RESUMEN
Devil facial tumour disease (DFTD) is a transmissible cancer that has brought the host species, the Tasmanian devil, to the brink of extinction. The cancer cells avoid allogeneic immune recognition by downregulating cell surface major histocompatibility complex (MHC) I expression. This should prevent CD8(+) T cell, but not natural killer (NK) cell, cytotoxicity. The reason why NK cells, normally reactive to MHC-negative cells, are not activated to kill DFTD cells has not been determined. The immune response of wild devils to DFTD, if it occurs, is uncharacterised. To investigate this, we tested 12 wild devils with DFTD, and found suggestive evidence of low levels of antibodies against DFTD cells in one devil. Eight of these devils were also analysed for cytotoxicity, however, none showed evidence for cytotoxicity against cultured DFTD cells. To establish whether mimicking activation of antitumour responses could induce cytotoxic activity against DFTD, Tasmanian devil peripheral blood mononuclear cells (PBMCs) were treated with either the mitogen Concanavalin A, the Toll-like receptor agonist polyinosinic:polycytidylic acid or recombinant Tasmanian devil IL-2. All induced the PBMC cells to kill cultured DFTD cells, suggesting that activation does not occur after encounter with DFTD cells in vivo, but can be induced. The identification of agents that activate cytotoxicity against DFTD target cells is critical for developing strategies to protect against DFTD. Such agents could function as adjuvants to induce functional immune responses capable of targeting DFTD cells and tumours in vivo.
Asunto(s)
Neoplasias Faciales/patología , Leucocitos Mononucleares/citología , Marsupiales/metabolismo , Mitógenos/farmacología , Animales , Formación de Anticuerpos/efectos de los fármacos , Formación de Anticuerpos/inmunología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Concanavalina A/farmacología , Medios de Cultivo Condicionados/farmacología , Citotoxicidad Inmunológica/efectos de los fármacos , Neoplasias Faciales/inmunología , Interleucina-2/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Poli I-C/farmacología , Receptor Toll-Like 3/agonistasRESUMEN
Devil facial tumor disease (DFTD) encompasses two independent transmissible cancers that have killed the majority of Tasmanian devils. The cancer cells are derived from Schwann cells and are spread between devils during biting, a common behavior during the mating season. The Centers for Disease Control and Prevention (CDC) defines a parasite as "An organism that lives on or in a host organism and gets its food from, or at, the expense of its host." Most cancers, including DFTD, live within a host organism and derive resources from its host, and consequently have parasitic-like features. Devil facial tumor disease is a transmissible cancer and, therefore, DFTD shares one additional feature common to most parasites. Through direct contact between devils, DFTD has spread throughout the devil population. However, unlike many parasites, the DFTD cancer cells have a simple lifecycle and do not have either independent, vector-borne, or quiescent phases. To facilitate a description of devil facial tumor disease, this review uses life cycles of parasites as an analogy.
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INTRODUCTION: To help prevent future morbidity and mortality, this study examined Australian Antarctic expeditioners' first aid credentials and self-efficacy in providing emergency first aid in extreme environments. METHODS: A mixed method survey assessed Australian personnel working on Antarctic stations. Volunteer participants (n = 83) provided data on first aid training, self-confidence of first aid readiness, and first aid preparations. The Extreme Conditions First Aid Confidence Scale (EC-FACS) was developed and validated for this study. Multivariate analyses tested associations between first aid background, demographics and EC-FACS. Open-ended comments were subjected to thematic analysis. RESULTS: Over one-third of participants did not hold current first aid certificates at expedition commencement. Factor analysis demonstrated the EC-FACS was unidimensional, and internal consistency was high (α = 0.94), and showed first aid self-efficacy was moderately high, but participants' confidence decreased as first aid scenarios became more complex. Experience providing emergency first aid and level of first aid qualification were the strongest predictors of overall first aid self-efficacy. Thematic analysis revealed expeditioners support higher first aid qualifications and want Antarctic-specific wilderness first aid training. CONCLUSIONS: These findings revealed that many Antarctic expeditioners may not be adequately prepared for first aid emergencies and have low confidence in handling complex medical situations. Based on these findings, we recommend higher first aid qualifications and training tailored to the Antarctic context. These modest steps can help prevent unnecessary and costly morbidity and mortality for extreme-condition expeditioners.
