Quantitative and qualitative changes in gene expression patterns characterize the activity of plaques in multiple sclerosis

Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS with both genetic and environmental contributing factors. Clinical symptoms are broadly characterized by initial onset, and progressive debilitating neurological impairment. In this study, RNA from MS chronic active and MS acute lesions was extracted, and compared with patient matched normal white matter by fluorescent cDNA microarray hybridization analysis. This resulted in the identification of 139 genes that were differentially regulated in MS plaque tissue compared to normal tissue. Of these, 69 genes showed a common pattern of expression in the chronic active and acute plaque tissues investigated (Pvalue<0.0001, ρ=0.73, by Spearman's ρ analysis); while 70 transcripts were uniquely differentially expressed (≥1.5-fold) in either acute or chronic active tissues. These results included known markers of MS such as the myelin basic protein (MBP) and glutathione S-transferase (GST) M1, nerve growth factors, such as nerve injury-induced protein 1 (NINJ1), X-ray and excision DNA repair factors (XRCC9 and ERCC5) and X-linked genes such as the ribosomal protein, RPS4X. Primers were then designed for seven array-selected genes, including transferrin (TF), superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), GSTP1, crystallin, alpha-B (CRYAB), phosphomannomutase 1 (PMM1) and tubulin β-5 (TBB5), and real time quantitative (Q)-PCR analysis was performed. The results of comparative Q-PCR analysis correlated significantly with those obtained by array analysis (r=0.75, Pvalue<0.01, by Pearson's bivariate correlation). Both chronic active and acute plaques shared the majority of factors identified suggesting that quantitative, rather than gross qualitative differences in gene expression pattern may define the progression from acute to chronic active plaques in MS.

Developing targets and strategies for school-based injury prevention programs to reduce alcohol associated transport risks

Background There is considerable and ongoing debate about the role and effectiveness of school-based injury prevention programs in reducing students’ later involvement in alcohol associated transport injuries. Most relevant literature is concerned with pre-driving and licensing programs for middle age range adolescents (15-17 years). This research team is concerned with prevention at an earlier stage by targeting interventions to young adolescents (13-14 years). There is strong evidence that young adolescents who engage in unsafe and illegal alcohol associated transport risks are significantly likely to incur serious related injuries in longitudinal follow up. For example, a state-wide representative sample of male adolescents (mean age 14.5 years) who reported being passengers of drink drivers were significantly more likely to have incurred a hospitalised injury related to traffic events at a 20 year follow up. Aim This paper reports on first aid training integrated with peer protection and school connectedness within the Skills for Preventing Injury in Youth (SPIY) program. A component of the intervention is concerned with providing strategies to reduce the likelihood of being a passenger of a drink driver and effectiveness is followed up at six months post-intervention. Method In early 2012 the study was undertaken in 35 high schools throughout Queensland that were randomly assigned to intervention and control conditions. A total of 2,521 Year 9 students (mean age 13.5years, 43% male) completed surveys prior to the intervention. Results Of these students 316 (13.7%) reported having ridden in a car with someone who has been drinking. This is a traffic safety behaviour that is particularly relevant to a peer protection intervention and the findings of the six month follow up will be reported. Discussion and conclusions This research will provide evidence as to whether this approach to the introduction of first aid skills within a school-based health education curriculum has traffic safety implications.

The effects of risk factors and protective factors on influencing engagement in risky behaviours and injury experiences for high-risk adolescents

High-risk adolescents are most vulnerable to the negative outcomes of risk taking behaviour, such as injury. It has been theorised by Jessor (1987) that adolescent risk behaviours (e.g. violence, alcohol use) can be predicted by assessing the risk factors (e.g. peer models for violence) and protective factors (e.g. school connectedness) in a young person’s life. The aim of this research is to examine the influence of risk factors and protective factors on the proneness of high-risk adolescents to engage in risky behaviour. 2,521 Grade 9 students (13-14 years of age) from 35 schools in Queensland, Australia participated in this study. The findings examine the influence of risk factors and protective factors on self-reported risky behaviour and injury experiences for adolescents who have been categorized as high-risk. Thereby, providing insight that may be used to target preventive interventions aimed at high-risk adolescents.

