Interaction between APOE4 genotype and environmental risk factors in Alzheimer's disease

Alzheimer's disease (AD) is probably caused by both genetic and environmental risk factors. The major genetic risk factor is the E4 variant of apolipoprotein E gene called apoE4. Several risk factors for developing AD have been identified including lifestyle, such as dietary habits. The mechanisms behind the AD pathogenesis and the onset of cognitive decline in the AD brain are presently unknown. In this study we wanted to characterize the effects of the interaction between environmental risk factors and apoE genotype on neurodegeneration processes, with particular focus on behavioural studies and neurodegenerative processes at molecular level. Towards this aim, we used 6 months-old apoE4 and apoE3 Target Replacement (TR) mice fed on different diets (high intake of cholesterol and high intake of carbohydrates). These mice were evaluated for learning and memory deficits in spatial reference (Morris Water Maze (MWM)) and contextual learning (Passive Avoidance) tasks, which involve the hippocampus and the amygdala, respectively. From these behavioural studies we found that the initial cognitive impairments manifested as a retention deficit in apoE4 mice fed on high carbohydrate diet. Thus, the genetic risk factor apoE4 genotype associated with a high carbohydrate diet seems to affect cognitive functions in young mice, corroborating the theory that the combination of genetic and environmental risk factors greatly increases the risk of developing AD and leads to an earlier onset of cognitive deficits. The cellular and molecular bases of the cognitive decline in AD are largely unknown. In order to determine the molecular changes for the onset of the early cognitive impairment observed in the behavioural studies, we performed molecular studies, with particular focus on synaptic integrity and Tau phosphorylation. The most relevant finding of our molecular studies showed a significant decrease of Brain-derived Neurotrophic Factor (BDNF) in apoE4 mice fed on high carbohydrate diet. Our results may suggest that BDNF decrease found in apoE4 HS mice could be involved in the earliest impairment in long-term reference memory observed in behavioural studies. The second aim of this thesis was to study possible involvement of leptin in AD. There is growing evidence that leptin has neuroprotective properties in the Central Nervous System (CNS). Recent evidence has shown that leptin and its receptors are widespread in the CNS and may provide neuronal survival signals. However, there are still numerous questions, regarding the molecular mechanism by which leptin acts, that remain unanswered. Thus, given to the importance of the involvement of leptin in AD, we wanted to clarify the function of leptin in the pathogenesis of AD and to investigate if apoE genotype affect leptin levels through studies in vitro, in mice and in human. Our findings suggest that apoE4 TR mice showed an increase of leptin in the brain. Leptin levels are also increased in the cerebral spinal fluid of AD patients and apoE4 carriers with AD have higher levels of leptin than apoE3 carriers. Moreover, leptin seems to be expressed by reactive glial cells in AD brains. In vitro, ApoE4 together with Amyloid beta increases leptin production by microglia and astrocytes. Taken together, all these findings suggest that leptin replacement might not be a good strategy for AD therapy. Our results show that high leptin levels were found in AD brains. These findings suggest that, as high leptin levels do not promote satiety in obese individuals, it might be possible that they do not promote neuroprotection in AD patients. Therefore, we hypothesized that AD brain could suffer from leptin resistance. Further studies will be critical to determine whether or not the central leptin resistance in SNC could affect its potential neuroprotective effects.

