Three-dimensional numerical simulation of blood flow in mouse aortic arch around atherosclerotic plaques

Atherosclerosis is a progressive disease, involving the build-up of lipid streaks in artery walls, leading to plaques. Understanding the development of atherosclerosis and plaque vulnerability is critically important since plaque rupture can result in heart attack or stroke. Plaques can be divided into two distinct types: those likely to rupture (vulnerable) or less likely to rupture (stable). In the last decade, researchers have been interested in studying the influence of the mechanical effects (blood shear stress, pressure forces and structural stress) on the plaque formation, progression and rupture processes but no general agreement has been found. The purpose of the present work is to include more realistic conditions for the numerical calculations of the blood flow by implementing real geometries with plaques in the numerical model. Hemodynamical parameters are studied in both diseased and healthy configurations. The healthy configuration is obtained by removing numerically the plaques from three dimensional geometries obtained by micro-computed tomography. A new hemodynamical parameter is also introduced to relate the location of plaques to the characteristics of the flow in the healthy configuration. © 2014 .

Analysis of 177Lu-octreotate therapy-induced DNA damage in peripheral blood lymphocytes of patients with neuroendocrine tumors

Ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) can lead to cell death, genome instability and carcinogenesis. Immunofluorescence detection of phosphorylated histone variant H2AX (γ-H2AX) is a reliable and sensitive technique to monitor external beam IR-induced DSBs in peripheral blood lymphocytes (PBL). Here, we investigated whether γ-H2AX could be used as an in vivo marker to assess normal tissue toxicity after extended internal irradiation with (177)Lu-DOTA-octreotate peptide receptor radionuclide therapy (LuTate PRRT) of neuroendocrine tumors.

The evolution of nitric oxide signalling in vertebrate blood vessels

Nitric oxide is one of the most important signalling molecules involved in the regulation of physiological function. It first came to prominence when it was discovered that the vascular endothelium of mammals synthesises and releases nitric oxide (NO) to mediate a potent vasodilation. Subsequently, it was shown that NO is synthesised in the endothelium by a specific isoform of nitric oxide synthase (NOS) called NOS3. Following this discovery, it was assumed that an endothelial NO/NOS3 system would be present in all vertebrate blood vessels. This review will discuss the latest genomic, anatomical and physiological evidence which demonstrates that an endothelial NO/NOS3 signalling is not ubiquitous in non-mammalian vertebrates, and that there have been key evolutionary steps that have led to the endothelial NO signalling system being a regulatory system found only in reptiles, birds and mammals. Furthermore, the emerging role of nitrite as an endocrine source of NO for vascular regulation is discussed.

CD8+ T cells from a novel T cell receptor transgenic mouse induce liver-stage immunity that can be boosted by blood-stage infection in rodent malaria

To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA) infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen. T cells from this line, termed PbT-I T cells, were able to respond to blood-stage infection by PbA and two other rodent malaria species, P. yoelii XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to sporozoites and to protect mice from liver-stage infection. Examination of the requirements for priming after intravenous administration of irradiated sporozoites, an effective vaccination approach, showed that the spleen rather than the liver was the main site of priming and that responses depended on CD8α+ dendritic cells. Importantly, sequential exposure to irradiated sporozoites followed two days later by blood-stage infection led to augmented PbT-I T cell expansion. These findings indicate that PbT-I T cells are a highly versatile tool for studying multiple stages and species of rodent malaria and suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage vaccine design to enable boosting by blood-stage infections.

Feasibility of trialling cord blood stem cell treatments for cerebral palsy in Australia

Umbilical cord blood may have therapeutic benefit in children with cerebral palsy (CP), but further studies are required. On first appearance it seems that Australia is well placed for such a trial because we have excellence in CP research backed by extensive CP registers, and both public and private cord blood banks. We aimed to examine the possibilities of conducting a trial of autologous umbilical cord blood cells (UCBCs) as a treatment for children with CP in Australia.

ETV6 (TEL1) in blood cell development and malignancy

 The ETV6 (TEL1) gene encodes a member of the ETS family of transcriptional regulators. It represents one of the most frequently disrupted genes in haematological malignancies, with over 50 different translocations described. Moreover, deletion, silencing or truncating mutations have also been reported, suggesting a potential tumor suppressor function. Recent studies have shown that ETV6 plays a broad and complex role in early hematopoiesis, impacting on the development of multiple lineages, providing new insights into how its perturbation contributes to disease.

