Inactivation of the Huntington's disease gene (Hdh) impairs anterior streak formation and early patterning of the mouse embryo

Background Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdhex4/5 huntingtin deficient embryos. Results In the absence of huntingtin, expression of nutritive genes appears normal but E7.0–7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury) and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE) are specified. Conclusion Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in Huntington's disease.

Antenatal ureaplasma infection impairs development of the fetal ovine gut in an IL-1-dependent manner

Ureaplasma infection of the amniotic cavity is associated with adverse postnatal intestinal outcomes. We tested whether interleukin-1 (IL-1) signaling underlies intestinal pathology following ureaplasma exposure in fetal sheep. Pregnant ewes received intra-amniotic injections of ureaplasma or culture media for controls at 3, 7, and 14 d before preterm delivery at 124 d gestation (term 150 d). Intra-amniotic injections of recombinant human interleukin IL-1 receptor antagonist (rhIL-1ra) or saline for controls  were given 3 h before and every 2 d after Ureaplasma injection. Ureaplasma exposure caused fetal gut inflammation within 7 d with damaged villus epithelium and gut barrier loss. Proliferation, differentiation, and maturation of enterocytes were significantly reduced after 7 d of ureaplasma exposure, leading to severe villus atrophy at 14 d. Inflammation, impaired development and villus atrophy of the fetal gut was largely prevented by intra-uterine rhIL-1ra treatment. These data form the basis for a clinical understanding of the role of ureaplasma in postnatal intestinal pathologies.

One night CPAP withdrawal impairs performance at a driving simulator task faster than sleep restriction to 5 hours with treatment in OSA patients

Introduction Sleep restriction and missing 1 night’s continuous positive air pressure (CPAP) treatment are scenarios faced by obstructive sleep apnoea (OSA) patients, who must then assess their own fitness to drive. This study aims to assess the impact of this on driving performance. Method 11 CPAP treated participants (50–75 yrs), drove an interactive car simulator under monotonous motorway conditions for 2 hours on 3 afternoons, following;(i)normal night’s sleep (average 8.2 h) with CPAP (ii) sleep restriction (5 h), with CPAP (iii)normal length of sleep, without CPAP. Driving incidents were noted if the car came out of the designated driving lane. EEG was recorded continually and KSS reported every 200 seconds. Results Driving incidents: Incidents were more prevalent following CPAP withdrawal during hour 1, demonstrating a significant condition time interaction [F(6,60) = 3.40, p = 0.006]. KSS: At the start of driving participants felt sleepiest following CPAP withdrawal, by the end of the task KSS levels were similar following CPAP withdrawal and sleep restriction, demonstrating a significant condition, time interaction [F(3.94,39.41) = 3.39, p = 0.018]. EEG: There was a non significant trend for combined alpha and theta activity to be highest throughout the drive following CPAP withdrawal. Discussion CPAP withdrawal impairs driving simulator performance sooner than restricting sleep to 5 h with CPAP. Participants had insight into this increased sleepiness reflected by the higher KSS reported following CPAP withdrawal. In the practical terms of driving any one incident could be fatal. The earlier impairment reported here demonstrates the potential danger of missing CPAP treatment and highlights the benefit of CPAP treatment even when sleep time is short.

Alcohol ingestion impairs maximal post-exercise rates of myofibrillar protein synthesis following a single bout of concurrent training

