Isolation of microvascular endothelial cells from cadaveric corneal limbus

Limbal microvascular endothelial cells (L-MVEC) contribute to formation of the corneal-limbal stem cell niche and to neovascularization of diseased and injuries corneas. Nevertheless, despite these important roles in corneal health and disease, few attempts have been made to isolate L-MVEC with the view to studying their biology in vitro. We therefore explored the feasibility of generating primary cultures of L-MVEC from cadaveric human tissue. We commenced our study by evaluating growth conditions (MesenCult-XF system) that have been previously found to be associated with expression of the endothelial cell surface marker thrombomodulin/CD141, in crude cultures established from collagenase-digests of limbal stroma. The potential presence of L-MVEC in these cultures was examined by flow cytometry using a more specific marker for vascular endothelial cells, CD31/PECAM-1. These studies demonstrated that the presence of CD141 in crude cultures established using the MesenCult-XF system is unrelated to L-MVEC. Thus we subsequently explored the use of magnetic assisted cell sorting (MACS) for CD31 as a tool for generating cultures of L-MVEC, in conjunction with more traditional endothelial cell growth conditions. These conditions consisted of gelatin-coated tissue culture plastic and MCDB-131 medium supplemented with fetal bovine serum (10% v/v), D-glucose (10 mg/mL), epidermal growth factor (10 ng/mL), heparin (50 μg/mL), hydrocortisone (1 μg/mL) and basic fibroblast growth factor (10 ng/mL). Our studies revealed that use of endothelial growth conditions are insufficient to generate significant numbers of L-MVEC in primary cultures established from cadaveric corneal stroma. Nevertheless, through use of positive-MACS selection for CD31 we were able to routinely observe L-MVEC in cultures derived from collagenase-digests of limbal stroma. The presence of L-MVEC in these cultures was confirmed by immunostaining for von Willebrand factor (vWF) and by ingestion of acetylated low-density lipoprotein. Moreover, the vWF+ cells formed aligned cell-to-cell ‘trains’ when grown on Geltrex™. The purity of L-MVEC cultures was found to be unrelated to tissue donor age (32 to 80 years) or duration in eye bank corneal preservation medium prior to use (3 to 10 days in Optisol) (using multiple regression test). Optimal purity of L-MVEC cultures was achieved through use of two rounds of positive-MACS selection for CD31 (mean ± s.e.m, 65.0 ± 20.8%; p<0.05). We propose that human L-MVEC cultures generated through these techniques, in conjunction with other cell types, will provide a useful tool for exploring the mechanisms of blood vessel cell growth in vitro.

Book review - Richard Goldberg, Medicinal Product Liability and Regulation (Hart Publishing, Oxford, 2013) 214pp

In December 2013, settlement was reached between approximately 100 Australian and New Zealand Thalidomide victims and the company which had acted as the Australian distributor of the infamous drug, thus putting to rest the possibility of litigation. Around the same time, Thalidomide victims in the United Kingdom (UK) launched a similar bid for compensation against the manufacturer and distributor. It is clear that despite a lengthy amount of time having passed ever since the thalidomide disaster commenced in 1962, the controversy over compensation continues. Indeed, the author of Medicinal Product Liability and Regulation (published before the announcement of the British legal claim), Professor Goldberg, notes that claims for resulting birth defects continue to emerge right into the present day. His prescient insight into the contemporary relevance of compensation for pharmaceutical injuries thus makes Medicinal Product Liability and Regulation a very relevant addition to the small body of scholarship that is available on this rather specific and complex issue.

