Prebiotics and resistance to gastrointestinal infections

Acute gut disorder is a cause for significant medicinal and economic concern. Certain individual pathogens of the gut, often transmitted in food or water, have the ability to cause severe discomfort. There is a need to manage such conditions more effectively. The route of reducing the risk of intestinal infections through diet remains largely unexplored. Antibiotics are effective at inhibiting pathogens; however, these should not be prescribed in the absence of disease and therefore cannot be used prophylactically. Moreover, their indiscriminate use has reduced effectiveness. Evidence has accumulated to suggest that some of the health-promoting bacteria in the gut (probiotics) can elicit a multiplicity of inhibitory effects against pathogens. Hence, an increase in their numbers should prove effective at repressing pathogen colonisation if/when infectious agents enter the gut. As such, fortification of indigenous bifidobacteria/lactobacilli by using prebiotics should improve protection. There are a number of potential mechanisms for lactic acid bacteria to reduce intestinal infections. Firstly, metabolic endproducts such as acids excreted by these micro-organisms may lower the gut pH to levels below those at which pathogens are able to effectively compete. Also, many lactobacilli and bifidobacteria species are able to excrete natural antibiotics, which can have a broad spectrum of activity. Other mechanisms include an improved immune stimulation, competition for nutrients and blocking of pathogen adhesion sites in the gut. Many intestinal pathogens like type 1 fimbriated Escherichia coli, salmonellae and campylobacters utilise oligosaccharide receptor sites in the gut. Once established, they can then cause gastroenteritis through invasive and/or toxin forming properties. One extrapolation of the prebiotic concept is to simulate such receptor sites in the gut lumen. Hence, the pathogen is 'decoyed' into not binding at the host mucosal interface. The combined effects of prebiotics upon the lactic acid flora and anti-adhesive strategies may lead towards new dietary interventions against food safety agents.

The role of monounsaturated fatty acids in the mitigation of insulin resistance

With the rising rate of obesity, there is considerable interest in dietary strategies to reduce insulin resistance, a major characteristic of the metabolic syndrome and type 2 diabetes. Diets rich in monounsaturated fatty acids (MUFA) have been suggested as an alternative to low-fat, high-carbohydrate diets to improve glycemic control. However, inconsistent effects have been observed with MUFA-rich diets in both healthy and insulin-resistant individuals. In studies that have reported favorable effects on insulin sensitivity, Mediterranean-style diets have been used that are rich not only in MUFA but also whole-grain foods, fiber, and carbohydrates with a low glycemic index. There is a need for intervention studies to examine the true impact of MUFA-rich oils on glycemic control in both Mediterranean and non-Mediterranean populations. In addition, the metabolic and genotypic status of the participants may also play a role in the inter-individual variability in insulin sensitivity in response to MUFA-rich diets.

Insights into exazaphosphorine resistance and possible approaches to its circumvention

The oxazaphosphorines cyclophosphamide, ifosfamide and trofosfamide remain a clinically useful class of anticancer drugs with substantial antitumour activity against a variety of solid tumors and hematological malignancies. A major limitation to their use is tumour resistance, which is due to multiple mechanisms that include increased DNA repair, increased cellular thiol levels, glutathione S-transferase and aldehyde dehydrogenase activities, and altered cell-death response to DNA damage. These mechanisms have been recently re-examined with the aid of sensitive analytical techniques, high-throughput proteomic and genomic approaches, and powerful pharmacogenetic tools. Oxazaphosphorine resistance, together with dose-limiting toxicity (mainly neutropenia and neurotoxicity), significantly hinders chemotherapy in patients, and hence, there is compelling need to find ways to overcome it. Four major approaches are currently being explored in preclinical models, some also in patients: combination with agents that modulate cellular response and disposition of oxazaphosphorines; antisense oligonucleotides directed against specific target genes; introduction of an activating gene (CYP3A4) into tumor tissue; and modification of dosing regimens. Of these approaches, antisense oligonucleotides and gene therapy are perhaps more speculative, requiring detailed safety and efficacy studies in preclinical models and in patients. A fifth approach is the design of novel oxazaphosphorines that have favourable pharmacokinetic and pharmacodynamic properties and are less vulnerable to resistance. Oxazaphosphorines not requiring hepatic CYP-mediated activation (for example, NSC 613060 and mafosfamide) or having additional targets (for example, glufosfamide that also targets glucose transport) have been synthesized and are being evaluated for safety and efficacy. Characterization of the molecular targets associated with oxazaphosphorine resistance may lead to a deeper understanding of the factors critical to the optimal use of these agents in chemotherapy and may allow the development of strategies to overcome resistance.

