Mesenchymal to epithelial transition in development and disease

Cellular plasticity is fundamental to embryonic development. The importance of cellular transitions in development is first apparent during gastrulation when the process of epithelial to mesenchymal transition transforms polarized epithelial cells into migratory mesenchymal cells that constitute the embryonic and extraembryonic mesoderm. It is now widely accepted that this developmental pathway is exploited in various disease states, including cancer progression. The loss of epithelial characteristics and the acquisition of a mesenchymal-like migratory phenotype are crucial to the development of invasive carcinoma and metastasis. However, given the morphological similarities between primary tumour and metastatic lesions, it is likely that tumour cells re-activate certain epithelial properties through a mesenchymal to epithelial transition (MET) at the secondary site, although this is yet to be proven. MET is also an essential developmental process and has been extensively studied in kidney organogenesis and somitogenesis. In this review we describe the process of MET, highlight important mediators, and discuss their implication in the context of cancer progression.

Obesity and comorbid risk factors for cardiovascular disease among physically inactive patients with musculoskeletal disorders : a targeted intervention for this priority patient group is warranted

Introduction The benefits of physical activity are established and numerous; not the least of which is reduced risk of negative cardiovascular events. While sedentary lifestyles are having negative impacts across populations, people with musculoskeletal disorders may face additional challenges to becoming physically active. Unfortunately, interventions in ambulatory hospital clinics for people with musculoskeletal disorders primarily focus on their presenting musculoskeletal complaint with cursory attention given to lifestyle risk factors; including physical inactivity. This missed opportunity is likely to have both personal costs for patients and economic costs for downstream healthcare funders. Objectives The objective of this study was to investigate the presence of obesity, diabetes, diagnosed cardiac conditions, and previous stroke (CVA) among insufficiently physically active patients accessing (non-surgical) ambulatory hospital clinics for musculoskeletal disorders to indicate whether a targeted risk-reducing intervention is warranted. Methods A sub-group analysis of patients (n=110) who self-reported undertaking insufficient physical activity level to meet national (Australian) minimum recommended guidelines was conducted. Responses to the Active Australia Survey were used to identify insufficiently active patients from a larger cohort study being undertaken across three (non-surgical) ambulatory hospital clinics for musculoskeletal disorders. Outcomes of interest included body mass index, Type-II diabetes, diagnosed cardiac conditions, previous CVA and patients’ current health-related quality of life (Euroqol-5D). Results The mean (standard deviation) age of inactive patients was 56 (14) years. Body mass index values indicated that n=80 (73%) were overweight n=26 (24%), or obese n=45 (49%). In addition to their presenting condition, a substantial number of patients reported comorbid diabetes n=23 (21%), hypertension n=25 (23%) or an existing heart condition n=14 (13%); 4 (3%) had previously experienced a CVA as well as other comorbid conditions. Health-related quality of life was also substantially impacted, with a mean (standard deviation) multi-attribute utility score of 0.51 (0.32). Conclusion A range of health conditions and risk factors for further negative health events, including cardiovascular complications, consistent with physically inactive lifestyles were evident. A targeted risk-reducing intervention is warranted for this high risk clinical group.

The epithelial-mesenchymal transition : new insights in signaling, development, and disease

The conversion of an epithelial cell to a mesenchymal cell is critical to metazoan embryogenesis and a de. ning structural feature of organ development. Current interest in this process, which is described as an epithelial- mesenchymal transition (EMT), stems from its developmental importance and its involvement in several adult pathologies. Interest and research in EMT are currently at a high level, as seen by the attendance at the recent EMT meeting in Vancouver, Canada (October 1-3, 2005). The meeting, which was hosted by The EMT International Association, was the second international EMT meeting, the . rst being held in Port Douglas, Queensland, Australia in October 2003. The EMT International Association was formed in 2002 to provide an international body for those interested in EMT and the reverse process, mesenchymal-epithelial transition, and, most importantly, to bring together those working on EMT in development, cancer, . brosis, and pathology. These themes continued during the recent meeting in Vancouver. Discussion at the Vancouver meeting spanned several areas of research, including signaling pathway activation of EMT and the transcription factors and gene targets involved. Also covered in detail was the basic cell biology of EMT and its role in cancer and . brosis, as well as the identi. cation of new markers to facilitate the observation of EMT in vivo. This is particularly important because the potential contribution of EMT during neoplasia is the subject of vigorous scientific debate (Tarin, D., E.W. Thompson, and D.F. Newgreen. 2005. Cancer Res. 65:5996-6000; Thompson, E.W., D.F. Newgreen, and D. Tarin. 2005. Cancer Res. 65:5991-5995).

