Atrioventricular pacemaker. Incidence and causes of reprogramming in long-term follow-up

OBJECTIVE: To assess the incidence of problems requiring reprogramming of atrioventricular pacemakers in a long-term follow-up, and also the causes for this procedure. METHODS: During the period from May '98 to December '99, 657 patients were retrospectively studied, An actuarial curve for the event reprogramming of the stimulation mode was drawn. RESULTS: The follow-up period ranged from 12 to 178 months (mean = 81 months). Eighty-two (12.4%) patients underwent reprogramming of the stimulation mode as follows: 63 (9.5%) changed to VVI,(R/C); 10 (1.5%) changed to DVI,C; 6 (0.9%) changed to VDD,C; and 3 (0.5%) changed to DOO. The causes for the reprogramming were as follows: arrhythmia conducted by the pacemaker in 39 (37.6%) patients; loss of atrial sensitivity or capture, or both, in 39 (38.6%) patients; and microfracture of atrial electrode in 5 (4.9%) patients. The stimulation mode reprogramming free probability after 15 years was 58%. CONCLUSION: In a long-term follow-up, the atrioventricular pacemaker provided a low incidence of complications, a high probability of permanence in the DDD,C mode, and the most common cause of reprogramming was arrhythmia conducted by the pacemaker.

Toxicity induced by a metal mixture (Cd, Pb and Zn) in the yeast Pichia kudriavzevii: The role of oxidative stress

The present work aims to contribute for the elucidation of the role of oxidative stress in the toxicity associated with the exposure of Pichia kudriavzevii to multi-metals (Cd, Pb and Zn). Cells of the non-conventional yeast P. kudriavzevii exposed for 6 h to the action of multi-metals accumulated intracellular reactive oxygen species (ROS), evaluated through the oxidation of the probe 2,7-dichlorodihydrofluorescein diacetate. A progressive loss of membrane integrity (monitored using propidium iodide) was observed in multi-metal-treated cells. The triggering of intracellular ROS accumulation preceded the loss of membrane integrity. These results suggest that the disruption of membrane integrity can be attributed to the oxidative stress. The exposure of yeast cells to single metal showed that, under the concentrations tested, Pb was the metal responsible for the induction of the oxidative stress. Yeast cells coexposed to an antioxidant (ascorbic acid) and multi-metals did not accumulate intracellular ROS, but loss proliferation capacity. Together, the data obtained indicated that intracellular ROS accumulation contributed to metal toxicity, namely for the disruption of membrane integrity of the yeast P. kudriavzevii. It was proposed that Pb toxicity (the metal responsible for the toxic symptoms under the conditions tested) result from the combination of an ionic mechanism and the intracellular ROS accumulation.

Production of whey protein-based aggregates under ohmic heating

Formation of whey protein isolate protein aggregates under the influence of moderate electric fields upon ohmic heating (OH) has been monitored through evaluation of molecular protein unfolding, loss of its solubility, and aggregation. To shed more light on the microstructure of the protein aggregates produced by OH, samples were assayed by transmission electron microscopy (TEM). Results show that during early steps of an OH thermal treatment, aggregation of whey proteins can be reduced with a concomitant reduction of the heating chargeby reducing the come-up time (CUT) needed to reach a target temperatureand increase of the electric field applied (from 6 to 12 V cm1). Exposure of reactive free thiol groups involved in molecular unfolding of -lactoglobulin (-lg) can be reduced from 10 to 20 %, when a CUT of 10 s is combined with an electric field of 12 V cm1. Kinetic and multivariate analysis evidenced that the presence of an electric field during heating contributes to a change in the amplitude of aggregation, as well as in the shape of the produced aggregates. TEM discloses the appearance of small fibrillar aggregates upon the influence of OH, which have recognized potential in the functionalization of food protein networks. This study demonstrated that OH technology can be used to tailor denaturation and aggregation behavior of whey proteins due to the presence of a constant electric field together with the ability to provide a very fast heating, thus overcoming heat transfer limitations that naturally occur during conventional thermal treatments.

