Advances in sickle cell disease treatment: From drug discovery until the patient monitoring

Sickle Cell Disease (SCD) is one of the most prevalent hematological diseases in the world. Despite the immense progress in molecular knowledge about SCD in last years few therapeutical sources are currently available. Nowadays the treatment is performed mainly with drugs such as hydroxyurea or other fetal hemoglobin inducers and chelating agents. This review summarizes current knowledge about the treatment and the advancements in drug design in order to discover more effective and safe drugs. Patient monitoring methods in SCD are also discussed. © 2011 Bentham Science Publishers Ltd.

Innovations in health care services: The CAALYX system

Purpose: This paper describes proposed health care services innovations, provided by a system called CAALYX (Complete Ambient Assisted Living eXperiment). CAALYX aimed to provide healthcare innovation by extending the state-of-the-art in tele-healthcare, by focusing on increasing the confidence of elderly people living autonomously, by building on the knowledge base of the most common disorders and respective characteristic vital sign changes for this age group. Methods: A review of the state-of-the-art on health care services was carried out. Then, extensive research was conducted on the particular needs of the elderly in relation to home health services that, if offered to them, could improve their day life by giving them greater confidence and autonomy. To achieve this, we addressed issues associated with the gathering of clinical data and interpretation of these data, as well as possibilities of automatically triggering appropriate clinical measures. Considering this initial work we started the identification of initiatives, ongoing works and technologies that could be used for the development of the system. After that, the implementation of CAALYX was done. Findings: The innovation in CAALYX system considers three main areas of contribution: (i) The Roaming Monitoring System that is used to collect information on the well-being of the elderly users; (ii) The Home Monitoring System that is aimed at helping the elders independently living at home being implemented by a device (a personal computer or a set top box) that supports the connection of sensors and video cameras that may be used for monitoring and for interaction with the elder; (iii) The Central Care Service and Monitoring System that is implemented by a Caretaker System where attention and care services are provided to elders, where actors as Caretakers, Doctors and Relatives are logically linked to elders. Innovations in each of these areas are presented here. Conclusions: The ageing European society is placing an added burden on future generations, as the 'elderly-to-working-age-people' ratio is set to steadily increase in the future. Nowadays, quality of life and fitness allows for most older persons to have an active life well into their eighties. Furthermore, many older persons prefer to live in their own house and choose their own lifestyle. The CAALYX system can have a clear impact in increasing older persons' autonomy, by ensuring that they do not need to leave their preferred environment in order to be properly monitored and taken care of. © 2011 Elsevier B.V. All rights reserved.

Toxicogenetic monitoring in urban cities exposed to different airborne contaminants

Microparticles found in the air may be associated with organic matter that contains several compounds, such as Polycyclic Aromatic Hydrocarbons (PAHs) and nitro-PAHs, and may pose a significant risk to human health, possibly leading to DNA mutations and cancers. This study associated genotoxicity assays for evaluating human exposure with the atmospheric air of two urban areas in southern Brazil, that received different atmospheric contributions. Site 1 was under urban-industrial influence and the other was a non-industrial reference, Site 2. Organic extracts from the airborne particulate matter were tested for mutagenicity via the Salmonella/microsome assay and analyzed for PAH composition. Cells samples of people residing in these two cities were evaluated using the comet and micronucleus assay (MN).Concentrations of the individual PAHs ranged from 0.01ng/m3 (benzo[a]anthracene) to 5.08ng/m3 (benzo[ghi]perylene). As to mutagenicity analysis of airborne, Site 1 presented all the mutagenic responses, which varied from 3.2±1.22rev/m3 (TA98 no S9) to 32.6±2.05rev/m3 (TA98, S9), while Site 2 ranged from negative to minimal responses. Site 1 presented a high quantity of nitro and amino derivatives of PAHs, and peaked at 56.0±3.68rev/μg (YG1024 strain). The two groups presented very low DNA damage levels without intergroup difference. Although Site 1 presented high mutagenic responses in the air samples, high PAH levels, healthy people exposed to this environment did not show significative damage in their genetic material. However, the evaluation of different environmental and genetic damage in such population is necessary to monitor possible damages. © 2013 Elsevier Inc.