Improving safety communication of ethnic minorities in the construction industry of Hong Kong

The construction workforce in Hong Kong is experiencing a severe ageing problem and labour shortage. One initiative to enhance the supply of manpower is to assist ethnic minorities joining the industry. It is foreseeable that the percentage of ethnic minorities in the construction workforce will keep increasing. Statistics show that ethnic minorities were nearly 30% more likely to have work-related injuries than local workers in some developed countries. However, official statistics on the safety of ethnic minorities are not available in Hong Kong. A search in newspaper archive revealed that ethnic minorities in the construction industry of Hong Kong are subjected to higher fatality rate than local workers, just as is the case in many developed countries. This reflects that the safety of ethnic minorities has not received the attention it rightly deserves. Safety communication has been one of the key factors leading to accidents. Safety communication barriers of ethnic minorities impede them from receiving safety training and acquiring safety information effectively. Research towards improving the safety communication of ethnic minorities in the construction industry of Hong Kong becomes more urgent. This paper will provides an initial report on a research project which focuses on improving the safety communication of ethnic minorities in the construction industry of Hong Kong. Quantitative and qualitative research methods including Social Network Analysis (SNA) applied in conducting the research are first discussed. Preliminary statistics of construction accidents related to ethnic minorities in Hong Kong are then presented.

Longitudinal performance of polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in large preclinical animal model : 6- versus 12 months

There is strong current interest in the use of biodegradable scaffolds in combination with bone growth factors as a valuable alternative to the current gold standard autograft in spinal fusion surgery Yong et al. (2013). Here we report on 6- vs 12- month data set evaluating the longitudinal performance of a CaP coated polycaprolactone (PCL) scaffold loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within a preclinical ovine thoracic spine. The results of this study demonstrate the efficacy of scaffold-based delivery of rhBMP-2 in promoting higher fusion grades at 6- and 12- months in comparison to the scaffold alone or autograft group within the same time frame. Fusion grades achieved at six months using PCL+rhBMP-2 are not significantly increased at twelve months post surgery.

The role of university research centres in building road safety capacity : implications for China

In recent decades, highly motorised countries, such as Australia, have witnessed significant improvements in population health through reductions in fatalities and injuries from road traffic crashes. In Australia, concerted efforts have been made to reduce the road trauma burden since road fatalities reached their highest level in in the early 1970s. Since that time, many improvements have been made drawing on various disciplines to reduce the trauma burden (e.g., road and vehicle design, road user education, traffic law enforcement practices and enforcement technologies). While road fatalities have declined significantly since the mid-1970s, road trauma remains a serious public health concern in Australia. China has recently become the largest car market in the world (Ma, Li, Zhou, Duan, & Bishai, 2012). This rapid motorisation has been accompanied by substantial expansion of the road network as well as a large road trauma burden. Road traffic injuries are a major cause of death in China, reported as accounting for one third of all injury-deaths between 2002 and 2006 (Ma et al., 2012). In common with Australia, China has experienced a reported decline in fatalities since 2002 (see Hu, Wen & Baker, 2008). However, there remains a strong need for action in this area as rates of motorisation continue to climb in China. In Australia, a wide range of organisations have contributed to the improvements in road safety including government agencies, professional organisations, advocacy groups and research centres. In particular, Australia has several highly regarded and multi-disciplinary, university-based research centres that work across a range of road safety fields, including engineering, intelligent transportation systems, the psychology of road user behaviour, and traffic law enforcement. Besides conducting high-quality research, these centres fulfil an important advocacy role in promoting safer road use and facilitating collaborations with government and other agencies, at both the national and international level. To illustrate the role of these centres, an overview will be provided of the Centre for Accident Research and Road Safety-Queensland (CARRS-Q), which was established in 1996 and has gone on to become a recognised world-leader in road safety and injury prevention research. The Centre’s research findings are used to provide evidence-based recommendations to government and have directly contributed to promoting safer road use in Australia. Since 2006, CARRS-Q has also developed strong collaborative links with various universities and organisations in China to assist in building understanding, connections and capacity to assist in reducing the road trauma burden. References Hu, G., Wen, M., Baker, T. D., & Baker, S. P. (2008). Road-traffic deaths in China, 1985–2005: threat and opportunity. Injury Prevention, 14, 149-153. Ma, S., Li, Q., Zhou, M., Duan, L., & Bishai, D. (2012). Road Traffic Injury in China: A Review of National Data Sources. Traffic Injury Prevention, 13(S1), 57-63.

