The effect of benznidazole dose among the efficacy outcome in the murine animal model. A quantitative integration of the literature.

Despite more than 100 years since it was firstly described Chagas disease, only two drugs are available to treat Chagas disease: Nifurtimox launched by Bayer in 1965 and benznidazole launched by Roche in 1971. Drug discovery initiatives have been looking for new compounds as an alternative to these old drugs. Although new platforms have been used with the latest technologies, a critical step on that process still relies on the in vivo model. Unfortunately, to date, available animal models have limited predictive value and there is no standardization. With the aim to better understand the role of benznidazole, the current standard of care of Chagas disease, we performed this review. We intend to analyze the influence of the experimental design of the most used animal model, the murine model, in the assessment of the efficacy endpoint

The introduction of dengue follows transportation infrastructure changes in the state of Acre, Brazil : a network-based analysis.

Human mobility, presence and passive transportation of Aedes aegypti mosquito, and environmental characteristics are a group of factors which contribute to the success of dengue spread and establishment. To understand this process, we assess data from dengue national and municipal basins regarding population and demographics, transportation network, human mobility, and Ae. aegypti monitoring for the Brazilian state of Acre since the first recorded dengue case in the year 2000 to the year 2015. During this period, several changes in Acre?s transport infrastructure and urbanization have been started. To reconstruct the process of dengue introduction in Acre, we propose an analytic framework based on concepts used in malaria literature, namely vulnerability and receptivity, to inform risk assessments in dengue-free regions as well as network theory concepts for disease invasion and propagation. We calculate the probability of dengue importation to Acre from other Brazilian states, the evolution of dengue spread between Acrean municipalities and dengue establishment in the state. Our findings suggest that the landscape changes associated with human mobility have created favorable conditions for the establishment of dengue virus transmission in Acre. The revitalization of its major roads, as well as the increased accessibility by air to and within the state, have increased dengue vulnerability. Unplanned urbanization and population growth, as observed in Acre during the period of study, contribute to ideal conditions for Ae. aegypti mosquito establishment, increase the difficulty in mosquito control and consequently its local receptivity

New "light" for one-world approach toward safe and effective control of animal diseases and insect vectors from leishmaniac perspectives

Light is known to excite photosensitizers (PS) to produce cytotoxic reactive oxygen species (ROS) in the presence of oxygen. This modality is attractive for designing control measures against animal diseases and pests. Many PS have a proven safety record. Also, the ROS cytotoxicity selects no resistant mutants, unlike other drugs and pesticides. Photodynamic therapy (PDT) refers to the use of PS as light activable tumoricides, microbicides and pesticides in medicine and agriculture.Here we describe "photodynamic vaccination" (PDV) that uses PDT-inactivation of parasites, i.e. Leishmania as whole-cell vaccines against leishmaniasis, and as a universal carrier to deliver transgenic add-on vaccines against other infectious and malignant diseases. The efficacy of Leishmania for vaccine delivery makes use of their inherent attributes to parasitize antigen (vaccine)-presenting cells. Inactivation of Leishmania by PDT provides safety for their use. This is accomplished in two different ways: (i) chemical engineering of PS to enhance their uptake, e.g. Si-phthalocyanines; and (ii) transgenic approach to render Leishmania inducible for porphyrinogenesis. Three different schemes of Leishmania-based PDV are presented diagrammatically to depict the cellular events resulting in cell-mediated immunity, as seen experimentally against leishmaniasis and Leishmania-delivered antigen in vitro and in vivo. Safety versus efficacy evaluations are under way for PDT-inactivated Leishmania, including those further processed to facilitate their storage and transport. Leishmania transfected to express cancer and viral vaccine candidates are being prepared accordingly for experimental trials.We have begun to examine PS-mediated photodynamic insecticides (PDI). Mosquito cells take up rose bengal/cyanosine, rendering them light-sensitive to undergo disintegration in vitro, thereby providing a cellular basis for the larvicidal activity seen by the same treatments. Ineffectiveness of phthalocyanines and porphyrins for PDI underscores its requirement for different PS. Differential uptake of PS by insect versus other cells to account for this difference is under study.The ongoing work is patterned after the one-world approach by enlisting the participation of experts in medicinal chemistry, cell/molecular biology, immunology, parasitology, entomology, cancer research, tropical medicine and veterinary medicine. The availability of multidisciplinary expertise is indispensable for implementation of the necessary studies to move the project toward product development

Understanding the experience of initiating community-based physical activity and social support by people with serious mental illness: a systematic review using a meta-ethnographic approach

Background People with long-term serious mental illness live with severe and debilitating symptoms that can negatively influence their health and quality of life, leading to outcomes such as premature mortality, morbidity and obesity. An interplay of social, behavioural, biological and psychological factors is likely to contribute to their poor physical health. Participating in regular physical activity could bring symptomatic improvements, weight loss benefits, enhanced wellbeing and when undertaken in a community-based group setting can yield additional, important social support benefits. Yet poor uptake of physical activity by people with serious mental illness is a problem. This review will systematically search, appraise and synthesise the existing evidence that has explored the experience of community-based physical activity initiation and key features of social support within these contexts by adults with schizophrenia, bipolar affective disorder, major depressive disorder or psychosis using the meta-ethnography approach. This new understanding may be key in designing more acceptable and effective community-based group PA programmes that meet patients’ need and expectations. Methods This will be a systematic review of qualitative studies using the meta-ethnography approach. The following databases will be searched: ASSIA, CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, Health Technology Assessment Database, MEDLINE, PsycINFO, Sociological Abstracts, SPORTDiscus and Web of Science. Grey literature will also be sought. Eligible studies will use qualitative methodology; involve adults (≥18 years) with schizophrenia, bipolar affective disorder, major depressive disorder or psychosis; will report community-based group physical activity; and capture the experience of physical activity initiation and key features of social support from the perspective of the participant. Study selection and assessment of quality will be performed by two reviewers. Data will be extracted by one reviewer, tabled, and checked for accuracy by the second reviewer. The meta-ethnography approach by Noblit and Hare [1] will be used to synthesise the data. Discussion This systematic review is expected to provide new insights into the experience of community-based group physical activity initiation for adults who have a serious mental illness to inform person-centred improvements to the management of serious mental illness through physical activity. Registration The protocol has been registered on the International Prospective Register of Systematic Reviews (PROSPERO) on 22/03/2017; http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42017059948 (registration number CRD42017059948). Keywords Serious mental illness - Physical activity - Community - Social support - Exercise - Sport - Adults - Patient experience - Qualitative research - Meta-ethnography - Systematic revie