Neonate Aortic Stenosis: Importance of Myocardial Perfusion in Prognosis

OBJECTIVE: To analyze our experience with percutaneous aortic balloon valvuloplasty in newborn infants with aortic stenosis, emphasizing the extraordinary importance of myocardial perfusion.METHODS: Over a 10-year-period, 21 neonates underwent percutaneous aortic balloon valvuloplasty. Age ranged from 2 to 27 days, weight ranged from 2.2 to 4.1 kg and 19 were males. All patients presented with congestive heart failure that could not be treated clinically. The onset of symptoms in the first week of life occurred in 9 patients considered as having critical aortic stenosis. Severe aortic stenosis occurred in 12 patients with the onset of symptoms in the second week of life.RESULTS: Mortality reached 100% in the patients with critical aortic stenosis. The procedure was considered effective in the 12 patients with severe aortic stenosis. Vascular complications included the loss of pulse in 12 patients and rupture of the femoral artery in 2 patients. Cardiac complications included acute aortic regurgitation in 2 patients and myocardial perforation in one. In an 8.2±1.3-year follow-up, 5 of the 12 patients died (2 patients due to septicemia and 3 patients due to congestive heart failure). Five of the other 7 patients underwent a new procedure and 2 required surgery.CONCLUSION: Percutaneous aortic valvuloplasty in neonates is not an effective procedure in the 1st week of life, because at this age the common presentation is cardiogenic shock. It is possible that, in those patients with critical aortic stenosis, dilation of the aortic valve during fetal life may change the prognosis of its clinical outcome.

Caracterización funcional de zeb1 en células en diferenciación y metastásicas. Functional characterization of zeb1 in differentiating and metastatic cells

IDENTIFICACIÓN ZEB1 (Zinc Finger E-box Binding Homeobox) es un factor de transcripción funcionalmente asociado con la diferenciación de células como miocitos, neuronas, células de sostén y linfocitos T, además de estar involucrado en la Transición Epitelial-Mesenquimatosa (EMT) de los tumores sólidos epiteliales. Aún no se ha revelado en profundidad la participación de ZEB1 en los procesos de proliferación y diferenciación en los que participa. Estamos interesados en los mecanismos de regulación de ZEB1 y los factores que intervienen en los procesos de diferenciación y transformación celular. HIPÓTESIS 1. Las vías de señalamiento regulan el estado de fosforilación y la función de ZEB1 en la célula normal, el cual se desregularía en la célula neoplásica llevando a cambios en la función normal de ZEB1 y consecuentemente a metástasis. 2. IGF-1 es la señal que, en asociación con el supresor de tumores CCN6, juega un rol causal en la regulación de ZEB1 y esto a su vez en la metástasis del cáncer de mama. OBJETIVO GENERAL: establecer el rol funcional de ZEB1, su interrelación con otros factores y su regulación en los procesos de diferenciación y transformación celular. OBJETIVOS ESPECIFICOS (incluye Materiales y Métodos) 1. Estudiar la participación de vías de señalización sobre la función biológica de ZEB1 en células normales y neoplásicas. Analizaremos la participación de señales intracelulares en la fosforilación de ZEB1 por experimentos de ganancia/pérdida de función de la vía (por uso de inhibidores farmacologicos, mutantes silenciadoras y siRNAs), lo cual sera evaluado en EMSAs, ChIP, transfecciones, inmunofluoresc, etc. 2. Estudiar el rol de IGF-1 y CCN6 sobre la expresión y el estado de fosforilación de ZEB1 en tumores mamarios benignos, no invasivos e invasivos y metastatizantes. A) Se estudiará la expresión y localización subcelular de ZEB1 en líneas celulares de cáncer mamario y en xenotransplantes de ratón con variada expresión de CCN6. B) Investigar la relevancia de la fosforilación de ZEB1 mediada por IGF-1 en el EMT por experimentos con ganancia/pérdida de función. RESULTADOS ESPERADOS Esperamos poder delinear la/s vía/s de señalización intracelular que fosforilan ZEB1 y así conocer sobre la regulación del mismo. Podremos establecer algunas bases para entender la biología básica del cáncer de mama e identificar blancos terapéuticos. IMPORTANCIA Un amplio conocimiento de los factores de transcripción y sus vías de señalamiento es necesario para el desarrollo tanto de pruebas diagnósticas como para la identificación de nuevos blancos terapéuticos para neoplasias. De modo que resulta de gran importancia clínica determinar el rol de ZEB1, sus proteínas y vías reguladoras en el proceso de oncogénesis. El desarrollo del proyecto prevé la formación de dos tesistas. Se continuaran colaboraciones con dos grupos extranjeros y se iniciara una tercera. ZEB1 (Zinc Finger E-box Binding Homeobox) is a transcription factor involved in cell differentiation and Epithelial Mesenchymal Transition (EMT) of epithelial tumors. We are interested in the study of mechanisms of regulation (pre and post transcriptional). S.A.1. To investigate post translational mechanisms of ZEB1 regulation in normal and cancer cells. We will analyze the involvement of intracellular signals in phosphorylation of ZEB1 by gain- and lost-of-function experiments. S.A.2. A) To determine the role of IGF-1 signaling and CCN6 in regulating the expression of hypo- and hyperphosphorylated forms of ZEB1 in benign and malignant breast cell lines and in xenograft mouse models by overexpressing and inhibiting CCN6 in breast cancer cells. B) To investigate the relevance of CCN6-mediated ZEB1 phosphorylation to EMT, breast cancer invasion and metastasis. The role of CCN6 on ZEB1 phosphorylation and regulation of E-cadherin, induction of EMT, invasion and metastasis of breast cells will be investigated using gain- and loss-of-function experiments.

