Evaluating Quality-of-Life, Length of Stay and Cost-Effectiveness of a Front-Door Geriatrics Program: An Exploratory Proof-of-Concept Study.

BACKGROUND: The Emergency Department Interventions for Frailty (EDIFY) program was developed to deliver early geriatric specialist interventions at the Emergency Department (ED). EDIFY has been successful in reducing acute admissions among older adults. OBJECTIVES: We aimed to examine the effectiveness of EDIFY in improving health-related quality-of-life (HRQOL) and length of stay (LOS), and evaluate EDIFY's cost-effectiveness. DESIGN: A quasi-experiment study. SETTING: The ED of a 1700-bed tertiary hospital. PARTICIPANTS: Patients (≥85 years) pending acute hospital admission and screened by the EDIFY team to be potentially suitable for discharge or transfer to low-acuity care areas. INTERVENTION: EDIFY versus standard-care. MEASUREMENTS: Data on demographics, comorbidities, premorbid function, and frailty status were gathered. HRQOL was measured using EQ-5D-5L over 6 months. We used a crosswalk methodology to compute Singapore-specific index scores from EQ-5D-5L responses and calculated quality-adjusted life-years (QALYs) gained. LOS and bills in Singapore-dollars (SGD) before subsidy from ED attendances (including admissions, if applicable) were obtained. We estimated average programmatic EDIFY cost and performed multiple imputation (MI) for missing data. QALYs gained, LOS and cost were compared. Potential uncertainties were also examined. RESULTS: Among 100 participants (EDIFY=43; standard-care=57), 61 provided complete data. For complete cases, there were significant QALYs gained at 3-month (coefficient=0.032, p=0.004) and overall (coefficient=0.096, p=0.002) for EDIFY, whilst treatment cost was similar between-groups. For MI, we observed only overall QALYs gained for EDIFY (coefficient=0.102, p=0.001). EDIFY reduced LOS by 17% (Incident risk ratio=0.83, p=0.015). In a deterministic sensitivity analysis, EDIFY's cost-threshold was SGD$2,500, and main conclusions were consistent in other uncertainty scenarios. Mean bills were: EDIFY=SGD$4562.70; standard-care=SGD$5530.90. EDIFY's average programmatic cost approximated SGD$469.30. CONCLUSIONS: This exploratory proof-of-concept study found that EDIFY benefits QALYs and LOS, with equivalent cost, and is potentially cost-effective. The program has now been established as standard-care for older adults attending the ED at our center.

Spatially variable pesticide application in olive groves: Evaluation of potential pesticide-savings through stochastic spatial simulation algorithms.

Site-specific management using spatial crown volume characterization can greatly reduce the amount of pesticides applied in agricultural treatments performed with air-assisted sprayers, while helping farmers achieve the European legislation on safe use of pesticides. Nevertheless, variable rate treatments in olive groves have received little attention. Thus, field research was conducted in a 20.6-ha traditional olive grove. Two attributes of the trees - tree crown volume (V) and tree projected area - were determined, using 67 samples for V and all trees of the field (1433) for tree projected area. Spatial continuity of both attributes was modelled with exponential variograms. To gain a measure of local uncertainty, stochastic simulation algorithms were applied. One hundred simulated images were obtained for tree projected area using direct sequential simulation. Tree projected area simulations were used to improve spatial prediction of V, more difficult and more expensive to obtain, taking advantage of the high linear correlation between both variables (rxy = 0.72,p < 0.001). Thus, direct sequential cosimulation was employed to predict the spatial distribution of V, obtaining 100 geostatistical realizations of V. In order to estimate the potential reduction of pesticide use in the farm with variable rate treatments, two cut-off values of V were considered (50 and 100 m3crown volume). Local uncertainty, understood as the probability of each tree belonging to a given crown volume interval was determined. Probability maps were further transformed to morphological maps and finally to variable prescription maps. Two scenarios with 2 and 3 management zones (MZs) were obtained. In comparison with a conventional phytosanitary application, the variable rate treatments could reduce the pesticide amounts by 21.3% with 2 MZs, and by 38% with 3 MZs. The joint use of V and tree projected area in stochastic sequential simulation algorithms has shown to be useful to determine MZs in olive groves.