Development of school connectedness as a component of an injury prevention program for early adolescents

The current program of research addresses the need for multi-level programs to target the major increase in injury rates that occurs throughout adolescence. Specifically, it involves the investigation of school connectedness as a protective factor for adolescent injury, and the development of school connectedness as a component of an injury prevention program. To date, school-based risk taking and injury prevention has frequently been limited to addressing adolescents' knowledge and attitudes to risk behaviours, and has largely overlooked the importance of the wider school social context as a protective factor in adolescent development. Additionally, school connectedness has been primarily studied in terms of its impact on student achievement, wellbeing and risk taking behaviour, and research has not yet addressed possible links with injury. Further, school connectedness intervention programs have targeted risk taking behaviours without evaluating their potential impact on injury outcomes. This is the first reported research to develop strategies to increase school connectedness as part of a school-based injury prevention program. The research program was conceptualised as three distinct stages. The development of these research stages was informed by a comprehensive review of the literature on adolescent risk taking, injury and school-based prevention, as well as on school connectedness and its importance in adolescence. A review of the school connectedness literature indicated that students' connectedness is largely influenced by relationships within the school context including with teachers and other school staff, and is therefore a potentially modifiable factor that may be targeted in school-based programs. Overall, the literature shows school connectedness to be a key protective factor in adolescent development. This review established a foundation from which the current program of research was designed. The first stage of the research involved an empirical investigation of the relationship between adolescent risk taking-related injuries and school connectedness. Stage one incorporated two studies. The first involved the development of a measure of adolescent injury, the Extended Adolescent Injury Checklist (E-AIC), for use in the current research as well as in future school-based studies and program evaluation. The results of this study also highlighted the extent of the problem of risk-related injury in adolescence. The second study in Stage one examined the relationship between students' reports of school connectedness, risk taking behaviour and risk taking-related injuries on the E-AIC. The results of this study showed significant relationships between increased school connectedness and reduced reported engagement in transport and violence risk taking, and fewer associated injuries. This study therefore suggested the potential for school-based injury prevention programs to incorporate strategies targeting increased adolescent connectedness to school. The second stage of this research involved the compilation of an evidence base to inform the design of a school connectedness intervention. Stage two also incorporated two studies. The first study in Stage two involved a systematic review of programs that have targeted school connectedness for reduced risk taking and injury. The results of this study revealed that interventions targeting school connectedness can be effective in reducing adolescent risk taking behaviour, and also provided an evidence base for the design of the current school connectedness intervention. The second study in Stage two examined teachers' understanding and perceptions of school connectedness. This qualitative study indicated that teachers consider students' connectedness to be an important factor that relates to their risk taking behaviour; and also provided directions and content for the intervention design stage. The third stage of this research built upon the findings of each of the previous studies, and involved the design, implementation and evaluation of a school connectedness intervention as a component of an adolescent injury prevention program, Skills for Preventing Injury in Youth (SPIY). This connectedness intervention was designed as a professional development workshop for teachers of 13 to 14 year old adolescents, and was developed as a complementary component to the curriculum-based SPIY program. The SPIY connectedness component was implemented and evaluated using process and six-month impact evaluation methodologies. The results of this study revealed that teachers saw value in the program and made use of the strategies presented, and that program school students' self-reported violence risk behaviour was reduced at six-month follow-up. Despite these promising findings, the results of this study did not demonstrate a significant impact of the program on change in students' connectedness to school, relative to comparison schools. The positive impact on self-reported violence risk behaviour was however replicated in additional analyses comparing students participating in the connectedness version of SPIY with students participating in an earlier curriculumonly version of the program. This finding indicated that the connectedness component has additional benefits relating to reduction in violence risks, over and above a curriculum-only version of the program. This research was the first reported to address the relationship between school connectedness and adolescent injury outcomes, and to develop school connectedness as a component of an adolescent injury prevention program. Overall, the results of this program of research have demonstrated the importance of incorporating strategies targeting the wider school social context, including school connectedness, in adolescent injury prevention programs. This research has important implications for future research and practice in adolescent injury prevention.

Injury severity of pedestrian crashes in Singapore

Singapore is a highly urbanized city-state country where walking is an important mode of travel. Pedestrians form about 25% of road fatalities every year, making them one of the most vulnerable road user groups in Singapore. Engineering measures like provision of overhead pedestrian crossings and raised zebra crossings tend to address pedestrian safety in general, but there may be occasions where pedestrians are particularly vulnerable so that targeted interventions are more appropriate. The objective of this study is to identify factors and situations that affect the injury severity of pedestrians involved in traffic crashes. Six years of crash data from 2003 to 2008 containing around four thousands pedestrian crashes at roadway segments were analyzed. Injury severity of pedestrians—recorded as slight injury, major injury and fatal—were modeled as a function of roadway characteristics, traffic features, environmental factors and pedestrian demographics by an ordered probit model. Results suggest that the injury severity of pedestrians involved in crashes during night time is higher indicating that pedestrian visibility during night is a key issue in pedestrian safety. The likelihood of fatal or serious injuries is higher for crashes on roads with high speed limit, center and median lane of multi-lane roads, school zones, roads with two-way divided traffic type, and when pedestrians cross the roads. Elderly pedestrians appear to be involved in fatal and serious injury crashes more when they attempt to cross the road without using nearby crossing facilities. Specific countermeasures are recommended based on the findings of this study.