The IHR (2005), disease surveillance, and the individual in global health politics

Since the revisions to the International Health Regulations (IHR) in 2005, much attention has turned to two concerns relating to infectious disease control. The first is how to assist states to strengthen their capacity to identify and verify public health emergencies of international concern (PHEIC). The second is the question of how the World Health Organization (WHO) will operate its expanded mandate under the revised IHR. Very little attention has been paid to the potential individual power that has been afforded under the IHR revisions – primarily through the first inclusion of human rights principles into the instrument and the allowance for the WHO to receive non-state surveillance intelligence and informal reports of health emergencies. These inclusions mark the individual as a powerful actor, but also recognise the vulnerability of the individual to the whim of the state in outbreak response and containment. In this paper we examine why these changes to the IHR occurred and explore the consequence of expanding the sovereignty-as-responsibility concept to disease outbreak response. To this end our paper considers both the strengths and weaknesses of incorporating reports from non-official sources and including human rights principles in the IHR framework.

Nowhere to hide: informal disease surveillance networks tracing state behaviour

Since the revisions to the International Health Regulations (IHR) in 2005, much attention has turned to how states, particularly developing states, will address core capacity requirements attached to the revised IHR. Primarily, how will states strengthen their capacity to identify and verify public health emergencies of international concern (PHEIC)? Another important but under-examined aspect of the revised IHR is the empowerment of the World Health Organization (WHO) to act upon non-governmental reports of disease outbreaks. The revised IHR potentially marks a new chapter in the powers of ‘disease intelligence’ and how the WHO may press states to verify an outbreak event. This article seeks to understand whether internet surveillance response programs (ISRPs) are effective in ‘naming and shaming’ states into reporting disease outbreaks.

The challenge to know and control: Disease outbreak surveillance and alerts in China and India

Since the revisions to the International Health Regulations (IHR) in 2005, much attention has been turned to how states, particularly developing states, will address core capacity requirements. The question often examined is how states with poor health systems can strengthen their capacity to identify and verify public health emergencies of international concern. A core capacity requirement is that by 2012 states will have a surveillance and response network that operates from the local community to the national level. Much emphasis has turned to the health system capacity required for this task. In this article, I seek to understand the political capacity to perform this task. This article considers how the world's two most populous states,1 1. For the purposes of this paper, I use the word ‘state’ as a shorthand for the nation-state of China and India, or member state as used by the United Nations. View all notes China and India, have sought to communicate outbreak events in times of crisis and calm. I consider what this reporting performance tells us of their capacity to meet their IHR obligations given the two countries differing political institutions.

The duty to report disease outbreaks : of interest or value? Lessons from H5N1

Since the severe acute respiratory syndrome outbreak in 2003, it has been argued that there has been a substantial revision to the norm dictating the behaviour of states in the event of a disease outbreak. This article examines the evolution of the norm to ‘report and verify’ disease outbreaks and evaluates the extent to which this revised norm has begun to guide state behaviour. Examination of select East Asian countries affected by human infections of the H5N1 (avian influenza) virus strain reveals the need to further understand the mutually constitutive relationship between the value attached to prompt reporting against the capacity to report, and how states manage both in fulfilling their duty to report.

Securitizing infectious disease

Over the past decade there has been an increased awareness in the field of international relations of the potential impact of an infectious disease epidemic on national security. While states’ attempts to combat infectious disease have a long history, what is new in this area is the adoption at the international level of securitized responses regarding the containment of infectious disease. This article argues that the securitization of infectious disease by states and the World Health Organization (WHO) has led to two key developments. First, the WHO has had to assert itself as the primary actor that all states, particularly western states, can rely upon to contain the threat of infectious diseases. The WHO's apparent success in this is evidenced by the development of the Global Outbreak Alert Response Network (GOARN), which has led to arguments that the WHO has emerged as the key authority in global health governance. The second outcome that this article seeks to explore is the development of the WHO's authority in the area of infectious disease surveillance. In particular, is GOARN a representation of the WHO's consummate authority in the area of coordinating infectious disease response or is GOARN the product of the WHO's capitulation to western states’ concerns with preventing infectious disease outbreaks from reaching their borders and as a result, are arguments expressing the authority of the WHO in infectious disease response premature?

