Transcriptional analysis of nasal polyps fibroblasts reveals a new source of pro-inflammatory signaling in CRSwNP.

BACKGROUND: Fibroblasts and others mesenchymal cells have recently been identified as critical cells triggering tissue-specific inflammatory responses. Persistent activation of fibroblasts inflammatory program has been suggested as an underlying cause of chronic inflammation in a wide range of tissues and pathologies. Nevertheless, the role of fibroblasts in the emergence of chronic inflammation in the upper airway has not been previously addressed. We aimed to elucidate whether fibroblasts could have a role in the inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: We performed whole-transcriptome microarray in fibroblast cultured from CRSwNP samples and confirmed our results by qRT-PCR. We selected patients without other associated diseases in upper airway. To investigate shifts in transcriptional profile we used fibroblasts from nasal polyps and uncinate mucosae from patient with CRSwNP, and fibroblasts from uncinate mucosae from healthy subjects as controls. RESULTS: This study exposes activation of a pro-inflammatory and pro-fibrotic transcriptional program in nasal polyps and CRSwNP fibroblasts when compared to controls. Our Gene-set Enrichment Analysis (GSEA) pointed to common up-regulation of several pro-inflammatory pathways in patients-derived fibroblasts, along with higher mRNA expression levels of cytokines, growth factors and extracellular matrix components. CONCLUSIONS: Our work reveals a potential new source of inflammatory signaling in CRSwNP. Furthermore, our results suggest that deregulated inflammatory signaling in tissue-resident fibroblasts could support a Type-2 inflammatory response. Further investigations will be necessary to demonstrate the functionality of these novel results.

Monitoring a CuO gas sensor at work: an advanced in situ X-ray absorption spectroscopy study.

X-ray absorption near edge structure (XANES) and electrical measurements were used to elucidate the local structure and electronic changes of copper(II) oxide (CuO) nanostructures under working conditions. For this purpose, a sample holder layout was developed enabling the simultaneous analysis of the spectroscopic and electrical properties of the sensor material under identical operating conditions. The influence of different carrier gases (e.g., air and N2) on the CuO nanostructures behavior under reducing conditions (H2 gas) was studied to analyze how a particular gas atmosphere can modify the oxidation state of the sensor material in real time.

Effects of region of birth, educational level and age on late presentation among men who have sex with men newly diagnosed with HIV in a network of STI/HIV counselling and testing clinics in Spain.

This paper analyses late presentation (LP) of HIV infection, and its determinants, among men who have sex with men (MSM) in Spain, newly diagnosed with HIV (2003-2011) in 15 sexually transmitted infection/HIV counselling and testing clinics. LP was defined as <350 CD4 cells/µL or AIDS. In total, 3,081 MSM were included (2,499 having CD4/AIDS); overall LP was 25.3%. LP was higher in men older than 34 years, those not previously HIV-tested (adjusted odds ratio (aOR):3.1; 95% confidence intervals (CI):2.3-4.2) , and those tested > 12 months before diagnosis (12-24 months (aOR:1.4; 95% CI:1.0-2.0); > 24 months (aOR:2.2; 95% CI:1.7-3.0)). LP was less likely in MSM reporting a known HIV-infected partner as infection source or symptoms compatible with acute retroviral syndrome. 'Region of birth' interacted with 'educational level' and 'steady partner as infection source': only African and Latin-American MSM with low educational level were more likely to present late; Latin-American men attributing their infection to steady partner, but no other MSM, had LP more frequently. In Spain, HIV testing among MSM should be promoted, especially those > 34 years old and migrants with low educational level. The current recommendation that MSM be tested at least once a year is appropriate.

Zinc blende versus wurtzite ZnS nanoparticles: control of the phase and optical properties by tetrabutylammonium hydroxide.