Reliability in the Parameterization of the Functional Reach Test in Elderly Stroke Patients: A Pilot Study

BACKGROUND: Postural instability is one of the major complications found in stroke survivors. Parameterising the functional reach test (FRT) could be useful in clinical practice and basic research. OBJECTIVES: To analyse the reliability, sensitivity, and specificity in the FRT parameterisation using inertial sensors for recording kinematic variables in patients who have suffered a stroke. DESIGN: Cross-sectional study. While performing FRT, two inertial sensors were placed on the patient's back (lumbar and trunk). PARTICIPANTS: Five subjects over 65 who suffer from a stroke. MEASUREMENTS: FRT measures, lumbosacral/thoracic maximum angular displacement, maximum time of lumbosacral/thoracic angular displacement, time return initial position, and total time. Speed and acceleration of the movements were calculated indirectly. RESULTS: FRT measure is  12.75±2.06 cm. Intrasubject reliability values range from 0.829 (time to return initial position (lumbar sensor)) to 0.891 (lumbosacral maximum angular displacement). Intersubject reliability values range from 0.821 (time to return initial position (lumbar sensor)) to 0.883 (lumbosacral maximum angular displacement). FRT's reliability was 0.987 (0.983-0.992) and 0.983 (0.979-0.989) intersubject and intrasubject, respectively. CONCLUSION: The main conclusion could be that the inertial sensors are a tool with excellent reliability and validity in the parameterization of the FRT in people who have had a stroke.

Review of the long-term disability associated with hip fractures

Objectives To determine the proportion of hip fracture patients who experience long-term disability and to re-estimate the resulting burden of disease associated with hip fractures in Australia in 2003. Methods A literature review of the functional outcome following a hip fracture (keywords: morbidity, treatment outcome, disability, quality of life, recovery of function, hip fractures, and femoral neck fractures) was carried out using PubMed and Ovid MEDLINE. Results A range of scales and outcome measures are used to evaluate recovery following a hip fracture. Based on the available evidence on restrictions in activities of daily living, 29% of hip fracture cases in the elderly do not reach their pre-fracture levels 1 year post-fracture. Those who do recover tend to reach their pre-fracture levels of functioning at around 6 months. These new assumptions result in 8251 years lived with disability for hip fractures in Australia in 2003, a 4.5-fold increase compared with the previous calculation based on Global Burden of Disease assumptions that only 5% of hip fractures lead to long-term disability and that the duration of short-term disability is just 51 days. Conclusions The original assumptions used in burden of disease studies grossly underestimate the long-term disability from hip fractures. The long-term consequences of other injuries may similarly have been underestimated and need to be re-examined. This has important implications for modelling the cost-effectiveness of preventive interventions where disability-adjusted life years are used as a measure of health outcome.

Initial burden of disease estimates for South Africa, 2000

BACKGROUND This paper describes the first national burden of disease study for South Africa. The main focus is the burden due to premature mortality, i.e. years of life lost (YLLs). In addition, estimates of the burden contributed by morbidity, i.e. the years lived with disability (YLDs), are obtained to calculate disability-adjusted life years (DALYs); and the impact of AIDS on premature mortality in the year 2010 is assessed. METHOD Owing to the rapid mortality transition and the lack of timely data, a modelling approach has been adopted. The total mortality for the year 2000 is estimated using a demographic and AIDS model. The non-AIDS cause-of-death profile is estimated using three sources of data: Statistics South Africa, the National Department of Home Affairs, and the National Injury Mortality Surveillance System. A ratio method is used to estimate the YLDs from the YLL estimates. RESULTS The top single cause of mortality burden was HIV/AIDS followed by homicide, tuberculosis, road traffic accidents and diarrhoea. HIV/AIDS accounted for 38% of total YLLs, which is proportionately higher for females (47%) than for males (33%). Pre-transitional diseases, usually associated with poverty and underdevelopment, accounted for 25%, non-communicable diseases 21% and injuries 16% of YLLs. The DALY estimates highlight the fact that mortality alone underestimates the burden of disease, especially with regard to unintentional injuries, respiratory disease, and nervous system, mental and sense organ disorders. The impact of HIV/AIDS is expected to more than double the burden of premature mortality by the year 2010. CONCLUSION This study has drawn together data from a range of sources to develop coherent estimates of premature mortality by cause. South Africa is experiencing a quadruple burden of disease comprising the pre-transitional diseases, the emerging chronic diseases, injuries, and HIV/AIDS. Unless interventions that reduce morbidity and delay morbidity become widely available, the burden due to HIV/AIDS can be expected to grow very rapidly in the next few years. An improved base of information is needed to assess the morbidity impact more accurately.

