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.

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.

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.

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.

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.

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.

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.

Obstructive sleep apnoea in people with Type 1 diabetes: prevalence and association with micro- and macrovascular complications.

AIMS: Few reports have assessed the relationship between Type 1 diabetes and sleep disorders. The purposes of our study were to determine the prevalence of obstructive sleep apnoea in Type 1 diabetes and to compare the clinical profile of people with Type 1 diabetes with or without obstructive sleep apnoea. METHODS: In this cross sectional study of 67 consecutive people with Type 1 diabetes, we performed polysomnography as part of their yearly check-ups. RESULTS: In our cohort, with a mean BMI of 25.8 ± 4.7 kg/m(2), the prevalence of obstructive sleep apnoea [apnoea-hypopnoea index (AHI) > 10/h] was 46%. Severe obstructive sleep apnoea (AHI ≥ 30/h) was present in 19% of the patients. We found no significant differences in age, sex, body mass index, HbA1c or Epworth sleepiness scale score between people with or without obstructive sleep apnoea. People with obstructive sleep apnoea had a longer course of diabetes mellitus (P < 0.01) and a higher prevalence of retinopathy (P < 0.01), neuropathy (P = 0.05), cardiovascular disease (P < 0.01) and hypertension (P < 0.01). The occurrence of macrovascular complications was independently associated with the presence of OSA [odds ratio (OR) 8.28; 95% confidence interval (CI), 1.56-43.97; P = 0.013] and the duration of diabetes (OR 1.08; 95% CI, 1.02-1.15; P = 0.01). Moreover, retinopathy was independently associated with OSA (OR 4.54; 95% CI, 1.09-18.82; P = 0.04) and the duration of diabetes (OR 1.09; 95% CI, 1.04-1.15; P = 0.001). CONCLUSIONS: The prevalence of obstructive sleep apnoea was high in people with Type 1 diabetes. Obstructive sleep apnoea was independently associated with macrovascular complications and retinopathy. Obesity and excessive daytime sleepiness were uncommon in this population.

Effects of total dietary polyphenols on plasma nitric oxide and blood pressure in a high cardiovascular risk cohort. The PREDIMED randomized trial.

BACKGROUND AND AIM: Hypertension is one of the main cardiovascular risk factors in the elderly. The aims of this work were to evaluate if a one-year intervention with two Mediterranean diets (Med-diet) could decrease blood pressure (BP) due to a high polyphenol consumption, and if the decrease in BP was mediated by plasma nitric oxide (NO) production. METHODS AND RESULTS: An intervention substudy of 200 participants at high cardiovascular risk was carried out within the PREDIMED trial. They were randomly assigned to a low-fat control diet or to two Med-diets, one supplemented with extra virgin olive oil (Med-EVOO) and the other with nuts (Med-nuts). Anthropometrics and clinical parameters were measured at baseline and after one year of intervention, as well as BP, plasma NO and total polyphenol excretion (TPE) in urine samples. Systolic and diastolic BP decreased significantly after a one-year dietary intervention with Med-EVOO and Med-nuts. These changes were associated with a significant increase in TPE and plasma NO. Additionally, a significant positive correlation was observed between changes in urinary TPE, a biomarker of TP intake, and in plasma NO (Beta = 4.84; 95% CI: 0.57-9.10). CONCLUSIONS: TPE in spot urine sample was positively correlated with plasma NO in Med-diets supplemented with either EVOO or nuts. The statistically significant increases in plasma NO were associated with a reduction in systolic and diastolic BP levels, adding to the growing evidence that polyphenols might protect the cardiovascular system by improving the endothelial function and enhancing endothelial synthesis of NO.

A mitochondrial analysis reveals distinct founder effect signatures in Canarian and Balearic goats.

In the course of human migrations, domestic animals often have been translocated to islands with the aim of assuring food availability. These founder events are expected to leave a genetic footprint that may be recognised nowadays. Herewith, we have examined the mitochondrial diversity of goat populations living in the Canarian and Balearic archipelagos. Median-joining network analysis produced very distinct network topologies for these two populations. Indeed, a majority of Canarian goats shared a single ancestral haplotype that segregated in all sampled islands, suggesting a single founder effect followed by a stepping-stone pattern of diffusion. This haplotype also was present in samples collected from archaeological assemblies at Gran Canaria and Lanzarote, making evident its widespread distribution in ancient times. In stark contrast, goats from Majorca and Ibiza did not share any mitochondrial haplotypes, indicating the occurrence of two independent founder events. Furthermore, in Majorcan goats, we detected the segregation of the mitochondrial G haplogroup that has only been identified in goats from Egypt, Iran and Turkey. This finding suggests the translocation of Asian and/or African goats to Majorca, possibly as a consequence of the Phoenician and Carthaginian colonisations of this island.

