Systemic Effects Induced by Hyperoxia in a Preclinical Model of Intra-abdominal Sepsis

Supplemental oxygen is a supportive treatment in patients with sepsis to balance tissue oxygen delivery and demand in the tissues. However, hyperoxia may induce some pathological effects. We sought to assess organ damage associated with hyperoxia and its correlation with the production of reactive oxygen species (ROS) in a preclinical model of intra-abdominal sepsis. For this purpose, sepsis was induced in male, Sprague-Dawley rats by cecal ligation and puncture (CLP). We randomly assigned experimental animals to three groups: control (healthy animals), septic (CLP), and sham-septic (surgical intervention without CLP). At 18 h after CLP, septic (n = 39), sham-septic (n = 16), and healthy (n = 24) animals were placed within a sealed Plexiglas cage and randomly distributed into four groups for continuous treatment with 21%, 40%, 60%, or 100% oxygen for 24 h. At the end of the experimental period, we evaluated serum levels of cytokines, organ damage biomarkers, histological examination of brain and lung tissue, and ROS production in each surviving animal. We found that high oxygen concentrations increased IL-6 and biomarkers of organ damage levels in septic animals, although no relevant histopathological lung or brain damage was observed. Healthy rats had an increase in IL-6 and aspartate aminotransferase at high oxygen concentration. IL-6 levels, but not ROS levels, are correlated with markers of organ damage. In our study, the use of high oxygen concentrations in a clinically relevant model of intra-abdominal sepsis was associated with enhanced inflammation and organ damage. These findings were unrelated to ROS release into circulation. Hyperoxia could exacerbate sepsis-induced inflammation, and it could be by itself detrimental. Our study highlights the need of developing safer thresholds for oxygen therapy

Quasi-Exact Solvability and the direct approach to invariant subspaces

We propose a more direct approach to constructing differential operators that preserve polynomial subspaces than the one based on considering elements of the enveloping algebra of sl(2). This approach is used here to construct new exactly solvable and quasi-exactly solvable quantum Hamiltonians on the line which are not Lie-algebraic. It is also applied to generate potentials with multiple algebraic sectors. We discuss two illustrative examples of these two applications: an interesting generalization of the Lam\'e potential which posses four algebraic sectors, and a quasi-exactly solvable deformation of the Morse potential which is not Lie-algebraic.Comment: 17 pages, 3 figure

Dislocations in Si-Doped LEC GaAs Revisited: a Spectrum Image Cathodoluminescence Study

The understanding of the role of impurities is crucial to semiconductor device technology, since all the devices are engineered by the selective incorporation of impurities. However, the incorporation of these impurities to the lattice and the resulting free charge concentration depend on the interaction with native defects. Dislocations in Si-doped substrates were studied in the nineties using highly sensitive DSL (Diluted Sirtl-Like) etching, SEM-EBIC (Electron Beam Induced Current) and microPL techniques. Both grown-in (G) dislocations, and grown-in dislocations glided (GS) by thermal stresses during post growth cooling were investigated aiming to understand the interaction between the dislocations and the doped GaAs matrix. CL spectrum imaging allows revisiting this problem supplying information about the defects forming the Cottrell atmospheres, and how they are distributed. By using a CCD multichannel detector it is possible to obtain the full spectral information over a selected area with submicrometric spatial resolution. The local spectra corresponding to the different regions of the dislocation atmosphere are available, allowing the identification of the different defects responsible for the luminescence emission. On the other hand, the use of fitting routines allows mapping the distribution of the different defects and impurities, providing a full scenario of the Cottrell atmosphere. The CL images are complemented with etching depth (using DSL) images obtained by Phase Stepping Microscopy

Increasing Competitiveness through the Implementation of Lean Management in Healthcare

The main aim of this paper was two-fold: first, to design a participative methodology that facilitates lean management implementation in healthcare by adopting the action research approach; second, to illustrate the usefulness of this methodology by applying it to the sleep unit of a public hospital in Spain. This methodology proposes the implementation of lean management in its broadest sense: adopting both lean principles and some of its practical tools or practices in order to achieve competitive advantage. The complete service value chain was considered when introducing changes through lean management implementation. This implementation involved training and involving staff in the project (personnel pillar), detecting and analysing "waste" in value chain processes (processes pillar) and establishing control and measurement mechanisms in line with objectives (key performance indicators pillar) and putting in place improvement actions to achieve these objectives. The application of this methodology brought about an improvement in the management of patient flow in terms of effectiveness, efficiency and quality but also an internal transformation towards lean culture