Reproduction of Hypoptopoma inexspectatum (Holmberg, 1893) (Siluriformes, Loricariidae) in the Southern Pantanal Floodplain, Upper Paraguay River Basin, Brazil.

This work aimed to describe the reproductive biology of Hypoptopoma inexspectatum in southern Pantanal. A total of 538 individuals were sampled and analyzed from February 2009 through January 2011 in southern Pantanal. We did not observe differences in sex-ratio, and both sexes presented positive allometric length/weight relationship (LWR). Reproduction occurs mainly from January to February. Females reached first maturation (L50) with 37.80 mm and males with 45.80 mm. Absolute fecundity is estimated in mean=177.43 (sd±127.06) oocytes and relative fecundity in 3.12 (sd±2.23) oocytes/mg. Fecundity is positively correlated with standard length (Spearman r= 0.43; p=0.013), and total spawning is a used spawning strategy for H. inexspectatum.

Reproduction of Hypoptopoma inexspectatum (Holmberg, 1893) (Siluriformes, Loricariidae) in the Southern Pantanal floodplain, upper Paraguay River basin, Brazil / Reprodução de Hypoptopoma inexspectatum (Holmberg, 1893) (Siluriformes, Loricariidae) na planície de inundação do Pantanal Sul, bacia do alto rio Paraguai, Brasil

This work aimed to describe the reproductive biology of Hypoptopoma inexspectatum in southern Pantanal. A total of 538 individuals were sampled and analyzed from February 2009 through January 2011 in southern Pantanal. We did not observe differences in sex-ratio, and both sexes presented positive allometric length/weight relationship (LWR). Reproduction occurs mainly from January to February. Females reached first maturation (L50) with 37.80 mm and males with 45.80 mm. Absolute fecundity is estimated in mean=177.43 (sd±127.06) oocytes and relative fecundity in 3.12 (sd±2.23) oocytes/mg. Fecundity is positively correlated with standard length (Spearman r= 0.43; p=0.013), and total spawning is a used spawning strategy for H. inexspectatum.

Este trabalho teve como objetivo descrever a biologia reprodutiva de Hypoptopoma inexspectatum na região do Pantanal Sul. Foram amostrados e analisados entre fevereiro de 2009 a janeiro de 2011 um total de 538 indivíduos. Não foi observada diferença na proporção sexual e ambos os sexos apresentam relação alométrica de peso/comprimento positiva. A reprodução ocorreu principalmente entre os meses de janeiro e fevereiro. Fêmeas atingiram o tamanho de primeira maturação (L50) com 37,80 mm e machos com 45,80 mm. A fecundidade absoluta média foi 177,43 (dp±127,06) ovócitos e a fecundidade relativa foi de 3,12 (dp±2,23) ovócitos/mg. A fecundidade foi positivamente correlacionada com o comprimento padrão (Spearman r= 0,43; p=0,013) e a desova parcelada foi a estratégia de desova utilizada por H. inexspectatum.

Validation of automated whole-body analysis of metabolic and morphological parameters from an integrated FDG-PET/MRI acquisition.

Automated quantification of tissue morphology and tracer uptake in PET/MR images could streamline the analysis compared to traditional manual methods. To validate a single atlas image segmentation approach for automated assessment of tissue volume, fat content (FF) and glucose uptake (GU) from whole-body [18F]FDG-PET/MR images. Twelve subjects underwent whole-body [18F]FDG-PET/MRI during hyperinsulinemic-euglycemic clamp. Automated analysis of tissue volumes, FF and GU were achieved using image registration to a single atlas image with reference segmentations of 18 volume of interests (VOIs). Manual segmentations by an experienced radiologist were used as reference. Quantification accuracy was assessed with Dice scores, group comparisons and correlations. VOI Dice scores ranged from 0.93 to 0.32. Muscles, brain, VAT and liver showed the highest scores. Pancreas, large and small intestines demonstrated lower segmentation accuracy and poor correlations. Estimated tissue volumes differed significantly in 8 cases. Tissue FFs were often slightly but significantly overestimated. Satisfactory agreements were observed in most tissue GUs. Automated tissue identification and characterization using a single atlas segmentation performs well compared to manual segmentation in most tissues and will be valuable in future studies. In certain tissues, alternative quantification methods or improvements to the current approach is needed.