Evaluation of a novel photography-based home assessment protocol for identification of environmental risk factors for falls in elderly persons

PRINCIPLES To evaluate the validity and feasibility of a novel photography-based home assessment (PhoHA) protocol, as a possible substitute for on-site home assessment (OsHA). METHODS A total of 20 patients aged ≥65 years who were hospitalised in a rehabilitation centre for musculoskeletal disorders affecting mobility participated in this prospective validation study. For PhoHA, occupational therapists rated photographs and measurements of patients' homes provided by patients' confidants. For OsHA, occupational therapists conducted a conventional home visit. RESULTS Information obtained by PhoHA was 79.1% complete (1,120 environmental factors identified by PhoHA vs 1416 by OsHA). Of the 1,120 factors, 749 had dichotomous (potential hazards) and 371 continuous scores (measurements with tape measure). Validity of PhoHA to potential hazards was good (sensitivity 78.9%, specificity 84.9%), except for two subdomains (pathways, slippery surfaces). Pearson's correlation coefficient for the validity of measurements was 0.87 (95% confidence interval [CI 0.80-0.92, p <0.001). Agreement between methods was 0.52 (95%CI 0.34-0.67, p <0.001, Cohen's kappa coefficient) for dichotomous and 0.86 (95%CI 0.79-0.91, p <0.001, intraclass correlation coefficient) for continuous scores. Costs of PhoHA were 53.0% lower than those of OsHA (p <0.001). CONCLUSIONS PhoHA has good concurrent validity for environmental assessment if instructions for confidants are improved. PhoHA is potentially a cost-effective method for environmental assessment.

The relationship between enterotoxigenic {\it Escherichia coli\/} infection and environmental risk factors in Bilbeis, Egypt, 1981--1983

Diarrheal disease associated with enterotoxigenic Escherichia coli (ETEC) infection is one of the major public health problems in many developing countries, especially in infants and young children. Because tests suitable for field laboratories have been developed only relatively recently, the literature on the environmental risk factors associated with ETEC is not as complete as for many other pathogens or for diarrhea of unspecified etiology.^ Data from a diarrheal disease surveillance project in rural Egypt in which stool samples were tested for a variety of pathogens, and in which an environmental questionnaire was completed for the same study households, provided an opportunity to test for an association between ETEC and various risk factors present in those households. ETEC laboratory-positive specimens were compared with ETEC laboratory-negative specimens for both symptomatic and asymptomatic children less than three years of age at the individual and household level using a case-comparison design.^ Individual children more likely to have LT infection were those who lived in HHs that had cooked food stored for subsequent consumption at the time of the visit, where caretakers used water but not soap to clean an infant after a diarrheal stool, and that had an indoor, private water source. LT was more common in HHs where the caretaker did not clean an infant with soap after a diarrheal stool, and where a sleeping infant was not covered with a net. At both the individual and HH level, LT was significantly associated with good water supply in terms of quantity and storage.^ ST was isolated more frequently at the individual level where a sleeping infant was covered with a net, where large animals were kept in or around the house, where water was always available and was not potable, and where the water container was not covered. At the HH level, the absence of a toilet or latrine and the indiscriminate disposal of animal waste decreased risk. Using animal feces for fertilizer, the presence of large animals, and poor water quality were associated with ST at both the individual and HH level.^ These findings are mostly consistent with those of other studies, and/or are biologically plausible, with the obvious exception of those from this study where poorer water supplies are associated with less infection, at least in the case of LT. More direct observation of how animal ownership and feces disposal relates to different types of water supply and usage might clarify mechanisms through which some ETEC infection could be prevented in similar settings. ^

Survey and brain storming studies about machines, constructions, human and environmental risk consideration in the careers of the Universidad Politécnica of Madrid

