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Given the extensive participation of myeloid cells (especially monocytes and macrophages) in both inflammation and resolution phases post-myocardial infarction (MI) owing to their biphasic role, these cells are considered as crucial players in the disease pathogenesis. Multiple studies have agreed on the significant contribution of macrophage polarization theory (M2 vs. M1) while determining the underlying reasons behind the observed biphasic effects; nevertheless, this simplistic classification attracts severe drawbacks. The advent of multiple advanced technologies based on OMICS platforms facilitated a successful path to explore comprehensive cellular signatures that could expedite our understanding of macrophage heterogeneity and plasticity. While providing an overall basis behind the MI disease pathogenesis, this review delves into the literature to discuss the current knowledge on multiple macrophage clusters, including the future directions in this research arena. In the end, our focus will be on outlining the possible therapeutic implications based on the emerging observations.

It is now well understood that the bone marrow (BM) compartment can sense systemic inflammatory signals and adapt through increased proliferation and lineage skewing. These coordinated and dynamic alterations in responding hematopoietic stem and progenitor cells (HSPCs), as well as in cells of the bone marrow niche, are increasingly viewed as key contributors to the inflammatory response. Growth factors, cytokines, metabolites, microbial products, and other signals can cause dysregulation across the entire hematopoietic hierarchy, leading to lineage-skewing and even long-term functional adaptations in bone marrow progenitor cells. These alterations may play a central role in the chronicity of disease as well as the links between many common chronic disorders. The possible existence of a form of "memory" in bone marrow progenitor cells is thought to contribute to innate immune responses via the generation of trained immunity (also called innate immune memory). These findings highlight how hematopoietic progenitors dynamically adapt to meet the demand for innate immune cells and how this adaptive response may be beneficial or detrimental depending on the context. In this review, we will discuss the role of bone marrow progenitor cells and their microenvironment in shaping the scope and scale of the immune response in health and disease.

OBJECTIVES: Dysregulation of cholesterol metabolism in the liver and hematopoietic stem and progenitor cells (HSPCs) promotes atherosclerosis development. Previously, it has been shown that HMG-CoA-Reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway, can be phosphorylated and inactivated by the metabolic stress sensor AMP-activated protein kinase (AMPK). However, the physiological significance of AMPK regulation of HMGCR to atherogenesis has yet to be elucidated. The aim of this study was to determine the role of AMPK/HMGCR axis in the development of atherosclerosis. METHODS: We have generated a novel atherosclerotic-prone mouse model with defects in the AMPK regulation of HMGCR (Apoe-/-/Hmgcr KI mice). Atherosclerotic lesion size, plaque composition, immune cell and lipid profiles were assessed in Apoe-/- and Apoe-/-/Hmgcr KI mice. RESULTS: In this study, we showed that both male and female atherosclerotic-prone mice with a disruption of HMGCR regulation by AMPK (Apoe-/-/Hmgcr KI mice) display increased aortic lesion size concomitant with an increase in plaque-associated macrophages and lipid accumulation. Consistent with this, Apoe-/-/Hmgcr KI mice exhibited an increase in total circulating cholesterol and atherogenic monocytes, Ly6-Chi subset. Mechanistically, increased circulating atherogenic monocytes in Apoe-/-/Hmgcr KI mice was associated with enhanced egress of bone marrow HSPCs and extramedullary myelopoiesis, driven by a combination of elevated circulating 27-hydroxycholesterol and intracellular cholesterol in HSPCs. CONCLUSIONS: Our results uncovered a novel signalling pathway involving AMPK-HMGCR axis in the regulation of cholesterol homeostasis in HSPCs, and that inhibition of this regulatory mechanism accelerates the development and progression of atherosclerosis. These findings provide a molecular basis to support the use of AMPK activators that currently undergoing Phase II clinical trial such as O-3O4 and PXL 770 for reducing ather

Smoking is one of the most prominent addictions of the modern world, and one of the leading preventable causes of death worldwide. Although the number of tobacco smokers is believed to be at a historic low, electronic cigarette use has been on a dramatic rise over the past decades. Used as a replacement for cigarette smoking, electronic cigarettes were thought to reduce the negative effects of burning tobacco. Nonetheless, the delivery of nicotine by electronic cigarettes, the most prominent component of cigarette smoke (CS) is still delivering the same negative outcomes, albeit to a lesser extent than CS. Smoking has been shown to affect both the structural and functional aspects of major organs, including the lungs and vasculature. Although the deleterious effects of smoking on these organs individually is well-known, it is likely that the adverse effects of smoking on these organs will have long-lasting effects on the cardiovascular system. In addition, smoking has been shown to play an independent role in the homeostasis of the immune system, leading to major sequela. Both the adaptive and the innate immune system have been explored regarding CS and have been demonstrated to be altered in a way that promotes inflammatory signals, leading to an increase in autoimmune diseases, inflammatory diseases, and cancer. Although the mechanism of action of CS has not been fully understood, disease pathways have been explored in both branches of the immune system. The pathophysiologically altered immune system during smoking and its correlation with cardiovascular diseases is not fully understood. Here we highlight some of the important pathological mechanisms that involve cigarette smoking and its many components on cardiovascular disease and the immune systems in order to have a better understanding of the mechanisms at play.

Hematopoiesis is the process of blood production, essential for the continued supply of immune cells and red blood cells. However, the proliferative nature of hematopoietic stem cells (HSCs) renders them susceptible to developing somatic mutations. HSCs carrying a mutation can gain a selective advantage over normal HSCs and result in hematological disorders. One such disorder is termed clonal hematopoiesis of indeterminate potential (CHIP), a premalignant state associated with aging, where the mutant HSCs are responsible for producing a small portion of mature immune cells in the circulation and subsequently in tissues. People with CHIP have been shown to have an increased risk of mortality due to cardiovascular disease (CVD). Why this occurs is under rigorous investigation, but the majority of the studies to date have suggested that increased atherosclerosis is due to heightened inflammatory cytokine release from mutant lesional macrophages. However, given CHIP is driven by several mutations, other hematopoietic lineages can be altered to promote CVD. In this review we explore the relationship between mutations in genes causing CHIP and atherothrombotic disorders, along with potential mechanisms of enhanced clonal outgrowth and potential therapies and strategies to slow CHIP progression.

