Modified lipids from LDL in the blood during mid-life increase blood brain barrier permeability

Low density lipoprotein levels (LDL) are consistently elevated in cardiovascular disease. It has been suggested that those with high circulating LDL levels in mid-life may be susceptible to develop neurodegenerative diseases in later life. In the circulation, high levels of LDL are associated with increased oxidative modification (oxLDL) and nitration. We have investigated the hypothesis that disruption of blood brain barrier function by oxLDL and their lipids may increase risk of neurodegeneration in later life and that statin intervention in mid-life can mitigate the neurodegenerative effects of hyperlipidaemia. Blood from statin-naïve, normo- and hyperlipidaemic subjects (n=10/group) was collected at baseline. Hyperlipidaemic subjects received statin-intervention whereas normolipidaemic subjects did not prior to a second blood sampling, taken after 3 months. The intervention will be completed in June 2013. Plasma was separated by centrifugation (200g, 30min) and LDL was isolated by potassium bromide density gradient ultracentrifugation. Total homocysteine, LDL cholesterol, 8-isoprostane F2α levels were measured in plasma using commercial kits. LDL were analysed by agarose gel electrophoresis. LDL-lipids were extracted by partitioning in 1:1 chloroform:methanol (v/v) and conjugated to fatty acid free-BSA in serum-free EGM-2 medium (4hrs, 370C) for co-culture with human microvascular endothelial cells (HMVEC). HMVEC were maintained on polycarbonate inserts for two weeks to create a microvascular barrier. Change in barrier permeability was measured by trans-endothelial electrical resistance (TER), FITC-dextran permeability and immunohistochemistry. HMVEC glutathione (GSH) levels were measured after 2 hours by GSH-glo assay. LDL isolated from statin-naïve hyperlipidaemic subjects had higher mobility by agarose gel electrophoresis (Rf;0.53±0.06) and plasma 8-isoprostane F2α (43.5±8.42 pg/ml) compared to control subjects (0.46±0.05 and 24.2±5.37 pg/ml; p<0.05). Compared to HMVEC treatment with the LDL-lipids (5μM) from normolipidaemic subjects, LDL-lipids from hyperlipidaemic subjects increased barrier permeability (103.4±12.5 Ωcm2 v 66.7±7.3 Ωcm2,P<0.01) and decreased GSH (18.5 nmol/mg v 12.3 nmol/mg; untreated cells 26.2±3.6 nmol/mg).

Rich and poor, white and black, free and slave: The social history of Cuba's tobacco farmers, 1763--1817

Tobacco was of primary importance to Spain, and its impact on Cuba's economy and society was greater than just the numbers of farms, workers, or production, demonstrated by the Spanish crown's outlay of monies for capital assets, bureaucrats' salaries, and payments to farmers for their crop. This study is a micro- and macro-level study of rural life in colonial Cuba and the interconnected relationships among society, agricultural production, state control, and the island's economic development. ^ By placing Cuba's tobacco farmers at the forefront of this social history, this work revisits and offers alternatives to two prevailing historiographical views of rural Cuba from 1763 (the year Havana returned to Spanish control following the Seven Years' War) to 1817 (the final year of the 100-year royal monopoly on Cuban tobacco). Firstly, it argues against the primacy of sugar over other agricultural crops, a view that has shaped decades of scholarship, and challenges the thesis which maintains the Cuban tobacco farmer was almost exclusively poor, white, and employed free labor, rather than slaves, in the production of their crop. ^ This study establishes the importance of tobacco as an agricultural product, and argues that Cuban tobacco growers were a heterogeneous group, revealing the role that its cultivation may have played in helping some slaves earn their freedom. ^

Relative basicities of free base porphyrins; understanding the role of macrocyclic distortion

