, and attention (P = 0.02). In men at increased risk for Alzheimer's disease, higher testosterone levels were not associated with better cognitive function.Cross-sectional and prospective studies of testosterone and cognition in older men should take into account APOE epsilon4 status.

The potential role of supplementing sex steroids for the prevention and delay of age-related cognitive decline has received a great deal of recent interest. Although the biological plausibility of hormone treatment has received considerable support, clinical studies of cognitive functioning after hormonal treatment in postmenopausal women with and without dementia have produced mixed results. Much less attention has been given to the corresponding role of androgens in men. In order to establish the relevance of hormonal supplementation for men in delaying or preventing cognitive decline, it is of importance to evaluate both adrenal and gonadal contributions to androgen status. Additionally, consideration must also be given to the potential interactions of androgens with risk and protective factors (e.g., apolipoprotein E genotype and education). Here we review experimental and epidemiological studies of the significance of androgens for cognitive function.

Dysregulation of the hypothalamic pituitary gonadal (HPG) axis during aging has been associated with increased risk of cognitive decline and developing dementia. Compared to controls, men with Alzheimer's disease (AD) have been shown to have lower serum testosterone levels and higher serum luteinizing hormone (LH) levels. As serum free testosterone concentration is negatively correlated with LH in older men, the independent contributions of these hormones to the pathogenesis of AD warrants further clarification. To explore this notion, we measured plasma amyloid-beta (Abeta), serum testosterone, serum LH and other biochemical parameters in 40 cognitively normal elderly men. Multiple linear regression analysis revealed that serum LH concentration is the only parameter that significantly correlates with plasma Abeta levels in these men (r=0.5, p=0.041). These results suggest that increased serum LH concentration, rather than lower serum free testosterone, is associated with the accumulation of Abeta in plasma. Larger, longitudinal human studies are needed to determine the significance of LH in the pathogenesis of AD.

There is currently intense controversy regarding the use of hormone replacement therapy (HRT) in postmenopausal women, in relation to its therapeutic efficacy in Alzheimer's disease (AD). It has been suggested that the benefits of HRT may be modified by apolipoprotein E (APOE) genotype (the major genetic risk factor for AD). Here we report the findings of the first study designed to systematically explore the interaction of (a) oestrogen replacement therapy (ERT) and (b) possession of an epsilon4 allele of APOE on specific elements of episodic learning and memory that are commonly used indices of age-related cognitive decline. This data represents a cross-sectional analysis of the interaction of ERT and APOE genotype on learning and memory in a cohort of 181 healthy postmenopausal women [ERT users (n = 101, mean age 65.40 +/- 6.34); ERT non-users (n = 80, mean age 67.03 +/- 6.80)] residing in Perth, Western Australia. The highest level of learning (trials 2-5; P0.05) and memory (e.g. total number of items recalled; P0.05) performance was observed in women taking ERT who were not carriers of the APOE epsilon4 allele. APOEepsilon4 carriers receiving ERT performed no better on episodic memory testing than APOE epsilon4 carriers who were not receiving ERT. These cognitive differences related to genetic profile, were noted on both recall and recognition (P = 0.005) tests of memory. The findings have significance for evaluating whether and when ERT may be clinically indicated. Specifically, ERT may benefit the cognitive functioning of women not carrying the APOE epsilon4 allele.