Amino acids, the building blocks of proteins in the cells and tissues, are of fundamental importance for cell survival, maintenance, and proliferation. The liver plays a critical role in amino acid metabolism and detoxication of byproducts such as ammonia. Urea cycle disorders with hyperammonemia remain difficult to treat and eventually necessitate liver transplantation. In this study, ornithine transcarbamylase deficient (Otcspf-ash ) mouse model was used to test whether knockdown of a key glutamine metabolism enzyme glutaminase 2 (GLS2, gene name: Gls2) or glutamate dehydrogenase 1 (GLUD1, gene name: Glud1) could rescue the hyperammonemia and associated lethality induced by a high protein diet. We found that reduced hepatic expression of Gls2 but not Glud1 by AAV8-mediated delivery of a short hairpin RNA in Otcspf-ash mice diminished hyperammonemia and reduced lethality. Knockdown of Gls2 but not Glud1 in Otcspf-ash mice exhibited reduced body weight loss and increased plasma glutamine concentration. These data suggest that Gls2 hepatic knockdown could potentially help alleviate risk for hyperammonemia and other clinical manifestations of patients suffering from defects in the urea cycle.

Mouse models of active systemic anaphylaxis rely predominantly on IgG Abs forming IgG-allergen immune complexes that induce IgG receptor-expressing neutrophils and monocytes/macrophages to release potent mediators, leading to systemic effects. Whether anaphylaxis initiates locally or systemically remains unknown. In this study, we aimed at identifying the anatomical location of IgG-allergen immune complexes during anaphylaxis. Active systemic anaphylaxis was induced following immunization with BSA and i.v. challenge with fluorescently labeled BSA. Ag retention across different organs was examined using whole-body fluorescence imaging, comparing immunized and naive animals. Various mouse models and in vivo deletion strategies were employed to determine the contribution of IgG receptors, complement component C1q, myeloid cell types, and anaphylaxis mediators. We found that following challenge, Ag diffused systemically, but specifically accumulated in the lungs of mice sensitized to that Ag, where it formed large Ab-dependent aggregates in the vasculature. Ag retention in the lungs did not rely on IgG receptors, C1q, neutrophils, or macrophages. IgG2a-mediated, but neither IgG1- nor IgG2b-mediated, passive systemic anaphylaxis led to Ag retention in the lung. Neutrophils and monocytes significantly accumulated in the lungs after challenge and captured high amounts of Ag, which led to downmodulation of surface IgG receptors and triggered their activation. Thus, within minutes of systemic injection in sensitized mice, Ag formed aggregates in the lung and liver vasculature, but accumulated specifically and dose-dependently in the lung. Neutrophils and monocytes recruited to the lung captured Ag and became activated. However, Ag aggregation in the lung vasculature was not necessary for anaphylaxis induction.

IntroductionA potential role for the orphan G protein-coupled receptor, GPR21, in linking immune cell infiltration into tissues and obesity-induced insulin resistance has been proposed, although limited studies in mice are complicated by non-selective deletion of Gpr21.Research design and methodsWe hypothesized that a Gpr21-selective knockout mouse model, coupled with type 2 diabetes patient samples, would clarify these issues and enable clear assessment of GPR21 as a potential therapeutic target.ResultsHigh-fat feeding studies in Gpr21−/− mice revealed improved glucose tolerance and modest changes in inflammatory gene expression. Gpr21−/− monocytes and intraperitoneal macrophages had selectively impaired chemotactic responses to monocyte chemoattractant protein (MCP)-1, despite unaltered expression of Ccr2. Further genotypic analysis revealed that chemotactic impairment was due to dysregulated monocyte polarization. Patient samples revealed elevated GPR21 expression in peripheral blood mononuclear cells in type 2 diabetes, which was correlated with both %HbA1c and fasting plasma glucose levels.ConclusionsCollectively, human and mouse data suggest that GPR21 influences both glucose homeostasis and MCP-1/CCL2-CCR2-driven monocyte migration. However, a Gpr21−/− bone marrow transplantation and high-fat feeding study in mice revealed no effect on glucose homeostasis, suggesting that there is no (or limited) overlap in the mechanism involved for monocyte-driven inflammation and glucose homeostasi

This study analyzed the effects of 24 h of cold stress (22°C or 5°C vs. mice maintained at 30 °C) on the plasma, brown adipose tissue (BAT), subcutaneous (SubQ) and epididymal (Epi) white adipose tissue (WAT), liver, and skeletal muscle lipidome of mice. Using mass spectrometry-lipidomics, 624 lipid species were detected, of which 239 were significantly altered in plasma, 134 in BAT, and 51 in the liver. In plasma, acylcarnitines and free fatty acids were markedly increased at 5°C. Plasma triacylglycerols (TGs) were reduced at 22°C and 5°C. We also identified ether lipids as a novel, cold-induced lipid class. In BAT, TGs were the principal lipid class affected by cold stress, being significantly reduced at both 22°C and 5°C. Interestingly, although BAT TG species were uniformly affected at 5°C, at 22°C we observed species-dependent effects, with TGs containing longer and more unsaturated fatty acids particularly sensitive to the effects of cold. In the liver, TGs were the most markedly affected lipid class, increasing in abundance at 5 °C. TGs containing longer and more unsaturated fatty acids accumulated to a greater degree. Our work demonstrates the following: 1) acute exposure to moderate (22°C) cold stress alters the plasma and BAT lipidome; although this effect is markedly less pronounced than at 5°C. 2) Cold stress at 5°C dramatically alters the plasma lipidome, with ether lipids identified as a novel lipid class altered by cold exposure. 3) Cold-induced alterations in liver and BAT TG levels are not uniform, with changes being influenced by acyl chain composition.

BACKGROUND: Diabetes is associated with a significantly elevated risk of cardiovascular disease and its specific pathophysiology remains unclear. Recent studies have changed our understanding of cardiac cellularity, with cellular changes accompanying diabetes yet to be examined in detail. This study aims to characterise the changes in the cardiac cellular landscape in murine diabetes to identify potential cellular protagonists in the diabetic heart. METHODS: Diabetes was induced in male FVB/N mice by low-dose streptozotocin and a high-fat diet for 26-weeks. Cardiac function was measured by echocardiography at endpoint. Flow cytometry was performed on cardiac ventricles as well as blood, spleen, and bone-marrow at endpoint from non-diabetic and diabetic mice. To validate flow cytometry results, immunofluorescence staining was conducted on left-ventricles of age-matched mice. RESULTS: Mice with diabetes exhibited hyperglycaemia and impaired glucose tolerance at endpoint. Echocardiography revealed reduced E:A and e':a' ratios in diabetic mice indicating diastolic dysfunction. Systolic function was not different between the experimental groups. Detailed examination of cardiac cellularity found resident mesenchymal cells (RMCs) were elevated as a result of diabetes, due to a marked increase in cardiac fibroblasts, while smooth muscle cells were reduced in proportion. Moreover, we found increased levels of Ly6Chi monocytes in both the heart and in the blood. Consistent with this, the proportion of bone-marrow haematopoietic stem cells were increased in diabetic mice. CONCLUSIONS: Murine diabetes results in distinct changes in cardiac cellularity. These changes-in particular increased levels of fibroblasts-offer a framework for understanding how cardiac cellularity changes in diabetes. The results also point to new cellular mechanisms in this context, which may further aid in development of pharmacotherapies to allay the progression of cardiomyopathy associated with diabet

