Mesenchymal stromal cells transiently alter the inflammatory milieu post-transplant to delay graft-versus-host disease

Background: Multipotent mesenchymal stromal cells suppress T-cell function in vitro, a property that has underpinned their use in treating clinical steroid-refractory graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. However the potential of mesenchymal stromal cells to resolve graft-versus-host disease is confounded by a paucity of pre-clinical data delineating their immunomodulatory effects in vivo. Design and Methods: We examined the influence of timing and dose of donor-derived mesenchymal stromal cells on the kinetics of graft-versus-host disease in two murine models of graft-versus-host disease (major histocompatibility complex-mismatched: UBI-GFP/BL6 [H-2b]→BALB/c [H-2d] and the sibling transplant mimic, UBI-GFP/BL6 [H-2b]→BALB.B [H-2b]) using clinically relevant conditioning regimens. We also examined the effect of mesenchymal stromal cell infusion on bone marrow and spleen cellular composition and cytokine secretion in transplant recipients. Results: Despite T-cell suppression in vitro, mesenchymal stromal cells delayed but did not prevent graft-versus-host disease in the major histocompatibility complex-mismatched model. In the sibling transplant model, however, 30% of mesenchymal stromal cell-treated mice did not develop graft-versus-host disease. The timing of administration and dose of the mesenchymal stromal cells influenced their effectiveness in attenuating graft-versus-host disease, such that a low dose of mesenchymal stromal cells administered early was more effective than a high dose of mesenchymal stromal cells given late. Compared to control-treated mice, mesenchymal stromal cell-treated mice had significant reductions in serum and splenic interferon-γ, an important mediator of graft-versus-host disease. Conclusions: Mesenchymal stromal cells appear to delay death from graft-versus-host disease by transiently altering the inflammatory milieu and reducing levels of interferon-γ. Our data suggest that both the timing of infusion and the dose of mesenchymal stromal cells likely influence these cells’ effectiveness in attenuating graft-versus-host disease.

Tissue-engineered fibroin scaffolds for ocular tissue reconstruction

The silk protein fibroin (Bombyx mori) provides a potential substrate for use in ocular tissue reconstruction. We have previously demonstrated that transparent membranes produced from fibroin support cultivation of human limbal epithelial (HLE) cells (Tissue Eng A. 14(2008)1203-11). We extend this body of work to studies of limbal mesenchymal stromal cell (L-MSC) growth on fibroin. Also, we investigate the ability to produce a fibroin dual-layer scaffold with an upper HLE layer and lower L-MSC layer...

Fibroin-based materials support co-cultivation of limbal epithelial and stromal cells

The silk protein fibroin (Bombyx mori) provides a potential substrate for use in ocular tissue reconstruction. We have previously demonstrated that transparent membranes produced from fibroin support cultivation of human limbal epithelial (HLE) cells (Tissue Eng A. 14(2008)1203-11). We extend this body of work to studies of human limbal stromal cell (HLS) growth on fibroin in the presence and absence of serum. Also, we investigate the ability to produce a bi-layered composite scaffold of fibroin with an upper HLE layer and lower HLS layer.

Transition metal layered double hydroxides for energy storage

Various types of layered double hydroxides, a type of clay, were synthesised. They were then electrochemically tested to determine whether the samples would be suitable to store energy as supercapacitors. A manganese aluminium layered double hydroxide was electrochemically tested for the first time and found to have a large capacitance.

Making the transition from pharmacy student to pharmacist: Australian interns' perceptions of professional identity formation

Objectives The experience of transitioning from university to practice influences professional identity formation. It is unclear how this transitioning experience influences pharmacy interns' professional identities. This study aims to examine pharmacy interns' perceptions of their transition from university to the workplace and the influence this had on their pharmacist identities. Methods A qualitative approach using in-depth interviews was adopted for this study. Fifteen interns (community and hospital) from one school of pharmacy in Australia were interviewed. Questions were asked about the nature of their current intern role, their university experiences, how they saw themselves as pharmacists and their perceptions of the transition to practice. Key findings The interns interviewed entered the workplace valuing patient-focused aspects of practice and contributing to patient care. The nature of work meant there were limited opportunities to enact these aspects of their professional identities. The interns were challenged by interactions with patients and doctors, and experienced difficulties reconciling this with their university-derived professional identities. Also, the interns lacked the confidence and strategies to overcome these challenges. Some were exploring alternative ways of being pharmacists. Conclusions This paper argues that graduates' experience of the transition to practice was challenging. This was due to nascent professional identities formed in university and a lack of workplace experiences enabling patient-centred practices. The interns' formation of professional identities was highly responsive to the context of work. To facilitate the development of Australian patient-centred pharmacy practice, supporting professional identity formation should be a focus within pharmacy education.

