Analysis of viral pneumonia and risk factors associated with severity of influenza virus infection in hospitalized patients from 2012 to 2016.

BACKGROUND: Influenza viruses cause pneumonia in approximately one-third of cases, and pneumonia is an important cause of death. The aim was to identify risk factors associated with severity and those that could predict the development of pneumonia. METHODS: This retrospective, observational study included all adult patients with confirmed influenza virus infection admitted to Son Espases University Hospital during four influenza seasons in Spain (October to May) from to 2012-2016. RESULTS: Overall, 666 patients with laboratory-confirmed influenza were included, 93 (14%) of which were severe; 73 (10.9%) were admitted to Intensive Care Unit (ICU), 39 (5.8%) died, and 185 (27.7%) developed pneumonia. Compared to less severe cases, patients with severe disease: were less vaccinated (40% vs. 28%, p = 0.021); presented with more confusion (26.9% vs. 6.8%), were more hypoxemic (Horowitz index (PaO2/FiO2) 261 vs. 280), had higher C-reactive protein (CRP) (12.3 vs. 4.0), had more coinfections (26.8% vs. 6.3%) and had more pleural effusion (14% vs. 2.6%) (last six all p < 0.001). Risk factors significantly associated with severity were pneumonia [OR (95% CI) = 4.14 (2.4-7.16)], history of heart disease (1.84, 1.03-3.28), and confusion at admission (4.99, 2.55-9.74). Influenza vaccination was protective (0.53, 0.28-0.98). Compared to those without pneumonia, the pneumonia group had higher CRP (11.3 vs. 4.0, p < 0.001), lower oxygen saturation (92% vs. 94%, p < 0.001), were more hypoxic (PaO2/FiO2 266 vs. 281, p < 0.001), and incurred more mechanical ventilation, septic shock, admission to the ICU, and deaths (all four p < 0.001). Higher CRP and lower oxygen saturation were independent variables for predicting the development of pneumonia. CONCLUSIONS: Pneumonia, history of heart disease, confusion and no influenza vaccination were independent variables to present complications in patients admitted with influenza infection.

Effects of chronic hydrogen peroxide exposure on mitochondrial oxidative stress genes, ROS production and lipid peroxidation in HL60 cells.

Hydrogen peroxide (H2O2) is a reactive species that is also involved in the redox regulation of cells because of it is relative stability. In numerous pathological situations, a chronic increase in the production of reactive species is observed, which is related to oxidative stress and cellular damage. This study aimed to evaluate the effects of long-term exposure to different H2O2 concentrations on oxidative stress biomarkers and mitochondrial dynamics in HL60 cells. HL60 cells were treated with a sustained production (0.1, 1.0 and 10.0 nM/s) of H2O2 for one hour. H2O2 production and malondialdehyde (MDA) levels, as a lipid peroxidation marker, increased progressively in HL60 cells in accordance with higher H2O2 exposure, with significant differences between the 10 nM/s H2O2 group and the control and 0.1 nM/s groups. Similarly, progressive increased expression in genes related to the mitochondrial antioxidant defences and mitochondrial dynamics were also observed. Significantly increased gene expression in the 10 nM/s H2O2 with respect to the control group was observed for manganese superoxide dismutase (MnSOD), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PCG1α), nuclear respiratory factor 2 (Nrf2), mitochondrial transcription factor A (Tfam), mitofusins 1 and 2 (Mfn1 and Mfn2) and uncoupling protein 3 (UCP3), whereas no significant changes were observed in the cytochrome c oxidase subunit IV (COXIV) gene expression. In conclusion, exposure to different sustained production of H2O2 is related to a progressive increase in the gene expression of mitochondrial dynamics and redox processes in HL60 cells, but also to oxidative damage at higher H2O2 production levels.

Parameter and coupling estimation in small networks of Izhikevich's neurons.