Porphyrins have been the center of numerous investigations in different areas of chemistry, geochemistry, and the life sciences. In nature the conformation of the porphyrin macrocycle varies, depending on the function of its apoenzyme. It is believed that the conformation of the porphyrin ring is necessary for the enzyme to achieve its function and modify its reactivity. It is important to understand how the conformation of the porphyrin ring will influence its properties. ^ In synthetic porphyrins particular conformations and ring deformations can be achieved by peripheral substitution, metallation, core substitution, and core protonation among other alterations of the macrocycle. The macrocyclic distortions will affect the ring current, the ability of pyrroles to intramolecularly hydrogen bond and the relative basicity of each of the porphyrins. To understand these effects different theoretical models are used. The ground state structure of each of 19 free base porphyrins is determined using molecular mechanics (MM+) and semiempirical methods (PM3). The energetics of deformation of the macrocyclic core is calculated by carrying out single point energy calculations for the conformation achieved by each synthetic compound. Enthalpies of solution and enthalpies of protonation of 10 porphyrins with varying degrees of macrocyclic deformation and varying electron withdrawing groups in the periphery are determined using solution calorimetry. Using Hess's Law, the relative basicity of each of the different free base porphyrins is calculated. NMR results are described, including the determination of free energies of activation of ring tautomerization and hydrogen bonding for several compounds. It was found that in the absence of electronic effects, the greater macrocyclic deformation, the greater the basicity of the porphyrins. This basicity is attenuated by the presence of electron withdrawing groups and ability to of the macrocycle to intramolecularly hydrogen bond. ^

Relative basicities of free base porphyrins : understanding the role of macrocyclic distortion

Porphyrins have been the center of numerous investigations in different areas of chemistry, geochemistry, and the life sciences. In nature the conformation of the porphyrin macrocycle varies, depending on the function of its apoenzyme. It is believed that the conformation of the porphyrin ring is necessary for the enzyme to achieve its function and modify its reactivity. It is important to understand how the conformation of the porphyrin ring will influence its properties. In synthetic porphyrins particular conformations and ring deformations can be achieved by peripheral substitution, metallation, core substitution, and core protonation among other alterations of the macrocycle. The macrocyclic distortions will affect the ring current, the ability of pyrroles to intramolecularly hydrogen bond and the relative basicity of each of the porphyrins. To understand these effects different theoretical models are used. The ground state structure of each of 19 free base porphyrins is determined using molecular mechanics (MM+) and semiempirical methods (PM3). The energetics of deformation of the macrocyclic core is calculated by carrying out single point energy calculations for the conformation achieved by each synthetic compound. Enthalpies of solution and enthalpies of protonation of 10 porphyrins with varying degrees of macrocyclic deformation and varying electron withdrawing groups in the periphery are determined using solution calorimetry. Using Hess's Law, the relative basicity of each of the different free base porphyrins is calculated. NMR results are described, including the determination of free energies of activation of ring tautomerization and hydrogen bonding for several compounds. It was found that in the absence of electronic effects, the greater macrocyclic deformation, the greater the basicity of the porphyrins. This basicity is attenuated by the presence of electron withdrawing groups and ability to of the macrocycle to intramolecularly hydrogen bond.

Castles in the air: the life, times and influence of the Reverend Moses Harvey (1820-1901).