A comparative study of the physical, chemical and microbiological status of soils, as influenced by conventional and reduced tillage

Historically, shifts to reduced and no-tillage management for production of crops were fostered by needs to decrease soil erosion and loss of organic matter, reduce fuel and labour costs and conserve soil water, as compared with conventional fallow tillage management. Recent interest in maintaining soil quality has been stimulated by a renewed awareness of the importance of soil condition to both the sustainability of agricultural production systems and environmental quality (Doran and Parkin, 1996). The aim of this project was to determine the impact on the physical, chemical and microbiological status of the soil of conventional and reduced tillage. It has been suggested that the reduced soil disturbance associated with the tine cultivator improves soil structure, increases nutrient content in the top 10cm of soil, increases microbial activity and improves physical characteristics. From this study it was determined that the environmental benefits linked to reduced tillage in literature, did not develop in the first two years of this programmes implementation. The results of this study determined that soil nutrients did not increase in concentration in the top 10 cm of soil under reduced cultivation. The only exception was exchangeable potassium. As potassium is not a mobile nutrient its movement is dependent on soil disturbance, therefore under reduced cultivation its concentration was allowed to accumulate in the upper horizon of the soil profile. Microbial activity was greater in the conventionally tilled treatments, as determined by total aerobic bacterial numbers. This could be due to the increased rates of soil aeration in this treatment. Numbers of aerobic bacteria were greater in the conventional tillage treatments at both incubation temperatures of 22 and 32° C. The physical characteristics of the soil determined, indicate that below the depth of soil cultivation, cone penetration resistance increases. Therefore the reduced cultivation treatments would be more prone to soil compaction, higher in the soil profile.

The spatial analysis and speciation of uranium and thorium series radionuclides in the soil of the Cronamuck Valley, County Donegal, Ireland

This thesis details the findings of a study into the spatial distribution and speciation of 238U, 226Ra and 228Ra in the soils of the Cronamuck valley, County Donegal . The region lies on the north-eastern edge of the Barnesmore granite and has been the subject of uranium prospecting efforts in the past. The results of the project provide information on the practicability of geostatistical techniques as a means of estimating the spatial distribution of natural radionuclides and provide insight into the behaviour of these nuclides and their modes of occurrence and enrichment in an upland bog environment. The results of the geostatistical survey conducted on the area indicate that the primary control over the levels of the studied nuclides in the soil of the valley is the underlying geology. Isopleth maps of nuclide levels in the valley indicate a predominance of elevated nuclide levels in the samples drawn from the granite region, statistical analysis of the data indicating that levels of the nuclides in samples drawn from the granite are greater than levels drawn from the non-granite region by up to a factor of 4.6 for 238U and 4.9 for 226Ra. Redistribution of the nuclides occurs via drainage systems within the valley, this process being responsible for transport of nuclides away from the granite region resulting in enrichment of nuclides in soils not underlain by the granite. Distribution of the nuclides within the valley is erratic, the effect of drainage f lows on the nuclides resulting in localized enriched areas within the valley. Speciation of the nuclides within one of the enriched areas encountered in the study indicates that enrichment is as a result of saturation of the soil with drainage water containing trace amounts of radionuclides. 238U is primarily held within the labile fractions (exchangeable cat ions + easily oxidisable organics + amorphous iron oxides ) of the soil , 226Ra being associated with the non- labile fractions, most probably the resistant organic material. 228Ra displays a significant occurrence in both the labile and non- labile fractions. The ability of the soil to retain uranium appears to be affected largely by the redox status of the soil, samples drawn from oxidizing environments tending to have little or no uranium in the easily oxidisable and amorphous iron oxide fractions. This loss of uranium from oxidised soil samples is responsible for the elevated 226Ra /238U disequilibrium encountered in the enriched areas of the valley. Analysis of the data indicates that samples displaying elevated 226Ra/238U ratios also exhibit elevated 228Ra/238U ratios indicating a loss of uranium from the samples as opposed to an enrichment of 226Ra.