The transition to palliative care: A critical exploration in the context of metastatic melanoma

This research explored the transition to palliative care process through critical analysis of the experiences of patients diagnosed with metastatic melanoma, family carers and health professionals. The outcomes depict a complex intersection between acute care services and palliative care where the discipline of palliative care struggled to position itself within a highly specialised health system. The findings indicate uncertainty around scopes of practice with ambiguity and tension around the transition to palliative care. The research thus argues for stronger and more coherent partnerships and a critical and interdisciplinary conversation about the positioning of palliative care in the acute care sector.

A smooth transition logit model of the effects of deregulation in the electricity market

This paper introduces the smooth transition logit (STL) model that is designed to detect and model situations in which there is structural change in the behaviour underlying the latent index from which the binary dependent variable is constructed. The maximum likelihood estimators of the parameters of the model are derived along with their asymptotic properties, together with a Lagrange multiplier test of the null hypothesis of linearity in the underlying latent index. The development of the STL model is motivated by the desire to assess the impact of deregulation in the Queensland electricity market and ascertain whether increased competition has resulted in significant changes in the behaviour of the spot price of electricity, specifically with respect to the occurrence of periodic abnormally high prices. The model allows the timing of any change to be endogenously determined and also market participants' behaviour to change gradually over time. The main results provide clear evidence in support of a structural change in the nature of price events, and the endogenously determined timing of the change is consistent with the process of deregulation in Queensland.

Learning experiences for the transition to professional work

A better educated workforce contributes to a more informed and tolerant society with higher economic output, and this is also associated with higher levels of personal health, interpersonal trust and civic and social engagement. Against this backdrop, the role of universities has expanded, as university learning has moved beyond providing an education to preparing students for leadership positions within society. This article examines the effectiveness of final-year learning experiences from the perception of recent graduates. The aim is to improve undergraduate curriculum to facilitate the transition to professional employment. An online quantitative and qualitative survey instrument was developed to investigate graduates’ perceptions of their different learning experiences and assessment types in their senior year. Four hundred and twelve alumni from five universities completed the survey. Our results indicate that graduates value case studies, group work and oral presentations, and that graduates rate lectures and guest lectures from practitioners as the least important in their transition to work. The results validate the use of graduate capability frameworks and mapping the development of the skills over the curriculum. These results are useful for curriculum designers to assist with designing programmes on the transition to professional work.

A humanized tissue-engineered in vivo model to dissect interactions between human prostate cancer cells and human bone

Currently used xenograft models for prostate cancer bone metastasis lack the adequate tissue composition necessary to study the interactions between human prostate cancer cells and the human bone microenvironment. We introduce a tissue engineering approach to explore the interactions between human tumor cells and a humanized bone microenvironment. Scaffolds, seeded with human primary osteoblasts in conjunction with BMP7, were implanted into immunodeficient mice to form humanized tissue engineered bone constructs (hTEBCs) which consequently resulted in the generation of highly vascularized and viable humanized bone. At 12 weeks, PC3 and LNCaP cells were injected into the hTEBCs. Seven weeks later the mice were euthanized. Micro-CT, histology, TRAP, PTHrP and osteocalcin staining results reflected the different characteristics of the two cell lines regarding their phenotypic growth pattern within bone. Microvessel density, as assessed by vWF staining, showed that tumor vessel density was significantly higher in LNCaP injected hTEBC implants than in those injected with PC3 cells (p\0.001). Interestingly, PC3 cells showed morphological features of epithelial and mesenchymal phenotypes suggesting a cellular plasticity within this microenvironment. Taken together, a highly reproducible humanized model was established which is successful in generating LNCaP and PC3 tumors within a complex humanized bone microenvironment. This model simulates the conditions seen clinically more closely than any other model described in the literature to date and hence represents a powerful experimental platform that can be used in future work to investigate specific biological questions relevant to bone metastasis.

Charge mediated semiconducting-to-metallic phase transition in molybdenum disulphide monolayer and hydrogen evolution reaction in New 1T’ phase

The phase transition of single layer molybdenum disulphide (MoS2) from semi-conducting 2H to metallic 1T and then to 1T' phases, and the effect of the phase transition on hydrogen evolution reaction (HER) are investigated within this work by density functional theory. Experimentally, 2H-MoS2 has been widely used as an excellent electrode for HER and can get charged easily. Here we find that the negative charge has a significant impact on the structural phase transition in a MoS2 monolayer. The thermodynamic stability of 1T-MoS2 increases with the negative charge state, comparing with the 2H-MoS2 structure before phase transition and the kinetic energy barrier for a phase transition from 2H to 1T decreases from 1.59 eV to 0.27 eV when 4 e- are injected per MoS2 unit. Additionally, 1T phase is found to transform into the distorted structure (1T' phase) spontaneously. On their activity toward hydrogen evolution reaction, 1T'-MoS2 structure hydrogen coverage shows comparable hydrogen evolution reaction activity to the 2H-MoS2 structure. If the charge transfer kinetics is taken into account, the catalytic activity of 1T'-MoS2 is superior to that of 2H-MoS2. Our finding provides a possible novel method for phase transition of MoS2, and enriches understanding of the catalytic properties of MoS2 for HER.