Adipose-tissue-resident macrophages (ATMs) maintain metabolic homeostasis but also contribute to obesity-induced adipose tissue inflammation and metabolic dysfunction. Central to these contrasting effects of ATMs on metabolic homeostasis is the interaction of macrophages with fatty acids. Fatty acid levels are increased within adipose tissue in various pathological and physiological conditions, but appear to initiate inflammatory responses only upon interaction with particular macrophage subsets within obese adipose tissue. The molecular basis underlying these divergent outcomes is likely due to phenotypic differences between ATM subsets, although how macrophage polarization state influences the metabolism of exogenous fatty acids is relatively unknown. Herein, using stable isotope-labeled and nonlabeled fatty acids in combination with mass spectrometry lipidomics, we show marked differences in the utilization of exogenous fatty acids within inflammatory macrophages (M1 macrophages) and macrophages involved in tissue homeostasis (M2 macrophages). Specifically, the accumulation of exogenous fatty acids within triacylglycerols and cholesterol esters is significantly higher in M1 macrophages, while there is an increased enrichment of exogenous fatty acids within glycerophospholipids, ether lipids, and sphingolipids in M2 macrophages. Finally, we show that functionally distinct ATM populations in vivo have distinct lipid compositions. Collectively, this study identifies new aspects of the metabolic reprogramming that occur in distinct macrophage polarization states. The channeling of exogenous fatty acids into particular lipid synthetic pathways may contribute to the sensitivity/resistance of macrophage subsets to the inflammatory effects of increased environmental fatty acid levels.

Plasmalogens are membrane glycerophospholipids with diverse biological functions. Reduced plasmalogen levels have been observed in metabolic diseases; hence, increasing their levels might be beneficial in ameliorating these conditions. Shark liver oil (SLO) is a rich source of alkylglycerols that can be metabolized into plasmalogens. This study was designed to evaluate the impact of SLO supplementation on endogenous plasmalogen levels in individuals with features of metabolic disease. In this randomized, double-blind, placebo-controlled cross-over study, the participants (10 overweight or obese males) received 4-g Alkyrol® (purified SLO) or placebo (methylcellulose) per day for 3 weeks followed by a 3-week washout phase and were then crossed over to 3 weeks of the alternate placebo/Alkyrol® treatment. SLO supplementation led to significant changes in plasma and circulatory white blood cell lipidomes, notably increased levels of plasmalogens and other ether lipids. In addition, SLO supplementation significantly decreased the plasma levels of total free cholesterol, triglycerides, and C-reactive protein. These findings suggest that SLO supplementation can enrich plasma and cellular plasmalogens and this enrichment may provide protection against obesity-related dyslipidemia and inflammation.

There is a strong association between hepatocyte phospholipid homeostasis and non-alcoholic fatty liver disease (NAFLD). The phosphatidylcholine to phosphatidylethanolamine ratio (PC/PE) often draws special attention as genetic and dietary disruptions to this ratio can provoke steatohepatitis and other signs of NAFLD. Here we demonstrated that excessive free fatty acid (1:2 mixture of palmitic and oleic acid) alone was able to significantly lower the phosphatidylcholine to phosphatidylethanolamine ratio, along with substantial alterations to phospholipid composition in rat hepatocytes. This involved both a decrease in hepatocyte phosphatidylcholine (less prominent) and an increase in phosphatidylethanolamine, with the latter contributing more to the lowered ratio. Stable isotopic tracer phospholipidomic analysis revealed several previously unidentified changes that were triggered by excessive free fatty acid. Importantly, the enhanced cytidine diphosphate (CDP)-ethanolamine pathway activity appeared to be driven by the increased supply of preferred fatty acid substrates. By contrast, the phosphatidylethanolamine N-methyl transferase (PEMT) pathway was restricted by low endogenous methionine and consequently low S-adenosylmethionine, which resulted in a concomitant decrease in phosphatidylcholine and accumulation of phosphatidylethanolamine. Overall, our study identified several previously unreported links in the relationship between hepatocyte free fatty acid overload, phospholipid homeostasis, and the development of NAFLD.

The development of myelodysplasia syndromes (MDS) is multiphasic and can be driven by a plethora of genetic mutations and/or abnormalities. MDS is characterized by a hematopoietic differentiation block, evidenced by increased immature hematopoietic cells, termed blast cells and decreased mature circulating leukocytes in at least one lineage (i.e., cytopenia). Clonal hematopoiesis of indeterminate potential (CHIP) is a recently described phenomenon preceding MDS development that is driven by somatic mutations in hemopoietic stem cells (HSCs). These mutant HSCs have a competitive advantage over healthy cells, resulting in an expansion of these clonal mutated leukocytes. In this review, we discuss the multiphasic development of MDS, the common mutations found in both MDS and CHIP, how a loss-of-function in these CHIP-related genes can alter HSC function and leukocyte development and the potential disease outcomes that can occur with dysfunctional HSCs. In particular, we discuss the novel connections between MDS development and cardiovascular disease.

Bone marrow is a preferred metastatic site for multiple solid tumours and is associated with poor prognosis and significant morbidity. Accumulating evidence indicates that cancer cells colonise specialised niches within the bone marrow to support their long-term propagation, but the precise location and mechanisms that mediate niche interactions are unknown. Using breast cancer as a model of solid tumour metastasis to the bone marrow, we applied large-scale quantitative three-dimensional imaging to characterise temporal changes in the bone marrow microenvironment during disease progression. We show that mouse mammary tumour cells preferentially home to a pre-existing metaphyseal domain enriched for type H vessels. Metastatic lesion outgrowth rapidly remodelled the local vasculature through extensive sprouting to establish a tumour-supportive microenvironment. The evolution of this tumour microenvironment reflects direct remodelling of the vascular endothelium through tumour-derived granulocyte-colony stimulating factor (G-CSF) in a hematopoietic cell-independent manner. Therapeutic targeting of the metastatic niche by blocking G-CSF receptor inhibited pathological blood vessel remodelling and reduced bone metastasis burden. These findings elucidate a mechanism of 'host' microenvironment hijacking by mammary tumour cells to subvert the local microvasculature to form a specialised, pro-tumorigenic niche.