Evaluation of fish pots as a feasible fishing method in Irish waters, with specific reference to the physiological effects of common and alternate pots on the lesser spotted dogfish (Scyliorhinus canicula).

Finfish pots have emerged as a “responsible” gear, when used in combination with conservational and technical measures to sustain fisheries. Previous trials in Irish waters have offered no published reported data and so three designs tested in the current study provide new information on this gear. The most successful traps in terms of fish catch were rigid steel framed rectangular pots used to target Conger eel. Although commercial yield was low (0.2 per trap haul), potential existed for a viable pot fishery. Deployment and storage of Norwegian floating pots was conducted with relative ease but performance in the water was poor resulting in loss of gear. Catch returns were notable even though effort was restricted as mega-faunal by-catch was a problem, which lead to ending this trial. From these initial trials it was evident that catch rates were low compared to established Norwegian fisheries (3.6 cod per pot), which resulted in the utilisation of pots, already established in the crustacean fishery, to find species readily accessible to pot capture. Although fished and designed differently, these gears provided an opportunity to establish the benefits of pot fishing to fish quality and to determine the effects on by-catch. The fishing effects of three catching methods (pots, angling and trawl) and the effects of air exposure on the physiological status of a common by-catch, the lesser spotted dogfish Scyliorhinus canícula (L.) were examined using a range of physiological biomarkers (plasma catecholamine, glucose, lactate, muscle pH and muscle lactate). Physiological responses of fish to an emersion stress regime resulted in a significant metabolic disturbance in groups, but may not have weakened the overall health of these fish, as signified in the revival of some metabolites. Plasma glucose and lactate concentrations did not however recovery to baseline levels indicating that to achieve an accurate profile, responses should be determined by a suite of biomarkers. Responses did not demonstrate that samples from the pots were significantly less stressed than for the other two methods; angling and trawling, which are in contrast to many other studies. Employment of finfish potting therefore in Irish waters needs further consideration before further promotion as a more responsible method to supplement or replace established techniques.

The concept of risk management in the renewable sector.

This study explores the perception of risk and the level of risk management implementation in the renewable sector. Risk management is emerging as a key issue due to the loss of confidence amongst banks, causing the attainment of financing to be difficult over the next few years. To attract financing, there is a fundamental requirement to manage risk in a way that minimizes the probability of a negative financial impact on the project. Miller and Lessard (2001) argue that successful projects are not selected but shaped with risk resolution in mind. Rather than evaluating projects at the outset based on projections of the full set of benefits, costs and risks over their lifetime, successful developers start with project ideas that have the potential of becoming viable. Therefore, this study bridges the gap that exists within the renewable sector in relation to risk management literature. This study succeeds through a detailed comparative case study analysis where two developers and two financiers were questioned through qualitative semi-structured interviews on the concept of risk management and its level implementation within the industry. It is believed that the growth in financed renewable energy projects depends on the adequate design and implementation of risk management to mitigate inherent project risks. However, this study revealed that are certain types of developers in existence within the renewable sector, which underestimate the magnitude of risk and view the development of projects as a ‘money racket’. Therefore, it can be concluded that perception of risk will also differ, causing risk and uncertainty to vary from project to project, resulting in investment reluctance to be associated with certain projects. The study originality lies in how it demonstrates to developers the concept of risk management, outlining the simplicity and benefits of implementing it in project development. Finally, this study contributes to the knowledge by enhancing the awareness and understanding of the presence and nature of risk in a RE project environment.