Caretta caretta nesting activity on Akumal Beaches, Mexico.

Mexico has made substantial contributions to marine turtle protection and conservation, especially since 1990. Several conservation projects entail monitoring efforts to recover nesting territories for marine turtles. The Sea Turtle Protection Program of Akumal, in the Mexican state of Quintana Roo, was created in 1993 and was developed by the Akumal Ecological Center. This paper provides the nesting ecology parameters for Caretta caretta over a protection period of 24 years (1995-2018). A well-defined nesting peak was observed in June, with a nesting success rate of 75.2 ± 23.0%. Nesting females showed a mean curved carapace length of 99.0 ± 5.6 cm. The mean clutch size was 108.6 ± 24.6 eggs, with variation among years. The mean incubation period was 57.2 ± 6.2 days. The hatching and emergence success rates were 87.2 ± 16.9% and 78.8 ± 24.4%, respectively. For the 926 tagged females that returned, the remigration interval peaked at 726 days, with a 12-day inter-nesting period. The results show not only the recovery of the nesting population over time but also a decrease in female size; we postulate that this decrease is due to the recruitment of young females, which has been increasingly pronounced since 2010. Hence, the Akumal rookery plays an important role in its corresponding regional management unit (Atlantic Northwest).

Reproductive ecology of Otocinclus vittatus (Regan, 1904) in the Pantanal floodplain, upper Paraguay River basin / Ecologia reprodutiva de Otocinclus vittatus (Regan, 1904) na planície de inundação do Pantanal, bacia do alto rio Paraguai

Abstract We studied the reproductive biology of Otocinclus vittatus in the southern Pantanal, Brazil. A total of 1066 fishes were analyzed (490 males, 488 females and 88 individuals of undetermined sex), sampled with a rectangular sieve and a seine net from February/2009 to January/2011. Variations in the sex ratio, seasonality in reproduction, fecundity, and size at first maturity were estimated. No variations were detected in the total sex ratio for the study period as a whole; although ratio has varied over time. The gonadosomatic index varied according to the river level, but not according to water temperature and rainfall. The mean fecundity was estimated at 84.1 oocytes, with a positive correlation with standard length. The size at first maturity (L50) estimated was 18.7 mm for females and 20.1 mm for males.

Resumo Estudamos a biologia reprodutiva de Otocinclus vittatus no Pantanal Sul, Brasil. Um total de 1066 peixes foram analisados (490 machos, 488 fêmeas e 88 de sexo indeterminado), amostrados com tela de isca e rede de arrasto entre Fevereiro/2009 e Janeiro/2011. Foram estimadas as variações na proporção sexual, a sazonalidade na reprodução e o tamanho da primeira maturação. Não foi detectada variação na proporção sexual total para o período de estudo como um todo; embora a proporção tenha variado ao longo do tempo. O índice ganadossomático variou de acordo com o nível do rio, mas não de acordo com a temperatura da água e a pluviosidade. A média de fecundidade foi estimada em 84.1 ovócitos, com uma correlação positiva com o comprimento padrão. O tamanho de primeira maturação (L50) foi estimado em 18.7 mm para fêmeas e 20.1 mm para machos.

Reproductive ecology of Otocinclus vittatus (Regan, 1904) in the Pantanal floodplain, upper Paraguay River basin.

We studied the reproductive biology of Otocinclus vittatus in the southern Pantanal, Brazil. A total of 1066 fishes were analyzed (490 males, 488 females and 88 individuals of undetermined sex), sampled with a rectangular sieve and a seine net from February/2009 to January/2011. Variations in the sex ratio, seasonality in reproduction, fecundity, and size at first maturity were estimated. No variations were detected in the total sex ratio for the study period as a whole; although ratio has varied over time. The gonadosomatic index varied according to the river level, but not according to water temperature and rainfall. The mean fecundity was estimated at 84.1 oocytes, with a positive correlation with standard length. The size at first maturity (L50) estimated was 18.7 mm for females and 20.1 mm for males.

Software for improved field surveys of nesting marine turtles.

