Improving Weight Loss By Intermittent Use Of Very Low Energy Diet: The TANGO Diet Trial (Temporary Phases Of Accelerated Weight Loss For Noticeably Greater Outcomes)
Funder
National Health and Medical Research Council
Funding Amount
$660,736.00
Summary
Very low energy diet (VLED) is being increasingly used for the treatment of obesity, but the resultant weight loss is usually transient, partly because it induces powerful adaptive responses that inhibit weight loss and promote regain. We have shown that 'taking a break from dieting' for 2 weeks reduces these adaptive responses. In this project we will thus test whether weight loss outcomes with VLED can be improved via intermittent use, where periods on the VLED are alternated with 'breaks'.
Neurosteroid Mediated Protection After Birth: Approaches For Maximising Protective Steroid Levels In The Neonatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$450,703.00
Summary
Complications during pregnancy, birth asphyxia or premature birth can lead to neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neurosteroids are a group of steroids that regulate brain activity. These steroids protect brain cells from damage caused by an inadequate supply of oxygen by suppressing toxicity caused by excessive activity. We have shown that the levels of these protective steroids are remarkably high in the ....Complications during pregnancy, birth asphyxia or premature birth can lead to neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neurosteroids are a group of steroids that regulate brain activity. These steroids protect brain cells from damage caused by an inadequate supply of oxygen by suppressing toxicity caused by excessive activity. We have shown that the levels of these protective steroids are remarkably high in the fetal brain and levels rise further in response to fetal stress. The placenta contributes steroid precursors that help maintain these high neurosteroid levels. This placenta-fetal brain interaction comprises an internal mechanism that protects the fetal brain from adverse events during pregnancy. At birth, however, there is a dramatic decline in neurosteroid concentrations in the brain after the loss of the placental precursor supply. The fall in concentrations is even greater in animals that are born growth restricted. This suggests that newborns, particularly those from compromised pregnancies, are at increased risk of brain damage due to low neurosteroid levels. We believe that certain commonly used steroid therapies may also lower steroid levels in the brain and result in increased vulnerability to brain damage during birth or in the early neonatal period. Alternatively, we propose that replacement of neurosteroid precursors in the newborn may raise brain neurosteroid levels and protect against brain damage. In the proposed studies we will evaluate treatments that can raise the concentration of steroids and determine the best strategy for reducing brain injury following complications during pregnancy, at birth and during the early newborn period. This work will determine the best therapeutic approaches for maximising neurosteroid-induced brain protection and for reducing the risk of brain damage.Read moreRead less
Studies Of The Effects Of Asymmetric Hearing Loss On The Brain
Funder
National Health and Medical Research Council
Funding Amount
$920,076.00
Summary
Hearing loss impairs the normal development and maintenance of auditory pathways. Irreversible pathologies persist when hearing is not restored in a timely manner. While cochlear implantation is the accepted treatment for profound sensorineural hearing loss, there is significant variability in outcomes. Some of this variability is linked to the degree of hearing asymmetry. Thus, we propose to study brain changes in the auditory system that accompany asymmetric hearing impairment.
Epigenetic Regulation Of Inflammatory Genes In The Fetal Membranes: Role In Term And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$468,534.00
Summary
Preterm birth is the leading cause of death among newborns and the biggest contributor to disability among infants. Here we propose research to define the mechanism that controls the length of pregnancy and is disrupted in preterm birth. Specifically, we will determine what causes the repression of the labour-promoting inflammatory genes in the uterus during pregnancy and what activates them at labour. We will identify new targets for interventions to block or prevent preterm birth.
