Prolonged hyperinsulinemia affects metabolic signal transduction markers in a tissue specific manner

Insulin dysregulation is common in horses although the mechanisms of metabolic dysfunction are poorly understood. We hypothesized that insulin signaling in striated (cardiac and skeletal) muscle and lamellae may be mediated through different receptors as a result of receptor content, and that transcriptional regulation of downstream signal transduction and glucose transport may also differ between tissues sites during hyperinsulinemia. Archived samples from horses treated with a prolonged insulin infusion or a balanced electrolyte solution were used. All treated horses developed marked hyperinsulinemia and clinical laminitis. Protein expression was compared across tissues for the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) by immunoblotting. Gene expression of metabolic insulin-signaling markers (insulin receptor substrate 1, Akt2, and glycogen synthase kinase 3 beta [GSK-3β]) and glucose transport (basal glucose transporter 1 and insulin-sensitive glucose transporter 4) was evaluated using real-time reverse transcription polymerase chain reaction. Lamellar tissue contained significantly more IGF-1R protein than skeletal muscle, indicating the potential significance of IGF-1R signaling for this tissue. Gene expression of the selected markers of insulin signaling and glucose transport in skeletal muscle and lamellar tissues was unaffected by prolonged hyperinsulinemia. In contrast, the significant upregulation of Akt2, GSK-3β, GLUT1, and GLUT4 gene expression in cardiac tissue suggested that the prolonged hyperinsulinemia induced an increase in insulin sensitivity and a transcriptional activation of glucose transport. Responses to insulin are tissue-specific, and extrapolation of data across tissue sites is inappropriate.

Consensus statement on the role of Accredited Exercise Physiologists within the treatment of mental disorders: A guide for mental health professionals

- Objective The aim is to identify the role and scope of Accredited Exercise Physiologist (AEP) services in the mental health sector and to provide insight as to how AEPs can contribute to the multidisciplinary mental health team. - Methods A modified Delphi approach was utilised. Thirteen AEPs with experience in mental health contributed to the iterative development of a national consensus statement. Six mental health professionals with expertise in psychiatry, mental health nursing, general practice and mental health research participated in the review process. Reviewers were provided with a template to systematically provide feedback on the language, content, structure and relevance to their professional group. - Results This consensus statement outlines how AEPs can contribute to the multidisciplinary mental health team, the aims and scope of AEP-led interventions in mental health services and examples of such interventions, the range of physical and mental health outcomes possible through AEP-led interventions and common referral pathways to community AEP services. - Outcome AEPs can play a key role in the treatment of individuals experiencing mental illness. The diversity of AEP interventions allows for a holistic approach to care, enhancing both physical and mental health outcomes.

The use of metabolomics to monitor simultaneous changes in metabolic variables following supramaximal low volume high intensity exercise

High Intensity Exercise (HIE) stimulates greater physiological remodeling when compared to workload matched low-moderate intensity exercise. This study utilized an untargeted metabolomics approach to examine the metabolic perturbations that occur following two workload matched supramaximal low volume HIE trials. In a randomized order, 7 untrained males completed two exercise protocols separated by one week; 1) HIE150%: 30 x 20s cycling at 150% VO2peak, 40s passive rest; 2) HIE300%: 30 x 10s cycling at 300% VO2peak, 50 s passive rest. Total exercise duration was 30 minutes for both trials. Blood samples were taken at rest, during and immediately following exercise and at 60 minutes post exercise. Gas chromatography-mass spectrometry (GC-MS) analysis of plasma identified 43 known metabolites of which 3 demonstrated significant fold changes (HIE300% compared to the HIE150% value) during exercise, 14 post exercise and 23 at the end of the recovery period. Significant changes in plasma metabolites relating to lipid metabolism [fatty acids: dodecanoate (p=0.042), hexadecanoate (p=0.001), octadecanoate (p=0.001)], total cholesterol (p=0.001), and glycolysis [lactate (p=0.018)] were observed following exercise and during the recovery period. The HIE300% protocol elicited greater metabolic changes relating to lipid metabolism and glycolysis when compared to HIE150% protocol. These changes were more pronounced throughout the recovery period rather than during the exercise bout itself. Data from the current study demonstrate the use of metabolomics to monitor intensity-dependent changes in multiple metabolic pathways following exercise. The small sample size indicates a need for further studies in a larger sample cohort to validate these findings.