Fluid intake from beverages across age groups: a systematic review.

BACKGROUND: Fluid intake, especially water, is essential for human life and also necessary for physical and mental function. The present study aimed to assess beverage consumption across age groups. METHODS: A systematic review was conducted. Original research in English language publications and available studies (or abstracts in English) from 2000 to 2013 was searched for by using the medical subheading (MeSH) terms: ('beverage' OR 'fluid' [Major]) AND ('consumption' [Mesh] OR 'drinking' [Mesh] OR 'intake' [Mesh]) AND ('child' [Mesh] OR 'adolescent' [Mesh] OR 'adult' [Mesh]). Article selection was restricted to those papers covering healthy populations of all age groups in a nationwide sample, or from a representative sample of the population of a city or cities, which examined the trends or patterns of beverage intake and the determinants of beverage intake. Sixty-five studies were identified with respect to beverage consumption across age groups. The papers were screened by thoroughly reading titles or abstracts. Full-text articles were assessed by three investigators. RESULTS: Total beverage intake varied between 0.6 and 3.5 L day(-1) among all age groups (males more than females). Plain water contributed up to 58%, 75% and 80% of the total beverage intake in children, adolescents and adults, respectively. Milk consumption was higher among children; consumption of soft drinks was higher among adolescents; and the consumption of tea, coffee and alcoholic beverages was higher among adults. CONCLUSIONS: Plain water is the main water source for all age groups and the consumption of other beverages varies according to age.

The biodiversity and genetic structure of Balearic sheep breeds.

The Balearic sheep breeds, Mallorquina, Menorquina, Roja Mallorquina, Ibicenca and one possible new genetic group, Formentera, constitute a unique genetic resource in the Mediterranean farming landscape, displaying high genetic diversity levels and being well differentiated among themselves and with respect to the continental sheep breeds. We used a microsatellite panel of markers to study genetic diversity and relationships with other Spanish breeds. The results reported in this study have important implications for the use, conservation and breeding of Balearic sheep stocks. A mean number of 7.59 alleles was found among the Balearic sheep breeds for the microsatellites scored. The whole mean value of observed heterozygosity amounted to 0.62, whereas the expected heterozygosity value was 0.69, suggesting the presence of a great degree of genetic variability, although a significant deficit of heterozygotes was detected for some markers. Genetic distance estimates showed that Balearic sheep are differentiated from the other Spanish breeds and in particular, from the Merino type. The Ibicenca breed showed the highest distance value from other breeds. The neighbour-net method of analysis clustered the Roja Mallorquina, Menorquina and Mallorquina breeds. The Structure results clearly demonstrated the genetic differentiation among the four Balearic sheep breeds, with the Ibicenca and Formentera races joined, with slight migration among them. Few external genetic influences from the Spanish mainland breeds were detected.

Modulation of TNF-α, TNF-α receptors and IL-6 after treatment with AM3 in professional cyclists.

AIM: Changes in IL-6, TNF-α, and TNF-α receptors - sTNFRI and sTNFRII - were evaluated in a group of professional cyclists treated with immunomodulator AM3 (Inmunoferón®) for 6 months of training and competition. METHODS: Sixteen male professional cyclists with a similar training program participated in the study which was designed as a randomized, placebo-controlled, double-blind clinical trial. Venous blood samples were collected in basal conditions, before beginning the supplementation program, and after 90 and 180 days of training and competition season. RESULTS: No significant differences in biochemical parameters or in IL-6 were evidenced between placebo and AM3-treated groups throughout the study. Plasma TNF-α levels significantly decreased (P<0.05) after 90 days of training in the AM3 treated group. TNF-α receptors increased during training season in both placebo and AM3 treated groups, although the increase was significantly higher (P<0.05) in the AM3 group with respect to the placebo group. CONCLUSION: The changes produced by regular training and competition were modified throughout the season by AM3 treatment which could reduce the inflammatory response to excessive exercise.

Docosahexanoic acid diet supplementation attenuates the peripheral mononuclear cell inflammatory response to exercise following LPS activation.

