Impact of short-acting vs. standard anaesthetic agents on obstructive sleep apnoea: a randomised, controlled, triple-blind trial.

Sleep apnoea is associated with negative outcomes following general anaesthesia. Current recommendations suggest using short-acting anaesthetic agents in preference to standard agents to reduce this risk, but there is currently no evidence to support this. This randomised controlled triple-blind trial tested the hypothesis that a combination of short-acting agents (desflurane-remifentanil) would reduce the postoperative impact of general anaesthesia on sleep apnoea severity compared with standard agents (sevoflurane-fentanyl). Sixty patients undergoing hip arthroplasty under general anaesthesia were randomised to anaesthesia with desflurane-remifentanil or sevoflurane-fentanyl. Respiratory polygraphy was performed before surgery and on the first and third postoperative nights. The primary outcome was the supine apnoea-hypopnoea index on the first postoperative night. Secondary outcomes were the supine apnoea-hypopnoea index on the third postoperative night, and the oxygen desaturation index on the first and third postoperative nights. Additional outcomes included intravenous morphine equivalent consumption and pain scores on postoperative days 1, 2 and 3. Pre-operative sleep study data were similar between groups. Mean (95%CI) values for the supine apnoea-hypopnoea index on the first postoperative night were 18.9 (12.7-25.0) and 21.4 (14.2-28.7) events.h <sup>-1</sup> , respectively, in the short-acting and standard anaesthesia groups (p = 0.64). Corresponding values on the third postoperative night were 28.1 (15.8-40.3) and 38.0 (18.3-57.6) events.h <sup>-1</sup> (p = 0.34). Secondary sleep- and pain-related outcomes were generally similar in the two groups. In conclusion, short-acting anaesthetic agents did not reduce the impact of general anaesthesia on sleep apnoea severity compared with standard agents. These data should prompt an update of current recommendations

Design and characterization of synthetic biodegradable films for musculoskeletal tissue engineering

To repair soft tissue, it is vital to ensure that the biomaterial is able to mimic the complex elasticity of the native tissue. It has been demonstrated that substrate stiffness has a huge influence on cellular growth, differentiation, motility and phenotype maintenance. The goal of the present study is to characterize extensively a set of polymeric films with variable mechanical profiles. A range of synthetic biodegradable polymers was selected according to the physico-chemical intrinsic properties of aliphatic polymers. They have similar chemistry (absorbable polyesters made from lactic acid, glycolic acid, trimethylene carbonate, dioxanone & β-caprolactone), however show different mechanical and degradation properties. The films were manufactured by thermal presser and then characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FTIR). The mechanical properties of the films were assessed by uniaxial tensile tests in wet conditions and also by atomic force microscopy (AFM) to assess the material's stiffness at a micro-level. In vitro assays were performed to assess the cell cytocompatibility, proliferation and differentiation potential of the films. The mechanical properties of the materials are within the range intended for musculoskeletal tissue repair. Biological assays showed good cell adhesion, cell proliferation and cell viability. Stem cells were able to differentiate into adipogenic, osteogenic, chondrogenic and tenogenic lineages. Overall the selection of polymers gave good options for a potential tissue repair scaffold. In the future, the combined effect of stiffness and topography will be assessed on cell phenotype maintenance

Initial analysis of peripheral lymphocytic extracellular signal related kinase activation in autism

BACKGROUND: Dysregulation of extracellular signal-related kinase (ERK) activity has been potentially implicated in the pathophysiology of autistic disorder (autism). ERK is part of a central intracellular signaling cascade responsible for a myriad of cellular functions. ERK is expressed in peripheral blood lymphocytes, and measurement of activated (phosphorylated) lymphocytic ERK is commonly executed in many areas of medicine. We sought to conduct the first study of ERK activation in humans with autism by utilizing a lymphocytic ERK activation assay. We hypothesized that ERK activation would be enhanced in peripheral blood lymphocytes from persons with autism compared to those of neurotypical control subjects. METHOD: We conducted an initial study of peripheral lymphocyte ERK activation in 45 subjects with autism and 26 age- and gender-matched control subjects (total n = 71). ERK activation was measured using a lymphocyte counting method (primary outcome expressed as lymphocytes staining positive for cytosolic phosphorylated ERK divided by total cells counted) and additional Western blot analysis of whole cell phosphorylated ERK adjusted for total ERK present in the lymphocyte lysate sample. RESULTS: Cytosolic/nuclear localization of pERK activated cells were increased by almost two-fold in the autism subject group compared to matched neurotypical control subjects (cell count ratio of 0.064 ± 0.044 versus 0.034 ± 0.031; p = 0.002). Elevated phosphorylated ERK levels in whole cell lysates also showed increased activated ERK in the autism group compared to controls (n = 54 total) in Western blot analysis. CONCLUSIONS: The results of this first in human ERK activation study are consistent with enhanced peripheral lymphocytic ERK activation in autism, as well as suggesting that cellular compartmentalization of activated ERK may be altered in this disorder. Future work will be required to explore the impact of concomitant medication use and other subject characteristics such as level of cognitive functioning on ERK activation