The period from 1874 to 1901 was a time of significant transition in the economic and political life of Newfoundland. Twenty years into responsible government and with Confederation on the backburner, the colony’s politicians turned their attention to economic diversification, landward development and carving out the island’s place in the British Empire. The period saw both economic prosperity and retrenchment; the construction of a trans-insular railway; the adoption of policies to foster agriculture, forestry, manufacturing and mining; and diplomatic efforts to resolve France’s outstanding claims on the northwest coast of the island. At the same time, the government made an attempt to intervene directly in its primary industry, the fisheries. It created a Fisheries Commission in 1889 that recommended conservation measures and artificial propagation as ways to restore the health of some of the island’s fish stocks. They also proposed new methods of curing, packaging and marketing Newfoundland’s cod, as well as a complete overhaul of the truck system. A major player in both the public and private debates surrounding all of these subjects was the Reverend Moses Harvey. Along with being minister of the Free Church of Scotland in St. John’s, Harvey was one of Newfoundland’s most active promoters in the late nineteenth century. He served as the media mouthpiece for both Prime Minister William Whiteway and Prime Minister Robert Thorburn; editing the Evening Mercury – the official organ of the Liberal Party and then the Reform Party – from 1882 to 1883 and 1885 until 1890. As well, Harvey wrote regular columns on Newfoundland issues for newspapers in London, New York, Boston, Montreal, Toronto, and Halifax. He also produced numerous books, articles, encyclopedia entries, and travel guides outlining the island’s attractions and its vast economic potential. In short, Harvey made a significant contribution in shaping the way residents and the outside world viewed Newfoundland during this period. This thesis examines late nineteenth-century Newfoundland through the writing of Moses Harvey. The biographical approach offers a fuller, more nuanced account of some of the major historical themes of the period including the politics of progress, opening up the interior, railway construction and attitudes toward the fisheries. It also provides an insider’s prospective on what led to some of the major political decisions, policy positions or compromises taken by the Whiteway and Thorburn governments. Finally, a more detailed review of Harvey’s work exposes the practical and political differences that he had with people like D.W. Prowse and Bishop Michael Howley. While these so-called “boomers” in Newfoundland’s historiography agreed on broad themes, they parted ways over what should be done with the fisheries and how best to channel the colony’s growing sense of nationalism.

Female employment from the household. Towards a comprehensive analysis of work-life articulation

Research on women’s employment has proliferated over recent decades, often under a perspective that conceptualizes female labour market activity as independent of male presences and absences in the productive and reproductive spheres. In the face of these approaches, the article argues the need to focus on the couple as the unit of analysis of work-life articulation. After referring to the main theoretical arguments that, from a gender perspective within labour studies, have pointed out the relevance of placing the household as the central space for the analysis of the sexual division of labour, the article reviews different empirical contributions that have incorporated such perspective in the international literature. Next, the state of the art in the Spanish literature is presented, before arguing the desirability of applying such framework of analysis to the study of employment and care work in Spanish households, which are at present undergoing major transformations.

Impact of oral diseases and disorders on oral health-related quality of life of preschool children

BACKGROUND The presence of oral diseases and disorders can produce an impact on the quality of life of preschool children and their parents, affecting their oral health and well-being. However, socioeconomic factors could confound this association, but it has not been yet tested at this age. OBJECTIVE To assess the impact of early childhood caries (ECC), traumatic dental injuries (TDI) and malocclusions on the oral health-related quality of life (OHRQoL) of children between 2 and 5 years of age adjusted by socioeconomic factors. METHODS Parents of 260 children answered the Early Childhood Oral Health Impact Scale (ECOHIS) (six domains) on their perception of the children's OHRQoL and socioeconomic conditions. Two calibrated dentists (κ>0.8) examined the severity of ECC according to dmft index, and children were categorized into: 0=caries free; 1-5=low severity; ≥6=high severity. TDI and malocclusions were examined according to Andreasen & Andreasen (1994) classification and for the presence or absence of three anterior malocclusion traits (AMT), respectively. OHRQoL was measured through ECOHIS domain and total scores, and poisson regression was used to associate the different factors with the outcome. RESULTS In each domain and overall ECOHIS scores, the severity of ECC showed a negative impact on OHRQoL (P<0.001). TDI and AMT did not show a negative impact on OHRQoL nor in each domain (P>0.05). The increase in the child's age, higher household crowding, lower family income and mother working out of home were significantly associated with OHRQoL (P<0.05). The multivariate adjusted model showed that the high severity of ECC (RR=3.81; 95% CI=2.66, 5.46; P<0.001) was associated with greater negative impact on OHRQoL, while high family income was a protective factor for OHRQoL (RR=0.93; 95% CI=0.87, 0.99; P<0.001). CONCLUSIONS The severity of ECC and a lower family income had a negative impact on the OHRQoL of preschool children and their parents.