BACKGROUND: Cardiovascular disease is the leading cause of death in Australia. Investment in research solutions has been demonstrated to yield health and a 9.8-fold return economic benefit. The sector, however, is severely challenged with success rates of traditional peer-reviewed funding in decline. Here, we aimed to understand the perceived challenges faced by the cardiovascular workforce in Australia prior to the COVID-19 pandemic. METHODS: We used an online survey distributed across Australian cardiovascular societies/councils, universities and research institutes over a period of 6 months during 2019, with 548 completed responses. Inclusion criteria included being an Australian resident or an Australian citizen who lived overseas, and a current or past student or employee in the field of cardiovascular research. RESULTS: The mean age of respondents was 42±13 years, 47% were male, 85% had a full-time position, and 40% were a group leader or laboratory head. Twenty-three per cent (23%) had permanent employment, and 82% of full-time workers regularly worked >40 hours/week. Sixty-eight per cent (68%) said they had previously considered leaving the cardiovascular research sector. If their position could not be funded in the next few years, a staggering 91% of respondents would leave the sector. Compared to PhD- and age-matched men, women were less likely to be a laboratory head and to feel they had a long-term career path as a cardiovascular researcher, while more women were unsure about future employment and had considered leaving the sector (all p<0.05). Greater job security (76%) and government and philanthropic investment in cardiovascular research (72%) were highlighted by responders as the main changes to current practices that would encourage them to stay. CONCLUSION: Strategic solutions, such as diversification of career pathways and funding sources, and moving from a competitive to a collaborative culture, need to be a priority to decrease reliance on gover

Macrophages are the first immune cells in the developing embryo and have a central role in organ development, homeostasis, immunity and repair. Over the last century, our understanding of these cells has evolved from being thought of as simple phagocytic cells to master regulators involved in governing a myriad of cellular processes. A better appreciation of macrophage biology has been matched with a clearer understanding of their diverse origins and the flexibility of their metabolic and transcriptional machinery. The understanding of the classical mononuclear phagocyte system in its original form has now been expanded to include the embryonic origin of tissue-resident macrophages. A better knowledge of the intrinsic similarities and differences between macrophages of embryonic or monocyte origin has highlighted the importance of ontogeny in macrophage dysfunction in disease. In this review, we provide an update on origin and classification of tissue macrophages, the mechanisms of macrophage specialisation and their role in health and disease. The importance of the macrophage niche in providing trophic factors and a specialised environment for macrophage differentiation and specialisation is also discussed.

The intrinsic apoptotic pathway is controlled by the BCL-2 family of proteins, which exhibit either a pro-death or pro-survival function. Gene knockout studies revealed that different pro-survival BCL-2 proteins are critical for the survival of distinct cell types, although overlapping functions amongst such proteins have also been identified. In the process of studying mice lacking single alleles of Mcl-1 (Mcl-1+/-), Bcl-2 (Bcl-2+/-), or both in combination (Mcl-1+/-Bcl-2+/-), we observed that Mcl-1+/-Bcl-2+/- mice weighed less when compared with their wild-type littermates as they aged. Body composition analysis demonstrated that while fat mass was similar to wild-type controls, lean mass was significantly reduced in Mcl-1+/-, Bcl-2+/-, and, most strikingly in Mcl-1+/-Bcl-2+/- mice. The weights of several tissues including the heart, tibialis anterior, and kidney were likewise reduced in Mcl-1+/-Bcl-2+/- mice. When lean mass and specific tissue weights were expressed relative to body weight, these differences were no longer significant, indicating that that Mcl-1+/-Bcl-2+/- mice, and to a lesser extent Mcl-1+/- and Bcl-2+/- mice, are smaller than their wild-type counterparts. Consistently, the anal-naso length was reduced in Mcl-1+/-Bcl-2+/- mice. While minor reductions in size were observed in female Mcl-1+/-Bcl-2+/- mice, these effects were most prominent in males. Notably, Mcl-1+/-Bcl-2+/- males had markedly smaller testes even after accounting for differences in body weight. Collectively, these data reveal that combined loss of a single allele of Mcl-1 and Bcl-2, while not overtly impairing organismal development, leads to a reduction in animal size.

Monocytes in humans consist of 3 subsets; CD14+CD16- (classical), CD14+CD16+ (intermediate) and CD14dimCD16+ (non-classical), which exhibit distinct and heterogeneous responses to activation. During acute inflammation CD14+CD16- monocytes are significantly elevated and migrate to the sites of injury via the adhesion cascade. The field of immunometabolism has begun to elucidate the importance of the engagement of specific metabolic pathways in immune cell function. Yet, little is known about monocyte metabolism and the role of metabolism in mediating monocyte activation and adherence to vessels. Accordingly, we aimed to determine whether manipulating the metabolism of CD14+CD16- monocytes alters their ability to become activated and adhere. We discovered that LPS stimulation increased the rate of glycolysis in human CD14+CD16- monocytes. Inhibition of glycolysis with 2-deoxy-D-glucose blunted LPS-induced activation and adhesion of monocytes. Mechanistically, we found that increased glycolysis was regulated by mTOR-induced glucose transporter (GLUT)-1. Furthermore, enhanced glycolysis increased accumulation of reactive oxygen species (ROS) and activation of p38 MAPK, which lead to activation and adhesion of monocytes. These findings reveal that glycolytic metabolism is critical for the activation of CD14+CD16- monocytes and contributes to our understanding of the interplay between metabolic substrate preference and immune cell function.

Circulating tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) levels are reduced in patients with cardiovascular disease, and TRAIL gene deletion in mice exacerbates atherosclerosis and inflammation. How TRAIL protects against atherosclerosis and why levels are reduced in disease is unknown. Here, multiple strategies were used to identify the protective source of TRAIL and its mechanism(s) of action. Samples from patients with coronary artery disease and bone-marrow transplantation experiments in mice lacking TRAIL revealed monocytes/macrophages as the main protective source. Accordingly, deletion of TRAIL caused a more inflammatory macrophage with reduced migration, displaying impaired reverse cholesterol efflux and efferocytosis. Furthermore, interleukin (IL)-18, commonly increased in plasma of patients with cardiovascular disease, negatively regulated TRAIL transcription and gene expression, revealing an IL-18-TRAIL axis. These findings demonstrate that TRAIL is protective of atherosclerosis by modulating monocyte/macrophage phenotype and function. Manipulating TRAIL levels in these cells highlights a different therapeutic avenue in the treatment of cardiovascular disease.

The anti-inflammatory, pro-resolving annexin-A1 protein acts as an endogenous brake against exaggerated cardiac necrosis, inflammation, and fibrosis following myocardial infarction (MI) in vivo. Little is known, however, regarding the cardioprotective actions of the N-terminal-derived peptide of annexin A1, Ac2-26, particularly beyond its anti-necrotic actions in the first few hours after an ischemic insult. In this study, we tested the hypothesis that exogenous Ac2-26 limits cardiac injury in vitro and in vivo. Firstly, we demonstrated that Ac2-26 limits cardiomyocyte death both in vitro and in mice subjected to ischemia-reperfusion (I-R) injury in vivo (Ac2-26, 1 mg/kg, i.v. just prior to post-ischemic reperfusion). Further, Ac2-26 (1 mg/kg i.v.) reduced cardiac inflammation (after 48 h reperfusion), as well as both cardiac fibrosis and apoptosis (after 7-days reperfusion). Lastly, we investigated whether Ac2-26 preserved cardiac function after MI. Ac2-26 (1 mg/kg/day s.c., osmotic pump) delayed early cardiac dysfunction 1 week post MI, but elicited no further improvement 4 weeks after MI. Taken together, our data demonstrate the first evidence that Ac2-26 not only preserves cardiomyocyte survival in vitro, but also offers cardioprotection beyond the first few hours after an ischemic insult in vivo. Annexin-A1 mimetics thus represent a potential new therapy to improve cardiac outcomes after MI.