Reversed-phase high-performance liquid chromatography–fluorescence detection for the analysis of glutathione and its precursor γ-glutamyl cysteine in wines and model wines supplemented with oenological inactive dry yeast preparations

El pdf del artículo es la versión pre-print.A reversed-phase high-performance liquid chromatography-fluorescence detection methodology involving a pre-column derivatization procedure using 2,3-naphtalenedialdehyde in the presence of 5 and 0. 5 mM of dithiothreitol to determine total and reduced glutathione (GSH) and γ-glutamyl-cysteine (γ-glu-cys) in musts and wines has been set up and validated. The proposed method showed good linearity (R 2 >99% for reduced and total GSH, and R 2 >98% for γ-glu-cys) in synthetic wines, over a wide range of concentration (0-10 mg L -1). The limits of detection for reduced GSH in synthetic and real wines were almost the same (0. 13 and 0. 15 mg L -1, respectively) and slightly higher for γ-glu-cys (0. 24 mg L -1). The application of the method allowed knowing, for the first time, the amount of total and reduced GSH and γ-glu-cys released into synthetic wines by oenological preparations of commercial inactive dry yeast (IDY). In addition, the evolution of these three compounds during the winemaking and shelf life (0-9 months) of an industrially manufactured rosé wine supplemented with a GSH-enriched IDY showed that although GSH is effectively released from IDY, it is rapidly oxidized during alcoholic fermentation, contributing to the higher total GSH content determined in wines supplemented with GSH-enriched IDYs compared to control wines. © 2011 Springer Science+Business Media, LLC.IAO and JJRB acknowledge CAM and CSIC for their respective research grants. This work has been founded by PET2007-0134 project.Peer Reviewe

Soil chemistry changes beneath decomposing cadavers over a one-year period

Decomposing vertebrate cadavers release large, localized inputs of nutrients. These temporally limited resource patches affect nutrient cycling and soil organisms. The impact of decomposing cadavers on soil chemistry is relevant to soil biology, as a natural disturbance, and forensic science, to estimate the postmortem interval. However, cadaver impacts on soils are rarely studied, making it difficult to identify common patterns. We investigated the effects of decomposing pig cadavers (Sus scrofa domesticus) on soil chemistry (pH, ammonium, nitrate, nitrogen, phosphorous, potassium and carbon) over a one-year period in a sprucedominant forest. Four treatments were applied, each with five replicates: two treatments including pig cadavers (placed on the ground and hung one metre above ground) and two controls (bare soil and bags filled with soil placed on the ground i.e. “fake pig” treatment). In the first two months (15–59 days after the start of the experiment), cadavers caused significant increases of ammonium, nitrogen, phosphorous and potassium (p The marker categories will enhance our understanding of soil processes and can be highly useful when changes in soil chemistry are related to changes in the composition of soil organism communities. For actual casework further studies and more data are necessary to refine the marker categories along a more precise timeline and to develop a method that can be used in court

Cyclophilins in Ischemic Heart Disease: Differences Between Acute and Chronic Coronary Artery Disease Patients

Background: Cyclophilins (Cyps) are a family of peptidyl-prolyl cis/trans isomerases consistently involved in cardiovascular diseases through the inflammation pathway. This study aims to investigate the serum levels of Cyps (CypA, CypB, CypC and CypD) in patients with coronary artery disease (CAD) and the correlation with clinical characteristics and inflammation parameters. Methods: We developed an observational prospective study with a total of 125 subjects: 40 patients with acute CAD, 40 patients with chronic CAD and 45 control volunteers, in whom serum levels of Cyps (CypA, CypB, CypC and CypD), interleukins and metalloproteinases were measured. Results: CypA levels increased significantly in CAD patients compared with control subjects, but no differences were noted between acute CAD (7.80 +/- 1.30 ng/mL) and chronic CAD (5.52 +/- 0.76 ng/mL) patients (P = 0.13). No differences in CypB and CypD levels were showed between CAD patients and controls and between acute CAD and chronic CAD patients. In relation with CypC, the levels in CAD patients were significantly higher compared to controls (32.42 +/- 3.71 pg/mL vs. 9.38 +/- 1.51 pg/mL, P 17.5 pg/mL cut-off point, and it was significantly associated with older age, hypertension, dyslipidemia and more extensive CAD in acute and chronic CAD groups. Conclusions: CypA and CypC levels are increased in CAD patients. High CypC serum levels could be a novel biomarker in CAD patients correlating with a more severe disease

