Long-term persistence of tissue-engineered adipose flaps in a murine model to 1 year : an update

BACKGROUND Tissue engineering of patient-specific adipose tissue has the potential to revolutionize reconstructive surgery. Numerous models have been described for the production of adipose tissue with success in the short term, but little has been reported on the stability of this tissue-engineered fat beyond 4 months. METHODS A murine model of de novo adipogenesis producing a potentially transplantable adipose tissue flap within 4 to 6 weeks was developed in the authors' laboratory. In this study, the authors assess the ability of three-chamber (44-μl volume) configurations shown to be adipogenic in previous short-term studies (autograft, n = 8; open, n = 6; fat flap, n = 11) to maintain their tissue volume for up to 12 months in vivo, to determine the most adipogenic configuration in the long term. RESULTS Those chambers having the most contact with existing vascularized adipose tissue (open and fat flap groups) showed increased mean adipose tissue percentage (77 ± 5.6 percent and 81 ± 6.9 percent, respectively; p < 0.0007) and volume (12 ± 6.8 μl and 30 ± 14 μl, respectively; p < 0.025) when compared with short-term controls and greater adipose tissue volume than the autograft (sealed) chamber group (4.9 ± 5.8 μl; p = 0.0001) at 1 year. Inclusion of a vascularized fat flap within the chamber produced the best results, with new fat completely filling the chamber by 1 year. CONCLUSIONS These findings demonstrate that fat produced by tissue engineering is capable of maintaining its volume when the appropriate microenvironment is provided. This has important implications for the application of tissue-engineering techniques in humans.

Patient perspectives of the impact and long-term management of lymphoedema

Lymphoedema following cancer treatment is characterized by swelling, and adversely influences mobility, function and quality of life. There is no cure, but without treatment lymphedema may progress. Since lymphedema treatment options are costly and time consuming, understanding the influence of these, and other potential barriers, on treatment adherence is vital in reducing the public health burden of lymphedema. Complex physical therapy and compression are supported by scientific evidence and patients also perceive these treatments as effective for improving symptoms and function. Multiple treatments may be required to treat all aspects of the condition. Patients and health professionals should consider effect and costs when identifying optimal treatment strategies.

MT1-MMP-dependent and -independent regulation of gelatinase A activation in long-term, ascorbate-treated fibroblast cultures: Regulation by fibrillar collagen

Human skin fibroblasts were cultured long-term in the presence of ascorbic acid to allow formation of a three-dimensional collagen matrix, and the effects of this on activation of secreted matrix metalloproteinase-2 (MMP-2) were examined. Accumulation of collagen over time correlated with increased levels of both mature MMP-2 and cell-associated membrane type 1-MMP (MT1-MMP), and subsequently increased mRNA levels for MT1-MMP, providing temporal resolution of the "nontranscriptional" and "transcriptional" effects of collagen on MT-1MMP functionality. MMP-2 activation by these cultures was blocked by inhibitors of prolyl-4-hydroxylase, or when fibroblasts derived from the collagen α1(I) gene-deficient Mov-13 mouse were used. MMP-2 activation by the Mov-13 fibroblasts was rescued by transfection of a full-length α1(I) collagen cDNA, and to our surprise, also by transfection with an α1(I) collagen cDNA carrying a mutation at the C-proteinase cleavage, which almost abrogated fibrillogenesis. Although studies with ascorbate-cultured MT1-MMP-/- fibroblasts showed that MT1-MMP played a significant role in the collagen-induced MMP-2 activation, a residual MT1-MMP-independent activation of MMP-2 was seen which resembled the level of MMP-2 activation persisting when wild-type fibroblasts were cultured in the presence of both ascorbic acid and MMP inhibitors. We were also unable to block this residual activation with inhibitors specific for serinyl, aspartyl, or cysteinyl enzymes.

Predicting positive and negative impacts of cancer among long-term endometrial cancer survivors

OBJECTIVE Although the survival outcomes among women diagnosed with endometrial cancer are very favorable, little is known about the long-term impact of their cancer experience. This study identifies the extent of positive and negative impacts of cancer and factors associated with this, amongst long-term survivors of endometrial cancer. METHODS Australian women diagnosed with endometrial cancer (N=632) were sent questionnaires at the time of diagnosis and 3-5 years later. Hierarchical multiple regression models were used to examine whether a range of variables at diagnosis/treatment predicted subsequent scores on the Impact of Cancer Scale, which examines positive (e.g. health awareness) and negative (e.g. appearance concerns) impacts amongst cancer survivors. RESULTS Overall, women had a higher mean score for the positive than negative impact scales (M=3.5 versus M=2.5, respectively). An intermediate grade of endometrial cancer, a prior diagnosis of cancer and lower levels of education were significant, but weak, predictors of higher scores on the positive impact scale. Higher scores on the negative impact scale were predicted by a higher grade of cancer, poor physical and mental health, a younger age, being single or having lower levels of education. CONCLUSIONS The study demonstrates that factors that predict positive impact in cancer survivors differ to those that predict negative impact, suggesting that interventions to optimize cancer survivors' quality of life will need to be multi-dimensional, and this supports the need for tailored intervention.