Small non-coding RNAs (ncRNAs) are emerging as important molecules for normal biological processes and are deregulated in disease. Exercise training is a powerful therapeutic strategy that prevents cardiometabolic disease and improves cardiorespiratory fitness and performance. Despite the known systemic health benefits of exercise training, the underlying molecular mechanisms are incompletely understood. Recent evidence suggests a role for epigenetic mechanisms, such as microRNAs, but whether other small ncRNAs are modulated by chronic exercise training is unknown. Here, we used small RNA sequencing to explore whether sprint interval training (SIT) controls the abundance of circulating small ncRNAs in human whole blood samples. Ten healthy men performed SIT three times a week for 6 weeks. After training, subjects showed marked improvements in maximal oxygen consumption and cycling performance with concurrent changes to the abundance of diverse species of circulating small ncRNAs (n = 1266 small ncRNAs, n = 13 microRNAs, q < 0.05). Twelve microRNAs altered by 6 weeks of SIT were ubiquitously expressed microRNAs and two regulated important signaling pathways, including p53, thyroid hormone and cell cycle signaling. MicroRNAs altered by 6 weeks of SIT were unchanged after a single session of SIT (n = 24, all P > 0.05). Relative to older individuals, younger subjects exhibited an increased acute SIT-induced fold change in miR-1301-3p (P = 0.02) – a microRNA predicted to target mRNAs involved in alternative splicing, phosphoprotein and chromosomal rearrangement processes (all P < 0.001). Our findings indicate many species of circulating small ncRNAs are modulated by exercise training and that they could control signaling pathways responsible for health benefits achieved from exercise.

Obesity enhances the risk of developing myelodysplastic syndromes. However, the effect of obesity on survival is unclear. Obese people present with monocytosis due to inflammatory signals emanating from obese adipose tissue. We hypothesized that obesity-induced myelopoiesis would promote the transition of myelodysplastic syndrome to acute myeloid leukemia and accelerate mortality in obesity. Obese Ob/Ob mice or their lean littermate controls received a bone marrow transplant from NUP98-HOXD13 transgenic mice, a model of myelodysplastic syndrome. The metabolic parameters of the mice were examined throughout the course of the study, as were blood leukocytes. Myeloid cells were analyzed in the bone, spleen, liver and adipose tissue by flow cytometry halfway through the disease progression and at the endpoint. Survival curves were also calculated. Contrary to our hypothesis, transplantation of NUP98-HOXD13 bone marrow into obese recipient mice significantly increased survival time compared with lean recipient controls. While monocyte skewing was exacerbated in obese mice receiving NUP98-HOXD13 bone marrow, transformation to acute myeloid leukemia was not enhanced. Increased survival of obese mice was associated with a preservation of fat mass as well as increased myeloid cell deposition within the adipose tissue, and a concomitant reduction in detrimental myeloid cell accumulation within other organs. The study herein revealed that obesity increases survival in animals with myelodysplastic syndrome. This may be due to the greater fat mass of Ob/Ob mice, which acts as a sink for myeloid cells, preventing their accumulation in other key organs, such as the liver.

Macrophages are abundant within adipose tissue depots where they are exposed to fatty acids, leading to lipid accumulation. Herein, we have determined the effects of various fatty acids on the macrophage lipidome. Using targeted mass-spectrometry, we were able to detect 641 individual lipid species in primary murine macrophages treated with a variety of saturated fatty acids and an un-saturated fatty acid, either alone or in combination. The most pronounced effects were observed for the long-chain saturated fatty acid palmitate, which increased the total abundance of numerous classes of lipids. While other medium- and long-chain saturated fatty acids, as well as the long-chain unsaturated fatty acid, had less pronounced effects on the total abundance of specific lipid classes, all fatty acids induced marked alterations in the abundance of numerous lipid species within given lipid classes. Fatty acid treatment markedly altered overall phospholipid saturation status; these effects were most pronounced for phosphatidylcholine and ether-phosphatidylcholine lipid species. Finally, treatment of macrophages with either palmitate or stearate in combination with oleate prevented many of the changes that were observed in macrophages treated with palmitate or stearate alone. Collectively, our results reveal substantial and specific remodelling of the macrophage lipidome following treatment with fatty acids.

UNLABELLED: Essentials Vessel stenosis due to large thrombus formation increases local shear 1-2 orders of magnitude. High shear at stenotic sites was exploited to trigger eptifibatide release from nanocapsules. Local delivery of eptifibatide prevented vessel occlusion without increased tail bleeding times. Local nanocapsule delivery of eptifibatide may be safer than systemic antiplatelet therapies. SUMMARY: Background Myocardial infarction and stroke remain the leading causes of mortality and morbidity. The major limitation of current antiplatelet therapy is that the effective concentrations are limited because of bleeding complications. Targeted delivery of antiplatelet drug to sites of thrombosis would overcome these limitations. Objectives Here, we have exploited a key biomechanical feature specific to thrombosis, i.e. significantly increased blood shear stress resulting from a reduction in the lumen of the vessel, to achieve site-directed delivery of the clinically used antiplatelet agent eptifibatide by using shear-sensitive phosphatidylcholine (PC)-based nanocapsules. Methods PC-based nanocapsules (2.8 × 1012 ) with high-dose encapsulated eptifibatide were introduced into microfluidic blood perfusion assays and into in vivo models of thrombosis and tail bleeding. Results Shear-triggered nanocapsule delivery of eptifibatide inhibited in vitro thrombus formation selectively under stenotic and high shear flow conditions above a shear rate of 1000 s-1 while leaving thrombus formation under physiologic shear rates unaffected. Thrombosis was effectively prevented in in vivo models of vessel wall damage. Importantly, mice infused with shear-sensitive antiplatelet nanocapsules did not show prolonged bleeding times. Conclusions Targeted delivery of eptifibatide by shear-sensitive nanocapsules offers site-specific antiplatelet potential, and may form a basis for developing more potent and safer antiplatelet drugs.