Field data are still recorded on paper in many worldwide beach surveys of nesting marine turtles. The data must be subsequently transferred into an electronic database, and this can introduce errors in the dataset. To minimize such errors, the "Turtles" software was developed and piloted to record field data by one software user accompanying one Tortuguero in Akumal beaches, Quintana Roo, Mexico, from June 1st to July 31st during the night patrols. Comparisons were made between exported data from the software with the paper forms entered into a database (henceforth traditional). Preliminary assessment indicated that the software user tended to record a greater amount of metrics (i.e., an average of 18.3 fields ± 5.4 sd vs. 8.6 fields ± 2.1 sd recorded by the traditional method). The traditional method introduce three types of "errors" into a dataset: missing values in relevant fields (40.1%), different answers for the same value (9.8%), and inconsistent data (0.9%). Only 5.8% of these (missing values) were found with the software methodology. Although only tested by a single user, the software may suggest increased efficacy and warrants further examination to accurately assess the merit of replacing traditional methods of data recording for beach monitoring programmes.

Using nitrogen concentration and isotopic composition in lichens to spatially assess the relative contribution of atmospheric nitrogen sources in complex landscapes.

Reactive nitrogen (Nr) is an important driver of global change, causing alterations in ecosystem biodiversity and functionality. Environmental assessments require monitoring the emission and deposition of both the amount and types of Nr. This is especially important in heterogeneous landscapes, as different land-cover types emit particular forms of Nr to the atmosphere, which can impact ecosystems distinctively. Such assessments require high spatial resolution maps that also integrate temporal variations, and can only be feasibly achieved by using ecological indicators. Our aim was to rank land-cover types according to the amount and form of emitted atmospheric Nr in a complex landscape with multiple sources of N. To do so, we measured and mapped nitrogen concentration and isotopic composition in lichen thalli, which we then related to land-cover data. Results suggested that, at the landscape scale, intensive agriculture and urban areas were the most important sources of Nr to the atmosphere. Additionally, the ocean greatly influences Nr in land, by providing air with low Nr concentration and a unique isotopic composition. These results have important consequences for managing air pollution at the regional level, as they provide critical information for modeling Nr emission and deposition across regional as well as continental scales.

Reproductive ecology of Otocinclus vittatus (Regan, 1904) in the Pantanal floodplain, upper Paraguay River basin

Abstract We studied the reproductive biology of Otocinclus vittatus in the southern Pantanal, Brazil. A total of 1066 fishes were analyzed (490 males, 488 females and 88 individuals of undetermined sex), sampled with a rectangular sieve and a seine net from February/2009 to January/2011. Variations in the sex ratio, seasonality in reproduction, fecundity, and size at first maturity were estimated. No variations were detected in the total sex ratio for the study period as a whole; although ratio has varied over time. The gonadosomatic index varied according to the river level, but not according to water temperature and rainfall. The mean fecundity was estimated at 84.1 oocytes, with a positive correlation with standard length. The size at first maturity (L50) estimated was 18.7 mm for females and 20.1 mm for males.

Resumo Estudamos a biologia reprodutiva de Otocinclus vittatus no Pantanal Sul, Brasil. Um total de 1066 peixes foram analisados (490 machos, 488 fêmeas e 88 de sexo indeterminado), amostrados com tela de isca e rede de arrasto entre Fevereiro/2009 e Janeiro/2011. Foram estimadas as variações na proporção sexual, a sazonalidade na reprodução e o tamanho da primeira maturação. Não foi detectada variação na proporção sexual total para o período de estudo como um todo; embora a proporção tenha variado ao longo do tempo. O índice ganadossomático variou de acordo com o nível do rio, mas não de acordo com a temperatura da água e a pluviosidade. A média de fecundidade foi estimada em 84.1 ovócitos, com uma correlação positiva com o comprimento padrão. O tamanho de primeira maturação (L50) foi estimado em 18.7 mm para fêmeas e 20.1 mm para machos.