Health outcomes of adults 3 months after injury

Background: Injury is a leading cause of preventable mortality and morbidity in Australia and the world. Despite this there is little research examining the health related quality of life of adults following general trauma. Methods: A prospective cohort design was used to study adults who presented to hospital following injury. Data regarding injury and demographic details was collected through the routine operation of the Queensland Trauma Registry (QTR). In addition, the short form 36 (SF-36) was mailed to patients approximately 3 months following injury. Results: Participants included 339 injured patients who were hospitalised for ≥24 h in March-June 2003. A secondary group of 145 patients completed the SF-36, but did not have QTR data collected due to hospitalisation being <24 h. Both groups of participants reported significantly lower scores on all subscales of the SF-36 when compared to Australian norms. Conclusions: Health related quality of life of injured survivors is markedly reduced 3 months after injury. Ongoing treatment and support is necessary to improve these health outcomes.

Multilineage differentiation potential of bone and cartilage cells derived from explant culture

To date, mesenchymal stem cells (MSCs) from various tissues have been reported, but the yield and differentiation potential of different tissue-derived MSCs is still not clear. This study was undertaken in an attempt to investigate the multilineage stem cell potential of bone and cartilage explant cultures in comparison with bone marrow derived mesenchymal stem cells (BMSCs). The results showed that the surface antigen expression of tissue-derived cells was consistent with that of mesenchymal stem cells, such as lacking the haematopoietic and common leukocyte markers (CD34, CD45) while expressing markers related to adhesion (CD29, CD166) and stem cells (CD90, CD105). The tissue-derived cells were able to differentiate into osteoblast, chondrocyte and adipocyte lineage pathways when stimulated in the appropriate differentiating conditions. However, compared with BMSCs, tissue-derived cells showed less capacity for multilineage differentiation when the level of differentiation was assessed in monolayer culture by analysing the expression of tissue-specific genes by reverse transcription polymerase chain reaction (RT-PCR) and histology. In high density pellet cultures, tissue-derived cells were able to differentiate into chondrocytes, expressing chondrocyte markers such as proteoglycans, type II collagen and aggrecan. Taken together, these results indicate that cells derived from tissue explant cultures reserved certain degree of differentiation properties of MSCs in vitro.

Lifting the lifegiving dollar : case samples of creative practice in health and medical research philanthropy

This study aims to stimulate thought, debate and action for change on this question of more vigorous philanthropic funding of Australian health and medical research (HMR). It sharpens the argument with some facts and ideas about HMR funding from overseas sources. It also reports informed opinions from those working, giving and innovating in this area. It pinpoints the range of attitudes to HMR giving, both positive and negative. The study includes some aspects of Government funding as part of the equation, viewing Government as major HMR givers, with particular ability to partner, leverage and create incentives. Stimulating new philanthropy takes active outreach. The opportunity to build more dialogue between the HMR industry and the wider community is timely given the ‘licence to practice’ issues and questioned trust that applies currently somewhat both to science and to the charitable sector. This interest in improving HMR philanthropy also coincides with the launch last year by the Federal Government of Nonprofit Australia Limited (NAL), a group currently assessing infrastructure improvements to the charitable sector. History suggests no one will create this change if Research Australia does not. However, interest in change exists in various quarters. For Research Australia to successfully change the culture of Australian HMR giving, the process will drive the outcomes. Obviously stakeholder buy-in and partners will be needed and the ultimate blueprint for greater philanthropic HMR funding here will not be this document. Instead it will be the one that wears the handprint and ‘mindprint’ of the many architects and implementers interested in promoting HMR philanthropy, from philanthropists to nonprofit peaks to government policy arms. As the African proverb says, ‘If you want to go fast, go alone; but if you want to go far, go with others’.