Nowadays, experimental techniques allow scientists to have access to large amounts of data. In order to obtain reliable information from the complex systems that produce these data, appropriate analysis tools are needed. The Kalman filter is a frequently used technique to infer, assuming a model of the system, the parameters of the model from uncertain observations. A well-known implementation of the Kalman filter, the unscented Kalman filter (UKF), was recently shown to be able to infer the connectivity of a set of coupled chaotic oscillators. In this work, we test whether the UKF can also reconstruct the connectivity of small groups of coupled neurons when their links are either electrical or chemical synapses. In particular, we consider Izhikevich neurons and aim to infer which neurons influence each other, considering simulated spike trains as the experimental observations used by the UKF. First, we verify that the UKF can recover the parameters of a single neuron, even when the parameters vary in time. Second, we analyze small neural ensembles and demonstrate that the UKF allows inferring the connectivity between the neurons, even for heterogeneous, directed, and temporally evolving networks. Our results show that time-dependent parameter and coupling estimation is possible in this nonlinearly coupled system.

Inferring the connectivity of coupled chaotic oscillators using Kalman filtering.

Inferring the interactions between coupled oscillators is a significant open problem in complexity science, with multiple interdisciplinary applications. While the Kalman filter (KF) technique is a well-known tool, widely used for data assimilation and parameter estimation, to the best of our knowledge, it has not yet been used for inferring the connectivity of coupled chaotic oscillators. Here we demonstrate that KF allows reconstructing the interaction topology and the coupling strength of a network of mutually coupled Rössler-like chaotic oscillators. We show that the connectivity can be inferred by considering only the observed dynamics of a single variable of the three that define the phase space of each oscillator. We also show that both the coupling strength and the network architecture can be inferred even when the oscillators are close to synchronization. Simulation results are provided to show the effectiveness and applicability of the proposed method.

Non-invasive high-speed blinking kinematics characterization.

PURPOSE: The objective of this study was to analyze the differences in blinking kinematics of spontaneous and voluntary blinks using for the first time a self-developed, non-invasive, and image processing-based method. METHODS: The blinks of 30 subjects were recorded for 1 min with the support of an eye-tracking device based on a high-speed infrared video camera, working at 250 frames per second, under two different experimental conditions. For the first condition, subjects were ordered to look in the straightforward position at a fixation target placed 1 m in front of them, with no further instructions. For the second, subjects were additionally asked to blink only following a sound signal every 6 s. RESULTS: Mean complete blinks increased by a factor of 1.7 from the spontaneous to the voluntary condition while mean incomplete blinks reduced significantly by a factor of 0.4. In both conditions, closing mean and peak velocities were always significantly greater and durations significantly lower than opening ones. When comparing the values for each condition, velocities and amplitudes for the voluntary condition were always greater than the corresponding values for spontaneous. CONCLUSION: Voluntary blinks revealed significant kinematic differences compared to spontaneous, thus supporting a different supranuclear pathway organization. This study presents a new method, based on image analysis, for the non-invasive kinematic characterization of blinking.

Simultaneous analysis of saturated and unsaturated oxylipins in 'ex vivo' cultured peripheral blood mononuclear cells and neutrophils.

Oxylipins are a family of saturated and unsaturated fatty acids peroxidation products with bioactive properties. We have developed an improved method for the measurement of ex vivo oxylipin production by peripheral blood mononuclear cells (PBMCs) and neutrophils. We aimed to develop an analytical method to determine the production rates of polyunsaturated fatty acids (PUFAs), PUFA-oxylipin, and saturated-oxylipins by stimulated PBMCs and neutrophils based on solid phase extraction and HPLC-MS/MS technology. A UHPLC system coupled to a Q-Exactive Hybrid Quadrupole-Orbitrap mass spectrometer was used to identify and quantify oxylipin production. For each oxylipin and PUFA their differential response was calculated with respect to a deuterated internal standard factor (ISF). To calculate oxylipin and PUFAs in the culture samples, the individual ISF was used for each oxylipin and PUFA with respect to the deuterated internal standard. PBMCs and neutrophils showed a different pattern of oxylipin production and fatty acid secretion. Lipopolysaccharide (LPS) did not stimulate oxylipin production or fatty acids secretion in PBMCs, whereas phorbol myristate acetate (PMA) stimulation increased the production rate of 5-HETE, 15-HETE, 15-HEPE, 17-DoHE, PGE2, AA, and DHA. LPS stimulation decreased 16-hydroxyl-palmitatte (16-OHPAL) production and DHA secretion in neutrophils, while PMA stimulation increased the production rate of AA and its derivate oxylipins, 5-HETE, 15-HETE, and PGE2. In conclusion, we have developed a new method to determine oxylipins derived from both saturated and unsaturated fatty acids in culture cell media. This method has enough sensitivity, and accuracy, to determine oxylipin production and fatty acid secretion by PBMCs and neutrophils.

