Patient-reported outcomes in ANCA-associated vasculitis: a cross-sectional study to explore the interactions between patients' and physicians' perspectives.

To evaluate associations between the domains of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) instrument and clinical variables. Patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), or renal-limited vasculitis (RLV) were recruited from a tertiary care center in Mexico City. Demographic, clinical, serological, and treatment-related data were retrieved. Disease activity, damage, patient and physician global assessments (PtGA and PhGA) were evaluated. All patients completed the AAV-PRO questionnaire, male patients also completed the International Index of Erectile Function (IIEF-5) questionnaire. Seventy patients (44 women and 26 men) were included, with a median age of 53.5 years (43-61), and a disease duration of 82 months (34-135). Moderate correlations were identified between the PtGA and the AAV-PRO domains: social and emotional impact, treatment side effects, organ-specific symptoms, and physical function. The PhGA correlated with the PtGA and prednisone doses. Subanalyses of the AAV-PRO domains according to sex, age, and disease duration showed significant differences in the treatment side effects domain, with higher scores in women, in patients < 50 years, and in patients with disease duration < 5 years. The domain of concerns about the future showed a higher score in patients with disease duration < 5 years. A total of 17/24 (70.8%) of men who completed the IIEF-5 questionnaire were classified as having some degree of erectile dysfunction. The domains of AAV-PRO correlated with other outcome measures, while differences were found between some of the domains according to sex, age, and disease duration.

Multi-stimuli-responsive chitosan-functionalized magnetite/poly(ε-caprolactone) nanoparticles as theranostic platforms for combined tumor magnetic resonance imaging and chemotherapy.

Chitosan-functionalized magnetite/poly(ε-caprolactone) nanoparticles were formulated by interfacial polymer disposition plus coacervation, and loaded with gemcitabine. That (core/shell)/shell nanostructure was confirmed by electron microscopy, elemental analysis, electrophoretic, and Fourier transform infrared characterizations. A short-term stability study proved the protection against particle aggregation provided by the chitosan shell. Superparamagnetic properties of the nanoparticles were characterized in vitro, while the definition of the longitudinal and transverse relaxivities was an initial indication of their capacity as T2 contrast agents. Safety of the particles was demonstrated in vitro on HFF-1 human fibroblasts, and ex vivo on SCID mice. The nanoparticles demonstrated in vitro pH- and heat-responsive gemcitabine release capabilities. In vivo magnetic resonance imaging studies and Prussian blue visualization of iron deposits in tissue samples defined the improvement in nanoparticle targeting into the tumor when using a magnetic field. This tri-stimuli (magnetite/poly(ε-caprolactone))/chitosan nanostructure could find theranostic applications (biomedical imaging & chemotherapy) against tumors.

Ambient temperature modulates body weight changes in patients with advanced oncological diseases and anorexia cachexia syndrome.

OBJECTIVE: To assess the impact of ambient temperature (AT) on the evolution of bodyweight in patients with heterogeneous types of cancer in advanced stages of the disease (stages III and IV) and anorexia- cachexia syndrome (ACS). METHODS: A prospective naturalistic multicenter study of patients undergoing oncological treatment at four hospitals during a three-year period (2017-2020) in the Autonomous Community of Extremadura in southwestern Spain with a continentalized Mediterranean climate of mild and relatively rainy winters, and particularly hot and sunny summers. Bodyweight changes were obtained from the medical records of 84 oncological patients (59 men and 25 women, age range 37-91 yrs). Mean monthly AT was used to examine the association of weight changes across cold and warm bimesters -BIMs (December and January, vs. July and August), Trimesters -TRIMs (July to September vs. December to February), and Semesters -SEMs (May to October vs. November to April). Weight changes between two consecutive weight measures were categorized as weight gain, weight loss, or no weight change. Differences across cold and warm seasons were analysed using parametric (ANOVA), and nonparametric statistics (Chi-square and binomial z tests). An alpha-rate of 0.05 was used for all analyses. RESULTS: A weight loss trend was observed during BIMs cold periods in comparison to warm ones (p 0.04). However, differences in average bodyweight were not significant. The negative impact of cold periods was more marked in men than in women, (p = 0.05; p = 0.03, for cold vs. warm BIMs and TRIMs, respectively). In contrast, significantly higher weight gain percentages were found in women during warm TRIMs and SEMs (p = 0.03, and p = 0.01, respectively). As for the number of patients dying during the study (N = 56; 39 men, 17 women), there were a significant interaction between temperature (cold/warm), and mean weight F (1, 499) = 6.06, p = 0.01, which revealed a pattern of weight loss in the cold semester as opposed to weight gain during the warm SEM months. CONCLUSIONS: AT temperature modulated body weight changes in patients with advanced oncological disease and ACS. Two main limitations of the study were the absence of information on diets as a moderating factor of weight loss/gain, and the lack of the patients' weight measurements closest to the date of diagnosis prior to admittance to the study. As for the practical implications, it remains to be seen whether an adjunctive heat supply will serve a buffering effect on weight loss during colder seasons for patients with advanced cancer and ACS.

Entropies and IPR as Markers for a Phase Transition in a Two-Level Model for Atom-Diatomic Molecule Coexistence.

