Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS: Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS: In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS: Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS: Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Post-market environmental monitoring of Bt maize in Spain: Non-target effects of varieties derived from the event MON810 on predatory fauna

The Spanish Government has established post-market environmental monitoring (PMEM) as mandatory for genetically modified (GM) crop varieties cultivated in Spain. In order to comply with this regulation, effects of Bt maize varieties derived from the event MON810 on the predatory fauna were monitored for two years in northeast and central Spain. The study was carried out with a randomized block design in maize fields of 3-4 ha on which the abundance of plant-dwelling predators and the activity-density of soil-dwelling predators in Bt vs. non-Bt near-isogenic varieties were compared. To this end, the plots were sampled by visual inspection of a certain number of plants and pitfall traps 6 or 7 times throughout two seasons. No significant differences in predator densities on plants were found between Bt and non-Bt varieties. In the pitfall traps, significant differences between the two types of maize were found only in Staphylinidae, in which trap catches in non-Bt maize were higher than in Bt maize in central Spain. Based on the statistical power of the assays, surrogate arthropods for PMEM purposes are proposed; Orius spp. and Araneae for visual sampling and Carabidae, Araneae, and Staphylinidae for pitfall trapping. The other predator groups recorded in the study, Nabis sp. and Coccinellidae in visual sampling and Dermaptera in pitfall trapping, gave very poor power results. To help to establish a standardized protocol for PMEM of genetically modified crops, the effect-detecting capacity with a power of 0.8 of each predator group is given.

BDNF promoter I methylation correlates between post-mortem human peripheral and brain tissues.

Several psychiatric disorders have been associated with CpG methylation changes in CG rich promoters of the brain-derived neurotrophic factor (BDNF) mainly by extracting DNA from peripheral blood cells. Whether changes in peripheral DNA methylation can be used as a proxy for brain-specific alterations remains an open question. In this study we aimed to compare DNA methylation levels in BDNF promoter regions in human blood cells, muscle and brain regions using bisulfite-pyrosequencing. We found a significant correlation between the levels of BDNF promoter I methylation measured in quadriceps and vPFC tissues extracted from the same individuals (n = 98, Pearson, r = 0.48, p = 4.5 × 10(-7)). In the hippocampus, BDNF promoter I and IV methylation levels were strongly correlated (Pearson, n = 37, r = 0.74, p = 1.4 × 10(-7)). We found evidence for sex-dependent effect on BDNF promoter methylation levels in the various tissues and blood samples. Taken together, these data indicate a strong intra-individual correlation between peripheral and brain tissue. They also suggest that sex determines methylation patterns in BDNF promoter region across different types of tissue, including muscle, brain, and blood.

Effects of a post-weaning cafeteria diet in young rats: metabolic syndrome, reduced activity and low anxiety-like behaviour.

Among adolescents, overweight, obesity and metabolic syndrome are rapidly increasing in recent years as a consequence of unhealthy palatable diets. Animal models of diet-induced obesity have been developed, but little is known about the behavioural patterns produced by the consumption of such diets. The aim of the present study was to determine the behavioural and biochemical effects of a cafeteria diet fed to juvenile male and female rats, as well as to evaluate the possible recovery from these effects by administering standard feeding during the last week of the study. Two groups of male and female rats were fed with either a standard chow diet (ST) or a cafeteria (CAF) diet from weaning and for 8 weeks. A third group of males (CAF withdrawal) was fed with the CAF diet for 7 weeks and the ST in the 8th week. Both males and females developed metabolic syndrome as a consequence of the CAF feeding, showing overweight, higher adiposity and liver weight, increased plasma levels of glucose, insulin and triglycerides, as well as insulin resistance, in comparison with their respective controls. The CAF diet reduced motor activity in all behavioural tests, enhanced exploration, reduced anxiety-like behaviour and increased social interaction; this last effect was more pronounced in females than in males. When compared to animals only fed with a CAF diet, CAF withdrawal increased anxiety in the open field, slightly decreased body weight, and completely recovered the liver weight, insulin sensitivity and the standard levels of glucose, insulin and triglycerides in plasma. In conclusion, a CAF diet fed to young animals for 8 weeks induced obesity and metabolic syndrome, and produced robust behavioural changes in young adult rats, whereas CAF withdrawal in the last week modestly increased anxiety, reversed the metabolic alterations and partially reduced overweight.