Acute hamstring strain injury in track and field athletes : a 3-year observational study at the Penn Relay Carnival

Purpose To observe the incidence rates of hamstring strain injuries (HSIs) across different competition levels and ages during the Penn Relays Carnival. Methods Over a 3-year period all injuries treated by the medical staff were recorded. The type of injury, anatomic location, event in which the injury occurred, competition level and demographic data were documented. Absolute and relative HSI (per 1000 participants) were determined and odds ratios (OR) were calculated between genders, competition levels and events. Results Throughout the study period 48,473 athletes registered to participate in the Penn Relays Carnival, with 118 HSIs treated by the medical team. High school females displayed lesser risk of HSI than high school males (OR = 0.55, p = 0.021), and masters athletes were more likely than high school (OR = 4.26, p < 0.001) and college (OR = 3.55, p = 0.001) level athletes to suffer a HSI. The 4x400m relay displayed a greater likelihood of HSI compared to the 4x100m relay (OR = 1.77, p = 0.008). Conclusions High school males and masters levels athletes are most likely to suffer HSI, and there is higher risk in 400m events compared to 100m events.

Neuromuscular hamstring function in response to intermittent running and previous injury

This thesis examined the impact of previous hamstring injury and fatigue on the function of the hamstring muscles and their neural control. The work established the role of neuromuscular inhibition after hamstring injury and involved the development of a new field testing device for eccentric hamstring strength, which is now in high demand in elite sport worldwide. David has four peer-reviewed publications from this doctoral work.

Comparative study on the protective effects of Yinchenhao Decoction against liver injury induced by alpha-naphthylisothiocyanate and carbon tetrachloride

OBJECTIVE: To optimize the animal model of liver injury that can properly represent the pathological characteristics of dampness-heat jaundice syndrome of traditional Chinese medicine. METHODS: The liver injury in the model rat was induced by alpha-naphthylisothiocyanate (ANIT) and carbon tetrachloride (CCl(4) ) respectively, and the effects of Yinchenhao Decoction (, YCHD), a proved effective Chinese medical formula for treating the dampness-heat jaundice syndrome in clinic, on the two liver injury models were evaluated by analyzing the serum level of alanine aminotransferase (ALT), asparate aminotransferase (AST), alkaline phosphatase (ALP), malondialchehyche (MDA), total bilirubin (T-BIL), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) as well as the ratio of liver weight to body weight. The experimental data were analyzed by principal component analytical method of pattern recognition. RESULTS: The ratio of liver weight to body weight was significantly elevated in the ANIT and CCl(4) groups when compared with that in the normal control (P<0.01). The contents of ALT and T-BIL were significantly higher in the ANIT group than in the normal control (P<0.05,P<0.01), and the levels of AST, ALT and ALP were significantly elevated in CCl(4) group relative to those in the normal control P<0.01). In the YCHD group, the increase in AST, ALT and ALP levels was significantly reduced (P<0.05, P<0.01), but with no significant increase in serum T-BIL. In the CCl(4) intoxicated group, the MDA content was significantly increased and SOD, GSH-PX activities decreased significantly compared with those in the normal control group, respectively (P<0.01). The increase in MDA induced by CCl(4) was significantly reduced by YCHD P<0.05). CONCLUSION: YCHD showed significant effects on preventing liver injury progression induced by CCl(4), and the closest or most suitable animal model for damp-heat jaundice syndrome may be the one induced by CCl(4).

Comparison between electrically-evoked and voluntary wrist movements on sensorimotor and prefrontal cortical activation : A multi-channel time domain fNIRS study

Neuromuscular electrical stimulation (NMES) has been consistently demonstrated to improve skeletal muscle function in neurological populations with movement disorders, such as poststroke and incomplete spinal cord injury (Vanderthommen and Duchateau, 2007). Recent research has documented that rapid, supraspinal central nervous system reorganisation/neuroplastic mechanisms are also implicated during NMES (Chipchase et al., 2011). Functional neuroimaging studies have shown NMES to activate a network of sub-cortical and cortical brain regions, including the sensorimotor (SMC) and prefrontal (PFC) cortex (Blickenstorfer et al., 2009; Han et al., 2003; Muthalib et al., 2012). A relationship between increase in SMC activation with increasing NMES current intensity up to motor threshold has been previously reported using functional MRI (Smith et al., 2003). However, since clinical neurorehabilitation programmes commonly utilise NMES current intensities above the motor threshold and up to the maximum tolerated current intensity (MTI), limited research has determined the cortical correlates of increasing NMES current intensity at or above MTI (Muthalib et al., 2012). In our previous study (Muthalib et al., 2012), we assessed contralateral PFC activation using 1-channel functional near infrared spectroscopy (fNIRS) during NMES of the elbow flexors by increasing current intensity from motor threshold to greater than MTI and showed a linear relationship between NMES current intensity and the level of PFC activation. However, the relationship between NMES current intensity and activation of the motor cortical network, including SMC and PFC, has not been clarified. Moreover, it is of scientific and clinical relevance to know how NMES affects the central nervous system, especially in comparison to voluntary (VOL) muscle activation. Therefore, the aim of this study was to utilise multi-channel time domain fNIRS to compare SMC and PFC activation between VOL and NMESevoked wrist extension movements.