Review of seasonal heat storage in large basins: water tanks and gravel-water pits

In order to respond to climatic change, many efforts have been made to reduce harmful gas emissions. According to energy policies, an important goal is the implementation of renewable energy sources, as well as electrical and oil combustion savings through energy conservation. This paper focuses on an extensive review of the technologies developed, so far, for central solar heating systems employing seasonal sensible water storage in artificial large scale basins. Among technologies developed since the late 70s, the use of underground spaces as an energy storage medium - Underground Thermal Energy Storage (UTES) - has been investigated and closely observed in experimental plants in many countries, most of them, as part of government programmes. These projects attempt to optimise technical and economic aspects within an international knowledge exchange; as a result, UTES is becoming a reliable option to save energy through energy conservation. Other alternatives to UTES include large water tanks and gravel-water pits, also called man-made or artificial aquifers. This implies developing this technology by construction and leaving natural aquifers untouched. The present article reviews most studies and results obtained in this particular area to show the technical and economical feasibility for each system and specifics problems occurred during construction and operation. Advantages and disadvantages are pointed out to compare both alternatives. The projects discussed have been carried out mainly in European states with some references to other countries

Fungal plant pathogen “mutagenomics” reveals tagged and untagged mutations in Zymoseptoria tritici and identifies SSK2 as key morphogenesis and stress-responsive virulence factor

“Mutagenomics” is the combination of random mutagenesis, phenotypic screening, and whole-genome re-sequencing to uncover all tagged and untagged mutations linked with phenotypic changes in an organism. In this study, we performed a mutagenomics screen on the wheat pathogenic fungus Zymoseptoria tritici for altered morphogenetic switching and stress sensitivity phenotypes using Agrobacterium-mediated “random” T-DNA mutagenesis (ATMT). Biological screening identified four mutants which were strongly reduced in virulence on wheat. Whole genome re-sequencing defined the positions of the T-DNA insertion events and revealed several unlinked mutations potentially affecting gene functions. Remarkably, two independent reduced virulence mutant strains, with similarly altered stress sensitivities and aberrant hyphal growth phenotypes, were found to have a distinct loss of function mutations in the ZtSSK2 MAPKKK gene. One mutant strain had a direct T-DNA insertion affecting the predicted protein’s N-terminus, while the other possessed an unlinked frameshift mutation towards the C-terminus. We used genetic complementation to restore both strains’ wild-type (WT) function (virulence, morphogenesis, and stress response). We demonstrated that ZtSSK2 has a non-redundant function with ZtSTE11 in virulence through the biochemical activation of the stress-activated HOG1 MAPK pathway. Moreover, we present data suggesting that SSK2 has a unique role in activating this pathway in response to specific stresses. Finally, dual RNAseq-based transcriptome profiling of WT and SSK2 mutant strains revealed many HOG1-dependent transcriptional changes in the fungus during early infection and suggested that the host response does not discriminate between WT and mutant strains during this early phase. Together these data define new genes implicated in the virulence of the pathogen and emphasise the importance of a whole genome sequencing step in mutagenomic discovery pipelines

Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency

Induced pluripotent stem cells (iPSCs) are a powerful tool for disease modeling. They are routinely generated from healthy donors and patients from multiple cell types at different developmental stages. However, reprogramming leukemias is an extremely inefficient process. Few studies generated iPSCs from primary chronic myeloid leukemias, but iPSC generation from acute myeloid or lymphoid leukemias (ALL) has not been achieved. We attempted to generate iPSCs from different subtypes of B-ALL to address the developmental impact of leukemic fusion genes. OKSM(L)-expressing mono/polycistronic-, retroviral/lentiviral/episomal-, and Sendai virus vector-based reprogramming strategies failed to render iPSCs in vitro and in vivo. Addition of transcriptomic-epigenetic reprogramming ‘‘boosters’’ also failed to generate iPSCs from B cell blasts and B-ALL lines, and when iPSCs emerged they lacked leukemic fusion genes, demonstrating non-leukemic myeloid origin. Conversely, MLL-AF4-overexpressing hematopoietic stem cells/B progenitors were successfully reprogrammed, indicating that B cell origin and leukemic fusion gene were not reprogramming barriers. Global transcriptome/DNA methylome profiling suggested a developmental/differentiation refractoriness of MLL-rearranged B-ALL to reprogramming into pluripotency