Dynamic modelling of long-term care decisions

This paper describes and analyzes research on the dynamics of long-term care and the policy relevance of identifying the sources of persistence in caregiving arrangements (including the effect of dynamics on parameter estimates, implications for family welfare, parent welfare, child welfare, and cost of government programs). We discuss sources and causes of observed persistence in caregiving arrangements including inertia/state dependence (confounded by unobserved heterogeneity) and costs of changing caregivers. We comment on causes of dynamics including learning/human capital accumulation; burnout; and game-playing. We suggest how to deal with endogenous geography; dynamics in discrete and continuous choices; and equilibrium issues (multiple equilibria, dynamic equilibria). We also present an overview of commonly used longitudinal data sets and evaluate their relative advantages/disadvantages. We also discuss other data issues related to noisy measures of wealth and family structure. Finally, we suggest some methods to handle econometric problems such as endogeneous geography. © 2014 Springer Science+Business Media New York.

Strategic play among family members when making long-term care decisions

This paper describes a strategic model of bargaining within a family to determine how to care for an elderly parent. We estimate the parameters of the model using data from the National Long-term Care Survey. We find that the parameter estimates generally make sense and that the model is consistent with the data. The results have strong implications for using less structural empirical models for policy analysis.

Long-term care and family bargaining

We present a structural model of how families decide who should care for elderly parents. We use data from the National Long-Term Care Survey to estimate and test the parameters of the model. Then we use the parameter estimates to simulate the effects of the existing long-term trends in terms of the common but untested explanations for them. Finally, we simulate the effects of alternative family bargaining rules on individual utility to measure the sensitivity of our results to the family decision-making assumptions we make.

Measuring child work and residence adjustments to parents' long-term care needs

This article estimates the effects of various parent and child characteristics on the choice of care arrangement of the parent, taking into account the potential endogeneity of some of the child characteristics. Three equations are estimated: a care choice equation, a child location equation, and a child work equation. Results suggest a hierarchy of family decision making; child locations affect the care decision, which affects child work decisions. The results also question previous research attempting to explain causes of secular trends in long-term care.

Gene electrotransfer into murine skeletal muscle: A systematic analysis of parameters for long-term gene expression

Skeletal muscle is an attractive target tissue for delivery of therapeutic genes, since it is well vascularized, easily accessible, and has a high capacity for protein synthesis. For efficient transfection in skeletal muscle, several protocols have been described, including delivery of low voltage electric pulses and a combination of high and low voltage electric pulses. The aim of this study was to determine the influence of different parameters of electrotransfection on short-term and long-term transfection efficiency in murine skeletal muscle, and to evaluate histological changes in the treated tissue. Different parameters of electric pulses, different time lags between plasmid DNA injection and application of electric pulses, and different doses of plasmid DNA were tested for electrotransfection of tibialis cranialis muscle of C57BI/6 mice using DNA plasmid encoding green fluorescent protein (GFP). Transfection efficiency was assessed on frozen tissue sections one week after electrotransfection using a fluorescence microscope and also noninvasively, followed by an in vivo imaging system using a fluorescence stereo microscope over a period of several months. Histological changes in muscle were evaluated immediately or several months after electrotransfection by determining infiltration of inflammatory mononuclear cells and presence of necrotic muscle fibers. The most efficient electrotransfection into skeletal muscle of C57BI/6 mice in our experiments was achieved when one high voltage (HV) and four low voltage (LV) electric pulses were applied 5 seconds after the injection of 30 μg of plasmid DNA. This protocol resulted in the highest short-term as well as long-term transfection. The fluorescence intensity of the transfected area declined after 2-3 weeks, but GFP fluorescence was still detectable 18 months after electrotransfection. Extensive inflammatory mononuclear cell infiltration was observed immediately after the electrotransfection procedure using the described parameters, but no necrosis or late tissue damage was observed. This study showed that electric pulse parameters, time lag between the injection of DNA and application of electric pulses, and dose of plasmid DNA affected the duration of transgene expression in murine skeletal muscle. Therefore, transgene expression in muscle can be controlled by appropriate selection of electrotransfection protocol.

Long-term exploration and tours for energy constrained robots with online proprioceptive traversability estimation

This paper is concerned with how a localised and energy-constrained robot can maximise its time in the field by taking paths and tours that minimise its energy expenditure. A significant component of a robot's energy is expended on mobility and is a function of terrain traversability. We estimate traversability online from data sensed by the robot as it moves, and use this to generate maps, explore and ultimately converge on minimum energy tours of the environment. We provide results of detailed simulations and parameter studies that show the efficacy of this approach for a robot moving over terrain with unknown traversability as well as a number of a priori unknown hard obstacles.