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Primeros Auxilios/normas , Autoeficacia , Adulto , Anciano , Regiones Antárticas , Australia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
The Tasmanian devil, a marsupial carnivore, has been restricted to the island state of Tasmania since its extinction on the Australian mainland about 3000 years ago. In the past two decades, this species has experienced severe population decline due to the emergence of devil facial tumor disease (DFTD), a transmissible cancer. During these 20 years, scientists have puzzled over the immunological and evolutionary responses by the Tasmanian devil to this transmissible cancer. Targeted strategies in population management and disease control have been developed as well as comparative processes to identify variation in tumor and host genetics. A multi-disciplinary approach with multi-institutional teams has produced considerable advances over the last decade. This has led to a greater understanding of the molecular pathogenesis and genomic classification of this cancer. New and promising developments in the Tasmanian devil's story include evidence that most immunized, and some wild devils, can produce an immune response to DFTD. Furthermore, epidemiology combined with genomic studies suggest a rapid evolution to the disease and that DFTD will become an endemic disease. Since 1998 there have been more than 350 publications, distributed over 37 Web of Science categories. A unique endemic island species has become an international curiosity that is in the spotlight of integrative and comparative biology research.
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Transmisión de Enfermedad Infecciosa/veterinaria , Neoplasias Faciales/veterinaria , Animales , Transmisión de Enfermedad Infecciosa/prevención & control , Neoplasias Faciales/inmunología , Neoplasias Faciales/patología , Neoplasias Faciales/prevención & control , Marsupiales , TasmaniaRESUMEN
Considerable effort has been made to address the issue of occupational health and environmental exposure to mercury. This review reports on the current literature of mercury exposure and health impacts on dental personnel. Citations were searched using four comprehensive electronic databases for articles published between 2002 and 2015. All original articles that evaluated an association between the use of dental amalgam and occupational mercury exposure in dental personnel were included. Fifteen publications from nine different countries met the selection criteria. The design and quality of the studies showed significant variation, particularly in the choice of biomarkers as an indicator of mercury exposure. In several countries, dental personnel had higher mercury levels in biological fluids and tissues than in control groups; some work practices increased mercury exposure but the exposure levels remained below recommended guidelines. Dental personnel reported more health conditions, often involving the central nervous system, than the control groups. Clinical symptoms reported by dental professionals may be associated with low-level, long-term exposure to occupational mercury, but may also be due to the effects of aging, occupational overuse, and stress. It is important that dental personnel, researchers, and educators continue to encourage and monitor good work practices by dental professionals.
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Timor-Leste faces an urgent set of challenges in oral health. The impact of oral diseases in terms of reduced quality of life and cost of treatment is considerable. This paper reviews progress on policy recommendations since the National Oral Health Survey in 2002, the first such national survey. Few proposals have been implemented to date, owing to (i) lack of local support for the recommendations, particularly on promotion of oral health; (ii) lack of financial and budgetary provisions for oral health; (iii) lack of focus on services, human resources and dental personnel; (iv) poor focus, design and implementation of policy and planning in oral health; and (v) lack of transport to facilitate health-care workers' access to remote areas. Based on this assessment, the present paper presents a reconfigured set of policies and recommendations for oral health that take into consideration the reasons for low uptake of previous guidance. Key priorities are promotion of oral health, legislative interventions, education of the oral-health workforce, dental outreach programmes, targeted dental treatment, dental infrastructure programmes, and research and evaluation. Interventions include promotion of oral health for schoolchildren, salt fluoridation, fluoride toothpaste and banning sweet stalls and use of tobacco and betel nut in, or near, schools. Timor-Leste should strengthen the availability and quality of outreach programmes for oral health. Dental therapists and dental nurses who can supply preventive and atraumatic restorative dental care should continue to be trained, and the planned dentistry school should be established. Ongoing research and evaluation is needed to ensure that the approach being used in Timor-Leste is leading to improved outcomes in oral health.