The realization that an intricate link exists between the metabolic state of immune cells and the nature of the elicited immune responses has brought a dramatic evolution to the field of immunology. We will focus on how metabolic reprogramming through the use of glycolysis and fatty-acid oxidation (sugar or fat) regulates the capacity of immune cells to mount robust and effective immune responses. We will also discuss how fine-tuning sugar and fat metabolism may be exploited as a novel immunotherapeutic strategy to fight viral infections or improve vaccine efficacy.

Endogenous anti-inflammatory annexin-A1 (ANX-A1) plays an important role in preserving left ventricular (LV) viability and function after ischaemic insults in vitro, but its long-term cardioprotective actions in vivo are largely unknown. We tested the hypothesis that ANX-A1-deficiency exaggerates inflammation, haematopoietic stem progenitor cell (HSPC) activity and LV remodelling in response to myocardial ischaemia in vivo. Adult ANX - A1 -/- mice subjected to coronary artery occlusion exhibited increased infarct size and LV macrophage content after 24-48 h reperfusion compared with wildtype (WT) counterparts. In addition, ANX - A1 -/- mice exhibited greater expansion of HSPCs and altered pattern of HSPC mobilisation 8 days post-myocardial infarction, with increased circulating neutrophils and platelets, consistent with increased cardiac inflammation as a result of increased myeloid invading injured myocardium in response to MI. Furthermore, ANX - A1 -/- mice exhibited significantly increased expression of LV pro-inflammatory and pro-fibrotic genes and collagen deposition after MI compared to WT counterparts. ANX-A1-deficiency increased cardiac necrosis, inflammation, hypertrophy and fibrosis following MI, accompanied by exaggerated HSPC activity and impaired macrophage phenotype. These findings suggest that endogenous ANX-A1 regulates mobilisation and differentiation of HSPCs. Limiting excessive monocyte/neutrophil production may limit LV damage in vivo. Our findings support further development of novel ANX-A1-based therapies to improve cardiac outcomes after MI.

© 2017 Informa UK Limited, trading as Taylor & Francis Group. The aim of this study was to provide contemporary information on injury rates in an elite and sub-elite netball population and to explore the relationship between lower body stiffness and lower body injuries. One elite and two sub-elite teams of female netballers (n = 29) performed the vertical hop test to assess active lower body stiffness (Kvert) and myometry to assess quasi-static stiffness. Lower body injuries were monitored via self-reporting and liaison with physiotherapists. Twelve lower body non-contact injuries were sustained by 10 players, equating to 11.29 lower body injuries per 1,000 exposure hours. The most commonly injured sites were the calf (33%) and ankle (25%). No significant differences between Kvert of injured and non-injured players were reported, however, injured elite players recorded significantly higher season mean quasi-static stiffness in the soleus (p = 0.037) and Achilles (p = 0.004) than non-injured elite players. Elite and sub-elite netball players recorded a higher injury incidence than previous reports of injuries in recreational netballers. Within the constraints of the study, relatively high stiffness of the soleus and Achilles appears to be related to lower body non-contact injury incidence in female netballers, particularly at the elite level. These results provide a basis for development of injury prevention strategies.

© 2016 Background Stiffness is commonly assessed in relation to injury and athletic performance. The purpose of this research was to compare the validity and reliability of 3 in vivo methods of stiffness assessment using 1 cohort of participants. Methods To determine inter-day reliability, 15 female netballers were assessed for stiffness twice within 1 week using unilateral hopping (vertical stiffness), free oscillations of the calf, and myometry of various muscles of the triceps surae. To establish convergent construct validity, stiffness was compared to static and dynamic strength measurements. Results Test–retest stiffness results revealed that vertical stiffness produced moderate to high reliability results and myometry presented moderate to very high reliability. In contrast, the free oscillation technique displayed low to moderate reliability. Vertical stiffness demonstrated a significant correlation with rate of force development during a squat jump, whilst myometer stiffness measurements from 3 sites in the lower limb revealed significant correlations with isometric rate of force development. Further, significant negative correlations were evident between the eccentric utilisation ratio and various myometer stiffness results. No relationships were established between the free oscillation technique and any of the performance measurements. Conclusion These results suggest that vertical stiffness and myometry are valid and reliable methods for assessing stiffness.

© 2016, National Research Council of Canada. All rights reserved. The aim of this study was to determine the effects of high- and low-cadence interval training on the freely chosen cadence (FCC) and performance in endurance-trained cyclists. Sixteen male endurance-trained cyclists completed a series of submaximal rides at 60% maximal power (Wmax) at cadences of 50, 70, 90, and 110 r·min-1, and their FCC to determine their preferred cadence, gross efficiency (GE), rating of perceived exertion, and crank torque profile. Performance was measured via a 15-min time trial, which was preloaded with a cycle at 60% Wmax. Following the testing, the participants were randomly assigned to a high-cadence (HC) (20% above FCC) or a low-cadence (LC) (20% below FCC) group for 18 interval-based training sessions over 6 weeks. The HC group increased their FCC from 92 to 101 r·min-1 after the intervention (p = 0.01), whereas the LC group remained unchanged (93 r·min-1). GE increased from 22.7% to 23.6% in the HC group at 90 r·min-1 (p = 0.05), from 20.0% to 20.9% at 110 r·min-1 (p = 0.05), and from 22.8% to 23.2% at their FCC. Both groups significantly increased their total distance and average power output following training, with the LC group recording a superior performance measure. There were minimal changes to the crank torque profile in both groups following training. This study demonstrated that the FCC can be altered with HC interval training and that the determinants of the optimal cycling cadence are multifactorial and not completely understood. Furthermore, LC interval training may significantly improve time-trial results of short duration as a result of an increase in strength development or possible neuromuscular adaptations.

© 2015 Human Kinetics, Inc. Purpose: To investigate the validity and reliability of accelerometry of the SPI-ProX II dual data logger (GPSports, Canberra, Australia). Methods: Controlled laboratory assessments determined the accuracy and reproducibility of raw accelerometer data. Intra- and interdevice reliability assessed the ability of the SPI-ProX II accelerometers to repeatedly measure peak gravitational accelerations (g) during impact-based testing. Static and dynamic validity testing assessed the accuracy of SPI-ProX II accelerometers against a criterion-referenced accelerometer. Dynamic validity was assessed over a range of frequencies from 5 to 15 Hz. Results: Intradevice reliability found no differences (P < .05) between 4 SPI-ProX II accelerometers, with a low coefficient of variation (1.87-2.21%). SPI-ProX II accelerometers demonstrated small to medium effect-size (ES) differences (0.10-0.44) between groups and excellent interdevice reliability, with no difference found between units (F = 0.826, P = .484). Validity testing revealed significant differences between devices (P = .001), with high percentage differences (27.5-30.5%) and a large ES (>3.44). Conclusions: SPI-ProX II accelerometers demonstrated excellent intra- and interaccelerometer reliability. However, static and dynamic validity were poor, and caution is recommended when measuring the absolute magnitude of acceleration, particularly for high-frequency movements. Regular assessment of individual devices is advised, particularly for mechanical damage and signal-drift errors. It is recommended that guidelines be provided by the manufacturer on measuring shifts in the base accelerometer signal, including time frames for assessing accelerometer axis, magnitude of errors, and calibration of accelerometers from a stable reference point.

