MicroRNA in human cancer and chronic inflammatory diseases

MicroRNAs (miRNAs) are the non-coding RNAs that act as post-translational regulators to their complimentary messenger RNAs (mRNA). Due to their specific gene silencing property, miRNAs have been implicated in a number of cellular and developmental processes. Also, it has been proposed that a particular set of miRNA spectrum is expressed only in a particular type of tissue. Many interesting findings related to the differential expression of miRNAs in various human diseases including several types of cancers, neurodegenerative diseases and metabolic diseases have been reported. Deregulation of miRNA expression in different types of human diseases and the roles various miRNAs play as tumour suppressors as well as oncogenes, suggest their contribution to cancer and/or in other disease development. These findings have possible implications in the development of diagnostics and/or therapeutics in human malignancies. In this review, we discuss various miRNAs that are differentially expressed in human chronic inflammatory diseases, neurodegenerative diseases, cancer and the further prospective development of miRNA based diagnostics and therapeutics.

The role and regulation of MAFbx/atrogin-1 and MuRF1 in skeletal muscle atrophy

Skeletal muscle atrophy occurs in many chronic diseases and disuse conditions. Its severity reduces patient recovery, independence and quality of life. The discovery of two muscle-specific E3 ubiquitin ligases, MAFbx/ atrogin-1 and Muscle RING Finger-1 (MuRF1), promoted an expectation of these molecules as targets for therapeutic development. While numerous studies have determined the conditions in which MAFbx/atrogin-1 and MuRF1 mRNA levels are regulated, few studies have investigated their functional role in skeletal muscle. Recently, studies identifying new target substrates for MAFbx/atrogin-1 and
MuRF1, outside of their response to the initiation of muscle atrophy, suggest that there is more to these proteins than
previously appreciated. This review will highlight our present knowledge of MAFbx/atrogin-1 and MuRF1 in skeletal muscle atrophy, the impact of potential therapeutics and their known regulators and substrates. Finally, we will comment on new approaches that may expand our knowledge of these two molecules in their control of skeletal muscle function.

Risk and protective factors for adolescent substance use in Washington State, the United States and Victoria, Australia : a longitudinal study

Purpose
To compare the levels of risk and protective factors and the predictive influence of these factors on alcohol, tobacco, and cannabis use over a 12-month follow-up period in Washington State in the United States and in Victoria, Australia.

Method
The study involved a longitudinal school-based survey of students drawn as a two-stage cluster sample recruited through schools, and administered in the years 2002 and 2003 in both states. The study used statewide representative samples of students in the seventh and ninth grades (n = 3,876) in Washington State and Victoria.

Results
Washington State students, relative to Victorian students, had higher rates of cannabis use but lower rates of alcohol and tobacco use at time 1. Levels of risk and protective factors showed few but important differences that contribute to the explanation of differences in substance use; Washington State students, relative to Victorian students, reported higher religiosity (odds ratio, .96 vs. .79) and availability of handguns (odds ratio, 1.23 vs. 1.18), but less favorable peer, community, and parental attitudes to substance use. The associations with substance use at follow-up are generally comparable, but in many instances were weaker in Washington State.

Conclusions
Levels of risk and protective factors and their associations with substance use at follow-up were mostly similar in the two states. Further high-quality longitudinal studies to establish invariance in the relations between risk and protective factors and substance use in adolescence across diverse countries are warranted.

The association between alcohol interventions and Dui incidents in Geelong, Victoria

Introduction and aims : Driving under the influence of alcohol is a major public health problem, every year affecting the lives of billions around the world - and not least in Australia. Since 2001, several Traffic Accident Commission (TAC), police, and community interventions have been implemented in Geelong, Australia to curb drink driving. The current paper aims to assess the impact of 13 alcohol interventions on drink-driving rates in the Geelong region of Australia. The interventions comprised seven TAC media campaigns, three Victoria Police operations, two community interventions targeting licensed premises, and the alcohol interlock program.

Method : This study examined two types of Victoria Police frequency data: Driving under the influence (DUI) offences, and roadside preliminary breath testing (PBT) rates. Multiple regressions were carried out to determine if any of the interventions were significantly associated with frequency fluctuations in the data.

Results : Of the 13 alcohol interventions examined, three TAC campaigns and one Victoria Police operation precipitated significant decreases in drink-driving rates, while another three TAC campaigns were associated with significant increases in drink-driving rates. Over one in five (22.5%) had recorded prior DUI offences.

Conclusions : The most promising approach to curbing DUI-rates in Geelong, appear to be through informative media campaigns which show people specific settings where they might become mildly intoxicated without being aware of it, such as TAC’s ‘Education 1’ campaign. However, there remains a worrying level of recidivist drink drivers in Geelong suggesting the need for tailored approaches.