Activation of innate immunity by 14-3-3 ε, a new potential alarmin in osteoarthritis.

OBJECTIVE: The innate immune system plays a central role in osteoarthritis (OA). We identified 14-3-3ε as a novel mediator that guides chondrocytes toward an inflammatory phenotype. 14-3-3ε shares common characteristics with alarmins. These endogenous molecules, released into extracellular media, are increasingly incriminated in sustaining OA inflammation. Alarmins bind mainly to toll-like receptor 2 (TLR2) and TLR4 receptors and polarize macrophages in the synovium. We investigated the effects of 14-3-3ε in joint cells and tissues and its interactions with TLRs to define it as a new alarmin involved in OA. DESIGN: Chondrocyte, synoviocyte and macrophage cultures from murine or OA human samples were treated with 14-3-3ε. To inhibit TLR2/4 in chondrocytes, blocking antibodies were used. Moreover, chondrocytes and bone marrow macrophage (BMM) cultures from knockout (KO) TLRs mice were stimulated with 14-3-3ε. Gene expression and release of inflammatory mediators [interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNFα)] were evaluated via reverse transcription quantitative polymerase chain reaction (RT-qPCR) and ELISA. RESULTS: In vitro, 14-3-3ε induced gene expression and release of IL6 and MCP1 in the treated cells. The inflammatory effects of 14-3-3ε were significantly reduced following TLRs inhibition or in TLRs KO chondrocytes and BMM. CONCLUSIONS: 14-3-3ε is able to induce an inflammatory phenotype in synoviocytes, macrophages and chondrocytes in addition to polarizing macrophages. These effects seem to involve TLR2 or TLR4 to trigger innate immunity. Our results designate 14-3-3ε as a novel alarmin in OA and as a new target either for therapeutic and/or prognostic purposes.

Low genome-wide homozygosity in 11 Spanish ovine breeds.

The population of Spanish sheep has decreased from 24 to 15 million heads in the last 75 years due to multiple social and economic factors. Such a demographic reduction might have caused an increase in homozygosity and inbreeding, thus limiting the viability of local breeds with excellent adaptations to harsh ecosystems. The main goal of our study was to investigate the homozygosity patterns of 11 Spanish ovine breeds and to elucidate the relationship of these Spanish breeds with reference populations from Europe, Africa and the Near East. By using Ovine SNP50 BeadChip data retrieved from previous publications, we have found that the majority of studied Spanish ovine breeds have close genetic relatedness with other European populations; the one exception is the Canaria de Pelo breed, which is similar to North African breeds. Our analysis has also demonstrated that, with few exceptions, the genomes of Spanish sheep harbor fewer than 50 runs of homozygosity (ROH) with a total length of less than 350 Mb. Moreover, the frequencies of very long ROH (>30 Mb) are very low, and the inbreeding coefficients (FROH ) are generally small (FROH  < 0.10), ranging from 0.008 (Rasa Aragonesa) to 0.086 (Canaria de Pelo). The low levels of homozygosity observed in the 11 Spanish sheep under analysis might be due to their extensive management and the high number of small to medium farms.

Adult orbital xanthogranuloma as a cause of recurrent palpebral swelling. / Xantogranuloma orbitario del adulto como causa de inflamación palpebral recidivante.