Sex ratio and morphological characteristics of rufous gnateaters, Conopophaga lineata (Aves, Passeriformes) in Atlantic forest fragments

Unequal sex ratios lead to the loss of genetic variability, decreasing the viability of populations in the long term. Anthropogenic activities often disturb the natural habitats and can cause alterations in sex ratio and morphological characteristics of several species. Forest fragmentation is a major conservation concern, so that understanding its effects in natural populations is essential. In this study, we evaluated the sex ratio and the morphological characteristics of Rufous Gnateaters (Conopophaga lineata (Wied, 1831)) in small and large forest fragments in Minas Gerais, Brazil. Birds (n = 89) were sexed by plumage characteristics and molecular markers. The molecular analysis showed that plumage is not a totally reliable method for sexing Rufous Gnateaters. We observed that sex ratio did not differ between large and small forest fragments, but birds in small fragments had larger wings and tarsus. Wing and tarsus changes may affect the movement ability of individuals within and among forest fragments. In conclusion, Rufous Gnateaters have been able to survive in both small and large Atlantic rain forest fragments without altering their sex ratio, but morphological changes can be prejudicial to their long term survival.

Diversity and structure of microcrustacean assemblages (Cladocera and Copepoda) and limnological variability in perennial and intermittent pools in a semi-arid region, Bahia, Brazil

Temporary wetlands undergo recurrent drought due to the scarcity of water, which disrupts the hydrological connectivity with adjacent aquatic systems. However, some environments retain water for longer periods, allowing greater persistence of the community. The current study evaluated differences in the microcrustacean assemblages and limnological variability between perennial and intermittent pools in a semi-arid region of Brazil. The abiotic features (water temperature, pH, total alkalinity, electrical conductivity and depth) of intermittent pools were affected more than perennial pools due to loss of water volume. This may have contributed to a higher average richness and diversity index in some intermittent pools and differences in the structure of the assemblages. The lowest species richness and diversity were recorded where physical factors, such as a large quantity of suspended solids and variability in the electrical conductivity of the water and pH, make the environment unsuitable for these organisms. These results suggest that community development in intermittent pools is interrupted by the dry season; when the water returns, due to rainfall or rising groundwater, each pond undergoes a different process of colonization. In these circumstances, the biological importance of temporary aquatic environments is clear, since such pools provide shelters and have an important role in the maintenance of the regional diversity of aquatic environments.

Features of reproduction in laboratory-reared Aedes fluviatilis (Lutz, 1904) (Diptera: Culicidae)

Observations were made on 100 female Aedes fluviatilis (Lutz) maintained individually from the first blood meal onwards and allowed one blood meal during each oviposition cycle, 5% dextrose solution been supplied throughout life. The average length of live was 49.9 ± 17.8 days; the logarithm of the mortality rate increased proportionately to physiological age. The insects took an average of 7.3 ± 3.2 blood meals and produced a mean of 7.9 ± 3.7 clutches of eggs. There was a progressive decrease, proportional to advancing physiological age, in the mean numbers of eggs laid in successive oviposition cycles, in the intervals between blood feeding oviposition, and in the numbers of larvae that hatched. Delayed oviposition, transient sterility and a total loss of fertility were also recorded.

Bioequivalence of meat products treated with high pressure processing

The effects of high pressure on the composition of food products have not been evaluated extensively. Since, it is necessary to take in consideration the possible effects in basis to the changes induced in the bio molecules by the application of high pressures. The main effect on protein is the denaturation, because the covalent bonds are not affected; however hydrogen bonding, hydrophobic and intermolecular interactions are modified or destroyed. 1 High pressure can modify the activity of some enzymes. If this is done the proteolysis and lipolysis could be more or less intense and the content of free amino acids and fatty acids will be different. This could be related to the bioavailability of these compounds. Low pressures (100 MPa) have been shown to activate some enzymes (monomeric enzymes). Higher pressures induce loss of the enzyme activity. However some enzymes are very stable (ex. Lipase ~ 600 - 1000 MPa). Lipoxygenase is less stable, and there is little information about the effects on antioxidant enzymes. Other important issue is the influence of high pressure on oxidation susceptibility. This could modify the composition of lipids if the degree of the oxidation would have been higher or lower than in the traditional product. Pressure produces the damage of cell membranes favouring the contact between substrates and enzymes, exposure to oxidation of membrane fatty acids and loos of the efficiency of vitamin E. These effects can also affect to protein oxidation. In this study different compounds were analysed to establish the differences between non-treated and high-pressure treated products.