The burden attributable to mental and substance use disorders as risk factors for suicide : findings from the Global Burden of Disease Study 2010

Background The Global Burden of Disease Study 2010 (GBD 2010) identified mental and substance use disorders as the 5th leading contributor of burden in 2010, measured by disability adjusted life years (DALYs). This estimate was incomplete as it excluded burden resulting from the increased risk of suicide captured elsewhere in GBD 2010's mutually exclusive list of diseases and injuries. Here, we estimate suicide DALYs attributable to mental and substance use disorders. Methods Relative-risk estimates of suicide due to mental and substance use disorders and the global prevalence of each disorder were used to estimate population attributable fractions. These were adjusted for global differences in the proportion of suicide due to mental and substance use disorders compared to other causes then multiplied by suicide DALYs reported in GBD 2010 to estimate attributable DALYs (with 95% uncertainty). Results Mental and substance use disorders were responsible for 22.5 million (14.8-29.8 million) of the 36.2 million (26.5-44.3 million) DALYs allocated to suicide in 2010. Depression was responsible for the largest proportion of suicide DALYs (46.1% (28.0%-60.8%)) and anorexia nervosa the lowest (0.2% (0.02%-0.5%)). DALYs occurred throughout the lifespan, with the largest proportion found in Eastern Europe and Asia, and males aged 20-30 years. The inclusion of attributable suicide DALYs would have increased the overall burden of mental and substance use disorders (assigned to them in GBD 2010 as a direct cause) from 7.4% (6.2%-8.6%) to 8.3% (7.1%-9.6%) of global DALYs, and would have changed the global ranking from 5th to 3rd leading cause of burden. Conclusions Capturing the suicide burden attributable to mental and substance use disorders allows for more accurate estimates of burden. More consideration needs to be given to interventions targeted to populations with, or at risk for, mental and substance use disorders as an effective strategy for suicide prevention.

Is there a potential relationship between prior h amstring strain injury and increased risk for future a nterior cruciate ligament injury?

Hamstring strain injuries (HSIs) are the most prevalent injury in a number of sports, and while anterior cruciate ligament (ACL) injuries are less common, they are far more severe and have long-term implications, such as an increased risk of developing osteoarthritis later in life. Given the high incidence and severity of these injuries, they are key targets of injury preventive programs in elite sport. Evidence has shown that a previous severe knee injury (including ACL injury) increases the risk of HSI; however, whether the functional deficits that occur after HSI result in an increased risk of ACL injury has yet to be considered. In this clinical commentary, we present evidence that suggests that the link between previous HSI and increased risk of ACL injury requires further investigation by drawing parallels between deficits in hamstring function after HSI and in women athletes, who are more prone to ACL injury than men athletes. Comparisons between the neuromuscular function of the male and female hamstring has shown that women display lower hamstring-to-quadriceps strength ratios during isokinetic knee flexion and extension, increased activation of the quadriceps compared with the hamstrings during a stop-jump landing task, a greater time required to reach maximal isokinetic hamstring torque, and lower integrated myoelectrical hamstring activity during a sidestep cutting maneuver. Somewhat similarly, in athletes with a history of HSI, the previously injured limb, compared with the uninjured limb, displays lower eccentric knee flexor strength, a lower hamstrings-to-quadriceps strength ratio, lower voluntary myoelectrical activity during maximal knee flexor eccentric contraction, a lower knee flexor eccentric rate of torque development, and lower voluntary myoelectrical activity during the initial portion of eccentric contraction. Given that the medial and lateral hamstrings have different actions at the knee joint in the coronal plane, which hamstring head is previously injured might also be expected to influence the likelihood of future ACL. Whether the deficits in function after HSI, as seen in laboratory-based studies, translate to deficits in hamstring function during typical injurious tasks for ACL injury has yet to be determined but should be a consideration for future work.