Structural and Phylogenetic Studies with MjTX-I Reveal a Multi-Oligomeric Toxin - a Novel Feature in Lys49-PLA2s Protein Class

The mortality caused by snakebites is more damaging than many tropical diseases, such as dengue haemorrhagic fever, cholera, leishmaniasis, schistosomiasis and Chagas disease. For this reason, snakebite envenoming adversely affects health services of tropical and subtropical countries and is recognized as a neglected disease by the World Health Organization. One of the main components of snake venoms is the Lys49-phospholipases A2, which is catalytically inactive but possesses other toxic and pharmacological activities. Preliminary studies with MjTX-I from Bothrops moojeni snake venom revealed intriguing new structural and functional characteristics compared to other bothropic Lys49-PLA2s. We present in this article a comprehensive study with MjTX-I using several techniques, including crystallography, small angle X-ray scattering, analytical size-exclusion chromatography, dynamic light scattering, myographic studies, bioinformatics and molecular phylogenetic analyses.Based in all these experiments we demonstrated that MjTX-I is probably a unique Lys49-PLA2, which may adopt different oligomeric forms depending on the physical-chemical environment. Furthermore, we showed that its myotoxic activity is dramatically low compared to other Lys49-PLA2s, probably due to the novel oligomeric conformations and important mutations in the C-terminal region of the protein. The phylogenetic analysis also showed that this toxin is clearly distinct from other bothropic Lys49-PLA2s, in conformity with the peculiar oligomeric characteristics of MjTX-I and possible emergence of new functionalities inresponse to environmental changes and adaptation to new preys. © 2013 Salvador et al.

Middle-income countries: a structural gap approach

Spanish version available

Lactobacillus acidophilus CRL 1014 improved gut health in the SHIME® reactor

Background: How to maintain gut health is a goal for scientists throughout the world. Therefore, microbiota management models for testing probiotics, prebiotics, and synbiotics have been developed.Methods: The SHIME® model was used to study the effect of Lactobacillus acidophilus 1014 on the fermentation pattern of the colon microbiota. Initially, an inoculum prepared from human feces was introduced into the reactor vessels and stabilized over 2-wk using a culture medium. This stabilization period was followed by a 2-wk control period during which the microbiota was monitored. The microbiota was then subjected to a 4-wk treatment period by adding 5 mL of sterile peptone water with L. acidophilus CRL1014 at the concentration of 108 CFU/mL to vessel one (the stomach compartment). Plate counts, Denaturing Gradient Gel Electrophoresis (DGGE), short-chain fatty acid (SCFA) and ammonium analyses were carried out for monitoring of the microbial community from the colon compartments.Results: A significant increase (p < 0.01) in the Lactobacillus spp. and Bifidobacterium spp. populations was observed during the treatment period. The DGGE obtained showed changes in the lactobacilli community from the colon compartments of the SHIME® reactor. The (SCFA) concentration increased (p < 0.01) during the treatment period, due mainly to significant increased levels of acetic, butyric, and propionic acids. However, ammonium concentrations decreased during the same period (p < 0.01).Conclusions: This study showed the beneficial influence of L. acidophilus CRL 1014 on microbial metabolism and lactobacilli community composition for improving human health. © 2013 Sivieri et al.; licensee BioMed Central Ltd.

Avaliação do potencial citotóxico, genotóxico e mutagênico de esgoto por meio dos sistemas-teste Allium cepa e Tradescantia pallida

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The digital economy for structural change and equality

Includes bibliography.

An assessment of the economic impact of climate change on the Agriculture, Health and Tourism sectors in Saint Lucia

