Osteocytes (OY) are the most abundant cell type in bone whose high density and viability are essential for healthy bone. We have found that vitamin K, vitamin D and strontium, promote human OY differentiation. We will test these in novel models of human OY differentiation and survival, and in animal models of bone loss associated with vitamin D deficiency, menopause and glucocorticoid treatment. Our work will lead to a better understanding of human OY and give a new approach to treat osteoporosi ....Osteocytes (OY) are the most abundant cell type in bone whose high density and viability are essential for healthy bone. We have found that vitamin K, vitamin D and strontium, promote human OY differentiation. We will test these in novel models of human OY differentiation and survival, and in animal models of bone loss associated with vitamin D deficiency, menopause and glucocorticoid treatment. Our work will lead to a better understanding of human OY and give a new approach to treat osteoporosis.Read moreRead less
Obesity In The Elderly: Impact Of Weight Loss Therapy On Physiology And Function.
Funder
National Health and Medical Research Council
Funding Amount
$613,213.00
Summary
The aim of this study is to assess the safety, tolerability, weight-loss efficacy, change in lean body mass and impact of cognition of three approaches to treat obesity in the elderly. We will compare dietary advice, an energy reduced diet and a very low calorie diet. All three groups will also have an exercise program. This study will be of major assistance in developing management guidelines for obesity in the elderly, which will likely be an emerging public health issue.
The Role Of Proteases In Deafness; Generation Of A Knockout Mouse For Tmprss3 As A Model Of Autosomal Recessive Deafness
Funder
National Health and Medical Research Council
Funding Amount
$70,880.00
Summary
Age-related hearing loss is the most common type of human hearing impairment, affecting approximately half the population by the age of 80. The interaction of predisposing genetic factors with environmental factors is responsible for most age-related hearing loss. Genes underlying genetically inherited hearing impairment also affect susceptibility to age-related hearing loss. Approximately 1-1000 children are born deaf and ~50% of these cases have a genetic cause. Autosomal recessively-inherited ....Age-related hearing loss is the most common type of human hearing impairment, affecting approximately half the population by the age of 80. The interaction of predisposing genetic factors with environmental factors is responsible for most age-related hearing loss. Genes underlying genetically inherited hearing impairment also affect susceptibility to age-related hearing loss. Approximately 1-1000 children are born deaf and ~50% of these cases have a genetic cause. Autosomal recessively-inherited defects are responsible for most cases of genetic deafness (70%) and patients have no other medical problems, indicating that only the inner ear is affected. Genes previously identified for genetic forms of deafness can be broadly classified as either ion channels (e.g. connexins) or structural proteins (e.g. myosins and collagens). We recently identified a novel gene, a transmembrane serine protease, TMPRSS3, which is mutated both in familial and sporadic cases of deafness. Different classes of mutations may cause either deafness from birth or childhood onset deafness. Thus, reduced expression or abnormal function of TMPRSS3 may be involved in age-related hearing loss. This discovery was the first description of a protease involved in hearing loss and the first gene family involved in congenital deafness for which a ready hypothesis for involvement in age-related hearing loss can be made. We will generate and characterize a mouse model to investigate the role of TMPRSS3 in inner ear function and development. We will also isolate and characterize additional members of the transmembrane protease gene family to investigate further the role of proteases in both genetic and age-related hearing loss. This may lead to a greater understanding of the function of the auditory system and, eventually, to new therapeutic protocols.Read moreRead less
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'.
We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately exp ....We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately explore the relationship between prothesis wear and PO, or the progression of PO, because of a lack of techniques to image and measure the volume of PO around metal prosthesis components. We have developed a means to accurately and reproducibly measure the volume of bone loss, using CT, and will do so longitudinally in joint replacement patients to obtain the first information about the progression of PO. New computer based methods will be used concurrently to relate prosthesis wear and migration parameters to PO. Patients who come to surgery for replacement of failed prostheses will be investigated further by analysis of the tissues involved in the bone loss around prostheses. Basic science experiments will seek to understand the underlying causes of PO and the findings will be important in interpreting the clinical results. An animal model will be used to seek approaches to inhibiting the pathological response to wear particles. The significance of these studies is that they will lead to improved outcomes for joint replacement patients, increasing the interval to revision surgery, which is both extremely costly and brings an attendant morbidity and mortality.Read moreRead less
This project will provide comprehensive nationally-representative data on the issue of hearing loss at work. We will undertake a large national survey to determine how many Australians are exposed to noise and ototoxic chemicals in the workplace and will use these data to estimate the future burden of work-related hearing loss. We will also estimate how changes in the use of noise control measures could alter the burden and the costs.
Managing Depression Within Low Vision Rehabilitation Services: The Effectiveness Of Integrating An Evidence-based Therapy ‘Problem-Solving Therapy For Primary Care’ On Depression, Quality Of Life And Service Utilisation In Those With Low Vision
Funder
National Health and Medical Research Council
Funding Amount
$92,785.00
Summary
This research will evaluate the integration of an evidence-based treatment for depression into low vision rehabilitation services. It is anticipated that this new program will lead to sustained improvements in participants’ quality of life and mental health. This is the first time a system to manage depression has been implemented into low vision services worldwide and if successful this intervention could be suitable for application to other chronic health conditions.