Exercise induces changes in circulating pro- and anti-inflammatory cytokines. The aim was to investigate the effect of docosahexaenoic acid (DHA) diet supplementation on the plasma cytokine levels and on the peripheral mononuclear (PBMCs) cells cytokine production after a training season or an acute bout of exercise. Fifteen male soccer players were randomly assigned to a placebo or an experimental group. The experimental group consumed an almond-based beverage enriched with DHA, whereas the placebo group consumed the same beverage without DHA. Three blood samples were taken: in basal conditions at the beginning of the nutritional intervention and after eight weeks of training season in basal and post-exercise conditions. The DHA content increased in erythrocytes after 8weeks of training and supplementation. Neither diet supplementation with DHA nor training season altered the basal plasma cytokines and growth factors. Only acute exercise significantly increased plasma IL6 in experimental and placebo groups. Lipopolysaccharide (LPS) activation induced the inflammatory response in PBMCs, with a significant production rate of TNFα, IL6 and IL8 mainly after acute exercise. DHA supplementation significantly reduced the rate of TNFα and IL6 production by stimulated PBMCs. Acute exercise increased the Toll-like receptor 4 (TLR4) protein levels in PBMCs, although the increase was only statistically significant in the placebo group. In conclusion, a training season does not induce significant changes in the circulating cytokine profile in well-trained soccer players. Exercise increases the PBMCs cell capabilities to produce cytokines after TLR4 stimulation with LPS and this rate of cytokine production is attenuated by diet DHA supplementation.

Color representation and interpretation of special effect coatings.

A representation of the color gamut of special effect coatings is proposed and shown for six different samples, whose colors were calculated from spectral bidirectional reflectance distribution function (BRDF) measurements at different geometries. The most important characteristic of the proposed representation is that it allows a straightforward understanding of the color shift to be done both in terms of conventional irradiation and viewing angles and in terms of flake-based parameters. A different line was proposed to assess the color shift of special effect coatings on a*,b*-diagrams: the absorption line. Similar to interference and aspecular lines (constant aspecular and irradiation angles, respectively), an absorption line is the locus of calculated color coordinates from measurement geometries with a fixed bistatic angle. The advantages of using the absorption lines to characterize the contributions to the spectral BRDF of the scattering at the absorption pigments and the reflection at interference pigments for different geometries are shown.

Technical note: Advantages and limitations of authenticating Palmera goat dairy products by pyrosequencing the melanocortin 1 receptor (MC1R) gene.

Inferring the breed of origin of dairy products can be achieved through molecular analysis of genetic markers with a population-specific pattern of segregation. The goal of the current work was to generate such markers in goats by resequencing several pigmentation genes [melanocortin 1 receptor (MC1R), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), tyrosinase (TYR), and tyrosinase-related protein 2 (TYRP2)]. This experiment revealed 10 single nucleotide polymorphisms (SNP), including 5 missense mutations and 1 nonsense mutation. These markers were genotyped in 560 goats from 18 breeds originally from Italy, the Iberian Peninsula, the Canary Islands, and North Africa. Although the majority of SNP segregated at moderate frequencies in all populations (including 2 additional markers that were used as a source of information), we identified a c.764G>A SNP in MC1R that displayed highly divergent allelic frequencies in the Palmera breed compared with the Majorera and Tinerfeña breeds from the Canary Islands. Thus, we optimized a pyrosequencing-based technique that allowed us to estimate, very accurately, the allele frequencies of this marker in complex DNA mixtures from different individuals. Once validated, we applied this method to generating breed-specific DNA profiles that made it possible to detect fraudulent cheeses in which Palmero cheese was manufactured with milk from Majorera goats. One limitation of this approach, however, is that it cannot be used to detect illegal manufacturing where Palmero dairy products are produced by mixing milk from Palmera and Majorera goats, because the c.764G>A SNP segregates in both breeds.

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.

A single analytical model for sparkle and graininess patterns in texture of effect coatings.

Flakes in effect coatings, which are responsible for its color shift, are not perfectly horizontally oriented, producing a non uniform texture when observed from a distance of around one meter or less. If the coating is illuminated by a diffuse source, a granular appearance is observed, called graininess. But when the coating is illuminated by unidirectional light, some luminous spots on a dark background appear, effect that is known as sparkle. The characterization of these two textures is getting more important for automotive industry because of the high percentage of cars with effect coatings and because improvements in imaging technology allows this effect to be measured by, for instance, commercial instruments as BYK-mac. A single analytical model to understand and radiometrically characterize both sparkle and graininess in effect coatings is presented and studied in this work. It allows both patterns to be explained and, despite its simplicity, includes variables related to the optical system (Point Spread Function (PSF) and size of the entrance pupil), its distance to the coating, the diffusion grade of the illumination, the illumination and observation directions, and coating parameters.

Dietary sources of omega 3 fatty acids: public health risks and benefits.

Omega 3 fatty acids can be obtained from several sources, and should be added to the daily diet to enjoy a good health and to prevent many diseases. Worldwide, general population use omega-3 fatty acid supplements and enriched foods to get and maintain adequate amounts of these fatty acids. The aim of this paper was to review main scientific evidence regarding the public health risks and benefits of the dietary sources of omega-3 fatty acids. A systematic literature search was performed, and one hundred and forty-five articles were included in the results for their methodological quality. The literature described benefits and risks of algal, fish oil, plant, enriched dairy products, animal-derived food, krill oil, and seal oil omega-3 fatty acids.