Introduction The culture in many team sports involves consumption of large amounts of alcohol after training/competition. The effect of such a practice on recovery processes underlying protein turnover in human skeletal muscle are unknown. We determined the effect of alcohol intake on rates of myofibrillar protein synthesis (MPS) following strenuous exercise with carbohydrate (CHO) or protein ingestion. Methods In a randomized cross-over design, 8 physically active males completed three experimental trials comprising resistance exercise (8×5 reps leg extension, 80% 1 repetition maximum) followed by continuous (30 min, 63% peak power output (PPO)) and high intensity interval (10×30 s, 110% PPO) cycling. Immediately, and 4 h post-exercise, subjects consumed either 500 mL of whey protein (25 g; PRO), alcohol (1.5 g·kg body mass−1, 12±2 standard drinks) co-ingested with protein (ALC-PRO), or an energy-matched quantity of carbohydrate also with alcohol (25 g maltodextrin; ALC-CHO). Subjects also consumed a CHO meal (1.5 g CHO·kg body mass−1) 2 h post-exercise. Muscle biopsies were taken at rest, 2 and 8 h post-exercise. Results Blood alcohol concentration was elevated above baseline with ALC-CHO and ALC-PRO throughout recovery (P<0.05). Phosphorylation of mTORSer2448 2 h after exercise was higher with PRO compared to ALC-PRO and ALC-CHO (P<0.05), while p70S6K phosphorylation was higher 2 h post-exercise with ALC-PRO and PRO compared to ALC-CHO (P<0.05). Rates of MPS increased above rest for all conditions (~29–109%, P<0.05). However, compared to PRO, there was a hierarchical reduction in MPS with ALC-PRO (24%, P<0.05) and with ALC-CHO (37%, P<0.05). Conclusion We provide novel data demonstrating that alcohol consumption reduces rates of MPS following a bout of concurrent exercise, even when co-ingested with protein. We conclude that alcohol ingestion suppresses the anabolic response in skeletal muscle and may therefore impair recovery and adaptation to training and/or subsequent performance.

Estrogen receptor β activation impairs mitochondrial oxidative metabolism and affects malignant mesothelioma cell growth in vitro and in vivo

Estrogen receptor (ER)-β has been shown to possess a tumor suppressive effect, and is a potential target for cancer therapy. Using gene-expression meta-analysis of human malignant pleural mesothelioma, we identified an ESR2 (ERβ coding gene) signature. High ESR2 expression was strongly associated with low succinate dehydrogenase B (SDHB) (which encodes a mitochondrial respiratory chain complex II subunit) expression. We demonstrate that SDHB loss induced ESR2 expression, and that activated ERβ, by over-expression or by selective agonist stimulation, negatively affected oxidative phosphorylation compromising mitochondrial complex II and IV activity. This resulted in reduced mitochondrial ATP production, increased glycolysis dependence and impaired cell proliferation. The observed in vitro effects were phenocopied in vivo using a selective ERβ agonist in a mesothelioma mouse model. On the whole, our data highlight an unforeseen interaction between ERβ-mediated tumor suppression and energy metabolism that may be exploited to improve on the therapy for clinical management of malignant mesothelioma.

Escherichia coli 83972 expressing a P fimbriae oligosaccharide receptor mimic impairs adhesion of Uropathogenic E. coli

Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are a significant health concern, exacerbated by the rapid emergence of multidrug resistant strains refractory to antibiotic treatment. P fimbriae are strongly associated with upper urinary tract colonization due to specific binding to α-D-galactopyranosyl-(1-4)-β-D-galactopyranoside receptors in the kidneys. Thus, inhibiting P-fimbrial adhesion may reduce the incidence of UPEC-mediated UTI. E. coli 83972 is an asymptomatic bacteriuria isolate successfully used as a prophylactic agent to prevent UTI in human studies. We constructed a recombinant E. coli 83972 strain displaying a surface-located oligosaccharide P fimbriae receptor mimic that bound to P-fimbriated E. coli producing any of the 3 PapG adhesin variants. The recombinant strain, E. coli 83972:: lgtCE, impaired P fimbriae–mediated adhesion to human erythrocytes and kidney epithelial cells. Additionally, E. coli 83972::lgtCE impaired urine colonization by UPEC in a mouse UTI model, demonstrating its potential as a prophylactic agent to prevent UTI.