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Servicios de Salud Dental/organización & administración , Política de Salud , Enfermedades de la Boca/prevención & control , Salud Bucal/normas , Servicios de Salud Dental/economía , Costos de la Atención en Salud , Empleos en Salud/educación , Promoción de la Salud/métodos , Promoción de la Salud/organización & administración , Humanos , Calidad de Vida , Timor OrientalRESUMEN
BACKGROUND: The association between Parkinson's disease and lifestyle exposures such as smoking, coffee and alcohol consumption have been the focus of research for several decades, with varying and often conflicting results. OBJECTIVE: This paper reviews the key features of observational studies investigating the relationship between alcohol drinking and PD risk, to determine potential sources of variability between the results. METHODS: Relevant literature from 2000-2014 was systematically retrieved using three databases. Primary research articles were included if they reported a measure of association between quantity and frequency of alcohol intake and PD risk, and adjusted at least for the potential confounding factors of smoking and age. RESULTS: Sixteen articles were identified. The seven case-control studies were more likely to report a weak protective association by level of alcohol consumption compared to the studies with prospective designs. Two studies reported the relationship between heavy (harmful to health) drinking and PD. There was weak evidence that associations varied by type of alcoholic beverage. Smoking may modify the association between alcohol intake and PD risk, however, the evidence does not support the theory that a confounder (such as an addiction-avoiding personality trait) produced the inverse associations between smoking, coffee and alcohol intake and PD risk. Methodological weaknesses of the studies, including selection and recall bias, residual confounding and lack of statistical power may in part account for their differences. CONCLUSION: The weak association between alcohol drinking and PD risk was found in studies at greater risk of selection and recall bias.
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Consumo de Bebidas Alcohólicas/epidemiología , Enfermedad de Parkinson/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Sesgo , Café , Humanos , Persona de Mediana Edad , Factores de Riesgo , Fumar/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: With the inclusion of elective programs, often overseas, in many medical courses, it was decided that a preliminary retrospective analysis of health problems associated with these programs in medical students from the University of Tasmania would be desirable. METHODS: A questionnaire covering general travel health issues was distributed to all medical students in the University of Tasmania, on return from their elective. They were asked to complete the questionnaire and return it on an anonymous and voluntary basis. In addition, student elective submissions were consulted for information relating to their chosen destination. RESULTS: Results of the study indicate that general practitioners were the most common source of pretravel advice for Tasmanian medical students. Overall, 64% of students experienced some sort of health problem of which travelers' diarrhea was the most common. Most problems were mild and self-limiting, but a number of serious infections were recorded, including acute leptospirosis, paratyphoid, and Staphylococcus aureus cellulitis. Of particular concern were the reports of assault and sexual harassment recorded by several students. CONCLUSIONS: Elective programs are an important part of many medical courses. With the widespread destinations chosen by students, it is important that they be given adequate pretravel health advice. Most of the health problems encountered by students from the University of Tasmania were mild, but exposure to serious infections was recorded. It is thus imperative that students take out travel health insurance and that they are counseled on how to avoid dangerous situations while abroad.
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Educación de Pregrado en Medicina/métodos , Estado de Salud , Intercambio Educacional Internacional/estadística & datos numéricos , Estudiantes de Medicina/estadística & datos numéricos , Viaje/estadística & datos numéricos , Animales , Antimaláricos/uso terapéutico , Humanos , Inmunización/estadística & datos numéricos , Insectos Vectores , Malaria/prevención & control , Servicios Preventivos de Salud/estadística & datos numéricos , Ropa de Protección/estadística & datos numéricos , Estudios Retrospectivos , TasmaniaRESUMEN
The largest carnivorous marsupial in Australia, the Tasmanian devil (Sarcophilus harrisii) is facing extinction in the wild due to a transmissible cancer known as Devil Facial Tumour Disease (DFTD). DFTD is a clonal cell line transmitted from host to host with 100% mortality and no known immunity. While it was first considered that low genetic diversity of the population of devils enabled the allograft transmission of DFTD recent evidence reveals that genetically diverse animals succumb to the disease. The lack of an immune response against the DFTD tumor cells may be due to a lack of immunogenicity of the tumor cells. This could facilitate transmission between devils. To test immunogenicity, mice were injected with viable DFTD cells and anti-DFTD immune responses analyzed. A range of antibody isotypes against DFTD cells was detected, indicating that as DFTD cells can induce an immune response they are immunogenic. This was supported by cytokine production, when splenocytes from mice injected with DFTD cells were cultured in vitro with DFTD cells and the supernatant analyzed. There was a significant production of IFN-γ and TNF-α following the first injection with DFTD cells and a significant production of IL-6 and IL-10 following the second injection. Splenocytes from naïve or immunized mice killed DFTD cells in in vitro cytotoxicity assays. Thus, they are also targets for immunological destruction. We conclude that as an immune response can be generated against DFTD cells they would be suitable targets for a vaccine.