Educational intervention for parents of adolescents with chronic illness: a pre-post test pilot study.

OBJECTIVE: This pilot experimental study tested the feasibility and intended effect of an educational intervention for parents to help them assist their adolescent child with chronic illness (CI) in becoming autonomous. METHODS: A two-phase pre-post pilot intervention study targeting parents of adolescents with CI was conducted. Parents were allocated to group 1 and 2 and received the four-module intervention consecutively. Intended effect was measured through online questionnaires for parents and adolescents before, at 2 months after, and at 4-6 months after the intervention. Feasibility was assessed through an evaluation questionnaire for parents. RESULTS: The most useful considered modules concerned the future of the adolescent and parents and social life. The most valued aspect was to exchange with other parents going through similar problems and receiving a new outlook on their relationship with their child. For parents, improvement trends appeared for shared management, parent protection, and self-efficacy, and worsening trends appeared for coping skills, parental perception of child vulnerability, and parental stress. For adolescents, improvement trends appeared for self-efficacy and parental bonding and worsening trends appeared for shared management and coping skills. CONCLUSION: Parents could benefit from peer-to-peer support and education as they support the needed autonomy development of their child. Future studies should test an online platform for parents to find peer support at all times and places.

Mutant huntingtin impairs the post-Golgi trafficking of brain-derived neurotrophic factor but not its Val66Met polymorphism.

Brain-derived neurotrophic factor (BDNF) polymorphism is associated with the pathophysiology of several neurodegenerative disorders, including Huntington"s disease. In view ofthese data andthe involvement of huntingtin in intracellular trafficking, we examined the intracellular transport and release of Val66Val BDNF (Val-BDNF) and Val66Met BDNF (Met-BDNF) in transfected striatal knock-in cells expressing wild-type or mutant full-length huntingtin. Colocalization studies with specific markers for endoplasmic reticulum showed no differences between the Val-BDNF and Met-BDNF and were not modified by mutant huntingtin. However, post-Golgi trafficking was altered by mutant huntingtin dependent on the BDNF form. Thus, fluorescence recovery after photobleaching (FRAP) and inverse FRAP analysis showed retention of Met-BDNF inthe Golgi apparatus with respectto Val-BDNF in wild-type cells. Strikingly, mutant huntingtin diminished post-Golgi trafficking of Val-BDNF, whereas Met-BDNF was not modified. Accordingly, a reduction in the number of transport vesicles was only observed in mutant huntingtin cells transfected with Val-BDNF but not Met-BDNF. Moreover, mutant huntingtin severely affectedthe KCl-evoked release of Val-BDNF, although it had little effect on Met-BDNF regulated release. The constitutive release of Val-BDNF or Met-BDNF in mutant cells was only slightly reduced. Interestingly, mutant huntingtin only perturbed post-Golgi trafficking of proteins that follow the regulated secretory pathway (epidermal growth factor receptor or atrial natriuretic factor), whereas it did not change those that follow the constitutive pathway (p75 NTR ). We conclude that mutant huntingtin differently affects intracellular transport and release of Val-BDNF and Met-BDNF. In addition, our findings reveal a new role for huntingtin in the regulation of the post-Golgi trafficking of the regulated secretory pathway.

Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial.