Enhancing Quality of Life for People who are Blind or Low Vision Using Computing Technology

Thesis (Ph.D.)--University of Washington, 2016-08

Evolution of protein bound Maillard reaction end-products and free Amadori compounds in low lactose milk in presence of fructosamine oxidase I

Thermal treatments and storage influence milk quality, particularly in low lactose milk as the higher concentration of reducing sugars can lead to the increased formation of the Maillard reaction products (MRPs). The control of the Amadori products (APs) formation is the key step to mitigate the Maillard reaction (MR) in milk. The use of fructosamine oxidases, (Faox) provided promising results. In this paper, the effects of Faox I were evaluated by monitoring the concentration of free and bound MRPs in low lactose milk during shelf life. Results showed that the enzyme reduced the formation of protein-bound MRPs down to 79% after six days at 37 °C. Faox I lowered the glycation of almost all the free amino acids resulting effective on basic and polar amino acids. Data here reported corroborate previous findings on the potentiality of Faox enzymes in controlling the early stage of the MR in foods.

got your dairy today? : 10 tips to help you eat and drink more fat-free or low-fat dairy foods

The Dairy Group includes milk, yogurt, cheese, and fortified soymilk. They provide calcium, vitamin D, potassium, protein, and other nutrients needed for good health throughout life. Choices should be lowfat or fat-free—to cut calories and saturated fat. How much is needed? Older children, teens, and adults need 3 cups* a day, while children 4 to 8 years old need 2½ cups, and children 2 to 3 years old need 2 cups.

Health-related quality of life and determinant factors in celiac disease: a population-based analysis of adult patients in Spain

Background: Celiac disease (CD) has a negative impact on the health-related quality of life (HRQL) of affected patients. Although HRQL and its determinants have been examined in Spanish CD patients specifically recruited in hospital settings, these aspects of CD have not been assessed among the general Spanish population. Methods: An observational, cross-sectional study of a non-randomized, representative sample of adult celiac patients throughout all of Spain's Autonomous Regions. Subjects were recruited through celiac patient associations. A Spanish version of the self-administered Celiac Disease-Quality of Life (CD-QOL) questionnaire was used. Determinant factors of HRQL were assessed with the aid of multivariate analysis to control for confounding factors. Results: We analyzed the responses provided by 1,230 patients, 1,092 (89.2%) of whom were women. The overall mean value for the CD-QOL index was 56.3 ± 18.27 points. The dimension that obtained the most points was dysphoria, with 81.3 ± 19.56 points, followed by limitations with 52.3 ± 23.43 points; health problems, with 51.6 ± 26.08 points, and inadequate treatment, with 36.1 ± 21.18 points. Patient age and sex, along with time to diagnosis, and length of time on a gluten-free diet were all independent determinant factors of certain dimensions of HRQL: women aged 31 to 40 expressed poorer HRQL while time to diagnosis and length of time on a gluten-free diet were determinant factors for better HRQL scores. Conclusions: The HRQL level of adult Spanish celiac subjects is moderate, improving with the length of time patients remain on a gluten-free diet.

Using an end-of-life care pathway in acute stroke: a mixed methods study of decision-making and care experiences