Lower protein-to-carbohydrate ratio in maternal diet is associated with higher childhood systolic blood pressure up to age four years

The prenatal environment can influence development of offspring blood pressure (BP), which tracks into adulthood. This prospective longitudinal study investigated whether maternal pregnancy dietary intake is associated with the development of child BP up to age four years. Data are from 129 mother-child dyads enrolled in the Women and Their Children's Health study. Maternal diet was assessed using a validated 74-item food frequency questionnaire at 18 to 24 weeks and 36 to 40 weeks, with a reference period of the previous three months. Child systolic and diastolic BP were measured at 3, 6, 9, 12, 24, 36 and 48 months, using an automated BP monitor. Using mixed-model regression analyses adjusted for childhood growth indices, pregnancy intakes of percentage of energy (E%) polyunsaturated fat (β coefficient 0.73; 95% CI 0.003, 1.45; p = 0.045), E% omega-6 fatty acids (β coefficient 0.89; 95% CI 0.09, 1.69; p = 0.03) and protein-to-carbohydrate (P:C) ratio (β coefficient -14.14; 95% CI -27.68, -0.60; p = 0.04) were associated with child systolic BP trajectory up to 4 years. Child systolic BP was greatest at low proportions of dietary protein (<16% of energy) and high carbohydrate (>40% of energy) intakes. There may be an ideal maternal macronutrient ratio associated with optimal infant BP. Maternal diet, which is potentially modifiable, may play an important role in influencing offspring risk of future hypertension.

Blood pressure and cognitive function: the role of central aortic and brachial pressures

Central (aortic) blood pressures differ from brachial pressures and may be more relevant to the study of cognitive function, given that blood is delivered to the brain through the central large arteries. Pulse-pressure amplification reflects the augmentation of blood pressure between the central and peripheral arteries, which diminishes with aging. We aimed to determine the association between central blood pressure and cognitive function in independently living adults aged 20 to 82 years (N = 493). In adjusted regression models, higher central systolic pressure and higher central pulse pressure were each associated with poorer processing speed, Stroop processing, and recognition memory. Lower amplification was associated with poorer Stroop processing, working memory, and recognition memory. Higher brachial systolic pressure and brachial pulse pressure were both associated with poorer Stroop processing. In summary, central pressures and amplification were sensitive indicators of cognitive aging, predicting aspects of cognitive performance not predicted by brachial blood pressure.

Effects of a multivitamin, mineral and herbal supplement on cognition and blood biomarkers in older men: a randomised, placebo-controlled trial

OBJECTIVE: Nutritional and vitamin status may be related to cognitive function and decline in older adults. The aim of this study was to investigate the effects of nutritional supplementation on cognition in older men. METHOD: The current study was an 8-week, placebo-controlled, double-blind investigation into the effects of a multivitamin, mineral and herbal supplement (Swisse Men's Ultivite®, Swisse Vitamins Pty Ltd, Melbourne, Australia) on cognitive performance in older men. Participants were 51 male individuals aged between 50 and 74 years, with a sedentary lifestyle. Cognitive performance was assessed at baseline and post-treatment using a computerised battery of cognitive tasks, enabling the measurement of a range of attentional and memory processes. Blood measures of vitamin B(12) , folate and homocysteine were collected prior to and after supplementation. RESULTS: The results of this study revealed that contextual recognition memory performance was significantly improved following multivitamin supplementation (p < 0.05). Performance on other cognitive tasks did not change. Levels of vitamin B(12) and folate were significantly increased with a concomitant decrease in homocysteine, indicating that relatively short-term supplementation with a multivitamin can benefit these risk factors for cognitive decline. CONCLUSION: Findings from this study indicate that daily multivitamin supplementation may improve episodic memory in older men at risk of cognitive decline.

Self-monitoring of blood glucose versus self-monitoring of urine glucose in adults with newly diagnosed Type 2 diabetes receiving structured education: a cluster randomized controlled trial.

AIMS: To compare the effectiveness and acceptability of self-monitoring of blood glucose with self-monitoring of urine glucose in adults with newly diagnosed Type 2 diabetes. METHODS: We conducted a multi-site cluster randomized controlled trial with practice-level randomization. Participants attended a structured group education programme, which included a module on self-monitoring using blood glucose or urine glucose monitoring. HbA1c and other biomedical measures as well as psychosocial data were collected at 6, 12 and 18 months. A total of 292 participants with Type 2 diabetes were recruited from 75 practices. RESULTS: HbA1c levels were significantly lower at 18 months than at baseline in both the blood monitoring group [mean (se) -12 (2) mmol/mol; -1.1 (0.2) %] and the urine monitoring group [mean (se) -13 (2) mmol/mol; -1.2 (0.2)%], with no difference between groups [mean difference adjusted for cluster effect and baseline value = -1 mmol/mol (95% CI -3, 2); -0.1% (95% CI -0.3, 0.2)]. Similar improvements were observed for the other biomedical outcomes, with no differences between groups. Both groups showed improvements in total treatment satisfaction, generic well-being, and diabetes-specific well-being, and had a less threatening view of diabetes, with no differences between groups at 18 months. Approximately one in five participants in the urine monitoring arm switched to blood monitoring, while those in the blood monitoring arm rarely switched (18 vs 1% at 18 months; P < 0.001). CONCLUSIONS: Participants with newly diagnosed Type 2 diabetes who attended structured education showed similar improvements in HbA1c levels at 18 months, regardless of whether they were assigned to blood or urine self-monitoring.

