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

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

The Broad Concept of "Spasticity-Plus Syndrome" in Multiple Sclerosis: A Possible New Concept in the Management of Multiple Sclerosis Symptoms

Multiple sclerosis (MS) pathology progressively affects multiple central nervous system (CNS) areas. Due to this fact, MS produces a wide array of symptoms. Symptomatic therapy of one MS symptom can cause or worsen other unwanted symptoms (anticholinergics used for bladder dysfunction produce impairment of cognition, many MS drugs produce erectile dysfunction, etc.). Appropriate symptomatic therapy is an unmet need. Several important functions/symptoms (muscle tone, sleep, bladder, pain) are mediated, in great part, in the brainstem. Cannabinoid receptors are distributed throughout the CNS irregularly: There is an accumulation of CB1 and CB2 receptors in the brainstem. Nabiximols (a combination of THC and CBD oromucosal spray) interact with both CB1 and CB2 receptors. In several clinical trials with Nabiximols for MS spasticity, the investigators report improvement not only in spasticity itself, but also in several functions/symptoms mentioned before (spasms, cramps, pain, gait, sleep, bladder function, fatigue, and possibly tremor). We can conceptualize and, therefore, hypothesize, through this indirect information, that it could be considered the existence of a broad "Spasticity-Plus Syndrome" that involves, a cluster of symptoms apart from spasticity itself, the rest of the mentioned functions/symptoms, probably because they are interlinked after the increase of muscle tone and mediated, at least in part, in the same or close areas of the brainstem. If this holds true, there exists the possibility to treat several spasticity-related symptoms induced by MS pathology with a single therapy, which would permit to avoid the unnecessary adverse effects produced by polytherapy. This would result in an important advance in the symptomatic management of MS

Temperature but not leptin prevents semi-starvation induced hyperactivity in rats: implications for anorexia nervosa treatment

The hypothesis linking hyperactivity with weight loss associated hypoleptinemia in anorexia nervosa gained momentum after a study showing that leptin suppressed semi-starvation induced hyperactivity in rats. Alternatively, ambient temperature is a key modulating factor of activity in semi-starved rats. The aim of the study is to compare the efficacy of leptin with increased ambient temperature in the prevention of hyperactivity in semi-starved rats. 74 Sprague-Dawley male rats were employed in two experiments with the difference residing in the length of baseline. After an extended (28 days), or shorter (14 days) baseline with free access to food and the running wheel, housed at 21 degrees C, animals were either ad-lib feed or food restricted (60% of food ingested during previous week) and infused with same amount of leptin at 21 degrees C, 25 degrees C, or vehicle at 21 degrees C, 25 degrees C and 32 degrees C for a week. Animals housed at 32 degrees C significantly reduced wheel running and weight loss during food restriction while animals given leptin did not yield no differences in activity or weight loss. Moreover, unlike animals housed at 32 degrees C, body temperature of leptin infused animals housed at 21 degrees C was significantly reduced during food restriction. Furthermore, leptin treated rats without a preceding stable pattern of activity displayed a severe dysregulation of circadian rhythm in activity and a collapse of body temperature. Housing temperature plays a more critical role than leptin in the regulation of semi-starvation induced hyperactivity in rats, which may be of relevance for the management of hyperactivity in anorexia nervosa

The social return on investment of a new approach to heart failure in the Spanish National Health System

AIMS: We aim to agree on a set of proposals to improve the current management of heart failure (HF) within the Spanish National Health System (SNHS) and apply the social return on investment (SROI) method to measure the social impact that these proposals would generate. METHODS AND RESULTS: A multidisciplinary working team of 16 experts was set up, with representation from the main stakeholders regarding HF: medical specialists (cardiologists, internal medicine physicians, general practitioners, and geriatric physicians), nursing professionals, health management professionals, patients, and informal caregivers. This team established a set of proposals to improve the management of HF according to the main areas of HF care: emergency and hospitalization, primary care, cardiology, and internal medicine. A forecast-type SROI method, with a 1-year time frame, was applied to measure the social impact resulting from the implementation of these proposals. The required investment and social return were estimated and summarized into a ratio indicating how much social return could be generated for each euro invested. Intangible returns were included and quantified through financial proxies. The approach to improve the management of HF consisted of 28 proposals, including the implementation of a case management nurse network, standardization of operational protocols, psychological support, availability of echocardiography machines at emergency departments, stationary units and primary care, early specialist visits after hospital discharge, and cardiac rehabilitation units, among others. These proposals would benefit not only patients and their informal caregivers but also the SNHS. Regarding patients, proposals would increase their autonomy in everyday activities, decrease anxiety, increase psychological and physical well-being, improve pharmacological adherence and self-care, enhance understanding of the disease, delay disease progression, expedite medical assessment, and prevent the decrease in work productivity associated with HF management. Regarding informal caregivers, proposals would increase their quality of life; improve their social, economic, and emotional well-being; and reduce their care burden. The SNHS would benefit from shorter stays of HF patients at intensive care units and reduction of hospitalizations and admissions to emergency departments. The investment needed to implement these proposals would amount to euro548m and yield a social return of euro1932m, that is, euro3.52 for each euro invested. CONCLUSIONS: The current management of HF could be improved by a set of proposals that resulted in an overall positive social return, varying between areas of analysis. This may guide the allocation of healthcare resources and improve the quality of life of patients with HF

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