© 2015 National Strength and Conditioning Association. There are many notable differences in physical and skill attributes between competition levels, especially in team sports. Stiffness is an important mechanical factor to measure when considering athletic performance and injury incidence. Active vertical stiffness (K vert) during hopping and passive stiffness during lying and standing were measured during the preseason period for 46 female netballers (24.0 ± 3.7 years, 72.2 ± 7.6 kg, 175.2 ± 6.7 cm). Participants were classified as elite, sub-elite, representative or recreational based on their current level of competition. A 1-way analysis of variance revealed that elite players possessed significantly higher K vert than recreational players (p 0.018). Large effect sizes (ES) suggested that elite players also possessed higher K vert than sub-elite (d 1.11) and representative (d 1.11) players. A number of large and moderate ES were also present when comparing the passive stiffness of elite players to their lower-ranked counterparts. The results of this study suggest that elite players possess higher levels of active stiffness when compared with their lower-ranked counterparts. The differences in stiffness levels may contribute to a player's ability to physically perform at an elite level and also provide one explanation into elevated rates of injury at higher levels of competition.

Leg stiffness (Kleg) is an important component to consider in both performance and injury in the Australian Football League (AFL). Kleg has not yet been examined longitudinally throughout an entire AFL season. A unilateral hop test was used to measure Kleg in the left and right legs of 25 professional AFL players (24.9 ± 4.3 years, 86.8 ± 8.1 kg, 187.0 ± 7.3 cm). Kleg was assessed at least once permonth for each participant. Furthermore, the session rate of perceived exertion method was used to quantify the average weekly training loads experienced by the participants. One-way analysis of variance revealed no significant difference between the average monthly bilateral Kleg scores; however, average weekly training loads varied between 1,400 and 2,000 AU, depending on the training period. Thirteen participants were randomly selected to perform hop tests on 2 consecutive weeks. Reliability tests revealed these measurements to have a typical error of the measurement of 4.15% and an intraclass correlation of 0.8, proving the methods to be reliable. Although training intensity appears to vary, Kleg does not fluctuate significantly across an entire AFL season, suggesting that weekly training loads between 1,400 and 2,000 AU may be prescribed without the risk of fluctuating stiffness levels. © 2013 National Strength and Conditioning Association.

A variety of resistance training interventions are used to improve field sport acceleration (e.g., free sprinting, weights, plyometrics, resisted sprinting). The effects these protocols have on acceleration performance and components of sprint technique have not been clearly defined in the literature. This study assessed 4 common protocols (free sprint training [FST], weight training [WT], plyometric training [PT], and resisted sprint training [RST]) for changes in acceleration kinematics, power, and strength in field sport athletes. Thirty-five men were divided into 4 groups (FST: n = 9; WT: n = 8; PT: n = 9; RST: n = 9) matched for 10-m velocity. Training involved two 60-minute sessions per week for 6 weeks. After the interventions, paired-sample t-tests identified significant (p ≤ 0.05) within-group changes. All the groups increased the 0- to 5-m and 0- to 10-m velocity by 9-10%. The WT and PT groups increased the 5- to 10-m velocity by approximately 10%. All the groups increased step length for all distance intervals. The FST group decreased 0- to 5-m flight time and step frequency in all intervals and increased 0- to 5-m and 0- to 10-m contact time. Power and strength adaptations were protocol specific. The FST group improved horizontal power as measured by a 5-bound test. The FST, PT, and RST groups all improved reactive strength index derived from a 40-cm drop jump, indicating enhanced muscle stretch-shortening capacity during rebound from impacts. The WT group increased absolute and relative strength measured by a 3-repetition maximum squat by approximately 15%. Step length was the major limiting sprint performance factor for the athletes in this study. Correctly administered, each training protocol can be effective in improving acceleration. To increase step length and improve acceleration, field sport athletes should develop specific horizontal and reactive power.

Session ratings of perceived exertion (session RPE) are commonly used to assess global training intensity for team sports. However, there is little research quantifying the intensity of field-based training protocols for speed development. The study's aim was to determine the session RPE of popular training protocols (free sprint [FST], resisted sprint [RST], and plyometrics [PT]) designed to improve sprint acceleration over 10 m in team sport athletes. Twenty-seven men (age = 23.3 ± 4.7 years; mass = 84.5 ± 8.9 kg; height = 1.83 ± 0.07 m) were divided into 3 groups according to 10-m velocity. Training consisted of an incremental program featuring two 1-hour sessions per week for 6 weeks. Subjects recorded session RPE 30 minutes post training using the Borg category-ratio 10 scale. Repeated measures analysis of variance found significant (p < 0.05) changes in sprint velocity and session RPE over 6 weeks. All groups significantly increased 0- to 5-m velocity and 0- to 10-m velocity by 4-7%, with no differences between groups. There were no significant differences in session RPE between the groups, suggesting that protocols were matched for intensity. Session RPE significantly increased over the 6 weeks for all groups, ranging from 3.75 to 5.50. This equated to intensities of somewhat hard to hard. Post hoc testing revealed few significant weekly increases, suggesting that session RPE may not be sensitive to weekly load increases in sprint and plyometric training programs. Another explanation, however, could be that the weekly load increments used were not great enough to increase perceived exertion. Nonetheless, the progressive overload of each program was sufficient to improve 10-m sprint performance. The session RPE values from the present study could be used to assess workload for speed training periodization within a team sports conditioning program.

The purpose of this research was to investigate the validity and the reliability of 5-Hz MinimaxX global positioning system (GPS) units measuring athlete movement demands. A team sport simulation circuit (files collected from each unit = 12) and flying 50-m sprints (files collected from each unit = 34) were undertaken, during which the total distance covered; peak speed; player load; the distance covered; time spent and number of efforts performed walking, jogging, running, highspeed running, and sprinting were examined. Movement demands were also separately categorized into low-intensity activity, high-intensity running, and very high-intensity running. The results revealed that GPS was a valid and reliable measure of total distance covered (p > 0.05, percentage typical error of measurement [%TEM] < 5%) and peak speed (p > 0.05, %TEM 5-10%). Further, GPS was found to be a reliable measure of player load (%TEM 4.9%) and the distance covered, time spent, and number of efforts performed at certain velocity zones (%TEM <5% to >10%). The level of GPS error was found to increase along with the velocity of exercise. The findings demonstrated that GPS is capable of measuring movement demands performed at velocities <20 km·h -1, whereas more caution is to be exercised when analyzing movement demands collected by using GPS velocities >20 km·h -1. © 2012 National Strength and Conditioning Association.