Psychiatric comorbidities in Asperger syndrome are related with polygenic overlap and differ from other Autism subtypes

There is great phenotypic heterogeneity within autism spectrum disorders (ASD), which has led to question their classification into a single diagnostic category. The study of the common genetic variation in ASD has suggested a greater contribution of other psychiatric conditions in Asperger syndrome (AS) than in the rest of the DSM-IV ASD subtypes (Non_AS). Here, using available genetic data from previously performed genome-wide association studies (GWAS), we aimed to study the genetic overlap between five of the most related disorders (schizophrenia (SCZ), major depression disorder (MDD), attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorders (OCD) and anxiety (ANX)), and AS, comparing it with the overlap in Non_AS subtypes. A Spanish cohort of autism trios (N = 371) was exome sequenced as part of the Autism Sequencing Consortium (ASC) and 241 trios were extensively characterized to be diagnosed with AS following DSM-IV and Gillberg's criteria (N = 39) or not (N = 202). Following exome imputation, polygenic risk scores (PRS) were calculated for ASD, SCZ, ADHD, MDD, ANX, and OCD (from available summary data from Psychiatric Genomic Consortium (PGC) repository) in the Spanish trios' cohort. By using polygenic transmission disequilibrium test (pTDT), we reported that risk for SCZ (Pscz = 0.008, corrected-PSCZ = 0.0409), ADHD (PADHD = 0.021, corrected-PADHD = 0.0301), and MDD (PMDD = 0.039, corrected-PMDD = 0.0501) is over-transmitted to children with AS but not to Non_AS. Indeed, agnostic clustering procedure with deviation values from pTDT tests suggested two differentiated clusters of subjects, one of which is significantly enriched in AS (P = 0.025). Subsequent analysis with S-Predixcan, a recently developed software to predict gene expression from genotype data, revealed a clear pattern of correlation between cortical gene expression in ADHD and AS (P < 0.001) and a similar strong correlation pattern between MDD and AS, but also extendable to another non-brain tissue such as lung (P < 0.001). Altogether, these results support the idea of AS being qualitatively distinct from Non_AS autism and consistently evidence the genetic overlap between AS and ADHD, MDD, or SCZ

Innovation, R&D and Productivity in the Costa Rican ICT Sector: A Case Study

This paper addresses the relationships between innovation, research and development (R&D) and productivity in domestic ICT firms in Costa Rica. Factors considered were the types of innovation outputs produced by domestic ICT firms, the relative importance of innovation inputs, the impacts of innovation on firm productivity, the protection of innovations, and impediments to innovation. While most firms engaged in all types of output and input innovations, they appear to be driven by retaining or increasing market share rather than increasing productivity. Half of firms do not formally protect the intellectual property created by their innovations, are not familiar with methods for protecting innovation or the availability of government grants for such purposes, and face barriers associated with the Costa Rican Patent Office. Other impediments include lack of knowledge about financial resources available and scarcity of human resources. There is also evidence of knowledge spillovers through worker mobility from multinationals operating in Costa Rica to domestic ICT firms

Study of factors influencing preoperative detection of alveolar antral artery by CBCT in sinus floor elevation

This study aimed at assessing the prevalence of alveolar antral artery (AAA) detection by CBCT, its related variables, and at describing explanatory models useful in surgical planning, by retrospective evaluation of CBCT explorations. The modelling of the probability for detecting AAA was undertaken using logistic generalized additive models (GAM). The capacity for discriminating detection/no detection was assessed by receiver operating characteristic curves. A total of 466 sinuses were studied. Univariate models showed detection probability was linked to sinus width and thickness of the lateral bony wall, together with the shape and height of the osseous crest. AAA detection probability increased steadily until the thickness of the bony wall reached 6 mm. Multivariate models resulted good discriminators for AAA detection, particularly for females, showing an area under the curve (AUC) of 0.85. Models considering patients altogether, and those including only males offered slightly lower values (AUC = 0.79). The probability of AAA detection by CBCT was influenced by gender (higher in males and for narrow sinuses) and increases with the thickness of the sinus lateral bony wall and the height of the residual alveolar ridge. Besides, and particularly for women, the thickness of the ridge at the basal level seems to improve the explanatory model for AAA detection