The Universidad Politécnica of Madrid (UPM) includes schools and faculties that were for engineering degrees, architecture and computer science, that are now in a quick EEES Bolonia Plan metamorphosis getting into degrees, masters and doctorate structures. They are focused towards action in machines, constructions, enterprises, that are subjected to machines, human and environment created risks. These are present in actions such as use loads, wind, snow, waves, flows, earthquakes, forces and effects in machines, vehicles behavior, chemical effects, and other environmental factors including effects of crops, cattle and beasts, forests, and varied essential economic and social disturbances. Emphasis is for authors in this session more about risks of natural origin, such as for hail, winds, snow or waves that are not exactly known a priori, but that are often considered with statistical expected distributions giving extreme values for convenient return periods. These distributions are known from measures in time, statistic of extremes and models about hazard scenarios and about responses of man made constructions or devices. In each engineering field theories were built about hazards scenarios and how to cover for important risks. Engineers must get that the systems they handle, such as vehicles, machines, firms or agro lands or forests, obtain production with enough safety for persons and with decent economic results in spite of risks. For that risks must be considered in planning, in realization and in operation, and safety margins must be taken but at a reasonable cost. That is a small level of risks will often remain, due to limitations in costs or because of due to strange hazards, and maybe they will be covered by insurance in cases such as in transport with cars, ships or aircrafts, in agro for hail, or for fire in houses or in forests. These and other decisions about quality, security for men or about business financial risks are sometimes considered with Decision Theories models, using often tools from Statistics or operational Research. The authors have done and are following field surveys about risk consideration in the careers in UPM, making deep analysis of curricula taking into account the new structures of degrees in the EEES Bolonia Plan, and they have considered the risk structures offered by diverse schools of Decision theories. That gives an aspect of the needs and uses, and recommendations about improving in the teaching about risk, that may include special subjects especially oriented for each career, school or faculty, so as to be recommended to be included into the curricula, including an elaboration and presentation format using a multi-criteria decision model.

Environmental risk assessment in open pit blasting operations: compliance with ISO 31010:2010

All activities of an organization involve risks that should be managed. The risk management process aids decision making by taking account of uncertainty and the possibility of future events or circumstances (intended or unintended) and their effects on agreed objectives. With that idea, new ISO Standard has been drawn up. ISO 31010 has been recently issued which provides a structured process that identifies how objectives may be affected, and analyses the risk in term of consequences and their probabilities before deciding on whether further treatment is required. In this lecture, that ISO Standard has been adapted to Open Pit Blasting Operations, focusing in Environmental effects which can be managed properly. Technique used is Fault Tree Analysis (FTA), which is applied in all possible scenarios, providing to Blasting Professionals the tools to identify, analyze and manage environmental effects in blasting operations. Also this lecture can help to minimize each effect, studying each case. This paper also can be useful to Project Managers and Occupational Health and Safety Departments (OH&S) because blasting operations can be evaluated and compared one to each other to determine the risks that should be managed in different case studies. The environmental effects studied are: ground vibrations, flyrock and air overpressure (airblast). Sometimes, blasting operations are carried out near populated areas where environmental effects may impose several limitations on the use of explosives. In those cases, where these factors approach certain limits, National Standards and Regulations have to be applied.

Social differentiation of risk: perceptions of the future in drought-prone Central Niger

A snapshot of two Tuareg-dominated 'communes rurales' in the pastoral-agricultural transition zones of Maradi and Tahoua regions, Central Niger, shows that, despite the openly shared 'inevitable natural hazard' drought discourse, risk-taking action in response to drought-related dangers is sharply polarized according to social position. On the one hand the dominant Tuareg minority perceive drought not only as danger for their herds but also as opportunity to increase their political following through the channelling of drought relief benefits to their supporters. On the other hand, the majority of commune households, living on the brink of economic viability, cultivate social links with the dominant families in order to secure access to water, land and humanitarian aid; and household members are forced into more and more frequent and distant out-migration. Certain leaders, well-informed about national land policy and practice, focus their efforts for a better future on the consolidation of community land rights through the promotion of certain sedentarization and land privatization initiatives; however the resulting increased land pressure in key locations may unwittingly expose inhabitants to even worse drought-linked crises in the future. Bibliogr., notes, sum. in English and French