Orbital adult-onset xanthogranuloma is a rare idiopathic inflammatory disorder included in the group of orbital xanthogranulomatous diseases with possible systemic associations. A 43 year-old woman presented with a deep fast-growing mass on the right upper eyelid. She had a past medical history of bilateral non-ulcerative nodules on the upper eyelid and two cosmetic upper lid blepharoplasties. An excisional biopsy was performed and the histopathology analysis confirmed the diagnosis of adult histiocytic xanthogranuloma. The systemic work up was negative and the patient is asymptomatic without treatment. Orbital xanthogranulomatous diseases are rare, but potentially life-threatening disorders. The ophthalmologist must be aware of this disease in order to make an early diagnosis using the anamnesis, clinical examination, and histology of the periocular lesions that may resemble palpebral xanthelasmas.

Changes in patellar height due to bone-tendon-bone graft. / Modificaciones en la altura patelar por el uso del injerto hueso-tendón-hueso.

PURPOSE: Complications related to anterior cruciate ligament (ACL) graft are common. Change in height, especially patella baja, can be a cause of anterior knee pain. Several studies have related ACL reconstruction with bone-tendon-bone graft to patella baja. METHODS: Forty-three patients with ACL reconstruction using a with bone-tendon-bone graft were included in this study. All patients underwent the same surgery, with closure of the paratenon of the patellar tendon. A radiological study was performed before surgery and 2 years after surgery. The Insall-Salvati index, axial view and patellar tilt were analyzed in all patients. The healthy contralateral knees were used as the control group. RESULTS: No significant differences were observed from the preoperative measurements or at the 2-year follow-up. CONCLUSIONS: The use of patellar tendon with closure of the paratenon in ACL reconstruction was not shown to modify patellar height within the radiological follow-up of two years.

Index for the evaluation of the general photometric performance of photometers.

The General V(λ) Mismatch Index, f1 ', was defined for a general description of the photometric performance of photometers. This index is widely-used in photometry, and it is very relevant for selecting photometers for low-uncertainty photometric measurements. It quantifies the spectral mismatch between the relative spectral responsivity of a photometer and the luminous efficiency function for photopic vision, V(λ). The linear correlation between the real general photometric measurement error and f1 ' of 77 photometers was studied for four sets of light sources: R, G and B LEDs (narrowband spectral power distributions, SPDs), blackbodies at different colour temperatures (broadband SPDs), phosphor-based LEDs at different correlated color temperatures (SPDs with narrow- and broad-band features), and a mixture of blackbodies and phosphor-based LED sources. This article shows that it can be defined an alternative index which is notably better correlated with the real general photometric measurement error of the photometers under light sources with broadband features in their SPDs, adequate for general lighting. This index is based on filtering the high spectral frequencies variations between the relative spectral responsivity of the photometer and V(λ). The use of this new index for the assessment of the general photometric performance of photometers would improve the selection of high quality photometers and, consequently, would contribute to the general improvement of photometric measurements.

Expression patterns and genetic variation of the ovine skeletal muscle transcriptome of sheep from five Spanish meat breeds.

The goal of the current study is to analyse the gene expression profile of the ovine skeletal muscle as well as to characterize the genetic variation of transcripts expressed in such tissue. This aim has been achieved by sequencing the longissimus dorsi transcriptomes of 50 sheep distributed in five pools representing the Canaria de Pelo, Roja Mallorquina, Gallega, Xisqueta and Ripollesa Spanish autochthonous breeds. Approximately, 363 million reads per pool have been produced and 71.9-82.9% have been successfully mapped to the ovine genome in a paired-end mode (2 × 75 bp). The 200 most expressed muscle transcripts (≈1% of the total transcript count) account for 51% (Canaria de Pelo) to 67% (Gallega) of the total ovine skeletal muscle mRNA expression. These highly expressed genes play key roles in pathways related with striated muscle contraction, gluconeogenesis, glycolysis, citric acid cycle and respiratory electron transport. RNA-Sequencing of muscle transcripts has also revealed that ~72% of the SNPs detected with this approach are shared by at least two pools, and 10% of them segregate in the five pools under analysis. Most of the substitutions detected by RNA-Seq are synonymous or missense and only a minority are predicted to have consequences on protein function.

