Contagion-diffusion processes with recurrent mobility patterns of distinguishable agents.

The analysis of contagion-diffusion processes in metapopulations is a powerful theoretical tool to study how mobility influences the spread of communicable diseases. Nevertheless, many metapopulation approaches use indistinguishable agents to alleviate analytical difficulties. Here, we address the impact that recurrent mobility patterns, and the spatial distribution of distinguishable agents, have on the unfolding of epidemics in large urban areas. We incorporate the distinguishable nature of agents regarding both their residence and their usual destination. The proposed model allows both a fast computation of the spatiotemporal pattern of the epidemic trajectory and the analytical calculation of the epidemic threshold. This threshold is found as the spectral radius of a mixing matrix encapsulating the residential distribution and the specific commuting patterns of agents. We prove that the simplification of indistinguishable individuals overestimates the value of the epidemic threshold.

Seroprevalence and risk factors associated with Brucella seropositivity in dairy and mixed cattle herds from Ecuador.

An extensive cross-sectional study to determine the seroprevalence of and associated risk factors for Brucella infection was performed in dairy and mixed (dairy-beef) cattle herds in Ecuador. A total of 2666 serum samples from 386 farms were analyzed using Rose Bengal test and a blocking ELISA test. In addition, a questionnaire with 57 variables related to management, feeding, facilities, biosecurity, and animal health was filled in every cattle farm. A Generalized Estimating Equations model was used to determine the factors associated with Brucella seropositivity. The true prevalence of Brucella seropositivity in dairy and mixed cattle from Ecuador reached 17.0% (CI95% 15.6-18.4%). The herd prevalence was 45.1% (174/386) (CI95% 40.1-50.1%), and the within-herd prevalence ranged from 10 to 100% (mean 38.9%; Q1 14.3%, Q2 26.8%, Q3 52.5%). Seven factors were included in the GEE model for Brucella seropositivity: the nominal variables sex (OR 2.03; CI95% 1.32-3.13), herd type (dairy) (OR 1.79; CI95% 1.11-2.87), closed facilities in the farm (OR 1.80; CI95% 1.19-2.74), and ad libitum feeding (OR: 0.32; CI95%: 0.19-0.54), and the quantitative variables age (OR 1.005; CI95% 1.001-1.009), average slope in the farm (%) (OR 1.013; CI95% 1.002-1.024), and annual abortion rate (OR 1.016; CI95% 1.002-1.031). This study remarks the high spread of Brucella infection in cattle farms from Ecuador. In addition, it reports the risk factors associated to this infection in the predominant extensive system existent in this country.

Effectiveness and Safety of CT-P13 (Biosimilar Infliximab) in Patients with Inflammatory Bowel Disease in Real Life at 6 Months.

BACKGROUND: CT-P13 is a biosimilar of Remicade®, an agent approved in some countries for use in inflammatory bowel disease (IBD). Controlled clinical trials have demonstrated the efficacy and safety of CT-P13 in rheumatic diseases, but not in IBD. AIMS: To assess the effectiveness and safety of CT-P13 in IBD patients in real clinical practice. METHODS: This is a prospective observational study in patients with moderate to severe Crohn's disease or ulcerative colitis treated with CT-P13. The study was performed in one single center. Patients included were naive or switched to anti-TNF treatment from the reference infliximab (Remicade®) to CT-P13. Efficacy and safety were assessed in naive and switched patients who were in remission at the time of the switch at months 3 and 6 of therapy. RESULTS: 87.5 and 83.9% of switched CD patients who were in remission at the time of the switch continued in remission, and 66.7 and 50% of naive CD patients reached remission, at months 3 and 6. In UC switched cases, 92 and 91.3% of patients in remission at the time of the switch continued in remission, at 3 and 6 months. In naive UC patients, the remission rates were 44.4 and 66.7%, at months 3 and 6. Adverse events occurred in 7.5% of patients during 6 months of study. CONCLUSIONS: CT-P13 was efficacious and well tolerated in patients with CD or UC.