The influence of tetrabutylammonium hydroxide on the phase composition (cubic zinc blende versus hexagonal wurtzite) of ZnS nanoparticles was studied. The ZnS nanoparticles were prepared by a microwave-assisted solvothermal method, and the phase structure and optical properties along with the growth process of ZnS nanoparticles were studied. We report XRD, FE-SEM, EDXS, UV-vis and PL measurements, and first-principles calculations based on TDDFT methods in order to investigate the structural and electronic properties and the growth mechanism of ZnS nanostructures. The effects as well as the merits of microwave heating on the process and characteristics of the obtained ZnS nanostructures and their performance are reported.

Controlled synthesis of layered Sn3O4 nanobelts by carbothermal reduction method and their gas sensor properties.

This paper reports both the controlled synthesis of Sn3O4 nanobelts by carbothermal reduction method and the gas sensor properties of these nanostructures. The synthesized material was characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray spectroscopy and gas sensor measurements. The results showed that the Sn3O4 nanobelts grow in a layered way and the careful control of experimental parameters is fundamental for stabilization of the correct phase. From the gas sensor measurements using oxygen as analyte gas, it was observed that the Sn3O4 nanobelts exhibit n-type behavior and both the sensitivity and the response time are dependent on the oxygen concentration. A model based on molecules adsorption was proposed to illustrate the mechanism of gas detection of these nanostructures. In summary, these results indicate that Sn3O4 nanobelts synthesized by carbothermal reduction method are promising to be applied as gas sensors.

Towards an insight on photodamage in hair fibre by UV-light: An experimental and theoretical study.

OBJECTIVES: In this research, an experimental and theoretical study was conducted to design a photodegradation mechanism of the amino acid tryptophan (Trp) in hair fibres. METHODS: For the experimental research, Caucasian hair fibres were exposed to several different solar radiation simulation periods. Then, Trp and its photoproducts (N-formylkynurenine and kynurenine) were assayed by excitation and emission spectroscopic analysis. RESULTS: For the theoretical study, reactions involved in the photodegradation of Trp were evaluated by high-level quantum mechanical calculations in a density functional theory (DFT) framework which indicate a probable Trp degradation mechanism with a minimum expended energy pathway. CONCLUSION: The biochemistry concerning these reactions is essentially important for a biological system where the degradation of Trp occurs.

Impact of prebriefing on emotions in a high-fidelity simulation session: A randomized controlled study.

INTRODUCTION: Medical simulation is associated with intense emotions which influence human behavior. We aim to investigate how prebriefing impacts on learners' emotions during a high-fidelity simulation (HFS) session. METHODS: This is a prospective randomized controlled study. Participants were randomly allocated to receive a standardized prebriefing (SP group) versus not receiving it (NSP group). Debriefing following the «good judgment¼ approach, structured in reactions, understanding and summary phases, was used in both groups. In order to assess emotions, we used the circumplex model of affect applying the Affect Grid scale, which was performed prior to prebriefing, following case performance and following debriefing. Debriefing times were also assessed. RESULTS: A total of 128 physicians participate in the study (64 vs. 64). Following case performance, this HFS session was experienced with significantly more pleasant emotions compared to baseline, that were maintained during debriefing (p < 0.01) while alertness increased after case performance diminishing after debriefing (p < 0.01). There were no statistical significant differences between groups. In the NSP group, total debriefing (p = 0.003) and understanding phase (p = 0.002) times were significantly longer. CONCLUSIONS: This HFS session was experienced as pleasant with high alertness with no specific emotional impact attributable to prebriefing. Prebriefing leads to a freer flowing debriefing.

Structure-specific amyloid precipitation in biofluids.

The composition of soluble toxic protein aggregates formed in vivo is currently unknown in neurodegenerative diseases, due to their ultra-low concentration in human biofluids and their high degree of heterogeneity. Here we report a method to capture amyloid-containing aggregates in human biofluids in an unbiased way, a process we name amyloid precipitation. We use a structure-specific chemical dimer, a Y-shaped, bio-inspired small molecule with two capture groups, for amyloid precipitation to increase affinity. Our capture molecule for amyloid precipitation (CAP-1) consists of a derivative of Pittsburgh Compound B (dimer) to target the cross ß-sheets of amyloids and a biotin moiety for surface immobilization. By coupling CAP-1 to magnetic beads, we demonstrate that we can target the amyloid structure of all protein aggregates present in human cerebrospinal fluid, isolate them for analysis and then characterize them using single-molecule fluorescence imaging and mass spectrometry. Amyloid precipitation enables unbiased determination of the molecular composition and structural features of the in vivo aggregates formed in neurodegenerative diseases.