Surveillance report on injury deaths in Shouguang, 1993-1997 [寿光市疾病监测点1993～1997年意外死亡报告]

In this rural population, injuries claimed 9% of all deaths and was the 4th cause of death. Injury mortality was much higher among men than that for women. The major injury causes were traffic accidents (39%) and suicide (38%). Traffic accidents were the first injury cause for men but suicide the first cause for women. Abstract in Chinese 为查明我市农村居民意外死亡情况，为制定相应控制措施提供参考，我们对寿光市疾病监测点１９９３～１９９７年的居民意外死亡资料进行了分析。死因分类按国际疾病分类（ＩＣＤ－９）标准，标化死亡率采用１９９０年全国标准人口构成计算。１９９３～１９９７年寿光市疾病...

Comparing outcomes of a school based injury prevention intervention for low-medium risk adolescents with high-risk adoelscents

High-risk adolescents are shown to jeopardise their future social and health functioning as well as placing themselves and others at immediate risk of harm. The challenge of “reaching” high-risk adolescents, who are often marginalised, is considerable. There is a positive relationship between age and risk taking behaviors during adolescence. This study examines outcomes (alcohol use, transport risk behaviors, violence) of a school based intervention (SPIY) by comparing low-medium risk adolescents with high-risk adolescents over a six month period.

An extracellular signal-regulated kinase 2 survival pathway mediates resistance of human mesothelioma cells to asbestos-induced injury

We hypothesized that normal human mesothelial cells acquire resistance to asbestos-induced toxicity via induction of one or more epidermal growth factor receptor (EGFR) - linked survival pathways (phosphoinositol-3-kinase/AKT/ mammalian target of rapamycin and extracellular signal - regulated kinase [ERK] 1/2) during simian virus 40 (SV40) transformation and carcinogenesis. Both isolated HKNM-2 mesothelial cells and a telomerase-immortalized mesothelial line (LP9/TERT-1) were more sensitive to crocidolite asbestos toxicity than an SV40 Tag-immortalized mesothelial line (MET5A) and malignant mesothelioma cell lines (HMESO and PPM Mill). Whereas increases in phosphorylation of AKT (pAKT) were observed in MET5A cells in response to asbestos, LP9/TERT-1 cells exhibited dose-related decreases in pAKT levels. Pretreatment with an EGFR phosphorylation or mitogen-activated protein kinase kinase 1/2 inhibitor abrogated asbestos-induced phosphorylated ERK (pERK) 1/2 levels in both LP9/TERT-1 and MET5A cells as well as increases in pAKT levels in MET5A cells. Transient transfection of small interfering RNAs targeting ERK1, ERK2, or AKT revealed that ERK1/2 pathways were involved in cell death by asbestos in both cell lines. Asbestos-resistant HMESO or PPM Mill cells with high endogenous levels of ERKs or AKT did not show dose-responsive increases in pERK1/ERK1, pERK2/ERK2, or pAKT/AKT levels by asbestos. However, small hairpin ERK2 stable cell lines created from both malignant mesothelioma lines were more sensitive to asbestos toxicity than shERK1 and shControl lines, and exhibited unique, tumor-specific changes in endogenous cell death - related gene expression. Our results suggest that EGFR phosphorylation is causally linkedto pERK and pAKT activation by asbestos in normal and SV40 Tag - immortalized human mesothelial cells. They also indicate that ERK2 plays a role in modulating asbestos toxicity by regulating genes critical to cell injury and survival that are differentially expressed in human mesotheliomas.

Development of an evidence-based framework to guide injury prevention interventions for off-road motorcyclists

There is little research on off-road motorcycle and all-terrain vehicle riders though injury levels are high. This thesis identified formal responsibility for monitoring injuries, targeting young male and recreational riders, promotion of family members as models, and controlled and accessible riding locations as ways to increase safety. These recommendations were based on analysis of Queensland hospitalisation records, rider personal reports and survey responses.