Extracorporeal membrane oxygenation support after heart explantation: a proposal on how to deal with hyperacute rejection of heart transplant

Purpose: In extreme situations, such as hyperacute rejection of heart transplant or major bleeding per-operating complications, an urgent heart explantation might be the only means of survival. The aim of this experimental study was to improve the surgical technique and the hemodynamics of an Extracorporeal Membrane Oxygenation (ECMO) support through a peripheral vascular access in an acardia model. Methods: An ECMO support was established in 7 bovine experiments (59±6.1 kg) by the transjugular insertion to the caval axis of a self-expanded cannula, with return through a carotid artery. After baseline measurements of pump flow and arterial and central venous pressure, ventricular fibrillation was induced (B), the great arteries were clamped, the heart was excised and right and left atria remnants, containing the pulmonary veins, were sutured together leaving an atrial septal defect (ASD) over the cannula in the caval axis. Measurements were taken with the pulmonary artery (PA) clamped (C) and anastomosed with the caval axis (D). Regular arterial and central venous blood gases tests were performed. The ANOVA test for repeated measures was used to test the null hypothesis and a Bonferroni t method for assessing the significance in the between groups pairwise comparison of mean pump flow. Results: Initial pump flow (A) was 4.3±0.6 L/min dropping to 2.8±0.7 L/min (P B-A= 0.003) 10 minutes after induction of ventricular fibrillation (B). After cardiectomy, with the pulmonary artery clamped (C) it augmented not significantly to 3.5±0.8 L/min (P C-B= 0.33, P C-A= 0.029). Finally, PA anastomosis to the caval axis was followed by an almost to baseline pump flow augmentation (4.1±0.7 L/min, P D-B= 0.009, P D-C= 0.006, P D-A= 0.597), permitting a full ECMO support in acardia by a peripheral vascular access. Conclusions: ECMO support in acardia is feasible, providing new opportunities in situations where heart must urgently be explanted, as in hyperacute rejection of heart transplant. Adequate drainage of pulmonary circulation is pivotal in order to avoid pulmonary congestion and loss of volume from the normal right to left shunt of bronchial vessels. Furthermore, the PA anastomosis to the caval axis not only improves pump flow but it also permits an ECMO support by a peripheral vascular access and the closure of the chest.

Mutational analysis of the highly conserved arginine within the Glu/Asp-Arg-Tyr motif of the alpha(1b)-adrenergic receptor: effects on receptor isomerization and activation.

We have suggested previously that both the negatively and positively charged residues of the highly conserved Glu/Asp-Arg-Tyr (E/DRY) motif play an important role in the activation process of the alpha(1b)-adreneric receptor (AR). In this study, R143 of the E/DRY sequence in the alpha(1b)-AR was mutated into several amino acids (Lys, His, Glu, Asp, Ala, Asn, and Ile). The charge-conserving mutation of R143 into lysine not only preserved the maximal agonist-induced response of the alpha(1b)-AR, but it also conferred high degree of constitutive activity to the receptor. Both basal and agonist-induced phosphorylation levels were significantly increased for the R143K mutant compared with those of the wild-type receptor. Other substitutions of R143 resulted in receptor mutants with either a small increase in constitutive activity (R143H and R143D), impairment (R143H, R143D), or complete loss of receptor-mediated response (R143E, R143A, R143N, R143I). The R413E mutant displayed a small, but significant increase in basal phosphorylation despite being severely impaired in receptor-mediated response. Interestingly, all the arginine mutants displayed increased affinity for agonist binding compared with the wild-type alpha(1b)-AR. A correlation was found between the extent of the affinity shift and the intrinsic activity of the agonists. The analysis of the receptor mutants using the allosteric ternary complex model in conjunction with the results of molecular dynamics simulations on the receptor models support the hypothesis that mutations of R143 can drive the isomerization of the alpha(1b)-AR into different states, highlighting the crucial role of this residue in the activation process of the receptor.