Urotensinergic system genes in experimental subarachnoid hemorrhage.

OBJECTIVE: Cerebral vasospasm, one of the main complications of subarachnoid hemorrhage (SAH), is characterized by arterial constriction and mainly occurs from day 4 until the second week after the event. Urotensin-II (U-II) has been described as the most potent vasoconstrictor peptide in mammals. An analysis is made of the serum U-II concentrations and mRNA expression levels of U-II, urotensin related peptide (URP) and urotensin receptor (UT) genes in an experimental murine model of SAH. DESIGN: An experimental study was carried out. SETTING: Experimental operating room of the Biomedicine Institute of Seville (IBiS), Virgen del Rocío University Hospital (Seville, Spain). PARTICIPANTS: 96 Wistar rats: 74 SAH and 22 sham intervention animals. INTERVENTIONS: Day 1: blood sampling, followed by the percutaneous injection of 100µl saline (sham) or blood (SAH) into the subarachnoid space. Day 5: blood sampling, followed by sacrifice of the animals. MAIN VARIABLES OF INTEREST: Weight, early mortality, serum U-II levels, mRNA values for U-II, URP and UT. RESULTS: Serum U-II levels increased in the SAH group from day 1 (0.62pg/mL [IQR 0.36-1.08]) to day 5 (0.74pg/mL [IQR 0.39-1.43]) (p<0.05), though not in the sham group (0.56pg/mL [IQR 0.06-0.83] day 1; 0.37pg/mL [IQR 0.23-0.62] day 5; p=0.959). Between-group differences were found on day 5 (p<0.05). The ROC analysis showed that the day 5 serum U-II levels (AUC=0.691), URP mRNA (AUC=0.706) and UT mRNA (AUC=0.713) could discriminate between sham and SAH rats. The normal serum U-II concentration range in rats was 0.56pg/mL (IQR 0.06-0.83). CONCLUSION: The urotensinergic system is upregulated on day 5 in an experimental model of SAH.

Acute predictors for mortality after severe TBI in Spain: Gender differences and clinical data.

OBJECTIVE: The main objective of this study is to determine whether gender affects global mortality and functional outcome after severe traumatic brain injury (TBI). METHODS: This retrospective cohort study included 629 patients with severe TBI (14.9% female) admitted to the ICU of a university hospital. Patients were split into gender groups to study potential differences in global mortality and functional outcome at ICU discharge and 6 months post-trauma using the GOS. The following variables were analysed: age, intracranial injury, injury mechanism, injury severity, factors contributing to secondary brain injury, monitoring level, treatment, complications, length of stay in the ICU and cause of death. RESULTS: No differences were found between gender groups in neuromonitoring level or surgical procedures. Women had higher APACHE II scores, a higher incidence of pre-hospital hypotension, anaemia and transfusion and higher mortality rates in the ICU (OR = 1.74; 95% CI = 1.09-2.77) and 6 months post-trauma (OR = 1.65; 95% CI = 1.02-2.67). There were no significant differences in functional outcome at ICU discharge or 6 months post-injury. The multivariate analysis did not show gender as an independent predictive factor in mortality after severe TBI. CONCLUSION: In this study, gender was not found to be an independent predictor for poorer outcome after severe TBI.

Predictors of mortality and poor functional outcome in severe spontaneous intracerebral hemorrhage: a prospective observational study.