Reproduction of Hypoptopoma inexspectatum (Holmberg, 1893) (Siluriformes, Loricariidae) in the Southern Pantanal Floodplain, Upper Paraguay River Basin, Brazil

Abstract This work aimed to describe the reproductive biology of Hypoptopoma inexspectatum in southern Pantanal. A total of 538 individuals were sampled and analyzed from February 2009 through January 2011 in southern Pantanal. We did not observe differences in sex-ratio, and both sexes presented positive allometric length/weight relationship (LWR). Reproduction occurs mainly from January to February. Females reached first maturation (L50) with 37.80 mm and males with 45.80 mm. Absolute fecundity is estimated in mean=177.43 (sd±127.06) oocytes and relative fecundity in 3.12 (sd±2.23) oocytes/mg. Fecundity is positively correlated with standard length (Spearman r= 0.43; p=0.013), and total spawning is a used spawning strategy for H. inexspectatum.

Resumo Este trabalho teve como objetivo descrever a biologia reprodutiva de Hypoptopoma inexspectatum na região do Pantanal Sul. Foram amostrados e analisados entre fevereiro de 2009 a janeiro de 2011 um total de 538 indivíduos. Não foi observada diferença na proporção sexual e ambos os sexos apresentam relação alométrica de peso/comprimento positiva. A reprodução ocorreu principalmente entre os meses de janeiro e fevereiro. Fêmeas atingiram o tamanho de primeira maturação (L50) com 37,80 mm e machos com 45,80 mm. A fecundidade absoluta média foi 177,43 (dp±127,06) ovócitos e a fecundidade relativa foi de 3,12 (dp±2,23) ovócitos/mg. A fecundidade foi positivamente correlacionada com o comprimento padrão (Spearman r= 0,43; p=0,013) e a desova parcelada foi a estratégia de desova utilizada por H. inexspectatum.

Neighbourhood Determinants of Caries Experience in Preschool Children: A Multilevel Study.

OBJECTIVES: To investigate the association between neighbourhood factors and decayed, missing, and filled teeth (dmft) index among preschool children. METHODS: The sample of this cross-sectional study comprised 1,110 children (0-5 years old) clustered in 16 official neighbourhoods of Canoas city, southern Brazil. Multilevel binomial models were used to estimate the association of contextual variables at neighbourhood level (Human Development Index, average income, and public primary health care units) with two oral health outcomes: decayed teeth (dt) and missing or filled teeth (mft), after adjusting for individual variables (gender, age, maternal education, equivalent household income logarithm, household, and point of care). RESULTS: Overall, 24.9% of the sample had dental caries experience (dmft >0), and 92.3% of the dmft was untreated caries. There was no statistical significant association (p > 0.05) of contextual characteristics with the decay component. The teeth of children living in richer areas had 2.87 (95% CI: 1.05-7.86) times more chances of being treated (mft component). Variance attributed to neighbourhood level was estimated as 5.9% (p < 0.01) and 4.1% (p = 0.17) for dt and mft, respectively, in adjusted models. CONCLUSIONS: Intra-urban areas seem homogeneous, with small variability between neighbourhoods, having no contextual effect on untreated dental caries (dt). Contextual variables may influence treatment access (mft) through the use of dental services in preschool children.

Toxicity of Piper aduncum (Piperaceae) Essential Oil Against Euschistus heros (F.) (Hemiptera: Pentatomidae) and Non-Effect on Egg Parasitoids.

Plant essential oils have been recognized as significant natural resources for insecticides. Herein, we have assessed the toxicity of the essential oil of Piper aduncum (Piperaceae) against Euschistus heros (F.) (Hemiptera: Pentatomidae), a key soybean pest in Neotropical America. In addition, we have assessed its effect on the performance of egg parasitoids. The essential oil was obtained from the leaves of P. aduncum via hydrodistillation. Subsequently, bioassays of the concentration response to eggs (contact and immersion methods), nymphs, and adults (topical application) were conducted, to assess the lethal effects on the stink bug. We also evaluated the performance of parasitism and adult emergence of egg parasitoids, when the host eggs were treated with essential oil. In the egg bioassay, both exposure methods were efficient for unviable eggs (immersion LC50 = 15.64 mg mL-1; contact LC50 = 21.29 mg mL-1), with the highlight on the immersion method. The bioassay with nymphs indicated a higher toxicity of essential oil, with lower concentrations (LC50 = 11.37 mg mL-1) being required to cause the death of insects. For adults, a reduction in survival of insects was observed, and consequently, there was a reduction in the number of individuals in the next generation. Although the essential oil was toxic to E. heros, it exhibited lower toxicity for egg parasitoids, as there was no effect on parasitism and the emergence of wasps. We discuss likely explanations for such selectivity. In summary, we found that the essential oil was promising for the control of E. heros, because it caused deleterious effects at all development stages of the stink bug and had no effect on parasitism and emergence of the egg parasitoids, which suggested compatibility with biological control.