Lipidomics Reveals Reduced Inflammatory Lipid Species and Storage Lipids after Switching from EFV/FTC/TDF to RPV/FTC/TDF: A Randomized Open-Label Trial

HIV and antiretroviral therapy affect lipid metabolism. Lipidomics quantifies several individual species that are overlooked using conventional biochemical analyses, outperforming traditional risk equations. We aimed to compare the plasma lipidomic profile of HIV patients taking efavirenz (EFV) or rilpivirine (RPV). Patients >/= 18 years old on EFV co-formulated with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) with HIV-RNA /=6 months were randomized to continue EFV/FTC/TDF (n = 14) or switch to RPV/FTC/TDF (n =15). Lipidomic analyses conducted by mass spectrometry (MS) were performed at baseline and after 12 and 24 weeks. OWLiver((R)) Care and OWLiver((R)) tests were performed to estimate the presence of fatty liver disease (NAFLD). No significant differences (83% male, median age 44 years, 6 years receiving EFV/FTC/TDF, CD4(+) count 740 cells/mm(3), TC 207 [57 HDL-C/133 LDL-C] mg/dL, TG 117 mg/dL) were observed between the groups at baseline. Significant reductions in plasma lipids and lipoproteins but increased circulating bilirubin concentrations were observed in patients who switched to RPV/FTC/TDF. Patients on RPV/FTC/TDF showed a decrease in the global amount of storage lipids (-0.137 log2 [fold-change] EFV vs. 0.059 log2 [fold-change] RPV) but an increase in lysophosphatidylcholines (LPCs) and total steroids. Compared with EFV, RPV increased metabolites with anti-inflammatory properties and reduced the repository of specific lipotoxic lipids

Points to consider in cardiovascular disease risk management among patients with rheumatoid arthritis living in South Africa, an unequal middle income country

Background: It is plausible that optimal cardiovascular disease (CVD) risk management differs in patients with rheumatoid arthritis (RA) from low or middle income compared to high income populations. This study aimed at producing evidence-based points to consider for CVD prevention in South African RA patients. Methods: Five rheumatologists, one cardiologist and one epidemiologist with experience in CVD risk management in RA patients, as well as two patient representatives, two health professionals and one radiologist, one rheumatology fellow and 11 rheumatologists that treat RA patients regularly contributed. Systematic literature searches were performed and the level of evidence was determined according to standard guidelines. Results: Eighteen points to consider were formulated. These were grouped into 6 categories that comprised overall CVD risk assessment and management (n = 4), and specific interventions aimed at reducing CVD risk including RA control with disease modifying anti-rheumatic drugs, glucocorticoids and non-steroidal anti-inflammatory drugs (n = 3), lipid lowering agents (n = 8), antihypertensive drugs (n = 1), low dose aspirin (n = 1) and lifestyle modification (n = 1). Each point to consider differs partially or completely from recommendations previously reported for CVD risk management in RA patients from high income populations. Currently recommended CVD risk calculators do not reliably identify South African black RA patients with very high-risk atherosclerosis as represented by carotid artery plaque presence on ultrasound. Conclusions: Our findings indicate that optimal cardiovascular risk management likely differs substantially in RA patients from low or middle income compared to high income populations. There is an urgent need for future multicentre longitudinal studies on CVD risk in black African patients with RA

Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma

Increasing evidence supports a potential role for STAT3 as a tumor driver in cutaneous T-cell lymphomas (CTCL). The mechanisms leading to STAT3 activation are not fully understood; however, we recently found that miR-124, a known STAT3 regulator, is robustly silenced in MF tumor-stage and CTCL cells. OBJECTIVE: We studied here whether deregulation of miR-124 contributes to STAT3 pathway activation in CTCL. METHODS: We measured the effect of ectopic mir-124 expression in active phosphorylated STAT3 (p-STAT3) levels and evaluated the transcriptional impact of miR-124-dependent STAT3 pathway regulation by expression microarray analysis. RESULTS: We found that ectopic expression of miR-124 results in massive downregulation of activated STAT3 in different CTCL lines, which resulted in a significant alteration of genetic signatures related with gene transcription and proliferation such as MYC and E2F. CONCLUSIONS: Our study highlights the importance of the miR-124/STAT3 axis in CTCL and demonstrates that the STAT3 pathway is regulated through epigenetic mechanisms in these cells. Since deregulated STAT3 signaling has a major impact on CTCL initiation and progression, a better understanding of the molecular basis of the miR-124/STAT3 axis may provide useful information for future personalized therapies