This report analyses the agriculture, health and tourism sectors in Saint Lucia to assess the potential economic impacts of climate change on the sectors. The fundamental aim of this report is to assist with the development of strategies to deal with the potential impact of climate change in Saint Lucia. It also has the potential to provide essential input for identifying and preparing policies and strategies to help advance the Caribbean subregion closer to solving problems associated with climate change and attaining individual and regional sustainable development goals. Some of the key anticipated impacts of climate change for the Caribbean include elevated air and sea-surface temperatures, sea-level rise, possible changes in extreme events and a reduction in freshwater resources. The economic impact of climate change on the three sectors was estimated for the A2 and B2 IPCC scenarios until 2050. An evaluation of various adaptation strategies for each sector was also undertaken using standard evaluation techniques. The key subsectors in agriculture are expected to have mixed impacts under the A2 and B2 scenarios. Banana, fisheries and root crop outputs are expected to fall with climate change, but tree crop and vegetable production are expected to rise. In aggregate, in every decade up to 2050, these sub-sectors combined are expected to experience a gain under climate change with the highest gains under A2. By 2050, the cumulative gain under A2 is calculated as approximately US$389.35 million and approximately US$310.58 million under B2, which represents 17.93% and 14.30% of the 2008 GDP respectively. This result was unexpected and may well be attributed to the unavailability of annual data that would have informed a more robust assessment. Additionally, costs to the agriculture sector due to tropical cyclones were estimated to be $6.9 million and $6.2 million under the A2 and B2 scenarios, respectively. There are a number of possible adaptation strategies that can be employed by the agriculture sector. The most attractive adaptation options, based on the benefit-cost ratio are: (1) Designing and implementation of holistic water management plans (2) Establishment of systems of food storage and (3) Establishment of early warning systems. Government policy should focus on the development of these adaption options where they are not currently being pursued and strengthen those that have already been initiated, such as the mainstreaming of climate change issues in agricultural policy. The analysis of the health sector placed focus on gastroenteritis, schistosomiasis, ciguatera poisoning, meningococal meningitis, cardiovascular diseases, respiratory diseases and malnutrition. The results obtained for the A2 and B2 scenarios demonstrate the potential for climate change to add a substantial burden to the health system in the future, a factor that will further compound the country’s vulnerability to other anticipated impacts of climate change. Specifically, it was determined that the overall Value of Statistical Lives impacts were higher under the A2 scenario than the B2 scenario. A number of adaptation cost assumptions were employed to determine the damage cost estimates using benefit-cost analysis. The benefit-cost analysis suggests that expenditure on monitoring and information provision would be a highly efficient step in managing climate change and subsequent increases in disease incidence. Various locations in the world have developed forecasting systems for dengue fever and other vector-borne diseases that could be mirrored and implemented. Combining such macro-level policies with inexpensive micro-level behavioural changes may have the potential for pre-empting the re-establishment of dengue fever and other vector-borne epidemic cycles in Saint Lucia. Although temperature has the probability of generating significant excess mortality for cardiovascular and respiratory diseases, the power of temperature to increase mortality largely depends on the education of the population about the harmful effects of increasing temperatures and on the existing incidence of these two diseases. For these diseases it is also suggested that a mix of macro-level efforts and micro-level behavioural changes can be employed to relieve at least part of the threat that climate change poses to human health. The same principle applies for water and food-borne diseases, with the improvement of sanitation infrastructure complementing the strengthening of individual hygiene habits. The results regarding the tourism sector imply that the tourism climatic index was likely to experience a significant downward shift in Saint Lucia under the A2 as well as the B2 scenario, indicative of deterioration in the suitability of the island for tourism. It is estimated that this shift in tourism features could cost Saint Lucia about 5 times the 2009 GDP over a 40-year horizon. In addition to changes in climatic suitability for tourism, climate change is also likely to have important supply-side effects on species, ecosystems and landscapes. Two broad areas are: (1) coral reefs, due to their intimate link to tourism, and, (2) land loss, as most hotels tend to lie along the coastline. The damage related to coral reefs was estimated at US$3.4 billion (3.6 times GDP in 2009) under the A2 scenario and US$1.7 billion (1.6 times GDP in 2009) under the B2 scenario. The damage due to land loss arising from sea level rise was estimated at US$3.5 billion (3.7 times GDP) under the A2 scenario and US$3.2 billion (3.4 times GDP) under the B2 scenario. Given the potential for significant damage to the industry a large number of potential adaptation measures were considered. Out of these a short-list of 9 potential options were selected by applying 10 evaluation criteria. Using benefit-cost analyses 3 options with positive ratios were put forward: (1) increased recommended design speeds for new tourism-related structures; (2) enhanced reef monitoring systems to provide early warning alerts of bleaching events, and, (3) deployment of artificial reefs or other fish-aggregating devices. While these options had positive benefit-cost ratios, other options were also recommended based on their non-tangible benefits. These include the employment of an irrigation network that allows for the recycling of waste water, development of national evacuation and rescue plans, providing retraining for displaced tourism workers and the revision of policies related to financing national tourism offices to accommodate the new climate realities.

An assessment of the economic impact of climate change on the Agriculture, Health and Tourism sectors in Jamaica

