Developing a therapeutic anti-dendritic cell antibody to prevent graft versus host disease

Host and donor dendritic cells (DC) stimulate alloreactive donor T lymphocytes, and initiate GVHD. We have shown that polyclonal antibody to the DC surface activation marker human CD83 (anti hCD83), which depletes activated DC, can prevent human DC and T cell induced lethal xenogeneic GVHD in SCID mice without impairing T cell mediated anti-leukaemic and anti-viral (CMV and influenza) immunity (J Exp Med 2009; 206: 387). Therefore, we made and tested a polyclonal anti mouse CD83 (RAM83) antibody in murine HSCT models and developed a human mAb against hCD83 as a potential new therapeutic immunosuppressive agent.

Differences in composition of symptom clusters between older and younger oncology patients

Context Older oncology patients have unique needs associated with the many physical, psychological,and social changes associated with the aging process. The mechanisms underpinning and the impact of these changes are not well understood. Identification of clusters of symptoms is one approach that has been used to elicit hypotheses about the biological and/or psychological basis for variations in symptom experiences. Objectives The purposes of this study were to identify and compare symptom clusters in younger (<60 years) and older ($60 years) patients undergoing cancer treatment. Methods. Symptom data from one Australian study and two U.S. studies were combined to conduct this analysis. A total of 593 patients receiving active treatment were dichotomized into younger (<60 years) and older ($60 years) groups. Separate exploratory factor analyses (EFAs) were undertaken within each group to identify symptom clusters from occurrence ratings of the 32 symptoms assessed by the Memorial Symptom Assessment Scale. Results In both groups, a seven-factor solution was selected. Four partially concordant symptom clusters emerged in both groups (i.e., mood/cognitive, malaise, body image, and genitourinary). In the older patients, the three unique clusters reflected physiological changes associated with aging, whereas in the younger group the three unique clusters reflected treatment-related effects. Conclusion The symptom clusters identified in older patients typically included a larger and more diverse range of physical and psychological symptoms. Differences also may be reflective of variations in treatment approaches between age groups. Findings highlight the need for better understanding of variation in treatment and symptom burden between younger and older adults with cancer.

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.

Medicines related dysphagia in primary care: The prevalence of and impact on community pharmacists

Dysphagia is a common and problematic symptom characterised by varying degrees of difficulty swallowing food, fluids and medicines of differing consistencies. International primary care based studies have identified that between 1 in 4 and 1 in 5 patients have some form of dysphagia, it can affect medicines taking behaviour and healthcare professionals are largely unaware of this1,2. Similar research has not been undertaken in the UK. Adherence related pharmacy based services in the UK provide an opportunity for community pharmacists to identify the problem and facilitate better medicines use. The aim of this pilot study was to estimate the level of patient reported dysphagia in older persons using community pharmacies in the UK, describe how it affects their medicine taking behaviour and identify whether advanced pharmacy services are related to improved awareness of this.

DNA repair pathways and their therapeutic potential in lung cancer

Lung cancer is the leading cause of cancer-related mortality. According to WHO, 1.37 million deaths occur globally each year as a result of this disease. More than 70% of these cases are associated with prior tobacco consumption and/or cigarette smoking, suggesting a direct causal relationship. The development and progression of lung cancer and other malignancies involves the loss of genetic stability, resulting in acquisition of cumulative genetic changes; this affords the cell increased malignant potential. As such, an understanding of the mechanisms through which these events may occur will potentially allow for development of new anticancer therapies. This review will address the association between lung cancer and genetic instability, with a central focus on genetic mutations in the DNA damage repair pathways. In addition, we will discuss the potential clinical exploitation of these pathways, both in terms of biomarker staging, as well as through direct therapeutic targeting.

A workplace-based Participatory Action Research project to investigate the effectiveness of nutrition and physical activity interventions for truck drivers in six Queensland transport industry workplaces: 2012-2015

The Queensland Transport Industry Workplace Health Intervention project was a Participatory Action Research (PAR) project to investigate the effectiveness of workplace-based nutrition and physical activity health promotion interventions for truck drivers in transport industry workplaces in south-east Queensland. The project was conducted by a research team at the Queensland University of Technology (QUT), and was funded by the Queensland Government under the Healthier.Happier.Workplaces initiative.

Monitoring changes of the tibialis anterior during dorsiflexion with electromyography, sonomyography, dynamometry and kinematic signals

Dorsiflexion (DF) of the foot plays an essential role in both controlling balance and human gait. Electromyography and Sonomyography can provide information on several aspects of muscle function. The aim was to describe a new method for real-time monitoring of muscular activity, as measured using EMG, muscular architecture, as measured using SMG, force, as measured using dynamometry, and kinematic parameters, as measured using IS during isometric and isotonic contractions of the foot DF. The present methodology may be clinically relevant because it involves a reproducible procedure which allows the function and structure of the foot DF to be monitored.