Leg stiffness is a modifiable mechanical property that may be related to soft tissue injury risk. The purpose of this study was to examine mean leg stiffness and bilateral differences in leg stiffness across an entire professional Australian Football League (AFL) season, and determine whether this parameter was related to the incidence of lower body soft tissue injury. The stiffness of the left and right legs of 39 professional AFL players (age 24.4 +/- 4.4 years, body mass 87.4 +/- 8.1 kg, stature 1.87 +/- 0.07 m) was measured using a unilateral hopping test at least once per month throughout the season. Injury data were obtained directly from the head medical officer at the football club. Mean leg stiffness and bilateral differences in leg stiffness were compared between the injured and non-injured players. There was no difference between the season mean leg stiffness values for the injured (219.3 +/- 16.1 N . m(-1) . kg(-1)) and non-injured (217.4 +/- 14.9 N . m(-1) . kg(-1); P = 0.721) groups. The injured group (7.5 +/- 3.0%) recorded a significantly higher season mean bilateral difference in leg stiffness than the non-injured group (5.5 +/- 1.3%; P = 0.05). A relatively high bilateral difference in leg stiffness appears to be related to the incidence of soft tissue injury in Australian football players. This information is of particular importance to medical and conditioning staff across a variety of sports.

Futsal is the Fèdèration de Internationale Football Association's officially recognized fivea-side indoor soccer, which although increasing in popularity worldwide, lacks the Australian or other English language research necessary to enable the growth of the sport. The purpose of this study was to establish a comprehensive overview of the demands of futsal by a time-motion analysis on 8 Australian National Team players and 10 State League Team players over 4 futsal matches. The study analyzed 6 locomotor activity categories, focusing on total distance covered, total duration of activities, total frequency of activities, effort distance, and effort duration. The national team covered a 42% greater overall distance than the state league team. In terms of relative data normalized for match duration, only the standing duration value was significantly different between the teams. Furthermore, futsal players of elite and subelite level in Australia perform a change in activity every 8-9 seconds on the court, and the national team athletes attained a higher, yet nonsignificant, average match-play velocity. This may be because of the national futsal athletes participating in an extended game duration, potentially suggesting that higher levels of competition facilitate a higher intensity of match play and greater physiological demands on individual players. Apart from the differences in timing structure and overall metabolic work, there was no real difference between the levels of competition within the Australian futsal analysis, although at higher levels of competition, there may be a need for more recovery because of the elevated intensity of the match. When comparing the data with other countries, however, Australian futsal players produce less distance and duration than Spanish futsal players. © 2011 National Strength and Conditioning Association.

Speed and acceleration are essential for field sport athletes. However, the mechanical factors important for field sport acceleration have not been established in the scientific literature. The purpose of this study was to determine the biomechanical and performance factors that differentiate sprint acceleration ability in field sport athletes. Twenty men completed sprint tests for biomechanical analysis and tests of power, strength, and leg stiffness. The sprint intervals analyzed were 0-5, 5-10, and 0-10 m. The subjects were split into a faster and slower group based on 0- to 10-m velocity. A 1-way analysis of variance determined variables that significantly (p ≤ 0.05) distinguished between faster and slower acceleration. All subject data were then pooled for a correlation analysis to determine factors contributing most to acceleration. The results showed that 0- to 5-m (∼16% difference) and 0- to 10-m (∼11% difference) contact times for the faster group were significantly lower. Times to peak vertical and horizontal force during ground contact were lower for the faster group. This was associated with the reduced support times achieved by faster accelerators and their ability to generate force quickly. Ground contact force profiles during initial acceleration are useful discriminators of sprint performance in field sport athletes. For the strength and power measures, the faster group demonstrated a 14% greater countermovement jump and 48% greater reactive strength index. Significant correlations were found between velocity (0-5, 5-10, and 0-10 m) and most strength and power measures. The novel finding of this study is that training programs directed toward improving field sport sprint acceleration should aim to reduce contact time and improve ground force efficiency. It is important that even during the short sprints required for field sports, practitioners focus on good technique with short contact times.

Subjective notational analysis can be used to track players and analyse movement patterns during match-play of team sports such as futsal. The purpose of this study was to establish the validity and reliability of the Event Recorder for subjective notational analysis. A course was designed, replicating ten minutes of futsal match-play movement patterns, where ten participants undertook the course. The course allowed a comparison of data derived from subjective notational analysis, to the known distances of the course, and to GPS data. The study analysed six locomotor activity categories, focusing on total distance covered, total duration of activities and total frequency of activities. The values between the known measurements and the Event Recorder were similar, whereas the majority of significant differences were found between the Event Recorder and GPS values. The reliability of subjective notational analysis was established with all ten participants being analysed on two occasions, as well as analysing five random futsal players twice during match-play. Subjective notational analysis is a valid and reliable method of tracking player movements, and may be a preferred and more effective method than GPS, particularly for indoor sports such as futsal, and field sports where short distances and changes in direction are observed. © 2011 National Strength and Conditioning Association.

Background: Hamstring strains remain one of the most prevalent injuries in Australian Rules football. The authors prospectively examined the relationship between musculotendinous stiffness of the hamstring and leg stiffness with hamstring injury in professional Australian Rules footballers during the 2006 season. Hypothesis: Higher hamstring stiffness and leg stiffness are related to noncontact, soft tissue hamstring injury risk in professional Australian Rules footballers. Study Design: Case-control study; Level of evidence, 3. Methods: Unilateral hamstring stiffness and leg stiffness were assessed in 136 professional footballers in the month before the commencement of the competitive season. This information was then investigated relative to players who suffered noncontact, soft tissue hamstring injuries during either matches or training throughout the season to identify whether preseason stiffness was related to injury occurrence. Results: Fourteen tested players recorded acute, noncontact hamstring injuries, resulting in 3.3 ± 2.8 weeks of missed match play per injury. At preseason testing, the players who ended up sustaining a hamstring injury during the season recorded significantly higher mean hamstring stiffness (11%, P =.04) and leg stiffness (5%, P =.03). When considering the injured players, the leg stiffness of the involved limb was significantly higher than the noninjured players ( P =.02), whereas hamstring stiffness was significantly higher on the noninvolved limb (P =.01). Further, those players who suffered a hamstring injury were significantly older than the noninjured players (P =.01). Conclusion: It appears that a high bilateral hamstring stiffness and leg stiffness may be a determinant in the risk of sustaining a hamstring injury. Further, relatively lower hamstring stiffness in the involved limb of injured players appears to be associated with increased injury and may be related to a lack of strength. The information from stiffness assessment m