A systematic review of the impact of including both waist and hip circumference in risk models for cardiovascular diseases, diabetes and mortality

Both a larger waist and narrow hips are associated with heightened risk of diabetes, cardiovascular diseases and premature mortality. We review the risk of these outcomes for levels of waist and hip circumferences when terms for both anthropometric measures were included in regression models. MEDLINE and EMBASE were searched (last updated July 2012) for studies reporting the association with the outcomes mentioned earlier for both waist and hip circumferences (unadjusted and with both terms included in the model). Ten studies reported the association between hip circumference and death and/or disease outcomes both unadjusted and adjusted for waist circumference. Five studies reported the risk associated with waist circumference both unadjusted and adjusted for hip circumference. With the exception of one study of venous thromboembolism, the full strength of the association between either waist circumference or hip circumference with morbidity and/or mortality was only apparent when terms for both anthropometric measures were included in regression models. Without accounting for the protective effect of hip circumference, the effect of obesity on risk of death and disease may be seriously underestimated. Considered together (but not as a ratio measure), waist and hip circumference may improve risk prediction models for cardiovascular disease and other outcomes.

Nano-lactoferrin in diagnostic, imaging and targeted delivery for cancer and infectious diseases

Lactoferrin (Lf) is a natural occurring iron binding protein present in many mammalian excretions and involved in various physiological processes. Lf is used in the transport of iron along with other molecules and ions from the digestive system. However its the modulatory functions exhibited by Lf in connection to immune response, disease regression and diagnosis that has made this protein an attractive therapeutic against chronic diseases. Further, the exciting potentials of employing nanotechnology in advancing drug delivery systems, active disease targeting and prognosis have also shown some encouraging outcomes. This review focuses on the role of Lf in diagnosing infection, cancer, neurological and inflammatory diseases and the recent nanotechnology based strategies.

Aptamer-based therapeutics of the past, present and future: from the perspective of eye-related diseases

 Aptamers have emerged as a novel and powerful class of biomolecules with an immense untapped potential. The ability to synthesise highly specific aptamers against any molecular target make them a vital cog in the design of effective therapeutics for the future. However, only a minutia of the enormous potential of this dynamic class of molecule has been exploited. Several aptamers have been studied for the treatment of eye-related disorders, and one such strategy has been successful in therapy. This review gives an account of several eye diseases and their regulatory biomolecules where other nucleic acid therapeutics have been attempted with limited success and how aptamers, with their exceptional flexibility to chemical modifications, can overcome those inherent shortcomings.

Exploring motivation and confidence in taking prescribed medicines in coexisting diseases: a qualitative study

Aims and objectives: To explore the motivation and confidence of people with coexisting diabetes, chronic kidney disease (CKD) and hypertension to take their medicines as prescribed. Background: These comorbidities are major contributors to disease burden globally. Self-management of individuals with these coexisting diseases is much more complicated than that of those with single diseases and is critical for improved health outcomes. Design: Motivational interviewing telephone calls were made with participants with coexisting diabetes, CKD and hypertension. Methods: Patients aged ≥18 years with diabetes, CKD and systolic hypertension were recruited from outpatient clinics of an Australian metropolitan hospital between 2008-2009. An average of four motivational interviewing telephone calls was made with participants (n = 39) in the intervention arm of a randomised controlled trial. Data were thematically analysed using the modified Health Belief Model as a framework. Results: Participants' motivation and confidence in taking prescribed medicines was thwarted by complex medicine regimens and medical conditions. Participants wanted control over their health and developed various strategies to confront threats to health. The perceived barriers of taking recommended health action outweighed the benefits of taking medicines as prescribed and were primarily related to copious amounts of medicines. Conclusion: Taking multiple prescribed medicines in coexisting diabetes, CKD and hypertension is a perpetual vocation with major psychosocial effects. Participants were overwhelmed by the number of medicines that they were required to take. The quest for personal control of health, fear of the future and the role of stress and gender in chronic disease management have been highlighted. Participants require supportive emotional interventions to self-manage their multiple medicines on a daily basis. Relevance to clinical practice: Reducing the complexity of medicine regimens in coexisting diseases is paramount. Individualised psychosocial approaches that address the emotional needs of patients with regular follow-up and feedback are necessary for optimal chronic disease self-management. © 2013 John Wiley & Sons Ltd.

Interleukin-10 inhibits bone resorption: a potential therapeutic strategy in periodontitis and other bone loss diseases

Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on long-term medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy.

