One Health: The global challenge of epidemic and endemic leishmaniasis

'One Health' proposes the unification of medical and veterinary sciences with the establishment of collaborative ventures in clinical care, surveillance and control of cross-species disease, education, and research into disease pathogenesis, diagnosis, therapy and vaccination. The concept encompasses the human population, domestic animals and wildlife, and the impact that environmental changes ('environmental health') such as global warming will have on these populations. Visceral leishmaniasis is a perfect example of a small companion animal disease for which prevention and control might abolish or decrease the suffering of canine and human patients, and which aligns well with the One Health approach. In this review we discuss how surveillance for leishmaniases is undertaken globally through the control of anthroponootic visceral leishmaniasis (AVL) and zoonotic visceral leishmaniasis (ZVL). The ZVL epidemic has been managed to date by the culling of infected dogs, treatment of human cases and control of the sandfly vector by insecticidal treatment of human homes and the canine reservoir. Recently, preventive vaccination of dogs in Brazil has led to reduction in the incidence of the canine and human disease. Vaccination permits greater dog owner compliance with control measures than a culling programme. Another advance in disease control in Africa is provided by a surveillance programme that combines remote satellite sensing, ecological modelling, vector surveillance and geo-spatial mapping of the distribution of vectors and of the animal-to-animal or animal-to-human pathogen transmission. This coordinated programme generates advisory notices and alerts on emerging infectious disease outbreaks that may impede or avoid the spreading of visceral leishmaniasis to new areas of the planet as a consequence of global warming

Effects of gamma rays on the stability and size of DNA

The effects of gamma radiation on the stability and size of mammalian DNA were studied by using thermal transition spectrophotometry and pulsed-field and standard agarose gel electrophoresis. The experiments were performed using deproteinized calf thymus DNA in buffered deaerated aqueous solutions. A dual dose response was observed: a tendency for increased helix stability at “low” doses (0-4 Gy) accompanied by a high tendency of the DNA molecules to interact, forming larger molecules, followed by a gradual increase of degradation and helix instability at higher doses. The results reported here for the low-dose region are consistent with the hypothesis of inter- and intramolecular interactions of covalent character (crosslinking) in irradiated DNA molecules. (C) 1998 by Radiation Research Society

Why I Am A Science-Inspired Naturalist but Not a Philosophical Naturalist nor a Religious Naturalist

Ever since I published a book with the title Religion, Science and Naturalism (1996), some have considered me a ‘religious naturalist’. However, I decline this label for myself. In this contribution, I seek to articulate my position more clearly. I advocate science-inspired naturalism. I will argue that this need not imply philosophical naturalism and religious naturalism. If not, as I will argue, why not? When one considers the interpretation of science and of mathematical objects and moral values, one cannot just turn to science. More is needed. A question is whether that ‘more’ falls within the ambit of ‘naturalism’, as a philosophical naturalist seems to hold. As I see it, for all practical purposes one might take a science-inspired naturalistic stance in daily life (e.g. when needing medical assistance), consider Kantian constructivism an attractive strategy when it comes to philosophical justification of values, appreciate the motivating and identity-defining power of religious and personal narratives that integrate ethos, loves, and one’s worldview, while considering oneself agnostic on matters of ultimate explanations and values

Androgen receptor expression in Circulating Tumor Cells from castration-resistant prostate cancer patients with novel endocrine agents

Background: Abiraterone and enzalutamide are novel endocrine treatments that abrogate androgen receptor (AR) signalling in castration-resistant prostate cancer (CRPC). Here, we developed a circulating tumour cells (CTCs)-based assay to evaluate AR expression in real-time in CRPC and investigated nuclear AR expression in CTCs in patients treated with enzalutamide and abiraterone. Methods: CTCs were captured and characterised using the CellSearch system. An automated algorithm to identify CTCs and quantify AR expression was employed. The primary aim was to evaluate the association between CTC AR expression and prior treatment with abiraterone or enzalutamide. Results: AR expression in CTCs was evaluated in 94 samples from 48 metastatic CRPC patients. We observed large intra-patient heterogeneity of AR expression in CTCs. Prior exposure to abiraterone or enzalutamide was not associated with a change in CTCs AR expression (median intensity and distribution of AR-positive classes). In support of this, we also confirmed maintained nuclear AR expression in tissue samples collected after progression on abiraterone. AR staining also identified additional AR-positive CD45-negative circulating cells that were CK-negative/weak and therefore missed using standard protocols. The number of these events correlated with traditional CTCs and was associated with worse outcome on univariate analysis. Conclusions: We developed a non-invasive method to monitor AR nuclear expression in CTCs. Our studies confirm nuclear AR expression in CRPC patients progressing on novel endocrine treatments. Owing to the significant heterogeneity of AR expression in CTCs, studies in larger cohorts of patients are required to identify associations with outcom