Defining plant resistance against Phytophthora Cinnamomi and application of resistance to revegetation

Phytophthora cinnamomi is a soil borne plant pathogen that causes devastating disease in many Australian ecosystems and threatens the survival of native flora. Compared with the number of plant species that are susceptible to P. cinnamomi, only a few species are known to be resistant and control of this pathogen by chemicals is difficult and undesirable in natural systems. The major aim of our research is therefore to characterise natural resistance and determine which signalling pathways and defence responses are involved. Our examination of resistance is being approached at several levels, one of which is through the use of the model plant, Arabidopsis. Previously, Arabidopsis had been shown to display ecotypic variation in responses to P. cinnamomi and we are exploring this further in conjunction with the analysis of a bank of Arabidopsis defence pathway mutants for their responses to the pathogen. These experiments will provide a fundamental basis for further analysis of the defence responses of native plants. Native species (susceptible and resistant) are being assessed for their responses to P. cinnamomi at morphological, biochemical and molecular levels. This research also involves field-based studies of plants under challenge at various sites throughout Victoria, Australia. The focus of this field-based research is to assess the responses of individual species to P. cinnamomi in the natural environment with the goal of identifying individuals within susceptible species that display 'resistance'. Understanding how plants are able to resist this pathogen will enable strategies to be developed to enhance species survival and to restore structure and biodiversity to the ecosystems under threat.

Moving beyond resistance to restraint minimization : a case study of change management in aged care

Aim: This case study describes a quality initiative to minimize restraint in an Australian residential aged care facility.

Approach: The process of improving practice is examined with reference to the literature on implementation of research into practice and change management. The differences between planned and emergent approaches to change management are discussed. The concepts of resistance and attractors are explored in relation to our experiences of managing the change process in this initiative. The importance of the interpersonal interactions that were involved in facilitating the change process is highlighted.

Implications: Recommendations are offered for dealing with change management processes in clinical environments, particularly the need to move beyond an individual mind-set to a systems-based approach for quality initiatives in residential aged care.

Development of strategies to increase commercial production of mohair and cashmere in Australia

We aimed to identify impediments to investing into mohair and cashmere production and to suggest programs and strategies to attract investors. Targeted interviews of people focussed on attributes of an investment opportunity. Analysis differentiated views of small and large-scale producers and those not involved in these industries. Potential investors into mohair and cashmere make decisions based on the compatibility of the enterprise to their farm system, the technical, financial and market feasibility of the enterprise and its comparative advantage with other possible courses of action. They are sceptical of information coming from within these industries that is not sufficiently supported by fact. There are many implications from these findings including the need for the industries to: understand the investment decision process; provide objective financial and benchmarking data; make information more accessible; overcome resistance to these industries; and increase the visibility of the industries.

Risk, resistance and the neoliberal agenda: young people, health and well-being in the UK, Canada and Australia

In this article we describe how concepts of risk are both generated by and used to reinforce a neoliberal agenda in relation to the health and well-being of young people. We examine how risk may be used as a tool to advance ideals such as rational choice and individual responsibility, and how this can further disadvantage young people living within the contexts of structural disadvantage (such as geographic areas of long-term unemployment; communities that experience racial discrimination). We also identify the ways in which risk is applied in uneven ways within structurally disadvantaged contexts. To suggest a way forward, we articulate a set of principles and strategies that offer up a means of resisting neoliberal imperatives and suggest how these might play out at the micro-, meso- and macro-levels. To do this, we discuss examples from the UK, Canadian and Australian contexts to illustrate how young people resist being labelled as risky, and how it is possible to engage in health equity-enhancing actions, despite seemingly deterministic forces. The cases we describe reveal some of the vulnerabilities (and hence opportunities) within the seemingly impenetrable world view and powers of neoliberals, and point towards the potential to formulate an agenda of resistance and new directions for young people's health promotion.