Consistency of heterogeneous synchronization patterns in complex weighted networks.

Synchronization within the dynamical nodes of a complex network is usually considered homogeneous through all the nodes. Here we show, in contrast, that subsets of interacting oscillators may synchronize in different ways within a single network. This diversity of synchronization patterns is promoted by increasing the heterogeneous distribution of coupling weights and/or asymmetries in small networks. We also analyze consistency, defined as the persistence of coexistent synchronization patterns regardless of the initial conditions. Our results show that complex weighted networks display richer consistency than regular networks, suggesting why certain functional network topologies are often constructed when experimental data are analyzed.

Effects of dexmedetomidine administered at acupuncture point GV20 compared to intramuscular route in dogs.

OBJECTIVE: To compare the sedative effects produced by dexmedetomidine in dogs, administered either intramuscularly or into the Governing Vessel 20 acupuncture point. MATERIALS AND METHODS: Six dogs were sedated with 125 µg/m2 dexmedetomidine injected either intramuscularly in the gluteal muscles or subcutaneously into the acupuncture point and in random order. Sedation and analgesia were assessed blindly before and after treatments at regular intervals for 90 minutes or until the dogs fully recovered. Duration and quality of sedation were assessed with a numerical sedation rating scale and a dynamic and interactive visual analogue scale. Analgesia was also assessed with a numerical rating scale. Heart and respiratory rates and rectal temperatures were recorded. RESULTS: Sedative and analgesic scores were significantly increased when dexmedetomidine was administered at the Governing Vessel 20 acupuncture point compared with the routine intramuscular route. Duration of sedation was longer in the acupuncture site injection group compared to the intramuscular group (93 ±38 and 41 ±16 minutes). Bradycardia was significantly more pronounced in the acupuncture site group than the intramuscular group, whereas respiratory rates and rectal temperatures did not differ between administration routes. CLINICAL SIGNIFICANCE: Administration at the Governing Vessel 20 acupuncture point increased the duration and degree of sedation and analgesic effects of dexmedetomidine compared with the intramuscular route.

Effects of dietary almond- and olive oil-based docosahexaenoic acid- and vitamin E-enriched beverage supplementation on athletic performance and oxidative stress markers.

Functional beverages based on almonds and olive oil and enriched with α-tocopherol and docosahexaenoic acid (DHA) could be useful in modulating oxidative stress and enhancing physical performance in sportsmen. The aim of this work was to evaluate the effects of supplementation with functional beverages on physical performance, plasma and erythrocyte fatty acids' and polyphenol handling, oxidative and nitrative damage, and antioxidant and mitochondrial gene expression in young and senior athletes. Athletes performed maximal exercise tests before and after one month of dietary supplementation and blood samples were taken immediately before and one hour after each test. The beverages did not alter performance parameters during maximal exercise. Supplementation increased polyunsaturated and reduced saturated plasma fatty acids while increasing the DHA erythrocyte content; it maintained basal plasma and blood polyphenol levels, but increased the blood cell polyphenol concentration in senior athletes. Supplementation protects against oxidative damage although it enhances nitrative damage in young athletes. The beverages enhance the gene expression of antioxidant enzymes in peripheral blood mononuclear cells after exercise in young athletes.

Preradiotherapy MR Imaging: A Prospective Pilot Study of the Usefulness of Performing an MR Examination Shortly before Radiation Therapy in Patients with Glioblastoma.