Reproductive dynamics shapes genomotype composition in an allopolyploid complex.

Hybrid complexes are composed of organisms with multiple combinations of parental genomes (genomotypes) that interconnect through nets of crosses. Although several such complexes are well established without speciation or extinction, mechanisms shaping their dynamics remain poorly understood. In this study, we quantified the reproductive success of the allopolyploid Iberian fish Squalius alburnoides in experimental free-access and directional crosses involving the most common genomotypes. Specifically, we analysed the paternity of the offspring produced when females had free access to male genomotypes and quantified variations in egg allocation, fertilization rate, and offspring survival among crosses involving each male genomotype. The composition of the offspring produced from free-access crosses varied significantly from that expected from random mating, suggesting that offspring production and viability are not independent of parental male genomotype. Moreover, directional crosses producing the genomotype most commonly found in wild populations appeared to be the most successful, with females laying more eggs, and fertilization rate and offspring survival being the highest. These results suggest that reproductive dynamics plays a relevant role in structuring the genomotype composition of populations and opens a path to future research on the ecology and evolutionary biology of allopolyploids and their multiplicity of possible evolutionary pathways.

Lethal and Sublethal Effects of Insecticides on the Egg Parasitoid Telenomus podisi (Hymenoptera: Platygastridae).

Insecticide use remains controversial, and subjected to increasing environmental and health concerns, even when recent insecticide groups are considered. Neonicotinoids and even bioinsecticides are in the forefront of discussions regarding their nontarget safety. The ubiquitous focus on the lethal effects of insecticides on nontarget species has been expanding to sublethal effects, as sublethal exposure extends for a longer time and affects a broader range of (nontarget) species. Here we explored the lethal and sublethal effects of a lambda-cyhalothrin + thiamethoxan mixture, the neonicotinoid imidacloprid, and the bioinsecticide azadirachtin on the egg parasitoid Telenomus podisi Ashmead, an important parasitoid of stink bug Euschistus heros (F.), a key soybean pest in neotropical America. Contact with dry insecticide residue on glass surface and (parasitized and healthy) host egg immersion exposure bioassays were performed, assessing their acute lethal effects, and their potential sublethal impairment of parasitism, adult emergence, and fertility of the egg parasitoid. Both imidacloprid and the insecticide mixture exhibited high acute lethal activity toward the parasitoid under contact with dry insecticide residue. These insecticides compromised parasitism and wasp emergence when exposure took place before parasitism. In contrast, azadirachtin did not affect adult survival. However, this bioinsecticide compromised parasitism and progeny production, impairing the female parasitoid reproductive potential. Our results indicate strong negative effects of imidacloprid, and specially of the mixture lambda-cyhalthrin + thiamethoxan. However, even azadirachtin, which exhibited low acute lethality, exhibited significant negative sublethal effects on parasitism and population growth of egg parasitoid, cautioning against their use and the need of semifield and field assessments to confirm such an impact.

A case report of improved metabolic control after conversion from everolimus to cyclosporin A: role of adipose tissue mechanisms?

BACKGROUND: New-onset diabetes after transplantation is associated with an increase in risk of graft failure, cardiovascular disease, and mortality. Therefore, it compromises the overall beneficial outcome of organ transplantation. CASE REPORT: A patient with new-onset diabetes after renal transplantation showed glucose and lipid metabolism improvements after switching immunosuppressant from everolimus to cyclosporin A. A subcutaneous adipose tissue biopsy displayed changes in gene and protein expression that could contribute to the clinical improvement of hyperglycemia and dyslipidemia.