GENETIC PREDICTION OF FRACTURE IN A RISK-STRATIFIED POPULATION
Funder
National Health and Medical Research Council
Funding Amount
$363,000.00
Summary
Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of indivi ....Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of individuals with osteoporosis (e.g., low BMD) did not sustain a fracture, while approximately 60% of fracture cases had BMD above the high risk levels. Thus, BMD alone is not a good discriminant of fracture versus non-fracture cases. It is widely known that the liability to fracture is determined in part by genes. Previous studies, including from our group, have suggested a number of candidate genes that are associated with fracture risk. The fundamental issue that this study is concerned is that how and whether genetic markers could be used to facilitate case finding. It is proposed that common variations of certain genes are associated with fracture risk independent of BMD. That is, they can identify individuals at relatively high and low fracture risk after stratification for BMD. Hence, some markers may identify those individuals likely (and unlikely) to fracture even with low (osteoporotic) BMD. Similarly, some, possibly the same, markers may identify individuals at high risk of fracture despite relatively good (ie non-osteoporotic) BMD. It is further proposed that no single gene will achieve this outcome, but rather a small set of such gene polymorphisms will provide clinically useful risk information. This effect is entirely analogous to the use of clinical risk indicators (eg, age, weight, sex, family history, etc) to assess the risk of future fracture.Read moreRead less
Estimating And Alleviating The Impacts Of Age-Related Sensory Decline
Funder
National Health and Medical Research Council
Funding Amount
$323,767.00
Summary
Sensory loss and dementia disproportionately affect older adults, often co-occur, and are the two leading contributors to disability burden among older Australians. This research will investigate the consequences that hearing and vision loss have for older adult health and wellbeing, informing strategies to reduce the disability burden of age-related sensory loss. These impacts include cognitive decline and dementia, mental health, quality of life, disability and independent living.
Neuroactive Steroids In The Developing Brain: Potential For Preventing Perinatal Brain Damage
Funder
National Health and Medical Research Council
Funding Amount
$481,500.00
Summary
Complications during pregnancy, birth asphyxia or premature birth can lead to serious neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neuroactive steroids are a group of neuromodulators that are derived from the hormone progesterone. These steroids fall into two groups, those that appear to protect brain cells from damage caused by an inadequate supply of oxygen and those that may increase cell death. We have shown tha ....Complications during pregnancy, birth asphyxia or premature birth can lead to serious neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neuroactive steroids are a group of neuromodulators that are derived from the hormone progesterone. These steroids fall into two groups, those that appear to protect brain cells from damage caused by an inadequate supply of oxygen and those that may increase cell death. We have shown that protective neuroactive steroids are present in very large amounts in the fetal brain. Steroids produced by the placenta are converted to these neuroactive products by enzymes in the brain leading to the high levels that are seen during fetal life. Certain adverse conditions during pregnancy as well as preterm birth may cause marked changes in the balance of steroids that could increase susceptibility to brain injury. We have found that areas of the brain, where damage most often occurs, normally contain the highest amount of protective steroids, but only in late pregnancy. This suggests that disturbances that lower steroid production in these areas could contribute to the death of cells, particularly in mid-pregnancy and after premature birth. In the proposed studies, we will examine whether a toxic balance of steroids develops following adverse events in pregnancy as well as the areas of the brain where this is most pronounced. We will examine the changes in the expression of enzymes that can potentially cause the accumulation of protective steroids in the brain. We will then examine treatments that can raise the concentration of steroids and determine which combination of steroids best reduces cell death and brain injury following complications during pregnancy. The findings of this work will indicate the best therapeutic approach that may be adopted to modify the concentration of certain steroids so as to reduce the risk of brain damage in the fetus and neonate.Read moreRead less
Optimising Benefits And Minimising Potential Harms Of Obesity Treatments
Funder
National Health and Medical Research Council
Funding Amount
$707,370.00
Summary
This work aims to find safe and more effective obesity treatments for the over 2.1 billion people worldwide with overweight or obesity. Severely energy restricted diets are currently the most effective dietary obesity treatment, but these are underutilized due to concerns about potential harms. This work will investigate using severe diets intermittently rather than continuously, as a means of enhancing their benefits of long-term weight/fat loss while also reducing potential harmful effects.
Reducing The Effects Of Antenatal Alcohol On Child Health (REAACH)
Funder
National Health and Medical Research Council
Funding Amount
$2,497,397.00
Summary
Use of alcohol in pregnancy can affect the developing baby and cause Fetal Alcohol Spectrum Disorders (FASD). Children with FASD have lifelong brain injury that can lead to poor school performance, poor mental health and trouble with the law. This CRE builds on our strong background in research and community engagement to improve FASD prevention, diagnosis and treatment across Australia.