Simulated astigmatism impairs academic-related performance in children

Purpose: Astigmatism is an important refractive condition in children. However, the functional impact of uncorrected astigmatism in this population is not well established, particularly with regard to academic performance. This study investigated the impact of simulated bilateral astigmatism on academic-related tasks before and after sustained near work in children. Methods: Twenty visually normal children (mean age: 10.8 ± 0.7 years; 6 males and 14 females) completed a range of standardised academic-related tests with and without 1.50 D of simulated bilateral astigmatism (with both academic-related tests and the visual condition administered in a randomised order). The simulated astigmatism was induced using a positive cylindrical lens while maintaining a plano spherical equivalent. Performance was assessed before and after 20 minutes of sustained near work, during two separate testing sessions. Academic-related measures included a standardised reading test (the Neale Analysis of Reading Ability), visual information processing tests (Coding and Symbol Search subtests from the Wechsler Intelligence Scale for Children) and a reading-related eye movement test (the Developmental Eye Movement test). Each participant was systematically assigned either with-the-rule (WTR, axis 180°) or against-the-rule (ATR, axis 90°) simulated astigmatism to evaluate the influence of axis orientation on any decrements in performance. Results: Reading, visual information processing and reading-related eye movement performance were all significantly impaired by both simulated bilateral astigmatism (p<0.001) and sustained near work (p<0.001), however, there was no significant interaction between these factors (p>0.05). Simulated astigmatism led to a reduction of between 5% and 12% in performance across the academic-related outcome measures, but there was no significant effect of the axis (WTR or ATR) of astigmatism (p>0.05). Conclusion: Simulated bilateral astigmatism impaired children’s performance on a range of academic–related outcome measures irrespective of the orientation of the astigmatism. These findings have implications for the clinical management of non-amblyogenic levels of astigmatism in relation to academic performance in children. Correction of low to moderate levels of astigmatism may improve the functional performance of children in the classroom.

Early maternal deprivation reduces prepulse inhibition and impairs spatial learning ability in adulthood: No further effect of post-pubertal chronic corticosterone treatment

Prolonged maternal deprivation leads to long-term alterations in hypothalamic–pituitary–adrenal (HPA) axis activity, disturbances of auditory information processing and neurochemical changes in the adult brain, some of which are similar to that observed in schizophrenia. Here we report the adult behavioural effects of maternal deprivation (12 h on postnatal days 9 and 11) in Wistar rats on paradigms of auditory information processing (prepulse inhibition), sensitivity to dopamimetics (amphetamine-induced hyper-locomotion) and cognition (T-maze delayed alternation and Morris water-maze). In addition, we examined the long-lasting effect of chronic 21-day corticosterone treatment during the post-pubertal period (i.e., postnatal days 56–76) on each of these behavioural paradigms in maternally deprived and control rats. Behavioural testing commenced 2 weeks after the termination of corticosterone treatment. Maternal deprivation led to a significant reduction in PPI and impaired spatial learning ability in adulthood, but did not affect the behavioural response to amphetamine. Post-pubertal chronic corticosterone treatment did not have any major long-lasting effects on any of the behavioural measures in either maternally deprived or control rats. Our findings further support maternal deprivation as an animal model of specific aspects of schizophrenia.

Cyclic strain disrupts endothelial network formation on Matrigel

Most forms of tissue healing depend critically on revascularisation. In soft tissues and in vitro, mechanical stimuli have been shown to promote vessel-forming activity. However, in bone defects, increased interfragmentary motion impairs vascular regeneration. Because these effects seem contradictory, we aimed to determine whether a range of mechanical stimuli exists in which angiogenesis is favoured. A series of cyclic strain magnitudes were applied to a Matrigel-based “tube formation” assay and the total lengths of networks formed by human microvascular endothelial cells measured at 24 h. Network lengths were reduced at all strain levels, compared to unstretched controls. However, the levels of pro-angiogenic matrix metalloproteases-2 and -9 in the corresponding conditioned media were unchanged by strain, and vascular endothelial growth factor was uniformly elevated in stretched conditions. By repeating the assay with the addition of conditioned media from mesenchymal stem cells cultivated in similar conditions, paracrine stimuli were shown to increase network lengths, but not to alter the negative effect of cyclic stretching. Together, these results demonstrate that directly applied periodic strains can inhibit endothelial organisation in vitro, and suggest that this may be due to physical disruption rather than biochemical modulation. Most importantly, the results indicate that the straining of endothelial cells and their assembly into vascular-like structures must be studied simultaneously to adequately characterise the mechanical influence on vessel formation.