A description of neck motor performance, neck pain, fatigue, and mental effort while driving in a sample with chronic whiplash-associated disorders

Objective: Individuals with chronic whiplash-associated disorders (WADs) often note driving as a difficult task. This study’s aims were to (1) compare, while driving, neck motor performance, mental effort, and fatigue in individuals with chronic WAD against healthy controls and (2) investigate the relationships of these variables and neck pain to self-reported driving difficulty in the WAD group. Design: This study involved 14 participants in each group (WAD and control). Measures included self-reported driving difficulty and measures of neck pain intensity, overall fatigue, mental effort, and neck motor performance (head rotation and upper trapezius activity) while driving a simulator. Results: The WAD group had greater absolute path of head rotation in a simulated city area and used greater mental effort (P = 0.04), but there were no differences in other measures while driving compared with the controls (all P Q 0.05). Self-reported driving difficulty correlated moderately with neck pain intensity, fatigue level, and maximum velocity of head rotation while driving in the WAD group (all P G 0.05). Conclusions: Individuals with chronic WAD do not seem to have impaired neck motor performance while driving yet use greater mental effort. Neck pain, fatigue, and maximum head rotation velocity could be potential contributors to self-reported driving difficulty in this group.

Estimating the burden of disease attributable to interpersonal violence in South Africa in 2000

Violence, previously considered a social issue, is now an acknowledged public health problem. It is defined as the intentional use of physical force or power, threatened or actual, against another person, against oneself, or against a group or community, that results in injury, death or deprivation.1 In this study we focus on exposure to the interpersonal type of violence, which includes acts of family violence and community violence. Family violence is further categorised by victim: child, intimate partner, or elder. Community violence occurs among unrelated individuals and includes sexual assault and rape by strangers as well as youth violence...

Interpersonal violence : an important risk factor for disease and injury in South Africa

Background Burden of disease estimates for South Africa have highlighted the particularly high rates of injuries related to interpersonal violence compared with other regions of the world, but these figures tell only part of the story. In addition to direct physical injury, violence survivors are at an increased risk of a wide range of psychological and behavioral problems. This study aimed to comprehensively quantify the excess disease burden attributable to exposure to interpersonal violence as a risk factor for disease and injury in South Africa. Methods The World Health Organization framework of interpersonal violence was adapted. Physical injury mortality and disability were categorically attributed to interpersonal violence. In addition, exposure to child sexual abuse and intimate partner violence, subcategories of interpersonal violence, were treated as risk factors for disease and injury using counterfactual estimation and comparative risk assessment methods. Adjustments were made to account for the combined exposure state of having experienced both child sexual abuse and intimate partner violence. Results Of the 17 risk factors included in the South African Comparative Risk Assessment study, interpersonal violence was the second leading cause of healthy years of life lost, after unsafe sex, accounting for 1.7 million disability-adjusted life years (DALYs) or 10.5% of all DALYs (95% uncertainty interval: 8.5%-12.5%) in 2000. In women, intimate partner violence accounted for 50% and child sexual abuse for 32% of the total attributable DALYs. Conclusions The implications of our findings are that estimates that include only the direct injury burden seriously underrepresent the full health impact of interpersonal violence. Violence is an important direct and indirect cause of health loss and should be recognized as a priority health problem as well as a human rights and social issue. This study highlights the difficulties in measuring the disease burden from interpersonal violence as a risk factor and the need to improve the epidemiological data on the prevalence and risks for the different forms of interpersonal violence to complete the picture. Given the extent of the burden, it is essential that innovative research be supported to identify social policy and other interventions that address both the individual and societal aspects of violence.