OBJECTIVE: To analyze mortality and functional outcome in patients with severe spontaneous intracerebral hemorrhage (ICH), and identify the clinical characteristics, radiological findings and therapeutic procedures predictive of mortality in the Intensive Care Unit (ICU) and during hospitalization, as well as of poor functional results at 6 months. DESIGN: A prospective, observational study was carried out. SETTING: Neurocritical Care Unit of a university hospital. PATIENTS: Patients diagnosed with ICH were included over a period of 23 months. VARIABLES OF INTEREST: Demographic characteristics, cardiovascular risk factors, regular medication, laboratory test parameters, cranial CT findings, therapeutic procedures and outcome data. INTERVENTION: None. RESULTS: A total of 186 patients with ICH met the inclusion criteria. Surgery to evacuate ICH was performed in 25.8% of the patients. The mortality rate was 46.7%. The modified Rankin score at 6 months was 5 (RI: 4.6). Multivariate Cox regression analysis showed the presence of diabetes, prior anticoagulation, as well as APACHE II severity and the type of bleeding on the cranial CT scan to be predictors of mortality and poor functional outcomes. On the other hand, neurosurgical procedures and intracranial pressure (ICP) monitoring were associated with better outcomes. CONCLUSION: The presence of comorbidities such as diabetes, or previous anticoagulation, as well as the CT findings were associated to poorer outcomes. In contrast, ICP monitoring and early neurosurgery were predictive of longer survival and better functional outcomes.

[An experimental model of mass-type brain damage in the rat: expression of brain damage based on neurospecific enolase and protein S100B]. / Modelo experimental de lesión cerebral tipo masa en rata: expresión del daño cerebral mediante enolasa neuroespecífica y proteína S100B.

OBJECTIVE: To determine whether a model of transient mass-type brain damage (MTBD) in the rat produces early release of neurospecific enolase (NSE) and protein S100B in peripheral blood, as an expression of the induced brain injury. DESIGN: An experimental study with a control group. SETTING: Experimental operating room of the Institute of Biomedicine (IBiS) of Virgen del Rocío University Hospital (Seville, Spain). PARTICIPANTS: Fourteen adult Wistar rats. INTERVENTIONS: Blood was sampled at baseline, followed by: MTBD group, a trephine perforation was used to insert and inflate the balloon of a catheter at a rate of 500 µl/20 sec, followed by 4 blood extractions every 20 min. Control group, the same procedure as before was carried out, though without trephine perforation. PRIMARY STUDY VARIABLES: Weight, early mortality, serum NSE and S100B concentration. RESULTS: Differences in NSE and S100B concentration were observed over time within the MTBD group (P<.001), though not so in the control group. With the exception of the baseline determination, differences were observed between the two groups in terms of the mean NSE and S100B values. Following MTBD, NSE and S100B progressively increased at all measurement timepoints, with r=0.765; P=.001 and r=0.628; P=.001, respectively. In contrast, the control group showed no such correlation for either biomarker. CONCLUSIONS: Serum NSE and S100B concentrations offer an early indication of brain injury affecting the gray and white matter in an experimental model of mass-type MTBD in the rat.

Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function.

Combined antiretroviral therapy (cART) has been associated with increased body weight accompanied by metabolic alterations in people living with human immunodeficiency virus (PLWH). To gain insight into the combined effects of cART components on adipocyte dysfunction, we assessed whether and how treatment of human adipocytes with dolutegravir (DTG) and the nucleotide-analog reverse-transcriptase inhibitors (NRTIs), tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF), alone and in combination, altered biological processes related to adipose tissue dysfunction. DTG, TAF, and TDF were applied to human Simpson-Golabi-Behmel syndrome (SGBS) adipose cells during differentiation (day 10) and ensuing differentiation (day 14). Expression of selected marker genes was determined by qPCR, the release of adipokines and inflammatory cytokines to the culture media was assessed, and cell respiration was measured. Adipogenesis was not altered by the combined treatment of human adipocytes. However, DTG at the highest dose repressed adipogenesis marker genes expression, and TAF and TDF appeared to mitigate this effect. DTG repressed the expression of adiponectin and the release of adiponectin and leptin in differentiating adipocytes, and these effects were mantained in combination with TAF and TDF. DTG plus TAF or TDF on human adipocytes enhanced inflammation and stress and increased the release of proinflammatory cytokines to the culture media. Together, our results show that combined therapy with these drugs can alter inflammation, cellular stress, and fibrosis in human adipocytes. These findings may improve our understanding and management of the effects of cART on body adiposity and metabolic dysregulation in PLWH.