The effect of monocular and binocular cataract blur on postural stability among older adults

Purpose: First-eye cataract surgery can reduce the rate of falls among older adults, yet the effect of second-eye surgery on the rate of falling remains unclear. The present study investigated the effect of monocular and binocular simulated cataract blur on postural stability among older adults. Methods: Postural stability was assessed on 34 healthy older adults (mean 68.2 years, SD 3.5) with normal vision, using a portable force platform (BT4, HUR Labs, Finland) which collected data on centre of pressure (COP) displacement. Stability was assessed on firm and foam surfaces under four binocular viewing conditions using Vistech filters to simulate cataract blur: [1] best-corrected vision both eyes; [2] blur over non-dominant eye, [3] blur over dominant eye and [4] blur over both eyes. Binocular logMAR visual acuity, Pelli-Robson contrast sensitivity and stereoacuity were also measured under these viewing conditions and ocular dominance measured using the hole-in-card test. Generalized estimating equations with an exchangeable correlation structure examined the effect of the surface and vision conditions on postural stability. Results: Visual acuity and contrast sensitivity were significantly reduced under monocular and binocular cataract blur compared to normal viewing. All blur conditions resulted in loss of stereoacuity. Binocular cataract blur significantly reduced postural stability compared to normal vision on the firm (COP path length; p=0.013) and foam surface (anterior-posterior COP RMS, COP path length and COP area; p<0.01). However, no significant differences in postural stability were found between the monocular blur conditions compared to normal vision, or between the dominant and non-dominant monocular blur conditions on either the firm or foam surfaces. Conclusions: Findings indicate that binocular blur significantly impairs postural stability, and suggests that improvements in postural stability may justify first-eye cataract surgery, particularly during somatosensory disruption. Postural stability was not significantly impaired in the monocular cataract blur conditions compared to the normal vision condition, nor was there any effect of ocular dominance on postural stability in the presence of monocular cataract blur.

Driving performance on monotonous roads

Driving on motorways has largely been reduced to a lane-keeping task with cruise control. Rapidly, drivers are likely to get bored with such a task and take their attention away from the road. This is of concern in terms of road safety – particularly for professional drivers - since inattention has been identified as one of the main contributing factors to road crashes and is estimated to be involved in 20 to 30% of these crashes. Furthermore, drivers are not aware that their vigilance level has decreased and that their driving performance is impaired. Intelligent Transportation System (ITS) intervention can be used as a countermeasure against vigilance decrement. This paper aims to identify a variety of metrics impacted during monotonous driving - ranging from vehicle data to physiological variables - and relate them to two monotonous factors namely the monotony of the road design (straightness) and the monotony of the environment (landscape, signage, traffic). Data are collected in a driving simulator instrumented with an eye tracking system, a heart rate monitor and an electrodermal activity device (N=25 participants). The two monotonous factors are varied (high and low) leading to the use of four different driving scenarios (40 minutes each). We show with Generalised Linear Mixed Models that driver performance decreases faster when the road is monotonous. We also highlight that road monotony impairs a variety of driving performance and vigilance measures, ranging from speed, lateral position of the vehicle to physiological measurements such as heart rate variability, blink frequency and electrodermal activity. This study informs road designers of the importance of having a varied road environment. It also provides a range of metrics that can be used to detect in real-time the impairment of driving performance on monotonous roads. Such knowledge could result in the development of an in-vehicle device warning drivers at early signs of driving performance impairment on monotonous roads.

Socioeconomic inequality profiles in physical and developmental health from 0-7 years : Australian National Study

Background: Early and persistent exposure to socioeconomic disadvantage impairs children’s health and wellbeing. However, it is unclear at what age health inequalities emerge or whether these relationships vary across ages and outcomes. We address these issues using cross-sectional Australian population data on the physical and developmental health of children at ages 0-1, 2-3, 4-5 and 6-7 years. Methods: 10 physical and developmental health outcomes were assessed in 2004 and 2006 for two cohorts each comprising around 5000 children. Socioeconomic position was measured as a composite of parental education, occupation and household income. Results: Lower socioeconomic position was associated with increased odds for poor outcomes. For physical health outcomes and socio-emotional competence, associations were similar across age groups and were consistent with either threshold effects (for poor general health, special healthcare needs and socio-emotional competence) or gradient effects (for illness with wheeze, sleep problems and injury). For socio-emotional difficulties, communication, vocabulary and emergent literacy, stronger socioeconomic associations were observed. The patterns were linear or accelerated and varied across ages. Conclusions: From very early childhood, social disadvantage was associated with poorer outcomes across most measures of physical and developmental health and showed no evidence of either strengthening or attenuating at older compared to younger ages. Findings confirm the importance of early childhood as a key focus for health promotion and prevention efforts.