Recognition, resistance and reconstruction : an introduction to subjectivities and social justice

The aim of this book is to examine new forms of resistance to social injustices in contemporary Western societies. Resistance requires agency, and agency is grounded in notions of the subject and subjectivity. It is a premise of this book that new and/or reconstructed forms of subjectivity are required to challenge social relations of subordination and domination.
Subjectivity is primarily based on lived experience. While subjectivity is sometimes used to explore individualistic strategies for personal meaning, we argue that subjectivity is central to political struggles against regimes of power. Thus, understanding how subjects are constituted is important in fostering the capacity of critical reflection and social transformation.
Our aim  is to understand the relationship between subjectivity and the wider social order. The relationship between the psyche and society is one of the most challenging issues facing social theory. While there is a variety of theoretical approaches to subjectivity, those that explore the links between the subject and society are the most promising in developing strategies for resistance. In this introductory chapter, we review and interrogate what we believe are the most important theoretical approaches to subjectivity, drawing upon Marxism, critical theory, feminism, postcolonialism and post-structuralism. Our aim in this book is not to develop a new theory of subjectivities. Rather, we are more concerned with investigating how diverse subjectivities are constructed and reconstructed.

Current and emerging therapeutic strategies for preventing inflammation and aggrecanase-mediated cartilage destruction in arthritis

Arthritis is a multifactorial disease for which current therapeutic intervention with high efficacy remains challenging. Arthritis predominately affects articular joints, and cartilage deterioration and inflammation are key characteristics. Current therapeutics targeting inflammatory responses often cause severe side effects in patients because of the systemic inhibition of cytokines or other global immunosuppressive activities. Furthermore, a lack of primary response or failure to sustain a response to treatment through acquired drug resistance is an ongoing concern. Nevertheless, treatments such as disease-modifying anti-rheumatic drugs, biological agents, and corticosteroids have revealed promising outcomes by decreasing pain and inflammation in patients and in some cases reducing radiographic progression of the disease. Emerging and anecdotal therapeutics with anti-inflammatory activity, alongside specific inhibitors of the A Disintegrin-like And Metalloproteinase domain with Thrombospondin-1 repeats (ADAMTS) cartilage-degrading aggrecanases, provide promising additions to current arthritis treatment strategies. Thus, it is paramount that treatment strategies be optimized to increase efficacy, reduce debilitating side effects, and improve the quality of life of patients with arthritis. Here, we review the current strategies that attempt to slow or halt the progression of osteoarthritis and rheumatoid arthritis, providing an up-to-date summary of pharmaceutical treatment strategies and side effects. Importantly, we highlight their potential to indirectly regulate ADAMTS aggrecanase activity through their targeting of inflammatory mediators, thus providing insight into a mechanism by which they might inhibit cartilage destruction to slow or halt radiographic progression of the disease. We also contrast these with anecdotal or experimental administration of statins that could equally regulate ADAMTS aggrecanase activity and are available to arthritis sufferers worldwide. Finally, we review the current literature regarding the development of synthetic inhibitors directed toward the aggrecanases ADAMTS4 and ADAMTS5, a strategy that might directly inhibit cartilage destruction and restore joint function in both rheumatoid arthritis and osteoarthritis.

The effects of progressive resistance training combined with a whey-protein drink and vitamin D supplementation on glycaemic control, body composition and cardiometabolic risk factors in older adults with type 2 diabetes: study protocol for a randomized c

While physical activity, energy restriction and weight loss are the cornerstone of type 2 diabetes management, less emphasis is placed on optimizing skeletal muscle mass. As muscle is the largest mass of insulin-sensitive tissue and the predominant reservoir for glucose disposal, there is a need to develop safe and effective evidence-based, lifestyle management strategies that optimize muscle mass as well as improve glycaemic control and cardiometabolic risk factors in people with this disease, particularly older adults who experience accelerated muscle loss.

The effective radius and resistance to slippage

This work reveals that parallel gripper flat-jaw configuration affects grasping effectiveness. An important finding is the fact that object grasp reliability is influenced significantly by gripper's ability to develop high resistance to object rotation in the gripper. The concept of effective torque radius, which increases resistance to object rotation in the gripper, is presented here and can be extrapolated to other grasping devices and grasping strategies to improve their reliability and make them more effective. Grippers with full-jaw contact surface and those with discrete contact areas have been investigated using simple experimental setups. Essential mathematical models needed for analytical investigation, based on simple mechanics for full-jaw contact surfaces and discrete-jaw contact surfaces, are presented. These may be useful for gripper jaw design purposes.