Tranexamic acid use in severely injured patients, is it always appropriate?

Recently, it has been suggested that tranexamic acid should be administered only in those patients with hyperfibrinolysis determined using viscoelastic assays, as severely injured patients may present with fibrinolytic shutdown. However the last European guidelines on management of major bleeding and coagulopathy following trauma endorse the use of tranexamic acid to the trauma patient who is bleeding or at risk of significant hemorrhage as soon as possible without waiting for viscoelastic results. We present a severely blunt trauma patient treated with on-scene administration of tranexamic acid that developed immediate pulmonary embolism.

Tranexamic acid use in severely injured patients, is it always appropriate? / Ácido tranexámico en el paciente politraumatizado grave, ¿está siempre indicado?

Recently, it has been suggested that tranexamic acid should be administered only in those patients with hyperfibrinolysis determined using viscoelastic assays, as severely injured patients may present with fibrinolytic shutdown. However the last European guidelines on management of major bleeding and coagulopathy following trauma endorse the use of tranexamic acid to the trauma patient who is bleeding or at risk of significant hemorrhage as soon as possible without waiting for viscoelastic results. We present a severely blunt trauma patient treated with on-scene administration of tranexamic acid that developed immediate pulmonary embolism.

Monoacylglycerol lipase alpha inhibition alters prefrontal cortex excitability and blunts the consequences of traumatic stress in rat.

Neural activity within the ventromedial prefrontal cortex (vmPFC) is a critical determinant of stressor-induced anxiety. Pharmacological activation of the vmPFC during stress protects against stress-induced social anxiety suggesting that altering the excitatory/inhibitory (E/I) tone in the vmPFC may promote stress resilience. E/I balance is maintained, in part, by endogenous cannabinoid (eCB) signaling with the calcium dependent retrograde release of 2-arachidonoylglycerol (2-AG) suppressing presynaptic neurotransmitter release. We hypothesized that raising 2-AG levels, via inhibition of its degradation enzyme monoacylglycerol lipase (MAGL) with KML29, would shift vmPFC E/I balance and promote resilience. In acute slice experiments, bath application of KML29 (100 nM) augmented evoked excitatory neurotransmission as evidenced by a left-shift in fEPSP I/O curve, and decreased sIPSC amplitude. In whole-cell recordings, KML29 increased resting membrane potential but reduced the after depolarization, bursting rate, membrane time constant and slow after hyperpolarization. Intra-vmPFC administration of KML29 (200ng/0.5µL/hemisphere) prior to inescapable stress (IS) exposure (25, 5s tail shocks) prevented stress induced anxiety as measured by juvenile social exploration 24 h after stressor exposure. Conversely, systemic administration of KML29 (40 mg/kg, i.p.) 2 h before IS exacerbated stress induced anxiety. MAGL inhibition in the vmPFC may promote resilience by augmenting the output of neurons that project to brainstem and limbic structures that mediate stress responses.

Synaptic depression and cortical gain control.

Cortical neurons receive synaptic inputs from thousands of afferents that fire action potentials at rates ranging from less than 1 hertz to more than 200 hertz. Both the number of afferents and their large dynamic range can mask changes in the spatial and temporal pattern of synaptic activity, limiting the ability of a cortical neuron to respond to its inputs. Modeling work based on experimental measurements indicates that short-term depression of intracortical synapses provides a dynamic gain-control mechanism that allows equal percentage rate changes on rapidly and slowly firing afferents to produce equal postsynaptic responses. Unlike inhibitory and adaptive mechanisms that reduce responsiveness to all inputs, synaptic depression is input-specific, leading to a dramatic increase in the sensitivity of a neuron to subtle changes in the firing patterns of its afferents.

HIV/STI co-infection among men who have sex with men in Spain.