Pressure, oxygen tension and temperature in the periosteal callus during bone healing - An in vivo study in sheep

Adequate blood supply and sufficient mechanical stability are necessary for timely fracture healing. Damage to vessels impairs blood supply; hindering the transport of oxygen which is an essential metabolite for cells involved in repair. The degree of mechanical stability determines the mechanical conditions in the healing tissues. The mechanical conditions can influence tissue differentiation and may also inhibit revascularization. Knowledge of the actual conditions in a healing fracture in vivo is extremely limited. This study aimed to quantify the pressure, oxygen tension and temperature in the external callus during the early phase of bone healing. Six Merino-mix sheep underwent a tibial osteotomy. The tibia was stabilized with a standard mono-lateral external fixator. A multi-parameter catheter was placed adjacent to the osteotomy gap on the medial aspect of the tibia. Measurements of oxygen tension and temperature were performed for ten days post-op. Measurements of pressure were performed during gait on days three and seven. The ground reaction force and the interfragmentary movements were measured simultaneously. The maximum pressure during gait increased (p=0.028) from three (41.3 [29.2-44.1] mm Hg) to seven days (71.8 [61.8-84.8] mm Hg). During the same interval, there was no change (p=0.92) in the peak ground reaction force or in the interfragmentary movement (compression: p=0.59 and axial rotation: p=0.11). Oxygen tension in the haematoma (74.1 mm Hg [68.6-78.5]) was initially high post-op and decreased steadily over the first five days. The temperature increased over the first four days before reaching a plateau at approximately 38.5 degrees C on day four. This study is the first to report pressure, oxygen tension and temperature in the early callus tissues. The magnitude of pressure increased even though weight bearing and IFM remained unchanged. Oxygen tensions were initially high in the haematoma and fell gradually with a low oxygen environment first established after four to five days. This study illustrates that in bone healing the local environment for cells may not be considered constant with regard to oxygen tension, pressure and temperature.