Effect of broadcast baiting on abundance patterns of red imported fire ants (Hymenoptera: Formicidae) and key local ant genera at long-term monitoring sites in Brisbane, Australia

In 2001, the red imported fire ant (Solenopsis invicta Buren) was identified in Brisbane, Australia. An eradication program involving broadcast bait treatment with two insect growth regulators and a metabolic inhibitor began in September of that year and is currently ongoing. To gauge the impacts of these treatments on local ant populations, we examined long-term monitoring data and quantified abundance patterns of S. invicta and common local ant genera using a linear mixed-effects model. For S. invicta, presence in pitfalls reduced over time to zero on every site. Significantly higher numbers of S. invicta workers were collected on high-density polygyne sites, which took longer to disinfest compared with monogyne and low-density polygyne sites. For local ants, nine genus groups of the 10 most common genera analyzed either increased in abundance or showed no significant trend. Five of these genus groups were significantly less abundant at the start of monitoring on high-density polygyne sites compared with monogyne and low-density polygyne sites. The genus Pheidole significantly reduced in abundance over time, suggesting that it was affected by treatment efforts. These results demonstrate that the treatment regime used at the time successfully removed S. invicta from these sites in Brisbane, and that most local ant genera were not seriously impacted by the treatment. These results have important implications for current and future prophylactic treatment efforts, and suggest that native ants remain in treated areas to provide some biological resistance to S. invicta.

Fischer rats consume 20% ethanol in a long-term intermittent-access two-bottle-choice paradigm

The 20% ethanol intermittent-access (IAE) two-bottle-choice drinking procedure has been shown to produce high voluntary ethanol consumption in a number of rat strains. For this study, we applied this procedure to male Fischer (F344) rats, a strain previously reported to exhibit low levels of ethanol consumption. We also subjected these animals to a two-week ethanoldeprivation- period to see if they would exhibit an alcohol deprivation effect (ADE) signified by a transient increase in alcohol consumption following deprivation. Our data show a separation between high and low consuming animals within this strain, with high-consumers exhibiting an escalation in consumption. In contrast, Fischer rats did not show a significant separation between high and low consumers or any significant escalation in consumption, using the 20% ethanol continuous-access two-bottle-choice drinking protocol. Following the two-week deprivation period, animals in the high (but not the low) IAE group exhibited the transient increase in ethanol consumption and preference typically associated with an ADE. Together, the data suggest that the intermittent access protocol is a useful protocol for increasing ethanol consumption.

Influence of polymorphisms of GSTM1 and GSTT1 for risk of renal cell cancer in workers with long-term high occupational exposure to trichloroethene

Suspected nephrocarcinogenic effects of trichloroethene (TRI) in humans are attributed to metabolites derived from the glutathione transferase (GST) pathway. The influence of polymorphisms of GSTM1 and GSTT1 isoenzymes on the risk of renal cell cancer in subjects having been exposed to high levels of TRI over many years was investigated. GSTM1 and GSTT1 genotypes were determined by internal standard controlled polymerase chain reaction. Fourty-five cases with histologically verified renal cell cancer and a history of long-term occupational exposure to high concentrations of TRI were studied. A reference group consisted of 48 workers from the same geographical region with similar histories of occupational exposures to TRI but not suffering from any cancer. Among the 45 renal cell cancer patients, 27 carried at least one functional GSTM1 (GSTM1 +) and 18 at least one functional GSTT1 (GSTT1 +). Among the 48 reference workers, 17 were GSTM1 + and 31 were GSTT1 +. Odds ratios for renal cell cancer were 2.7 for GSTM1 + individuals (95% CI, 1.18-6.33; P < 0.02) and 4.2 for GSTT1 + individuals (95% CI, 1.16-14.91; P < 0.05), respectively. The data support the present concept of the nephrocarcinogenicity of TRI.

Foundations for the future : A long-term plan for Australian ecosystem science

Abstract: Australia’s ecosystems are the basis of our current and future prosperity, and our national well-being.A strong and sustainable Australian ecosystem science enterprise is vital for understanding and securing these ecosystems in the face of current and future challenges. This Plan defines the vision and key directions for a national ecosystem science capability that will enable Australia to understand and effectively manage its ecosystems for decades to come.The Plan’s underlying theme is that excellent science supports a range of activities, including public engagement, that enable us to understand and maintain healthy ecosystems.Those healthy ecosystems are the cornerstone of our social and economic well-being.The vision guiding the development of this Plan is that in 20 years’ time the status of Australian ecosystems and how they change will be widely reported and understood, and the prosperity and well-being they provide will be secure. To enable this, Australia’s national ecosystem science capability will be coordinated, collaborative and connected.The Plan is based on an extensive set of collaboratively generated proposals from national town hall meetings that also formthe basis for its implementation. Some directions within the Plan are for the Australian ecosystem science community itself to implement, others will involve the users of ecosystem science and the groups that fund ecosystem science.We identify six equal priority areas for action to achieve our vision: (i) delivering maximum impact for Australia: enhancing relationships between scientists and end-users; (ii) supporting long-termresearch; (iii) enabling ecosystem surveillance; (iv) making the most of data resources; (v) inspiring a generation: empowering the public with knowledge and opportunities; (vi) facilitating coordination, collaboration and leadership. This shared vision will enable us to consolidate our current successes, overcome remaining barriers and establish the foundations to ensure Australian ecosystem science delivers for the future needs of Australia..