BACKGROUND: The recent large randomized controlled trial of glutamine and antioxidant supplementation suggested that high-dose glutamine is associated with increased mortality in critically ill patients with multiorgan failure. The objectives of the present analyses were to reevaluate the effect of supplementation after controlling for baseline covariates and to identify potentially important subgroup effects. MATERIALS AND METHODS: This study was a post hoc analysis of a prospective factorial 2 × 2 randomized trial conducted in 40 intensive care units in North America and Europe. In total, 1223 mechanically ventilated adult patients with multiorgan failure were randomized to receive glutamine, antioxidants, both glutamine and antioxidants, or placebo administered separate from artificial nutrition. We compared each of the 3 active treatment arms (glutamine alone, antioxidants alone, and glutamine + antioxidants) with placebo on 28-day mortality. Post hoc, treatment effects were examined within subgroups defined by baseline patient characteristics. Logistic regression was used to estimate treatment effects within subgroups after adjustment for baseline covariates and to identify treatment-by-subgroup interactions (effect modification). RESULTS: The 28-day mortality rates in the placebo, glutamine, antioxidant, and combination arms were 25%, 32%, 29%, and 33%, respectively. After adjusting for prespecified baseline covariates, the adjusted odds ratio of 28-day mortality vs placebo was 1.5 (95% confidence interval, 1.0-2.1, P = .05), 1.2 (0.8-1.8, P = .40), and 1.4 (0.9-2.0, P = .09) for glutamine, antioxidant, and glutamine plus antioxidant arms, respectively. In the post hoc subgroup analysis, both glutamine and antioxidants appeared most harmful in patients with baseline renal dysfunction. No subgroups suggested reduced mortality with supplements. CONCLUSIONS: After adjustment for baseline covariates, early provision of high-dose glutamine administered separately from artificial nutrition was not beneficial and may be associated with increased mortality in critically ill patients with multiorgan failure. For both glutamine and antioxidants, the greatest potential for harm was observed in patients with multiorgan failure that included renal dysfunction upon study enrollment.

Effect of biogeographic history on population vulnerability in European amphibians.

The genetic diversity of populations, which contributes greatly to their adaptive potential, is negatively affected by anthropogenic habitat fragmentation and destruction. However, continental-scale losses of genetic diversity also resulted from the population expansions that followed the end of the last glaciation, an element that is rarely considered in a conservation context. We addressed this issue in a meta-analysis in which we compared the spatial patterns of vulnerability of 18 widespread European amphibians in light of phylogeographic histories (glacial refugia and postglacial routes) and anthropogenic disturbances. Conservation statuses significantly worsened with distances from refugia, particularly in the context of industrial agriculture; human population density also had a negative effect. These findings suggest that features associated with the loss of genetic diversity in post-glacial amphibian populations (such as enhanced fixation load or depressed adaptive potential) may increase their susceptibility to current threats (e.g., habitat fragmentation and pesticide use). We propose that the phylogeographic status of populations (i.e., refugial vs. post-glacial) should be considered in conservation assessments for regional and national red lists.

Johdon yritysoston onnistumisen tukeminen pääomasijoitusyhtiön post-buyout toiminnan avulla

Tutkielman tavoitteena on analysoida, miten pääomasijoitusyhtiö voi post-buyout toiminnallaan tukea sijoituksensa onnistumista erilaisissa johdon yritysostotapauksissa. Tutkielmassa rakennetaan teoreettinen viitekehys, jonka avulla pääomasijoitusyhtiö voi tukea sijoituksensa arvon säilymistä ja toisaalta lisäarvon syntymistä. Tätä viitekehystä tarkennetaan ja testataan empiirisellä aineistolla, joka koostuu suomalaisen pääomasijoitusyhtiön ja sen neljän johdon yritysoston läpikäyneen kohdeyrityksen haastatteluista sekä pääomasijoitusyhtiön tuottamasta kirjallisesta materiaalista. Teorian ja empiirisen materiaalin perusteella johdon yritysoston onnistu-minen on usein subjektiivista sekä suhteellista suunniteltuun irtautumistapaan nähden. Joissakin tapauksissa jo pelkkä pääomasijoittajan mukaantulo voi vaikuttaa positiivisesti kohdeyrityksen riskinottoon ja siten pääomasijoitusyhtiön post-buyout toiminnan onnistumiseen.

Post-translational modifications of voltage-gated sodium channels in chronic pain syndromes.