Cyclosporine A enhances gluconeogenesis while sirolimus impairs insulin signaling in peripheral tissues after 3 weeks of treatment.

Cyclosporine A (CsA) and sirolimus (SRL) are immunosuppressive agents (IA) associated with new-onset diabetes after transplantation (NODAT). This study aims to evaluate the effects of 3-weeks of treatment with either CsA (5 mg/kg BW/day) or SRL (1 mg/kg BW/day) on insulin signaling and expression of markers involved in glucose metabolism in insulin-sensitive tissues, in Wistar rats. Although no differences were observed in fasting glucose, insulin or C-peptide levels, both treated groups displayed an impaired glucose excursion during both glucose and insulin tolerance tests. These results suggest glucose intolerance and insulin resistance. An increase in glucose-6-phosphatase protein levels (68%, p < 0.05) and in protein-tyrosine phosphatase 1B (163%, p < 0.05), a negative regulator of insulin was observed in the CsA-treated group in the liver, indicating enhanced gluconeogenesis and increased insulin resistance. On the other hand, glucokinase protein levels were decreased in the SRL group (35%, p < 0.05) compared to vehicle, suggesting a decrease in glucose disposal. SRL treatment also reduced peroxisome proliferator-activated receptor γ coactivator 1 alpha protein expression in muscle (~50%, p < 0.05), while no further protein alterations were observed in muscle and perirenal adipose tissue nor with the CsA treatment. Moreover, the phosphorylation of key proteins of the insulin signaling cascade was suppressed in the SRL group, but was unchanged by the CsA treatment. Taken together, these data suggest that CsA treatment enhances gluconeogenic factors in liver, while SRL treatment impairs insulin signaling in peripheral tissues, which can contribute to the development of insulin resistance and NODAT associated with immunosuppressive therapy.

Tools for determining critical levels of atmospheric ammonia under the influence of multiple disturbances.

Critical levels (CLEs) of atmospheric ammonia based on biodiversity changes have been mostly calculated using small-scale single-source approaches, to avoid interference by other factors, which also influence biodiversity. Thus, it is questionable whether these CLEs are valid at larger spatial scales, in a multi- disturbances context. To test so, we sampled lichen diversity and ammonia at 80 sites across a region with a complex land-cover including industrial and urban areas. At a regional scale, confounding factors such as industrial pollutants prevailed, masking the CLEs. We propose and use a new tool to calculate CLEs by stratifying ammonia concentrations into classes, and focusing on the highest diversity values. Based on the significant correlations between ammonia and biodiversity, we found the CLE of ammonia for Mediterranean evergreen woodlands to be 0.69 µg m(-3), below the previously accepted value of 1.9 µg m(-3), and below the currently accepted pan-European CLE of 1.0 µg m(-3).

Molecular mechanisms underlying the effects of cyclosporin A and sirolimus on glucose and lipid metabolism in liver, skeletal muscle and adipose tissue in an in vivo rat model.

Cyclosporin A (CsA) and sirolimus (SRL) are immunosuppressive agents (IAs) associated with dyslipidemia, insulin resistance and new onset diabetes after transplantation (NODAT). However, the molecular mechanisms involved are not fully understood. We investigated the effects of six-week treatment of either CsA or SRL on glucose and lipid metabolism in Wistar rats. The results show that, compared with vehicle-treated rats, SRL-treated rats were significantly lighter starting at week 5. CsA or SRL caused glucose intolerance, increased storage of lipids in the liver and skeletal muscle, and decreased the insulin-stimulated glucose uptake in isolated adipocytes. Furthermore, these agents significantly decreased genes involved in insulin action and glucose uptake, such as, IRS-1, Glut4 and Glut1, and increased genes and/or proteins involved in hepatic lipogenesis and gluconeogenesis, while decreasing them in adipose tissue. After either treatment PGC1α gene expression was down regulated in skeletal muscle, an important player in fatty acid oxidation. Moreover, there was an increase in IL-6 gene expression in adipose tissue in the SRL-treated rats, suggesting stimulation of lipolysis. The results of the present study suggest that CsA and SRL lead to metabolic alterations in liver, muscle and adipose tissue, which may contribute to the development of dyslipidemia and insulin resistance associated with immunosuppressive therapy.