Diffusion dynamics on multiplex networks.

We study the time scales associated with diffusion processes that take place on multiplex networks, i.e., on a set of networks linked through interconnected layers. To this end, we propose the construction of a supra-laplacian matrix, which consists of a dimensional lifting of the laplacian matrix of each layer of the multiplex network. We use perturbative analysis to reveal analytically the structure of eigenvectors and eigenvalues of the complete network in terms of the spectral properties of the individual layers. The spectrum of the supra-laplacian allows us to understand the physics of diffusionlike processes on top of multiplex networks.

Early olfactory experience induces structural changes in the primary olfactory center of an insect brain.

The antennal lobe (AL) is the first olfactory center of the insect brain and is constituted of different functional units, the glomeruli. In the AL, odors are coded as spatiotemporal patterns of glomerular activity. In honeybees, olfactory learning during early adulthood modifies neural activity in the AL on a long-term scale and also enhances later memory retention. By means of behavioral experiments, we first verified that olfactory learning between the fifth and eighth day of adulthood induces better retention performances at a late adult stage than the same experience acquired before or after this period. We checked that the specificity of memory for the odorants used was improved. We then studied whether such early olfactory learning also induces long-term structural changes in the AL consistent with the formation of long-term olfactory memories. We also measured the volume of 15 identified glomeruli in the ALs of 17-day-old honeybees that either experienced an odor associated with sucrose solution between the fifth and eighth day of adulthood or were left untreated. We found that early olfactory experience induces glomerulus-selective increases in volume that were specific to the learned odor. By comparing our volumetric measures with calcium-imaging recordings from a previous study, performed in 17-day-old bees subjected to the same treatment and experimental conditions, we found that glomeruli that showed structural changes after early learning were those that exhibited a significant increase in neural activity. Our results make evident a correlation between structural and functional changes in the AL following early olfactory learning.

Explosive first-order transition to synchrony in networked chaotic oscillators.

Critical phenomena in complex networks, and the emergence of dynamical abrupt transitions in the macroscopic state of the system are currently a subject of the outmost interest. We report evidence of an explosive phase synchronization in networks of chaotic units. Namely, by means of both extensive simulations of networks made up of chaotic units, and validation with an experiment of electronic circuits in a star configuration, we demonstrate the existence of a first-order transition towards synchronization of the phases of the networked units. Our findings constitute the first prove of this kind of synchronization in practice, thus opening the path to its use in real-world applications.

Accuracy of the S100ß protein as a marker of brain damage in traumatic brain injury.

INTRODUCTION: This study tested the hypothesis that S100ß is a useful screening tool for detecting intracranial lesion (IL) in patients with a normal level of consciousness after traumatic brain injury (TBI). METHODS: One hundred and forty-three post-TBI patients without a decrease in consciousness (GCS = 15) and with at least one neurological symptom (e.g. transitory loss of consciousness, amnesia, headache, dizziness or vomiting) were prospectively included. A blood sample was drawn at 6-hours post-TBI. A routine CT scan was obtained within 24 hours post-injury. Diagnostic properties of S100ß for IL prediction in CT scan findings were tested using ROC-analysis. RESULTS: A total of 15 patients (10.5%) had IL. Serum levels were significantly higher in these patients. Significant differences were found between S100ß levels and CT scan findings (p = 0.007). ROC-analysis showed that S100ß is a useful tool for detecting the presence of IL in CT scans (p = 0.007). In this series, the best cut-off for S100ß is 0.130 µg L(-1), with 100% sensitivity and 32.81% specificity. CONCLUSION: Within the first 6 hours post-TBI, serum S100ß seems to be an effective biochemical indicator of IL in patients without a decrease in consciousness. These results indicate that higher S100ß cut-off values substantially improve the clinical relevance of this protein.

Perioperative analgesia by erector spinae plane block in left ventricular assist implant.