Pituitary volume predicts future transition to psychosis in individuals at ultra-high risk of developing psychosis

Background We examined pituitary volume before the onset of psychosis in subjects who were at ultra-high risk (UHR) for developing psychosis. Methods Pituitary volume was measured on 1.5-mm, coronal, 1.5-T magnetic resonance images in 94 UHR subjects recruited from admissions to the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia and in 49 healthy control subjects. The UHR subjects were scanned at baseline and were followed clinically for a minimum of 1 year to detect transition to psychosis. Results Within the UHR group, a larger baseline pituitary volume was a significant predictor of future transition to psychosis. The UHR subjects who later went on to develop psychosis (UHR-P, n = 31) had a significantly larger (+12%; p = .001) baseline pituitary volume compared with UHR subjects who did not go on to develop psychosis (UHR-NP, n = 63). The survival analysis conducted by Cox regression showed that the risk of developing psychosis during the follow-up increased by 20% for every 10% increase in baseline pituitary volume (p = .002). Baseline pituitary volume of the UHR-NP subjects was smaller not only compared with UHR-P (as described above) but also compared with control subjects (−6%; p = .032). Conclusions The phase before the onset of psychosis is associated with a larger pituitary volume, suggesting activation of the HPA axis.

Mesenchymal stem cells as mediators of the neuronal cell niche

This study examined the role of heparan sulfate proteoglycans (HSPGs) in neural lineage differentiation of human mesenchymal stem cells (hMSCs). Several HSPGs were identified as potential new targets controlling neural fate specification and may be applied to the development of improved models to examine and repair brain damage. hMSCs were characterised throughout extended in vitro expansion for neural lineage potential (neurons, astrocytes, oligodendrocytes) and differentiated using terminal differentiation and intermediate sphere formation. Brain damage and neurological disorders caused by injury or disease affect a large number of people often resulting in lifelong disabilities. Multipotent mesenchymal stem cells have a large capacity for self-renewal and provide an excellent model to examine the regulation and contribution of both stem cells and their surrounding microenvironment to the repair of neural tissue damage.

Using culture to manage the transition into university: Conceptualising the dynamics of withdrawal and engagement

This conceptual paper explored the purposes of using culture in the process of coping with stress by looking how first year undergraduate students used cultural elements and activities to aid their transition into university. Results supported two key conceptualisations of the use of culture. Firstly, results indicated that students used culture either for withdrawal purposes, i.e., for escaping from the stressful situation, or for engagement purposes, i.e., for actively engaging with the stressful situation. Secondly, the results suggested three different forms of using culture to engage with stressful situations: mood management, learning, and personal interaction. While the results of the study resonate with the distinction between avoidance versus approach-oriented coping strategies that are widely explored in the stress and coping literature, they also suggest that the relationship between withdrawal and engagement might be dynamic with those two strategies serving distinct purposes in the process of coping with stress. The paper thus suggests that there is a need to develop process-oriented models of coping that would allow identifying patterns in the way people fluctuate between withdrawal and engagement that support and facilitate their personal growth and development.

Treatment of silk fibroin with poly(ethylene glycol) for the enhancement of corneal epithelial cell growth

A silk protein, fibroin, was isolated from the cocoons of the domesticated silkworm (Bombyx mori) and cast into membranes to serve as freestanding templates for tissue-engineered corneal cell constructs to be used in ocular surface reconstruction. In this study, we sought to enhance the attachment and proliferation of corneal epithelial cells by increasing the permeability of the fibroin membranes and the topographic roughness of their surface. By mixing the fibroin solution with poly(ethylene glycol) (PEG) of molecular weight 300 Da, membranes were produced with increased permeability and with topographic patterns generated on their surface. In order to enhance their mechanical stability, some PEG-treated membranes were also crosslinked with genipin. The resulting membranes were thoroughly characterized and compared to the non-treated membranes. The PEG-treated membranes were similar in tensile strength to the non-treated ones, but their elastic modulus was higher and elongation lower, indicating enhanced rigidity. The crosslinking with genipin did not induce a significant improvement in mechanical properties. In cultures of a human-derived corneal epithelial cell line (HCE-T), the PEG treatment of the substratum did not improve the attachment of cells and it enhanced only slightly the cell proliferation in the longer term. Likewise, primary cultures of human limbal epithelial cells grew equally well on both non-treated and PEG-treated membranes, and the stratification of cultures was consistently improved in the presence of an underlying culture of irradiated 3T3 feeder cells, irrespectively of PEG-treatment. Nevertheless, the cultures grown on the PEG-treated membranes in the presence of feeder cells did display a higher nuclear-to-cytoplasmic ratio suggesting a more proliferative phenotype. We concluded that while the treatment with PEG had a significant effect on some structural properties of the B. mori silk fibroin (BMSF) membranes, there were minimal gains in the performance of these materials as a substratum for corneal epithelial cell growth. The reduced mechanical stability of freestanding PEG-treated membranes makes them a less viable choice than the non-treated membranes.