Is removing blood donation barriers a donation facilitator? Australian African migrants’ view

Purpose – The aim of this study was to assess whether the removal of blood donation “barriers” facilitates blood donation intentions, using a sample of African migrants, and to identify the implications for social marketing. African migrants are currently under-represented as blood donors in Australia. Some members of the African community have unique donation needs that can only be served by this community. Design/methodology/approach – Interviews were conducted with 425 people from the African community in Victoria and South Australia. Factor analysis was performed on the barriers and the removal of barriers. Item groupings for both constructs differed, suggesting that barriers and their removal are not necessarily opposite constructs. Findings – The cultural society factor was negatively associated with blood donation intention (i.e. a barrier), whereas engagement and overcoming fear were positively associated with blood donation intention (i.e. facilitators). Cultural issues and lack of understanding were not seen to impede blood donation. Additionally, the removal of cultural barriers did not facilitate increases in blood donation intentions. Thus, the removal of barriers may not be sufficient on their own to encourage donation Research limitations/implications – This only examines the issue with regards to whether the removal of barriers is a facilitator of blood donation with one group of migrants, and relationships may vary across other migrant and non-migrant groups. Practical implications – Policymakers often use social marketing interventions to overcome barriers as a way of facilitating blood donation. This research suggests that removing barriers is indeed important because these barriers impede people considering becoming blood donors. However, the findings also suggest that the removal of barriers is insufficient on its own to motivate blood donations (i.e. the removal of barriers is a hygiene factor). If this is the case, social marketing campaigns need to be multifaceted, removing barriers as well as leveraging facilitators, simultaneously. Social implications – This work identified that the impact of barriers and their removal may facilitate effective social marketing campaigns in differing ways, in the context of blood donation. Originality/value – How barriers and their removal impact social marketing activities (i.e. blood donation behaviour) has generally not been explored in research.

Classification of electrocardiogram and auscultatory blood pressure signals using machine learning models

In this paper, two real-world medical classification problems using electrocardiogram (ECG) and auscultatory blood pressure (Korotkoff) signals are examined. A total of nine machine learning models are applied to perform classification of the medical data sets. A number of useful performance metrics which include accuracy, sensitivity, specificity, as well as the area under the receiver operating characteristic curve are computed. In addition to the original data sets, noisy data sets are generated to evaluate the robustness of the classifiers against noise. The 10-fold cross validation method is used to compute the performance statistics, in order to ensure statistically reliable results pertaining to classification of the ECG and Korotkoff signals are produced. The outcomes indicate that while logistic regression models perform the best with the original data set, ensemble machine learning models achieve good accuracy rates with noisy data sets.

Effects of diet change on carbon and nitrogen stable-isotope ratios in blood cells and plasma of the long-nosed bandicoot (Perameles nasuta)

Carbon (C) and nitrogen (N) stable isotopes offer a powerful tool for assessing the extent of tissue assimilation of dietary components. However, the method relies on knowledge of diet-tissue isotopic discrimination and how quickly diet shifts become apparent in various tissues. In the present study, blood plasma and blood cells, tissues that are easily obtained under field conditions, were used to validate the stable isotope method over a period of 4-5 weeks using captive long-nosed bandicoots (Perameles nasuta). Diet-tissue discrimination effects appeared to be small. For C, derived diet-tissue isotopic discriminations were 1.4‰ for blood plasma and -0.2‰ for blood cells. For N the values were 2.8‰ and 2.1‰, respectively, and were independent of the nitrogen content of the food. C and N turnover measurements in the blood plasma and cells of the bandicoots indicated that blood plasma provides dietary information integrated over a period of ∼3 weeks, whereas blood cells give an impression of the assimilated diet over a period of as much as half a year. These turnover rates were low compared with the little information available for birds and eutherian mammals, and probably relate to the typically low metabolic rate of marsupials.