In recent years, left ventricular assist devices have become an important element in the management of left ventricular failure refractory to pharmacological treatment. Their implantation (performed by left thoracotomy or sternotomy) generates significant perioperative pain, which can be managed with locoregional anaesthesia techniques. However, opinions vary on their use in cardiac surgery due to interference with the anticoagulant therapy required in these patients. The erector spinae plane block is an alternative to classic locoregional techniques. It does not produce hemodynamic alterations and does not interfere with antiplatelet and anticoagulant therapy, and is therefore an alternative to be considered in cardiac surgery. We present a case of left ventricular assist device implantation under this block prior to the surgical procedure and postoperative infusion through a catheter, obtaining satisfactory results in the management of perioperative pain.

[Predictive models of gestational diabetes, a new prediction mode]. / Modelos predictivos de diabetes gestacional, un nuevo modelo de predicción.

OBJECTIVES: Recognized the value of gestational diabetes (GD) as a health problem, our aim in this work has been to analyze the diagnostic performance of the different today's existing criteria (GEDE, O'Sullivan and Carpenter) after the overload of 100 g of glucose and revise how to increase its efficiency. MATERIALS AND METHODS: We carried out a description of all the variables. In the analytical phase of the work, we used Pearson's Chi square to see if there were differences in the percentage of cases collected in each health center and the proportions contrast test to study the differences between the experimental prevalence. We completed binary logistic regression models using as result variable having or not having gestational diabetes (yes/no) and as predictors the four measurements of the curve with 100 g of glucose overload. To decide which model was better, the stepwise backward-forward analysis and the surface of the ROC curve generated by each of them were considered. RESULTS: We obtained a sample of 170 pregnant women from six different Primary Care Area of Seville health centers who had shown a positive O'Sullivan test with a median age of 35 years. There were significant differences in the prevalence proportions according to the criteria used: GEDE/O'Sullivan p < 0.001; GEDE/Carpenter p < 0.001. Logistic models with three and four predictor variables were equal in discriminatory diagnostic capacity when the GEDE criteria were used (area under the ROC curve = 0.96, 95% CI: 0.93-0.98). The back-forward stepwise analysis stayed with the three-variable model as the most parsimonious. The same did not occur when applying the other two criteria. CONCLUSIONS: Regarding an observational design, we state that there are significant differences in the prevalence proportions observed according to the criteria applied (p < 0.001) and we can also support that using the GEDE criteria, the taking of the third hour could be dispensed with, based on Bayesian criteria and the application of the ROC curve analysis.

Multivariate associative patterns between the gut microbiota and large-scale brain network connectivity.

Research on the gut-brain axis has accelerated substantially over the course of the last years. Many reviews have outlined the important implications of understanding the relation of the gut microbiota with human brain function and behavior. One substantial drawback in integrating gut microbiome and brain data is the lack of integrative multivariate approaches that enable capturing variance in both modalities simultaneously. To address this issue, we applied a linked independent component analysis (LICA) to microbiota and brain connectivity data.We analyzed data from 58 healthy females (mean age = â€¯21.5 years). Magnetic Resonance Imaging data were acquired using resting state functional imaging data. The assessment of gut microbial composition from feces was based on sequencing of the V4 16S rRNA gene region. We used the LICA model to simultaneously factorize the subjects' large-scale brain networks and microbiome relative abundance data into 10 independent components of spatial and abundance variation.LICA decomposition resulted in four components with non-marginal contribution of the microbiota data. The default mode network featured strongly in three components, whereas the two-lateralized fronto-parietal attention networks contributed to one component. The executive-control (with the default mode) network was associated to another component. We found that the abundance of Prevotella genus was associated with the strength of expression of all networks, whereas Bifidobacterium was associated with the default mode and frontoparietal-attention networks.We provide the first exploratory evidence for multivariate associative patterns between the gut microbiota and brain network connectivity in healthy humans considering the complexity of both systems.

Usefulness of optic nerve ultrasound to predict clinical progression in multiple sclerosis. / Utilidad de la ecografía de nervio óptico como predictor de progresión en esclerosis múltiple.