The impact of globalisation on health

After reading this chapter, you should be able to: • understand the concept of globalisation and appreciate its complexity • identify the significant impacts of globalisation on population health, particularly the incidence of communicable and non-communicable diseases • understand the distribution of the global burden of disease in high-, middle- and low-income countries • critically evaluate the factors contributing to the major causes of death in low-income countries • understand some of the achievements of the global public health community and appreciate the challenges it faces.

Transcutaneous immunization with novel lipid-based adjuvants induces protection against gastric Helicobacter pylori infection

The development of vaccines to combat pathogens that infect across mucosal surfaces has been a major goal of vaccine research. Successful mucosal vaccination requires the co-administration of adjuvants that can overcome the state of immune tolerance normally associated with mucosal application of proteins. In the case of oral immunization, delivery systems are also required to protect vaccine antigens against destruction by gastric pH and digestive enzymes. Furthermore, adjuvants used for mucosal delivery must be free of neurotoxic effects like those induced by the commonly used experimental mucosal adjuvant cholera toxin. Maintenance of the "cold chain" is also essential for the effectiveness of any vaccine and adjuvants/delivery systems that enhance the stability of a vaccine would offer a significant advantage. Needle-free methods of vaccination that induce protective immunity at multiple mucosal surfaces are also desirable for rapid vaccination of large populations. In the present study we show that transcutaneous immunization (TCI) using Lipid C, a novel lipid-based matrix originally developed for oral immunization, containing soluble Helicobacter sonicate significantly reduces the gastric bacterial burden in mice following gastric challenge with live Helicobacter pylori. Protection is associated with the production of splenic gamma interferon and gastric IgA and was achieved without the co-administration of potent and potentially toxic adjuvants, although protection was further enhanced by inclusion of CpG-ODN and cholera toxin in the lipid delivery system.

Probability distributed time delays: integrating spatial effects into temporal models

Background In order to provide insights into the complex biochemical processes inside a cell, modelling approaches must find a balance between achieving an adequate representation of the physical phenomena and keeping the associated computational cost within reasonable limits. This issue is particularly stressed when spatial inhomogeneities have a significant effect on system's behaviour. In such cases, a spatially-resolved stochastic method can better portray the biological reality, but the corresponding computer simulations can in turn be prohibitively expensive. Results We present a method that incorporates spatial information by means of tailored, probability distributed time-delays. These distributions can be directly obtained by single in silico or a suitable set of in vitro experiments and are subsequently fed into a delay stochastic simulation algorithm (DSSA), achieving a good compromise between computational costs and a much more accurate representation of spatial processes such as molecular diffusion and translocation between cell compartments. Additionally, we present a novel alternative approach based on delay differential equations (DDE) that can be used in scenarios of high molecular concentrations and low noise propagation. Conclusions Our proposed methodologies accurately capture and incorporate certain spatial processes into temporal stochastic and deterministic simulations, increasing their accuracy at low computational costs. This is of particular importance given that time spans of cellular processes are generally larger (possibly by several orders of magnitude) than those achievable by current spatially-resolved stochastic simulators. Hence, our methodology allows users to explore cellular scenarios under the effects of diffusion and stochasticity in time spans that were, until now, simply unfeasible. Our methodologies are supported by theoretical considerations on the different modelling regimes, i.e. spatial vs. delay-temporal, as indicated by the corresponding Master Equations and presented elsewhere.

Air quality and its impact on health: focus on particulate matter

Inadequate air quality and the inhalation of airborne pollutants pose many risks to human health and wellbeing, and are listed among the top environmental risks worldwide. The importance of outdoor air quality was recognised in the 1950s and indoor air quality emerged as an issue some time later and was soon recognised as having an equal, if not greater importance than outdoor air quality. Identification of ambient air pollution as a health hazard was followed by steps, undertaken by a broad range of national and international professional and government organisations, aimed at reduction or elimination of the hazard. However, the process of achieving better air quality is still in progress. The last 10 years or so have seen an unprecedented increase in the interest in, and attention to, airborne particles, with a special focus on their finer size fractions, including ultrafine (< 0.1 m) and their subset, nano particles (< 0.05 m). This paper discusses the current status of scientific knowledge on the links between air quality and health, with a particular focus on airborne particulate matter, and the directions taken by national and international bodies to improve air quality.