This report analyses the agriculture, health and tourism sectors in Jamaica to assess the potential economic impacts of climate change on the sectors. The fundamental aim of this report is to assist with the development of strategies to deal with the potential impact of climate change on Jamaica. It also has the potential to provide essential input for identifying and preparing policies and strategies to help move the Region closer to solving problems associated with climate change and attaining individual and regional sustainable development goals. Some of the key anticipated manifestations of climate change for the Caribbean include elevated air and sea-surface temperatures, sea-level rise, possible changes in extreme events and a reduction in freshwater resources. The economic impact of climate change on the three sectors was estimated for the A2 and B2 IPCC scenarios until 2050. An evaluation of various adaptation strategies was also undertaken for each sector using standard evaluation techniques. The outcomes from investigating the agriculture sector indicate that for the sugar-cane subsector the harvests under both the A2 and B2 scenarios decrease at first and then increase as the mid-century mark is approached. With respect to the yam subsector the results indicate that the yield of yam will increase from 17.4 to 23.1 tonnes per hectare (33%) under the A2 scenario, and 18.4 to 23.9 (30%) tonnes per hectare under the B2 scenario over the period 2011 to 2050. Similar to the forecasts for yam, the results for escallion suggest that yields will continue to increase to mid-century. Adaptation in the sugar cane sub-sector could involve replanting and irrigation that appear to generate net benefits at the three selected discount rates for the A2 scenario, but only at a discount rate of 1% for the B2 scenario. For yam and escallion, investment in irrigation will earn significant net benefits for both the A2 and B2 scenarios at the three selected rates of discount. It is recommended that if adaptation strategies are part of a package of strategies for improving efficiency and hence enhancing competitiveness, then the yields of each crop can be raised sufficiently to warrant investment in adaptation to climate change. The analysis of the health sector demonstrates the potential for climate change to add a substantial burden to the future health systems in Jamaica, something that that will only compound the country’s vulnerability to other anticipated impacts of climate change. The results clearly show that the incidence of dengue fever will increase if climate change continues unabated, with more cases projected for the A2 scenario than the B2. The models predicted a decrease in the incidence of gastroenteritis and leptospirosis with climate change, indicating that Jamaica will benefit from climate change with a reduction in the number of cases of gastroenteritis and leptospirosis. Due to the long time horizon anticipated for climate change, Jamaica should start implementing adaptation strategies focused on the health sector by promoting an enabling environment, strengthening communities, strengthening the monitoring, surveillance and response systems and integrating adaptation into development plans and actions. Small-island developing states like Jamaica must be proactive in implementing adaptation strategies, which will reduce the risk of climate change. On the global stage the country must continue to agitate for the implementation of the mitigation strategies for developed countries as outlined in the Kyoto protocol. The results regarding the tourism sector suggest that the sector is likely to incur losses due to climate change, the most significant of which is under the A2 scenario. Climatic features, such as temperature and precipitation, will affect the demand for tourism in Jamaica. By 2050 the industry is expected to lose US$ 132.2 million and 106.1 million under the A2 and B2 scenarios, respectively. In addition to changes in the climatic suitability for tourism, climate change is also likely to have important supply-side effects from extreme events and acidification of the ocean. The expected loss from extreme events is projected to be approximately US$ 5.48 billion (A2) and US$ 4.71 billion (B2). Even more devastating is the effect of ocean acidification on the tourism sector. The analysis shows that US$ 7.95 billion (A2) and US$ 7.04 billion is expected to be lost by mid-century. The benefit-cost analysis indicates that most of the adaptation strategies are expected to produce negative net benefits, and it is highly likely that the cost burden would have to be carried by the state. The options that generated positive ratios were: redesigning and retrofitting all relevant tourism facilities, restoring corals and educating the public and developing rescue and evacuation plans. Given the relative importance of tourism to the macroeconomy one possible option is to seek assistance from multilateral funding agencies. It is recommended that the government first undertake a detailed analysis of the vulnerability of each sector and, in particular tourism, to climate change. Further, more realistic socio-economic scenarios should be developed so as to inform future benefit-cost analysis.

An economic assessment of the impact of climate change on the health sector in Montserrat

Climate change has the potential to impact on global, regional, and national disease burdens both directly and indirectly. Projecting and valuing these health impacts is important not only in terms of assessing the overall impact of climate change on various parts of the world, but also in terms of ensuring that national and regional decision-making institutions have access to the data necessary to guide investment decisions and future policy design. This report contributes to the research focusing on projecting and valuing the impacts of climate change in the Caribbean by projecting the climate change-induced excess disease burden for two climate change scenarios in Montserrat for the period 2010 - 2050, and by estimating the monetary value associated with this excess disease burden. The diseases initially considered in this report are variety of vector and water-borne impacts and other miscellaneous conditions; specifically, malaria, dengue fever, gastroenteritis/diarrheal disease, schistosomiasis, leptospirosis, ciguatera poisoning, meningococcal meningitis, and cardio-respiratory diseases. Disease projections were based on derived baseline incidence and mortality rates, available dose-response relationships found in the published literature, climate change scenario population projections for the A2 and B2 IPCC SRES scenario families, and annual temperature and precipitation anomalies as projected by the downscaled ECHAM4 global climate model. Monetary valuation was based on a transfer value of statistical life approach with a modification for morbidity. Using discount rates of 1%, 2% and 4%, results show mean annual costs (morbidity and mortality) ranges of $0.61 million (in the B2 scenario, discounted at 4% annually) – $1 million (in the A2 scenario, discounted at 1% annually) for Montserrat. These costs are compared to adaptation cost scenarios involving increased direct spending on per capita health care. This comparison reveals a high benefit-cost ratio suggesting that moderate costs will deliver significant benefit in terms of avoided health burdens in the period 2010-2050. The methodology and results suggest that a focus on coordinated data collection and improved monitoring represents a potentially important no regrets adaptation strategy for Montserrat. Also the report highlights the need for this to be part of a coordinated regional response that avoids duplication in spending.