Background: The evidence base on end-of-life care in acute stroke is limited, particularly with regard to recognising dying and related decision-making. There is also limited evidence to support the use of end-of-life care pathways (standardised care plans) for patients who are dying after stroke. Aim: This study aimed to explore the clinical decision-making involved in placing patients on an end-of-life care pathway, evaluate predictors of care pathway use, and investigate the role of families in decision-making. The study also aimed to examine experiences of end-of-life care pathway use for stroke patients, their relatives and the multi-disciplinary health care team. Methods: A mixed methods design was adopted. Data were collected in four Scottish acute stroke units. Case-notes were identified prospectively from 100 consecutive stroke deaths and reviewed. Multivariate analysis was performed on case-note data. Semi-structured interviews were conducted with 17 relatives of stroke decedents and 23 healthcare professionals, using a modified grounded theory approach to collect and analyse data. The VOICES survey tool was also administered to the bereaved relatives and data were analysed using descriptive statistics and thematic analysis of free-text responses. Results: Relatives often played an important role in influencing aspects of end-of-life care, including decisions to use an end-of-life care pathway. Some relatives experienced enduring distress with their perceived responsibility for care decisions. Relatives felt unprepared for and were distressed by prolonged dying processes, which were often associated with severe dysphagia. Pro-active information-giving by staff was reported as supportive by relatives. Healthcare professionals generally avoided discussing place of care with families. Decisions to use an end-of-life care pathway were not predicted by patients’ demographic characteristics; decisions were generally made in consultation with families and the extended health care team, and were made within regular working hours. Conclusion: Distressing stroke-related issues were more prominent in participants’ accounts than concerns with the end-of-life care pathway used. Relatives sometimes perceived themselves as responsible for important clinical decisions. Witnessing prolonged dying processes was difficult for healthcare professionals and families, particularly in relation to the management of persistent major swallowing difficulties.

The impact of household size on poverty: An analysis of various low-income townships in the Northern Free State region, South Africa

Poverty is a multi-dimensional socio-economic problem in most sub-Saharan African countries. The purpose of this study is to analyse the relationship between household size and poverty in low-income communities. The Northern Free State region in South Africa was selected as the study region. A sample of approximately 2 900 households was randomly selected within 12 poor communities in the region. A poverty line was calculated and 74% of all households were found to live below the poverty line. The Pearson’s chi-square test indicated a positive relationship between household size and poverty in eleven of the twelve low-income communities. Households below the poverty line presented larger households than those households above the poverty line. This finding is in contradiction with some findings in other African countries due to the fact that South Africa has higher levels of modernisation with less access to land for subsistence farming. Effective provision of basic needs, community facilities and access to assets such as land could assist poor households with better quality of life. Poor households also need to be granted access to economic opportunities, while also receiving adult education regarding financial management and reproductive health.

Use of inert gas-enriched atmospheres and post-packaging irradiation in shelf-life extension of watercress

Watercress (Nasturtium officinale R. Br.) is a semi-aquatic plant of the Brassicaceae family highly appreciated in the Mediterranean cuisine. It features sharp, peppery and slightly tangy taste and contains health-promoting phytochemicals. Its consumption as a fresh-cut product has increased in recent years, as well as the global market of minimally processed vegetables. This demand is driven by the growing interest in the role of food in promoting the human health and wellbeing and to meet consumer needs for fresh-like and more convenient foods. Due to the reduced shelf-life of this plant, the suitability of inert gas-enriched atmospheres and ionizing irradiation for preserving visual, nutritional and functional quality attributes during cold storage was studied. Watercress samples were gathered in the Northeast region of Portugal, rinsed in tap water and a portion was immediately analyzed (non-stored control). The remaining fresh material was packaged in polyethylene bags under N2- and Ar-enriched atmospheres, conventional atmosphere (air) and vacuum (no atmosphere). Samples under conventional atmosphere were irradiated at 1, 2 and 5 kGy of gamma-rays (predicted doses) in a 60Co experimental chamber. A non-irradiated control followed all the experiment. Then, all packaged samples were stored at 4 ºC for 7 days. The studied quality parameters included the colour that was measured with a Konica Minolta colorimeter, and total soluble solids and pH determined in squeezed juice. The proximate composition (moisture, proteins, fat, ash, carbohydrates and energy) was evaluated using the AOA C procedures. Organic acids, free sugars, fatty acids and tocopherols were analyzed by chromatographic techniques. Samples were also evaluated for its DPPH• scavenging activity, reducing power, and lipid peroxidation inhibition capacity trough the inhibition of the β-carotene bleaching and thiobarbituric acid reactive substances (TBAR S) formation. Differences among treatments were analyzed using the one-way analysis of variance (ANO VA) and a linear discriminant analysis (LDA ) was used to evaluate the effects on the overall postharvest quality. After evaluating the effect on the individual quality parameters, the LDA revealed that the Ar-enriched atmosphere and the irradiation at 2 kGy were suitable processing choices for preserving the integrity of the non-stored control samples during cold storage. Thus, these non-thermal treatments were highlighted for shelf-life extension of fresh-cut watercress.