A kinematic analysis of the hand function

Background The evaluation of the hand function is an essential element within the clinical practice. The usual assessments are focus on the ability to perform activities of daily life. The inclusion of instruments to measure kinematic variables provides a new approach to the assessment. Inertial sensors adapted to the hand could be used as a complementary instrument to the traditional assessment. Material: clinimetric assessment (Upper Limb Functional Index, Quick Dash), antrophometric variables (eight and weight), dynamometry (palm preasure) was taken. Functional analysis was made with Acceleglove system for the right hand and computer system. The glove has six acceleration sensor, one on each finger and another one on the reverse palm. Method Analytic, transversal approach. Ten healthy subject made six task on evaluation table (tripod pinch, lateral pinch and tip pinch, extension grip, spherical grip and power grip). Each task was made and measure three times, the second one was analyze for the results section. A Matlab script was created for the analysis of each movement and detection phase based on module vector. Results The module acceleration vector offers useful information of the hand function. The data analysis obtained during the performance of functional gestures allows to identify five different phases within the movement, three static phase and tow dynamic, each module vector was allied to one task. Conclusion Module vector variables could be used for the analysis of the different task made by the hand. Inertial sensor could be use as a complement for the traditional assessment system.

Functional and structural of the erector spinae muscle during isometric lumbar extension

Study Design Cross-sectional study. Objectives To compare erector spinae (ES) muscle fatigue between chronic non-specific lower back pain (CNLBP) sufferers and healthy subjects from a biomechanical perspective during fatiguing isometric lumbar extensions. Background Paraspinal muscle maximal contraction and fatigue are used as a functional predictor for disabilities. The simplest method to determine muscle fatigue is by evaluating the evolution during specific contractions, such as isometric contractions. There are no studies that evaluate the evolution of the ES muscle during fatiguing isometric lumbar extensions and analyse functional and architectural variables. Methods In a pre-calibrated system, participants performed a maximal isometric extension of the lumbar spine for 5 and 30 seconds. Functional variables (torque and muscle activation) and architecture (pennation angle and muscle thickness) were measured using a load cell, surface electromyography and ultrasound, respectively. The results were normalised and a reliability study of the ultrasound measurement was made. Results: The ultrasound measurements were highly reliable, with Cronbach’s alpha values ranging from 0.951 0.981. All measured variables shown significant differences before and after fatiguing isometric lumbar extension. Conclusion During a lumbar isometric extension test, architecture and functional variables of the ES muscle could be analised using ultrasound, surface EMG and load cell. In adition, during an endurance test, ES muscle suffers an acute effect on architectural and functional variables.

Grassland productivity limited by multiple nutrients

Terrestrial ecosystem productivity is widely accepted to be nutrient limited1. Although nitrogen (N) is deemed a key determinant of aboveground net primary production (ANPP)2,3, the prevalence of co-limitation by N and phosphorus (P) is increasingly recognized4,​5,​6,​7,​8. However, the extent to which terrestrial productivity is co-limited by nutrients other than N and P has remained unclear. Here, we report results from a standardized factorial nutrient addition experiment, in which we added N, P and potassium (K) combined with a selection of micronutrients (K+μ), alone or in concert, to 42 grassland sites spanning five continents, and monitored ANPP. Nutrient availability limited productivity at 31 of the 42 grassland sites. And pairwise combinations of N, P, and K+μ co-limited ANPP at 29 of the sites. Nitrogen limitation peaked in cool, high latitude sites. Our findings highlight the importance of less studied nutrients, such as K and micronutrients, for grassland productivity, and point to significant variations in the type and degree of nutrient limitation. We suggest that multiple-nutrient constraints must be considered when assessing the ecosystem-scale consequences of nutrient enrichment.

Plant species’ origin predicts dominance and response to nutrient enrichment and herbivores in global grasslands

Exotic species dominate many communities; however the functional significance of species’ biogeographic origin remains highly contentious. This debate is fuelled in part by the lack of globally replicated, systematic data assessing the relationship between species provenance, function and response to perturbations. We examined the abundance of native and exotic plant species at 64 grasslands in 13 countries, and at a subset of the sites we experimentally tested native and exotic species responses to two fundamental drivers of invasion, mineral nutrient supplies and vertebrate herbivory. Exotic species are six times more likely to dominate communities than native species. Furthermore, while experimental nutrient addition increases the cover and richness of exotic species, nutrients decrease native diversity and cover. Native and exotic species also differ in their response to vertebrate consumer exclusion. These results suggest that species origin has functional significance, and that eutrophication will lead to increased exotic dominance in grasslands.

Undergraduate public health students and perceptions of qualitative research: A trajectory of understanding from airy fairy to a valuable tool

Many undergraduate public health students enter introductory qualitative research units with limited or negative perceptions of qualitative research, potentially compromising learning outcomes. Unit teaching, structure and assessment provide opportunities for students to develop positive perceptions of qualitative research. Through a mixed-methods study of undergraduate public health students enrolled in a qualitative research unit, we establish students’ perceptions of qualitative research at the commencement and conclusion of the unit, and determine the critical teaching and learning events which contributed to positive changes in students’ perceptions. This study demonstrates that the structuring of an introductory qualitative research unit around varied opportunities for experiential learning provides a positive introductory learning experience and enables undergraduate public health students to recognise the real-world uses and value of qualitative research.