The global burden attributable to low bone mineral density

Introduction The Global Burden of Disease Study 2010 estimated the worldwide health burden of 291 diseases and injuries and 67 risk factors by calculating disability-adjusted life years (DALYs). Osteoporosis was not considered as a disease, and bone mineral density (BMD) was analysed as a risk factor for fractures, which formed part of the health burden due to falls. Objectives To calculate (1) the global distribution of BMD, (2) its population attributable fraction (PAF) for fractures and subsequently for falls, and (3) the number of DALYs due to BMD. Methods A systematic review was performed seeking population-based studies in which BMD was measured by dual-energy X-ray absorptiometry at the femoral neck in people aged 50 years and over. Age- and sex-specific mean ± SD BMD values (g/cm2) were extracted from eligible studies. Comparative risk assessment methodology was used to calculate PAFs of BMD for fractures. The theoretical minimum risk exposure distribution was estimated as the age- and sex-specific 90th centile from the Third National Health and Nutrition Examination Survey (NHANES III). Relative risks of fractures were obtained from a previous meta-analysis. Hospital data were used to calculate the fraction of the health burden of falls that was due to fractures. Results Global deaths and DALYs attributable to low BMD increased from 103 000 and 3 125 000 in 1990 to 188 000 and 5 216 000 in 2010, respectively. The percentage of low BMD in the total global burden almost doubled from 1990 (0.12%) to 2010 (0.21%). Around one-third of falls-related deaths were attributable to low BMD. Conclusions Low BMD is responsible for a growing global health burden, only partially representative of the real burden of osteoporosis.

Global burden of disease attributable to mental and substance use disorders : findings from the Global Burden of Disease Study 2010

Background We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the burden of disease attributable to mental and substance use disorders in terms of disability-adjusted life years (DALYs), years of life lost to premature mortality (YLLs), and years lived with disability (YLDs). Methods For each of the 20 mental and substance use disorders included in GBD 2010, we systematically reviewed epidemiological data and used a Bayesian meta-regression tool, DisMod-MR, to model prevalence by age, sex, country, region, and year. We obtained disability weights from representative community surveys and an internet-based survey to calculate YLDs. We calculated premature mortality as YLLs from cause of death estimates for 1980–2010 for 20 age groups, both sexes, and 187 countries. We derived DALYs from the sum of YLDs and YLLs. We adjusted burden estimates for comorbidity and present them with 95% uncertainty intervals. Findings In 2010, mental and substance use disorders accounted for 183·9 million DALYs (95% UI 153·5 million–216·7 million), or 7·4% (6·2–8·6) of all DALYs worldwide. Such disorders accounted for 8·6 million YLLs (6·5 million–12·1 million; 0·5% [0·4–0·7] of all YLLs) and 175·3 million YLDs (144·5 million–207·8 million; 22·9% [18·6–27·2] of all YLDs). Mental and substance use disorders were the leading cause of YLDs worldwide. Depressive disorders accounted for 40·5% (31·7–49·2) of DALYs caused by mental and substance use disorders, with anxiety disorders accounting for 14·6% (11·2–18·4), illicit drug use disorders for 10·9% (8·9–13·2), alcohol use disorders for 9·6% (7·7–11·8), schizophrenia for 7·4% (5·0–9·8), bipolar disorder for 7·0% (4·4–10·3), pervasive developmental disorders for 4·2% (3·2–5·3), childhood behavioural disorders for 3·4% (2·2–4·7), and eating disorders for 1·2% (0·9–1·5). DALYs varied by age and sex, with the highest proportion of total DALYs occurring in people aged 10–29 years. The burden of mental and substance use disorders increased by 37·6% between 1990 and 2010, which for most disorders was driven by population growth and ageing. Interpretation Despite the apparently small contribution of YLLs—with deaths in people with mental disorders coded to the physical cause of death and suicide coded to the category of injuries under self-harm—our findings show the striking and growing challenge that these disorders pose for health systems in developed and developing regions. In view of the magnitude of their contribution, improvement in population health is only possible if countries make the prevention and treatment of mental and substance use disorders a public health priority.