Socio-economic distribution of environmental risk factors for childhood injury

Objective: Childhood injury remains the single most important cause of mortality in children aged between 1-14 years in many countries. It has been proposed that lower socio-economic status (SES) and poorer housing contribute to potential hazards in the home environment. This study sought to establish whether the prevalence of observed hazards in and around the home was differentially distributed by SES, in order to identify opportunities for injury prevention. Methods: This study was a cross-sectional, random sample survey of primary school children from 32 schools in Brisbane. Interviews and house audits were conducted between July 2000 and April 2003 to collect information on SES (income, employment and education) and previously identified household hazards. Results: There was evidence of a relationship between prevalence of household environmental hazards and household SES; however, the magnitude and direction of this relationship appeared to be hazard-specific. Household income was related to play equipment characteristics, with higher SES groups being more likely to be exposed to risk. All three SES indicators were associated with differences in the home safety characteristics, with the lower SES groups more likely to be exposed to risk. Conclusion:The differential distribution of environmental risk factors by SES of household may help explain the SES differential in the burden of injury and provides opportunities for focusing efforts to address the problem.

Four essays of environmental risk-mitigation

Expected damages of environmental risks depend both on their intensities and probabilities. There is very little control over probabilities of climate related disasters such as hurricanes. Therefore, researchers of social science are interested identifying preparation and mitigation measures that build human resilience to disasters and avoid serious loss. Conversely, environmental degradation, which is a process through which the natural environment is compromised in some way, has been accelerated by human activities. As scientists are finding effective ways on how to prevent and reduce pollution, the society often fails to adopt these effective preventive methods. Researchers of psychological and contextual characterization offer specific lessons for policy interventions that encourage human efforts to reduce pollution. This dissertation addresses four discussions of effective policy regimes encouraging pro-environmental preference in consumption and production, and promoting risk mitigation behavior in the face of natural hazards. The first essay describes how the speed of adoption of environment friendly technologies is driven largely by consumers' preferences and their learning dynamics rather than producers' choice. The second essay is an empirical analysis of a choice experiment to understand preferences for energy efficient investments. The empirical analysis suggests that subjects tend to increase energy efficient investment when they pay a pollution tax proportional to the total expenditure on energy consumption. However, investments in energy efficiency seem to be crowded out when subjects have the option to buy health insurance to cover pollution related health risks. In context of hurricane risk mitigation and in evidence of recently adopted My Safe Florida Home (MSFH) program by the State of Florida, the third essay shows that households with home insurance, prior experience with damages, and with a higher sense of vulnerability to be affected by hurricanes are more likely to allow home inspection to seek mitigation information. The fourth essay evaluates the impact of utility disruption on household well being based on the responses of a household-level phone survey in the wake of hurricane Wilma. Findings highlight the need for significant investment to enhance the capacity of rapid utility restoration after a hurricane event in the context of South Florida.

Oil spill environmental risk assessment of stationary sources in offshore zones (Innovating a mathematical model)

Nowadays, risks arising from the rapid development of oil and gas industries are significantly increasing. As a result, one of the main concerns of either industrial or environmental managers is the identification and assessment of such risks in order to develop and maintain appropriate proactive measures. Oil spill from stationary sources in offshore zones is one of the accidents resulting in several adverse impacts on marine ecosystems. Considering a site's current situation and relevant requirements and standards, risk assessment process is not only capable of recognizing the probable causes of accidents but also of estimating the probability of occurrence and the severity of consequences. In this way, results of risk assessment would help managers and decision makers create and employ proper control methods. Most of the represented models for risk assessment of oil spills are achieved on the basis of accurate data bases and analysis of historical data, but unfortunately such data bases are not accessible in most of the zones, especially in developing countries, or else they are newly established and not applicable yet. This issue reveals the necessity of using Expert Systems and Fuzzy Set Theory. By using such systems it will be possible to formulize the specialty and experience of several experts and specialists who have been working in petroliferous areas for several years. On the other hand, in developing countries often the damages to environment and environmental resources are not considered as risk assessment priorities and they are approximately under-estimated. For this reason, the proposed model in this research is specially addressing the environmental risk of oil spills from stationary sources in offshore zones.