Applied evolution: An integrated approach to studying life history traits in response to drug selection

The use of chemical control measures to reduce the impact of parasite and pest species has frequently resulted in the development of resistance. Thus, resistance management has become a key concern in human and veterinary medicine, and in agricultural production. Although it is known that factors such as gene flow between susceptible and resistant populations, drug type, application methods, and costs of resistance can affect the rate of resistance evolution, less is known about the impacts of density-dependent eco-evolutionary processes that could be altered by drug-induced mortality. The overall aim of this thesis was to take an experimental evolution approach to assess how life history traits respond to drug selection, using a free-living dioecious worm (Caenorhabditis remanei) as a model. In Chapter 2, I defined the relationship between C. remanei survival and Ivermectin dose over a range of concentrations, in order to control the intensity of selection used in the selection experiment described in Chapter 4. The dose-response data were also used to appraise curve-fitting methods, using Akaike Information Criterion (AIC) model selection to compare a series of nonlinear models. The type of model fitted to the dose response data had a significant effect on the estimates of LD50 and LD99, suggesting that failure to fit an appropriate model could give misleading estimates of resistance status. In addition, simulated data were used to establish that a potential cost of resistance could be predicted by comparing survival at the upper asymptote of dose-response curves for resistant and susceptible populations, even when differences were as low as 4%. This approach to dose-response modeling ensures that the maximum amount of useful information relating to resistance is gathered in one study. In Chapter 3, I asked how simulations could be used to inform important design choices used in selection experiments. Specifically, I focused on the effects of both within- and between-line variation on estimated power, when detecting small, medium and large effect sizes. Using mixed-effect models on simulated data, I demonstrated that commonly used designs with realistic levels of variation could be underpowered for substantial effect sizes. Thus, use of simulation-based power analysis provides an effective way to avoid under or overpowering a study designs incorporating variation due to random effects. In Chapter 4, I 3 investigated how Ivermectin dosage and changes in population density affect the rate of resistance evolution. I exposed replicate lines of C. remanei to two doses of Ivermectin (high and low) to assess relative survival of lines selected in drug-treated environments compared to untreated controls over 10 generations. Additionally, I maintained lines where mortality was imposed randomly to control for differences in density between drug treatments and to distinguish between the evolutionary consequences of drug treatment versus ecological processes affected by changes in density-dependent feedback. Intriguingly, both drug-selected and random-mortality lines showed an increase in survivorship when challenged with Ivermectin; the magnitude of this increase varied with the intensity of selection and life-history stage. The results suggest that interactions between density-dependent processes and life history may mediate evolved changes in susceptibility to control measures, which could result in misleading conclusions about the evolution of heritable resistance following drug treatment. In Chapter 5, I investigated whether the apparent changes in drug susceptibility found in Chapter 4 were related to evolved changes in life-history of C. remanei populations after selection in drug-treated and random-mortality environments. Rapid passage of lines in the drug-free environment had no effect on the measured life-history traits. In the drug-free environment, adult size and fecundity of drug-selected lines increased compared to the controls but drug selection did not affect lifespan. In the treated environment, drug-selected lines showed increased lifespan and fecundity relative to controls. Adult size of randomly culled lines responded in a similar way to drug-selected lines in the drug-free environment, but no change in fecundity or lifespan was observed in either environment. The results suggest that life histories of nematodes can respond to selection as a result of the application of control measures. Failure to take these responses into account when applying control measures could result in adverse outcomes, such as larger and more fecund parasites, as well as over-estimation of the development of genetically controlled resistance. In conclusion, my thesis shows that there may be a complex relationship between drug selection, density-dependent regulatory processes and life history of populations challenged with control measures. This relationship could have implications for how resistance is monitored and managed if life histories of parasitic species show such eco-evolutionary responses to drug application.