An assessment of the economic impact Of climate change on the health sector in Saint Lucia

Climate change has the potential to impact on global, regional, and national disease burdens both directly and indirectly. Projecting and valuing these health impacts is important not only in terms of assessing the overall impact of climate change on various parts of the world, but also of ensuring that national and regional decision-making institutions have access to the data necessary to guide investment decisions and future policy design. This report contributes to the research focusing on projecting and valuing the impacts of climate change in the Caribbean by projecting the climate change-induced excess disease burden for two climate change scenarios in Saint Lucia for the period 2010 - 2050, and by estimating the non-market, statistical life-based costs associated with this excess disease burden. The diseases initially considered in this report are a variety of vector and water-borne impacts and other miscellaneous conditions; specifically, malaria, dengue fever, gastroenteritis/diarrhoeal disease, schistosomiasis, leptospirosis, ciguatera poisoning, meningococcal meningitis, and cardio-respiratory diseases. Disease projections were based on derived baseline incidence and mortality rates, available dose-response relationships found in the published literature, climate change scenario population projections for the A2 and B2 IPCC SRES scenario families, and annual temperature and precipitation anomalies as projected by the downscaled ECHAM4 global climate model. Monetary valuation was based on a transfer value of statistical life approach with a modification for morbidity. Using discount rates of 1, 2, and 4%, results show mean annual costs (morbidity and mortality) ranges of $80.2 million (in the B2 scenario, discounted at 4% annually) -$182.4 million (in the A2 scenario, discounted at 1% annually) for St. Lucia.1 These costs are compared to adaptation cost scenarios involving direct and indirect interventions in health care. This comparison reveals a high benefit-cost ratio suggesting that moderate costs will deliver significant benefit in terms of avoided health costs from 2010-2050. In this context indirect interventions target sectors other than healthcare (e.g. water supply). It is also important to highlight that interventions can target both the supply of health infrastructure (including health status and disease monitoring), and households. It is suggested that a focus on coordinated data collection and improved monitoring represents a potentially important no regrets adaptation strategy for St Lucia. Also, the need for this to be part of a coordinated regional response that avoids duplication in spending is highlighted.

Report of the second expert group meeting on the development account supported project in MDG/IADG monitoring in the Caribbean

The Economic Commission for Latin America and the Caribbean (ECLAC), Subregional Headquarters for the Caribbean, held a two-day expert group meeting on Millennium Development Goals (MDG) monitoring and reporting with a particular focus on health-related indicators in Port of Spain, Trinidad and Tobago, on 16-17 June 2009. This meeting was convened within the framework of the United Nations Development Account-funded project ‘Strengthening the Capacity of National Statistical Offices in the Caribbean Small Island Developing States to fulfil the Millennium Development Goals (MDGs) and other Internationally Agreed Development Goals (IADGs)’.

The Caribbean and the post-2015 development agenda

This paper will contend that the post-2015 development agenda presents a major opportunity for Caribbean countries to reverse decades of lagging economic performance and make the transition to balanced, holistic, and people-centred growth and development. The MDGs, while valuable in promoting gains in poverty reduction, health, education, nutrition, and maternal well-being were not tailored to the growth and development needs of the region. This can now be changed by a post-2015 development agenda which goes beyond improving the welfare of citizens by meeting basic needs and enhancing access to primary services. The necessary scaling-up of the MDG framework will require that the sustainable development goals, which will anchor the post- 2015 development agenda, are capable of promoting structural change, competitiveness and output gains while advancing social development and meeting environmental concerns. They must also address the unfinished business of the millennium development goals, primarily in the area of human development.

Structural bases for a complete myotoxic mechanism: Crystal structures of two non-catalytic phospholipases A(2)-like from Bothrops brazili venom

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)