In Spain, neither the HIV nor the STI national surveillance systems collect information on HIV/STI co-infection. However, there are two networks based on HIV/STI clinics which gather this data. We describe HIV prevalence in men who have sex with men (MSM) diagnosed with infectious syphilis and/or gonorrhoea in 15 STI clinics; and concurrent diagnoses of STI in MSM newly diagnosed with HIV in 19 HIV/STI clinics. In total, 572 MSM were diagnosed with infectious syphilis and 580 with gonorrhoea during 2005-2007. HIV prevalence among syphilis and gonorrhoea cases was 29.8% and 15.2% respectively. In the multivariate analysis, HIV/syphilis co-infection was associated with being Latin American; having a history of STI; reporting exclusively anal intercourse; and having sex with casual or several types of partners. HIV and gonorrhoea co-infection was associated with age older than 45 years; having no education or only primary education completed; and having a history of STI. In total, 1,462 HIV infections were newly diagnosed among MSM during 2003-2007. Of these, 31.0% were diagnosed with other STI at the same time. Factors associated with STI co-infection among new HIV cases in MSM were being Latin American; and having sex with casual partners or with both steady and casual partners. In Spain, a considerable proportion of MSM are co-infected with HIV and STI.

Emotional response to a high-fidelity trauma simulation: An observational study. / Respuesta emocional a una simulación de alta fidelidad en trauma: Un estudio observacional.

INTRODUCTION: The emotional environment created during a simulation session can influence learning. Positive emotions improve perceptual processing and facilitate learning, while negative emotions can reduce working memory, resulting in poorer learning outcomes. OBJECTIVES: The aim of this study was to investigate the impact of simulation training on emotions during all phases of a high-fidelity simulation using standard prebriefing and «good judgement debriefing ¼ techniques. METHODS: This was an observational study that included 74 anesthesiologists participating in a simulation-based training. A standardized prebriefing was followed by «good judgement debriefing¼. In order to assess emotions, we used the circumplex model of emotion, and asked participants to complete the affect grid scale before prebriefing (Stage 1), before starting the simulation (Stage 2), before debriefing (Stage 3) and following debriefing (Stage 4). RESULTS: The affect grid scores obtained from 67 participants were analyzed. Following debriefing, the experience of the polytrauma patient simulation was significantly more pleasant compared to previous stages (P<0.01). In addition, participants perceived the activity as becoming increasingly active as it progressed (P<0.01). CONCLUSIONS: High-fidelity trauma simulation creating a safe environment using a standardized prebriefing and «good judgement debriefing¼ is experienced as a pleasant and active activity at all stages of the simulation. Further investigation is needed to assess the impact of these results on learning.

Influence of structural disorder on the photoluminescence emission of PZT powders.

Intense and broad visible photoluminescent (PL) band was observed at room temperature in disordered Pb(Zr0.53Ti0.47)O3 powders. Structural order-disorder was evaluated by different methods. XANES results pointed to the presence of different coordination modes of disordered Ti powders, and in the ordered sample the local structure around titanium atoms is characteristic of the structurally ordered PZT with only TiO6 units. Only samples containing simultaneous structural order and disorder in their network present the intense visible PL emission at room temperature.

Photoluminescence of barium titanate and barium zirconate in multilayer disordered thin films at room temperature.

The emission of wide band photoluminescence showed a synergic effect on barium zirconate and barium titanate thin films in alternate multilayer system at room temperature by 488 nm exiting wavelength. The thin films obtained by spin-coating were annealed at 350, 450, and 550 degrees C for 2 h. The X-ray patterns revealed the complete separation among the BaTiO3 and BaZrO3 phases in the adjacent films. Visible and intense photoluminescence was governed by BaZrO3 thin films in the multilayer system. Quantum mechanics calculations were used in order to simulate ordered and disordered thin films structures. The disordered models, which were built by using the displacement of formers and modifier networks, showed a different symmetry in each system, which is in accordance with experimental photoluminescence emission, thus allowing to establish a correlation among the structural and optical properties of these multilayered systems.