In the peripheral sensory nervous system the neuronal expression of voltage-gated sodium channels (Navs) is very important for the transmission of nociceptive information since they give rise to the upstroke of the action potential (AP). Navs are composed of nine different isoforms with distinct biophysical properties. Studying the mutations associated with the increase or absence of pain sensitivity in humans, as well as other expression studies, have highlighted Nav1.7, Nav1.8, and Nav1.9 as being the most important contributors to the control of nociceptive neuronal electrogenesis. Modulating their expression and/or function can impact the shape of the AP and consequently modify nociceptive transmission, a process that is observed in persistent pain conditions. Post-translational modification (PTM) of Navs is a well-known process that modifies their expression and function. In chronic pain syndromes, the release of inflammatory molecules into the direct environment of dorsal root ganglia (DRG) sensory neurons leads to an abnormal activation of enzymes that induce Navs PTM. The addition of small molecules, i.e., peptides, phosphoryl groups, ubiquitin moieties and/or carbohydrates, can modify the function of Navs in two different ways: via direct physical interference with Nav gating, or via the control of Nav trafficking. Both mechanisms have a profound impact on neuronal excitability. In this review we will discuss the role of Protein Kinase A, B, and C, Mitogen Activated Protein Kinases and Ca++/Calmodulin-dependent Kinase II in peripheral chronic pain syndromes. We will also discuss more recent findings that the ubiquitination of Nav1.7 by Nedd4-2 and the effect of methylglyoxal on Nav1.8 are also implicated in the development of experimental neuropathic pain. We will address the potential roles of other PTMs in chronic pain and highlight the need for further investigation of PTMs of Navs in order to develop new pharmacological tools to alleviate pain.

Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS: Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS: In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS: Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS: Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Effect of different substrates in aquaponic lettuce production associated with intensive tilapia farming with water recirculation systems

ABSTRACT The integration of fish farming in intensive system and plant production, called "aquaponics" is practiced successfully in countries like the USA, Australia and Europe. In Brazil, this integration has attracted the attention of researchers and producers. In this context, the aim of this study was to evaluate the effect of two substrates (crushed stone number 3, CS III and flexible polyurethane foam, FPF) on the production of aquaponic lettuce, moreover, to show that the residual water from intensive tilapia production provides sufficient qualitative characteristics for competitive production of lettuce without adding commercial fertilizers. The treatment in which FPF was used provided higher concentrations of macro and micronutrients in the shoots, higher production of fresh matter of shoots (95.48 g plant-1) and a larger number of leaves (14.90) relative to CS III. These results were attributed to the lower post-transplanting stress and the higher water retention time provided by the FPF. The residual water from tilapia intensive farming can provide sufficient nutrients for the production of lettuce, making the supplementary fertilization with commercial products unnecessary. Thus, the FPF presents the most suitable conditions to be used as substrate in aquaponics system with recirculation of the residual water from the intensive tilapia farming.

Freund's adjuvant-induced inflammation: clinical findings and its effect on hepcidin mRNA expression in horses

Hypoferremia observed during systemic inflammatory disorders is regulated by hepcidin. Hepcidin up-regulation is particularly important during acute inflammation, as it restricts the availability of iron, which is necessary for pathogenic microorganism growth before adaptive immunity occurs. The aim of this study was to evaluate the clinical findings and hepatic hepcidin mRNA expression in horses using a Freund's complete adjuvant (FCA) model of inflammation. The expression of hepcidin mRNA in the liver was determined in healthy horses following two intramuscular injections of FCA at 0 h and 12 h. Plasma iron and fibrinogen concentrations were measured at multiple time points between 0 h and 240 h post-FCA injection (PI). Hepcidin mRNA expression was determined by RT-qPCR using liver biopsy samples performed at 0 h (control), 6 h and 18 h PI. The mean plasma fibrinogen level was significantly different from the control values only between 120 and 216 h PI. The mean plasma iron level was significantly lower than the control between 16 and 72 h PI, reaching the lowest levels at 30 h PI (33 % of the initial value), and returned to the reference value from 96 h PI to the end of the experiment. Hepcidin mRNA expression increased at 6 h PI and remained high at 18 h PI. The iron plasma concentration was an earlier indicator of inflammatory processes in horses when compared with fibrinogen and might be useful for the early detection of inflammation in the horse. FCA administration caused the rapid onset of hypoferremia, and this effect was likely the result of up-regulated hepatic hepcidin gene expression. This study emphasizes the importance of hepcidin and iron metabolism during inflammation in horses.