BACKGROUND AND PURPOSE: Current protocols in patients with glioblastoma include performing an MR examination shortly after surgery and then 2-6 weeks after ending concomitant chemoradiotherapy. The assessment of this first postradiotherapy examination is challenging because the pseudoprogression phenomenon may appear. The aim of this study was to explore if performing an MR examination shortly before radiation therapy (preradiotherapy MR imaging) could improve the radiologic assessment of patients with glioblastoma. MATERIALS AND METHODS: A preradiotherapy MR imaging examination was prospectively performed before the start of radiation therapy in 28 consecutive patients with glioblastoma who had undergone surgical resection. Tumor response to chemoradiotherapy was assessed twice: with the early postoperative MR examination as baseline and with the preradiotherapy MR imaging examination as baseline. In addition, tumor growth in the preradiotherapy MR imaging examination was evaluated, and its correlation with patient survival was assessed with Kaplan-Meier analysis and Cox regression. RESULTS: Tumor progression after radiation therapy was found in 16 patients, corresponding to pseudoprogression in 7 of them (44%). Four assessments of pseudoprogression switched to partial response or stable disease when preradiotherapy MR imaging was the baseline examination, and the ratio of pseudoprogression was reduced to 25% (3 of 12). Significant differences in survival were found when patients were stratified according to the pattern of tumor growth on preradiotherapy MR imaging (median overall survival "no-growth," 837 days; "focal-growth," 582 days; "global-growth," 344 days; P = .001). CONCLUSIONS: Performing a preradiotherapy MR imaging examination may improve the clinical management of patients with glioblastoma by reducing the ratio of pseudoprogression assessments and providing prognostic information.

Discontinuation of echinocandin and azole treatments led to the disappearance of an FKS alteration but not azole resistance during clonal Candida glabrata persistent candidaemia.

To give an indication of a fitness cost conferred by FKS mutation-associated echinocandin resistance in Candida glabrata during human infection. Six C. glabrata clinical strains sequentially isolated from blood and a hepatic abscess in a solid organ transplant recipient were analysed. The patient had received long-term azole and echinocandin therapy for invasive aspergillosis and persistent candidaemia. Minimal inhibitory concentrations were determined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. Molecular mechanisms of antifungal resistance were determined by sequencing hot spots of the FKS. Strain relatedness was determined using a microsatellite-based typing method. Typing analysis revealed an identical microsatellite pattern for all isolates, supporting a close relation. The first C. glabrata isolate showed wild-type phenotype (i.e. susceptibility to echinocandins and low level of azole resistance). After voriconazole therapy, the C. glabrata quickly acquired pan-azole resistance. Later, echinocandin treatment led to the emergence of a FKS2 S663P alteration and echinocandin resistance. After disruption of both azole and echinocandin therapy in favour of liposomal amphotericin B, C. glabrata isolates regained full susceptibility to echinocandin and lost the FKS2 S663P alteration while nonetheless maintaining their pan-azole resistance. Our clinical report supports the potential existence of a fitness cost conferred by FKS mutation in C. glabrata, as disruption of treatment led to a rapid disappearance of the resistant clone. This suggests that a more restricted use and/or a discontinuous administration of echinocandins may limit the spread of clinical resistance to this class.

Population structure of eleven Spanish ovine breeds and detection of selective sweeps with BayeScan and hapFLK.

The goals of the current work were to analyse the population structure of 11 Spanish ovine breeds and to detect genomic regions that may have been targeted by selection. A total of 141 individuals were genotyped with the Infinium 50 K Ovine SNP BeadChip (Illumina). We combined this dataset with Spanish ovine data previously reported by the International Sheep Genomics Consortium (N = 229). Multidimensional scaling and Admixture analyses revealed that Canaria de Pelo and, to a lesser extent, Roja Mallorquina, Latxa and Churra are clearly differentiated populations, while the remaining seven breeds (Ojalada, Castellana, Gallega, Xisqueta, Ripollesa, Rasa Aragonesa and Segureña) share a similar genetic background. Performance of a genome scan with BayeScan and hapFLK allowed us identifying three genomic regions that are consistently detected with both methods i.e. Oar3 (150-154 Mb), Oar6 (4-49 Mb) and Oar13 (68-74 Mb). Neighbor-joining trees based on polymorphisms mapping to these three selective sweeps did not show a clustering of breeds according to their predominant productive specialization (except the local tree based on Oar13 SNPs). Such cryptic signatures of selection have been also found in the bovine genome, posing a considerable challenge to understand the biological consequences of artificial selection.