Administrative rationality and coping strategies in shift work

Shift work (SW) can affect worker health and productivity. Working at night, workers often accumulate fatigue and are less productive. In Brazil, laws have been drafted aiming to reduce night work and rotating shift hours. In order to slash costs, companies have been looking for new arrangements to improve productivity under these conditions. The purpose of this study was to examine management changes and their outcomes in a large glass factory located in an industrial region of Brazil. The results show that the management, seeking equal productivity among shifts, focused its efforts mainly on distributing employee expertise. The arrangement resulted in 12 different groups that combine to serve three fixed shifts. A same shift can be served by more than one group, and the members of a same group share days off on different days. There was no statistically significant productivity difference among the three shifts. The on-site examination showed that part of the production was held by the workers and transferred to the next shift in order for them to be able to meet the management's performance rate requirements. The finding shows how a Brazilian cultural trait (resistance without conflict) is used to drive coping in SW.

Microbiological evaluation of different strategies for management of snakes in captivity

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Antiretroviral resistance mutations in human immunodeficiency virus type 1 infected patients enrolled in genotype testing at the Central Public Health Laboratory, São Paulo, Brazil: preliminary results

Antiretroviral resistance mutations (ARM) are one of the major obstacles for pharmacological human immunodeficiency virus (HIV) suppression. Plasma HIV-1 RNA from 306 patients on antiretroviral therapy with virological failure was analyzed, most of them (60%) exposed to three or more regimens, and 28% of them have started therapy before 1997. The most common regimens in use at the time of genotype testing were AZT/3TC/nelfinavir, 3TC/D4T/nelfinavir and AZT/3TC/efavirenz. The majority of ARM occurred at protease (PR) gene at residue L90 (41%) and V82 (25%); at reverse transcriptase (RT) gene, mutations at residue M184 (V/I) were observed in 64%. One or more thymidine analogue mutations were detected in 73%. The number of ARM at PR gene increased from a mean of four mutations per patient who showed virological failure at the first ARV regimens to six mutations per patient exposed to six or more regimens; similar trend in RT was also observed. No differences in ARM at principal codon to the three drug classes for HIV-1 clades B or F were observed, but some polymorphisms in secondary codons showed significant differences. Strategies to improve the cost effectiveness of drug therapy and to optimize the sequencing and the rescue therapy are the major health priorities.

Fatigue resistance of the bond of a glass-infiltrated alumina ceramic to human dentin

Purpose: To evaluate the fatigue resistance of the bond between dentin and glass-infiltrated alumina ceramic, using different luting protocols. Materials and Methods: The null hypothesis is that the fatigue resistance varies with the luting strategy. Forty blocks of In-Ceram Alumina were prepared, and one surface of each block was abraded with 110-μm aluminum oxide particles. Then, the blocks were luted to flat dentin surfaces of 40 human third molars, using 4 different luting strategies (luting system [LS]/ceramic surface conditioning [CSC]) (n=10): (G1) [LS] RelyX-Unicem/[CSC] airborne abrasion with 110-μm Al2O3 particles; (G2) [LS] One-Step + Duo-Link (bis-GMA-based resin)/[CSC] etching with 4% hydrofluoric acid + silane agent; (G3) [LS] ED-Primer + Panavia F (MDP-based resin)/[CSC] Al2O 3; (G4) [LS] Scotchbond1+RelyX-ARC (bis-GMA-based resin)/[CSC] chairside tribochemical silica coating (air abrasion with 30-μm SiO x particles + silane). After 24 h of water storage at 37°C, the specimens were subjected to 106 fatigue cycles in shear with a sinusoidal load (0 to 21 N, 8 Hz frequency, 37°C water). A fatigue survivor score was given, considering the number of the fatigue cycles until fracture. The failure modes of failed specimens were observed in a SEM. Results: G3 (score = 5.9, 1 failure) and G4 (score = 6, no failures) were statistically similar (p = 0.33) and had significantly higher fatigue resistance than G1 (score = 3.9, 5 failures) and G2 (score = 3.7, 6 failures) (p < 0.03). SEM analysis of fractured specimens of G1 and G2 showed that almost all the failures were between ceramic and cement. Conclusion: The MDP-based resin cement + sandblasting with Al2O3 particles (G3) and bis-GMA-based resin cement + tribochemical silica coating (G4), both using the respective dentin bonding systems, were the best luting protocols for the alumina ceramic. The null hypothesis was confirmed.