Toward an understanding of intermediate- and short-range defects in ZnO single crystals. A combined experimental and theoretical study.

A joint use of experimental and theoretical techniques allows us to understand the key role of intermediate- and short-range defects in the structural and electronic properties of ZnO single crystals obtained by means of both conventional hydrothermal and microwave-hydrothermal synthesis methods. X-ray diffraction, Raman spectra, photoluminescence, scanning electronic and transmission electron microscopies were used to characterize the thermal properties, crystalline and optical features of the obtained nano and microwires ZnO structures. In addition, these properties were further investigated by means of two periodic models, crystalline and disordered ZnO wurtzite structure, and first principles calculations based on density functional theory at the B3LYP level. The theoretical results indicate that the key factor controlling the electronic behavior can be associated with a symmetry breaking process, creating localized electronic levels above the valence band.

[Pneumomediastinum and extensive subcutaneous emphysema after normal labor]. / Neumomediastino y enfisema subcutáneo extenso tras parto eutócico.

Spontaneous pneumomediastinum associated with subcutaneous emphysema is a rare, though life-threatening, complication of late pregnancy and labor. We report the case of a primipara who, after undergoing normal labor and delivery of a normal-weight baby, developed pneumomediastinum and extensive subcutaneous emphysema with significant symptoms within minutes of delivery. This peripartum complication is usually self-limiting when the aggravating factors are no louguer present. Management includes strict monitoring of the patient and conservative treatment of symptoms.

Breath-holding test in subjects with near-fatal asthma. A new index for dyspnea perception.

RATIONALE: Identification of asthmatic subjects with low perception of dyspnea (POD) that are at higher risk of hospitalization, near-fatal and fatal asthma could improve their management. OBJECTIVE: Create a simple procedure that facilitate the recognition of low POD. METHODS: We enrolled near fatal asthma (NFA) subjects and a wide spectrum of non-NFA subjects. Each subject was asked to stop breathing at end-expiration. Dyspnea was assesssed by a modified Borg scale. To design the new index, we combined the Borg score at the end of the voluntary breath-holding maneuver with the airway limitation. The equation was as follows: FEV(1)/FVC%/(breath-holding time in seconds/final Borg score minus basal Borg score). RESULTS: Eleven NFA subjects (4 females) aged 21-73yr and 55 non-NFA (14 severe, 18 moderate and 23 mild asthmatic subjects) completed the study. The threshold value of the index that could predict POD is <12. The mean (+/-sd) of the new index perception was significantly lower in NFA group (n=11; 5.21+/-3.59; vs. n=55; 13.67+/-11.08; P=0.006). This threshold value had 100% sensitivity and it best discriminated between mild and NFA groups. The negative likelihood ratio (when the index > or = 12) was zero. A result > or = 12 represented an almost null probability of poor POD. CONCLUSION: The breath-holding test is simple and rapid. Its negative likelihood ratio was zero. Accordingly, a test result of 12 or greater might exclude the probability of poor perception of dyspnea in subjects with stable asthma.

An automated method to find reaction mechanisms and solve the kinetics in organometallic catalysis.

A novel computational method is proposed in this work for use in discovering reaction mechanisms and solving the kinetics of transition metal-catalyzed reactions. The method does not rely on either chemical intuition or assumed a priori mechanisms, and it works in a fully automated fashion. Its core is a procedure, recently developed by one of the authors, that combines accelerated direct dynamics with an efficient geometry-based post-processing algorithm to find transition states (Martinez-Nunez, E., J. Comput. Chem.2015, 36, 222-234). In the present work, several auxiliary tools have been added to deal with the specific features of transition metal catalytic reactions. As a test case, we chose the cobalt-catalyzed hydroformylation of ethylene because of its well-established mechanism, and the fact that it has already been used in previous automated computational studies. Besides the generally accepted mechanism of Heck and Breslow, several side reactions, such as hydrogenation of the alkene, emerged from our calculations. Additionally, the calculated rate law for the hydroformylation reaction agrees reasonably well with those obtained in previous experimental and theoretical studies.