Model based analysis of the post-combustion calcium looping process for carbon dioxide capture

This thesis presents a one-dimensional, semi-empirical dynamic model for the simulation and analysis of a calcium looping process for post-combustion CO2 capture. Reduction of greenhouse emissions from fossil fuel power production requires rapid actions including the development of efficient carbon capture and sequestration technologies. The development of new carbon capture technologies can be expedited by using modelling tools. Techno-economical evaluation of new capture processes can be done quickly and cost-effectively with computational models before building expensive pilot plants. Post-combustion calcium looping is a developing carbon capture process which utilizes fluidized bed technology with lime as a sorbent. The main objective of this work was to analyse the technological feasibility of the calcium looping process at different scales with a computational model. A one-dimensional dynamic model was applied to the calcium looping process, simulating the behaviour of the interconnected circulating fluidized bed reactors. The model incorporates fundamental mass and energy balance solvers to semi-empirical models describing solid behaviour in a circulating fluidized bed and chemical reactions occurring in the calcium loop. In addition, fluidized bed combustion, heat transfer and core-wall layer effects were modelled. The calcium looping model framework was successfully applied to a 30 kWth laboratory scale and a pilot scale unit 1.7 MWth and used to design a conceptual 250 MWth industrial scale unit. Valuable information was gathered from the behaviour of a small scale laboratory device. In addition, the interconnected behaviour of pilot plant reactors and the effect of solid fluidization on the thermal and carbon dioxide balances of the system were analysed. The scale-up study provided practical information on the thermal design of an industrial sized unit, selection of particle size and operability in different load scenarios.

Weed control in young coffee plantations through post emergence herbicide application onto total area

This study was carried out to investigate the efficiency of several herbicides under field conditions, by post-emergence application onto the entire area, their effect on the control of weeds in young coffee plantations and commercial coffee and bean intercropping system, as well as on both crops. Seedlings of Coffea arabica cv. Red Catuaí with four to six leaf pairs were transplanted to the field and treated according to conventional agronomic practices. A bean and coffee intercropping system was established by sowing three lines of beans in the coffee inter-rows. At the time the herbicides were sprayed, the coffee plants had six to ten leaf pairs; the bean plants, three leaflets; and the weeds were at an early development stage. Fluazifop-p-butyl and clethodim were selective for coffee plants and controlled only Brachiaria plantaginea and Digitaria horizontalis efficiently. Broad-leaved weeds (Amaranthus retroflexus, Bidens pilosa, Coronopus didymus, Emilia sonchifolia, Galinsoga parviflora, Ipomoea grandifolia, Lepidium virginicum, and Raphanus raphanistrum) were controlled with high efficiency by sole applications of fomesafen, flazasulfuron, and oxyfluorfen, except B. pilosa, C. didymus, and R. raphanistrum for oxyfluorfen. Sequential applications in seven-day intervals of fomesafen + fluazifop-p-butyl, or clethodim, and two commercial mixtures of fomesafen + fluazifop-p-butyl simultaneously controlled both types of weed. Cyperus rotundus was only controlled by flazasulfuron. Except for fluazifop-p-butyl and clethodim, all herbicide treatments caused only slight injuries on younger coffee leaves. However, further plant growth was not impaired and coffee plant height and stem diameter were therefore similar in the treatments, as evaluated four months later. Fomesafen, fluazifop-p-butyl, and clethodim, at sole or sequential application, and the commercial mixtures of fomesafen + fluazifop-p-butyl were also highly selective for bean crop; thus at doses recommended for bean crop, these herbicides may be applied to control weeds in coffee and bean intercropping systems by spraying the entire area.