INTRODUCTION: Progressive neuronal and axonal loss are considered the main causes of disability in patients with multiple sclerosis (MS). The disease frequently involves the visual system; the accessibility of the system for several functional and structural tests has made it a model for the in vivo study of MS pathogenesis. Orbital ultrasound is a non-invasive technique that enables various structures of the orbit, including the optic nerve, to be evaluated in real time. MATERIAL AND METHODS: We conducted an observational, ambispective study of MS patients. Disease progression data were collected. Orbital ultrasound was performed on all patients, with power set according to the 'as low as reasonably achievable' (ALARA) principle. Optical coherence tomography (OCT) data were also collected for those patients who underwent the procedure. Statistical analysis was conducted using SPSS version 22.0. RESULTS: Disease progression was significantly correlated with ultrasound findings (P=.041 for the right eye and P=.037 for the left eye) and with Expanded Disability Status Scale (EDSS) score at the end of the follow-up period (P=.07 for the right eye and P=.043 for the left eye). No statistically significant differences were found with relation to relapses or other clinical variables. DISCUSSION: Ultrasound measurement of optic nerve diameter constitutes a useful, predictive factor for the evaluation of patients with MS. Smaller diameters are associated with poor clinical progression and greater disability (measured by EDSS).

[Pharmacological treatment in uncertainty times: Hydroxychloroquine/chloroquine use in the COVID-19 treatment]. / Tratamiento farmacológico en tiempos de incertidumbre: uso de la hidroxicloroquina/cloroquina en el tratamiento de COVID-19.

BACKGROUND AND OBJECTIVES: In this moments, of extreme gravity in which we find ourselves, and in the uncertainty face about the most effective treatment against COVID-19 disease and with the aim of find the evidence that support the chloroquine/hydroxychloroquine use recommendation to treat COVID-19 disease, a systematic review of published studies and RCT studies publishes until April 28, 2020 was carried out. MATERIAL AND METHODS: A systematic search was carried out in PubMed with the keywords COVID-19 and their synonyms and hydroxychloroquine/chloroquine. The data selection and extraction was elaborated by two researchers, independently. The results were discussed with a Primary Care physicians clinical group and the results were synthesized using GRADE methodology. RESULTS: A good quality systematic review was found that includes articles with a high risk of bias. And 8 EC launched that will produce results beyond May 2020. CONCLUSIONS: Although the conclusions of the systematic review generate a low confidence in the results, and the clinical variables that show benefit are intermediate variables, the side effects are acceptable and could be minimized with the use of QT lengthening risk tools, so it is could make a weak recommendation in favor of the use of chloroquine/hydroxychloroquine in patients with mild-moderate stage COVID-19.

Early olfactory experience modifies neural activity in the antennal lobe of a social insect at the adult stage.

In the antennal lobe (AL), the first olfactory centre of the insect brain, odorants are represented as spatiotemporal patterns of glomerular activity. Whether and how such patterns are modified in the long term after precocious olfactory experiences (i.e. in the first days of adulthood) remains unknown. To address this question, we used in vivo optical imaging of calcium activity in the antennal lobe of 17-day-old honeybees which either experienced an odorant associated with sucrose solution 5-8 days after emergence or were left untreated. In both cases, we imaged neural responses to the learned odor and to three novel odors varying in functional group and carbon-chain length. Two different odor concentrations were used. We also measured behavioral responses of 17-day-old honeybees, treated and untreated, to these stimuli. We show that precocious olfactory experience increased general odor-induced activity and the number of activated glomeruli in the adult AL, but also affected qualitative odor representations, which appeared shifted in the neural space of treated animals relative to control animals. Such effects were not limited to the experienced odor, but were generalized to other perceptually similar odors. A similar trend was found in behavioral experiments, in which increased responses to the learned odor extended to perceptually similar odors in treated bees. Our results show that early olfactory experiences have long-lasting effects, reflected in behavioral responses to odorants and concomitant neural activity in the adult olfactory system.