The international politics of disease reporting : towards post-Westphalianism?

Since the outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003, there has been much discussion about whether the international community has moved into a new post-Westphalian era, where states increasingly recognize certain shared norms that guide what they ought to do in responding to infectious disease outbreaks. In this article I identify this new obligation as the ‘duty to report’, and examine competing accounts on the degree to which states appreciate this new obligation are considered by examining state behaviour during the H5N1 human infectious outbreaks in East Asia (since 2004). The article examines reporting behaviour for H5N1 human infectious cases in Cambodia, China, Indonesia, Thailand and Vietnam from 2004 to 2010. The findings lend strong support to the claim that East Asian states have come to accept and comply with the duty to report infectious disease outbreaks and that the assertions of sovereignty in response to global health governance frameworks have not systematically inhibited reporting compliance.

Graft versus host disease in oncology nursing practice

INTRODUCTION: Gastrointestinal graft-versus-host disease (GI-GvHD) is extremely debilitating and is multifactorial in its causative factors, management and treatment. It is an exaggeration of normal physiological mechanisms wherein the donor immune system attempts to rid itself of the host. The inflammatory process that follows has the benefit of providing an anti-tumour effect for many diseases, but unfortunately in patients undergoing human stem-cell transplantation, the nature of the inflammation can result in disability, wasting and death. AIM: The aim of this article is to discuss the pathophysiology of this often misunderstood or misdiagnosed condition, as well as its signs and symptoms, management and considerations for nursing care. Considerations for nursing practice: While the medical management is aimed at minimising GvHD through the reduction of T-cell production and proliferation and gastrointestinal decolonisation, the nursing care is often focused on the signs and symptoms that can have the most prominent impact on patients. CONCLUSION: GI-GvHD has serious life-threatening complications, namely wasting syndrome, diarrhoea and dehydration. The basis of signs and symptomology is easily recognisable owing to the stages of progression through the human stem-cell transplantation process. Oncology nurses are in a prime position to identify these serious risks, initiate treatment immediately and collaborate effectively within the multidisciplinary team to minimise GvHD onset and provide expert support to patients, family and caregivers.

Executive function and postural instability in people with Parkinson’s disease

The specific aspects of cognition contributing to balance and gait have not been clarified in people with Parkinson’s disease (PD). Twenty PD participants and twenty age- and gender-matched healthy controls were assessed on cognition and clinical mobility tests. General cognition was assessed with the Mini Mental State Exam and the Addenbrooke’s Cognitive Exam. Executive function was evaluated using the Trail Making Tests (TMT-A and TMT-B) and a computerized cognitive battery which included a series of choice reaction time (CRT) tests. Clinical gait and balance measures included the Tinetti, Timed Up & Go, Berg Balance and Functional Reach tests. PD participants performed significantly worse than the controls on the tests of cognitive and executive function, balance and gait. PD participants took longer on Trail Making Tests, CRT-Location and CRT-Colour (inhibition response). Furthermore, executive function, particularly longer times on CRT-Distracter and greater errors on the TMT-B were associated with worse balance and gait performance in the PD group. Measures of general cognition were not associated with balance and gait measures in either group. For PD participants, attention and executive function were impaired. Components of executive function, particularly those involving inhibition response and distracters, were associated with poorer balance and gait performance in PD.