Review of the under the limit drink driving rehabilitation program

The combination of alcohol and driving is a major health and economic burden to most communities in industrialised countries. The total cost of crashes for Australia in 1996 was estimated at approximately 15 billion dollars and the costs for fatal crashes were about 3 billion dollars (BTE, 2000). According to the Bureau of Infrastructure, Transport and Regional Development and Local Government (2009; BITRDLG) the overall cost of road fatality crashes for 2006 $3.87 billion, with a single fatal crash costing an estimated $2.67 million. A major contributing factor to crashes involving serious injury is alcohol intoxication while driving. It is a well documented fact that consumption of liquor impairs judgment of speed, distance and increases involvement in higher risk behaviours (Waller, Hansen, Stutts, & Popkin, 1986a; Waller et al., 1986b). Waller et al. (1986a; b) asserts that liquor impairs psychomotor function and therefore renders the driver impaired in a crisis situation. This impairment includes; vision (degraded), information processing (slowed), steering, and performing two tasks at once in congested traffic (Moskowitz & Burns, 1990). As BAC levels increase the risk of crashing and fatality increase exponentially (Department of Transport and Main Roads, 2009; DTMR). According to Compton et al. (2002) as cited in the Department of Transport and Main Roads (2009), crash risk based on probability, is five times higher when the BAC is 0.10 compared to a BAC of 0.00. The type of injury patterns sustained also tends to be more severe when liquor is involved, especially with injuries to the brain (Waller et al., 1986b). Single and Rohl (1997) reported that 30% of all fatal crashes in Australia where alcohol involvement was known were associated with Breadth Analysis Content (BAC) above the legal limit of 0.05gms/100ml. Alcohol related crashes therefore contributes to a third of the total cost of fatal crashes (i.e. $1 billion annually) and crashes where alcohol is involved are more likely to result in death or serious injury (ARRB Transport Research, 1999). It is a major concern that a drug capable of impairment such as is the most available and popular drug in Australia (Australian Institute of Health and Welfare, 2007; AIHW). According to the AIHW (2007) 89.9% of the approximately 25,000 Australians over the age of 14 surveyed had consumed at some point in time, and 82.9% had consumed liquor in the previous year. This study found that 12.1% of individuals admitted to driving a motor vehicle whilst intoxicated. In general males consumed more liquor in all age groups. In Queensland there were 21503 road crashes in 2001, involving 324 fatalities and the largest contributing factor was alcohol and or drugs (Road Traffic Report, 2001). 23438 road crashes in 2004, involving 289 fatalities and the largest contributing factor was alcohol and or drugs (DTMR, 2009). Although a number of measures such as random breath testing have been effective in reducing the road toll (Watson, Fraine & Mitchell, 1995) the recidivist drink driver remains a serious problem. These findings were later supported with research by Leal, King, and Lewis (2006). This Queensland study found that of the 24661 drink drivers intercepted in 2004, 3679 (14.9%) were recidivists with multiple drink driving convictions in the previous three years covered (Leal et al., 2006). The legal definition of the term “recidivist” is consistent with the Transport Operations (Road Use Management) Act (1995) and is assigned to individuals who have been charged with multiple drink driving offences in the previous five years. In Australia relatively little attention has been given to prevention programs that target high-risk repeat drink drivers. However, over the last ten years a rehabilitation program specifically designed to reduce recidivism among repeat drink drivers has been operating in Queensland. The program, formally known as the “Under the Limit” drink driving rehabilitation program (UTL) was designed and implemented by the research team at the Centre for Accident Research and Road Safety in Queensland with funding from the Federal Office of Road Safety and the Institute of Criminology (see Sheehan, Schonfeld & Davey, 1995). By 2009 over 8500 drink-drivering offenders had been referred to the program (Australian Institute of Crime, 2009).

A randomised controlled trial to prevent hospital readmissions and loss of functional ability in high risk older adults: a study protocol

Background Older people have higher rates of hospital admission than the general population and higher rates of readmission due to complications and falls. During hospitalisation, older people experience significant functional decline which impairs their future independence and quality of life. Acute hospital services comprise the largest section of health expenditure in Australia and prevention or delay of disease is known to produce more effective use of services. Current models of discharge planning and follow-up care, however, do not address the need to prevent deconditioning or functional decline. This paper describes the protocol of a randomised controlled trial which aims to evaluate innovative transitional care strategies to reduce unplanned readmissions and improve functional status, independence, and psycho-social well-being of community-based older people at risk of readmission. Methods/Design The study is a randomised controlled trial. Within 72 hours of hospital admission, a sample of older adults fitting the inclusion/exclusion criteria (aged 65 years and over, admitted with a medical diagnosis, able to walk independently for 3 meters, and at least one risk factor for readmission) are randomised into one of four groups: 1) the usual care control group, 2) the exercise and in-home/telephone follow-up intervention group, 3) the exercise only intervention group, or 4) the in-home/telephone follow-up only intervention group. The usual care control group receive usual discharge planning provided by the health service. In addition to usual care, the exercise and in-home/telephone follow-up intervention group receive an intervention consisting of a tailored exercise program, in-home visit and 24 week telephone follow-up by a gerontic nurse. The exercise only and in-home/telephone follow-up only intervention groups, in addition to usual care receive only the exercise or gerontic nurse components of the intervention respectively. Data collection is undertaken at baseline within 72 hours of hospital admission, 4 weeks following hospital discharge, 12 weeks following hospital discharge, and 24 weeks following hospital discharge. Outcome assessors are blinded to group allocation. Primary outcomes are emergency hospital readmissions and health service use, functional status, psychosocial well-being and cost effectiveness. Discussion The acute hospital sector comprises the largest component of health care system expenditure in developed countries, and older adults are the most frequent consumers. There are few trials to demonstrate effective models of transitional care to prevent emergency readmissions, loss of functional ability and independence in this population following an acute hospital admission. This study aims to address that gap and provide information for future health service planning which meets client needs and lowers the use of acute care services.