Knowledge, attitudes, and self care practices associated with age related eye disease in Australia

AIM: To determine the level of correct knowledge about common eye disease and attitudes towards blindness prevention and treatment, and how these factors influence self care practices in a population based sample. METHODS: A cluster random sample of the Victorian population was interviewed. The study population comprised residents aged 40 years of age or older living in five randomly selected Melbourne metropolitan suburbs and four randomly selected rural areas of Victoria. Questions were asked to ascertain each person's knowledge of common age related eye disease--that is, cataract, age related macular degeneration (AMD), and glaucoma. A subsample of the population was also asked questions to determine their attitudes to blindness prevention and treatment. All respondents were asked the year of their last visit to an eye practitioner. RESULTS: A total of 3184 (89%) eligible residents were assessed. Sex (females), age (younger people), higher levels of education (secondary, trade, or tertiary education), recent visit to an eye practitioner (within the past 2 years) and English spoken at home appeared to be significant predictors of knowledge of common age related eye conditions. Younger people believed blindness prevention and blindness treatment were the highest priorities compared with other diseases; people who spoke English at home and people with knowledge of common age related eye disease also considered blindness treatment to be the highest priority compared with other diseases. People with a previous diagnosis of age related eye disease, older people, females, people with correct knowledge of common eye diseases, and those who spoke English at home were significantly more likely to be under eye care. No interaction was found between knowledge and positive attitudes to self care practices. CONCLUSION: These data show that there is a large gap in the public's knowledge and understanding of eye disease that will need to be understood for eye health promotion activities.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013

Background: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian metaregression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

Risk of cardiovascular disease and diabetes in a working population with sedentary occupations

OBJECTIVE: To assess the prevalence of risk factors and risk for cardiovascular disease and Type 2 diabetes in employees with sedentary occupations enrolled in a workplace health-promotion program. METHODS: Participants (n = 762) were recruited from ten Melbourne workplaces, participating in a physical activity program. Demographic, behavioral, biomedical, and physical measurements were collected. RESULTS: The majority of employees were not meeting recommended guidelines for physical activity (62%), fruit intake (70%), vegetable intake (86%), body mass index (58%), or waist circumference (53%). Most had intermediate (53%) or high (7%) risk of developing Type 2 diabetes. CONCLUSIONS: The majority of Australian adults in sedentary occupations were not meeting guidelines for a number of chronic disease risk factors and a substantial proportion were unaware of their increased risk. This study supports the potential of chronic disease risk factor detection and intervention programs in the workplace.

Copper in mammals: mechanisms of homeostasis and pathophysiology

The ability of mammals to tightly regulate systemic copper levels is vital for
health as demonstrated by the severity of the genetic copper deficiency and copper toxicity disorders, Menkes disease and Wilson disease, respectively. Analysis of these genetic disorders has led to a substantial increase in the understanding of the role of copper in health and disease. The isolation of the genes involved in these diseases and use of yeast mutants with altered copper and iron homeostasis has revealed a range of molecular mechanisms governing copper homeostasis. These mechanisms include regulation of cellular copper uptake and efflux and involve the use of chaperones for safe intracellular copper distribution. Here we provide an overview of the physiological role of copper and the molecular mechanisms
regulating systemic and cellular copper levels in mammals. Furthermore, we discuss the pathophysiological mechanisms and consequences of copper deficiency/overload in relation to disease.

The molecular basis of copper-transport diseases

Copper (Cu) is a potentially toxic yet essential element. Menkes disease, a copper deficiency disorder, and Wilson disease, a copper toxicosis condition, are two human genetic disorders, caused by mutations of two closely related Cu-transporting ATPases. Both molecules efflux copper from cells. Quite diverse clinical phenotypes are produced by different mutations of these two Cu-transporting proteins. The understanding of copper homeostasis has become increasingly important in clinical medicine as the metal could be involved in the pathogenesis of some important neurological disorders such as Alzheimer's disease, motor neurone diseases and prion diseases.

DDT and metabolites residues in the southern bent-wing bat (Miniopterus schreibersii bassanii) of south-eastern Australia

The southern bent-wing bat (Miniopterus schreibersii bassanii) is an insectivorous, obligate cave dwelling species found in south-eastern South Australia and western Victoria, Australia. In recent times, the finger of blame for an apparent population decline at Bat Cave, Naracoorte (one of only two known maternity roosts for this species, the other being Starlight Cave, Warrnambool) has been pointed at pesticide use in the region, following the finding of organochlorine and organophosphate insecticide residues in bat guano. This study sampled juvenile southern bent-wing bats from Bat Cave and Starlight Cave, and determined DDT, DDD and DDE concentrations in liver, pectoral muscle, brain and back-depot fat tissues.