Melanopsin expressing intrinsically photosensitive Retinal Ganglion cells in retinal disease

Melanopsin containing intrinsically photosensitive Retinal Ganglion Cells (ipRGCs) are a class of photoreceptors with established roles in non-image forming processes. Their contributions to image forming vision may include the estimation of brightness. Animal models have been central for understanding the physiological mechanisms of ipRGC function and there is evidence of conservation of function across species. ipRGCs can be divided into 5 ganglion cell subtypes that show morphological and functional diversity. Research in humans has established that ipRGCs signal environmental irradiance to entrain the central body clock to the solar day for regulating circadian processes and sleep. In addition, ipRGCs mediate the pupil light reflex (PLR), making the PLR a readily accessible behavioural marker of ipRGC activity. Less is known about ipRGC function in retinal and optic nerve disease, with emerging research providing insight into their function in diabetes, retinitis pigmentosa, glaucoma and hereditary optic neuropathy. We briefly review the anatomical distributions, projections and basic physiological mechanisms of ipRGCs, their proposed and known functions in animals and humans with and without eye disease. We introduce a paradigm for differentiating inner and outer retinal inputs to the pupillary control pathway in retinal disease and apply this paradigm to patients with age-related macular degeneration (AMD). In these cases of patients with AMD, we provide the initial evidence that ipRGC function is altered, and that the dysfunction is more pronounced in advanced disease. Our perspective is that with refined pupillometry paradigms, the pupil light reflex can be extended to AMD assessment as a tool for the measurement of inner and outer retinal dysfunction.

Outbreak detection algorithms for seasonal disease data : a case study using Ross River virus disease

Background Detection of outbreaks is an important part of disease surveillance. Although many algorithms have been designed for detecting outbreaks, few have been specifically assessed against diseases that have distinct seasonal incidence patterns, such as those caused by vector-borne pathogens. Methods We applied five previously reported outbreak detection algorithms to Ross River virus (RRV) disease data (1991-2007) for the four local government areas (LGAs) of Brisbane, Emerald, Redland and Townsville in Queensland, Australia. The methods used were the Early Aberration Reporting System (EARS) C1, C2 and C3 methods, negative binomial cusum (NBC), historical limits method (HLM), Poisson outbreak detection (POD) method and the purely temporal SaTScan analysis. Seasonally-adjusted variants of the NBC and SaTScan methods were developed. Some of the algorithms were applied using a range of parameter values, resulting in 17 variants of the five algorithms. Results The 9,188 RRV disease notifications that occurred in the four selected regions over the study period showed marked seasonality, which adversely affected the performance of some of the outbreak detection algorithms. Most of the methods examined were able to detect the same major events. The exception was the seasonally-adjusted NBC methods that detected an excess of short signals. The NBC, POD and temporal SaTScan algorithms were the only methods that consistently had high true positive rates and low false positive and false negative rates across the four study areas. The timeliness of outbreak signals generated by each method was also compared but there was no consistency across outbreaks and LGAs. Conclusions This study has highlighted several issues associated with applying outbreak detection algorithms to seasonal disease data. In lieu of a true gold standard, a quantitative comparison is difficult and caution should be taken when interpreting the true positives, false positives, sensitivity and specificity.

Geographical distribution of human Schistosoma japonicum infection in the Philippines : tools to support disease control and further elimination

S. japonicum infection is believed to be endemic in 28 of the 80 provinces of the Philippines and the most recent data on schistosomiasis prevalence have shown considerable variability between provinces. In order to increase the efficient allocation of parasitic disease control resources in the country, we aimed to describe the small scale spatial variation in S. japonicum prevalence across the Philippines, quantify the role of the physical environment in driving the spatial variation of S. japonicum, and develop a predictive risk map of S. japonicum infection. Data on S. japonicum infection from 35,754 individuals across the country were geo-located at the barangay level and included in the analysis. The analysis was then stratified geographically for Luzon, the Visayas and Mindanao. Zero-inflated binomial Bayesian geostatistical models of S. japonicum prevalence were developed and diagnostic uncertainty was incorporated. Results of the analysis show that in the three regions, males and individuals aged ≥ 20 years had significantly higher prevalence of S. japonicum compared with females and children <5 years. The role of the environmental variables differed between regions of the Philippines. S. japonicum infection was widespread in the Visayas whereas it was much more focal in Luzon and Mindanao. This analysis revealed significant spatial variation in prevalence of S. japonicum infection in the Philippines. This suggests that a spatially targeted approach to schistosomiasis interventions, including mass drug administration, is warranted. When financially possible, additional schistosomiasis surveys should be prioritized to areas identified to be at high risk, but which were underrepresented in our dataset.