A quantum phase transition (QPT) in a simple model that describes the coexistence of atoms and diatomic molecules is studied. The model, which is briefly discussed, presents a second-order ground state phase transition in the thermodynamic (or large particle number) limit, changing from a molecular condensate in one phase to an equilibrium of diatomic molecules-atoms in coexistence in the other one. The usual markers for this phase transition are the ground state energy and the expected value of the number of atoms (alternatively, the number of molecules) in the ground state. In this work, other markers for the QPT, such as the inverse participation ratio (IPR), and particularly, the Rényi entropy, are analyzed and proposed as QPT markers. Both magnitudes present abrupt changes at the critical point of the QPT.

Open surgery for in utero repair of spina bifida: Microneurosurgery versus standard technique - A systematic review.

BACKGROUND/OBJECTIVES: Prenatal myelomeningocele (MMC) repair has been shown to improve neurological outcomes. It has been suggested that decreases in the hysterotomy diameter during surgery can improve perinatal outcomes without altering neurologic outcomes. The objective of this study is to describe and compare the main maternal and fetal outcomes of fetuses undergoing open surgery for MMC repair, through the different modifications (standard-classical, mini-hysterotomy, and microneurosurgery). DATA SOURCE: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Ovid, SciELO, LILACS, PROSPERO. RESULTS: From a total of 112 studies, seven case series were selected including 399 fetuses with open fetal surgery, five studies using the classical technique (n = 181), one with mini-hysterotomy (n = 176), and one with the microneurosurgery technique (n = 42). The mini-hysterotomy and microneurosurgery techniques presented a lower risk of preterm delivery (21.4% and 30%, respectively) compared to the classic technique (47.3%), premature rupture of membranes (78%, 62%, and 72.5 %, respectively), oligohydramnios (0% and 72.5%, respectively), dehiscence of hysterotomy, maintaining the same frequency of Chiari reversion (78%, 62%, and 72.5%, respectively), postnatal correction requirement (0%, 4.8%, and 5.8%, respectively), and lower frequency of requirement for a ventriculoperitoneal shunt placement (13.0%, 7.5%, and 29.1%, respectively). CONCLUSION: The least invasive techniques (minihysterotomy-microneurosurgery) are possible and reproduceable, as they are associated with better maternal and perinatal outcomes.

An alternative model in the provision of CPAP in sleep apnea: a comparative cost analysis.

BACKGROUND: To conduct a pilot study on an alternative model for the provision of respiratory therapies in sleep apnea-hypopnea syndrome (SAHS) by internalizing the service with the purchase, monitoring and control of continuous positive airway pressure (CPAP) equipment by the hospital. METHODS: An observational, prospective pilot study of comparative cost analysis by internalizing the service to include all patients up to a budget limit of 5000 euros. The cost of internalizing the service included the acquisition of CPAP equipment and all the necessary accessories in addition to the nursing days necessary to track the patients. Patient satisfaction was assessed by a survey of the hospital service. RESULTS: Twenty-one patients with 23,046 patient-days of follow-up were included. The cost of the internalized system was 6825.11 €. The cost of the outsourced system over the same period would have been 22,781.18 €; thus, the direct saving was 15,956.07 €. The cost per device per day of the internalized system was 0.30 € versus the 0.99 € that the outsourced system would have cost during the study period. In the satisfaction survey, 12 (70.6%) patients indicated that they preferred the service of the hospital over that of the external company. No patient preferred the outsourced system. CONCLUSIONS: The internalization of CPAP service represents significant cost savings from a hospital perspective and an improvement in patients' perceptions of the quality of service.

Systematic Review of Electricity Demand Forecast Using ANN-Based Machine Learning Algorithms.

The forecast of electricity demand has been a recurrent research topic for decades, due to its economical and strategic relevance. Several Machine Learning (ML) techniques have evolved in parallel with the complexity of the electric grid. This paper reviews a wide selection of approaches that have used Artificial Neural Networks (ANN) to forecast electricity demand, aiming to help newcomers and experienced researchers to appraise the common practices and to detect areas where there is room for improvement in the face of the current widespread deployment of smart meters and sensors, which yields an unprecedented amount of data to work with. The review looks at the specific problems tackled by each one of the selected papers, the results attained by their algorithms, and the strategies followed to validate and compare the results. This way, it is possible to highlight some peculiarities and algorithm configurations that seem to consistently outperform others in specific settings.

COVID-19 effect on herding behaviour in European capital markets.

This article investigates whether COVID-19 pandemic had an effect on herding behaviour in Europe. Using a sample from the stock exchanges of France (Paris), Germany (Frankfurt), Italy (Milan), United Kingdom (London) and Spain (Madrid), over the period from January 03, 2000 to June 19, 2020, we found robust evidence that COVID-19 pandemic increased herding behaviour in the capital markets of Europe.

Improved personalized survival prediction of patients with diffuse large B-cell Lymphoma using gene expression profiling.

BACKGROUND: Thirty to forty percent of patients with Diffuse Large B-cell Lymphoma (DLBCL) have an adverse clinical evolution. The increased understanding of DLBCL biology has shed light on the clinical evolution of this pathology, leading to the discovery of prognostic factors based on gene expression data, genomic rearrangements and mutational subgroups. Nevertheless, additional efforts are needed in order to enable survival predictions at the patient level. In this study we investigated new machine learning-based models of survival using transcriptomic and clinical data. METHODS: Gene expression profiling (GEP) of in 2 different publicly available retrospective DLBCL cohorts were analyzed. Cox regression and unsupervised clustering were performed in order to identify probes associated with overall survival on the largest cohort. Random forests were created to model survival using combinations of GEP data, COO classification and clinical information. Cross-validation was used to compare model results in the training set, and Harrel's concordance index (c-index) was used to assess model's predictability. Results were validated in an independent test set. RESULTS: Two hundred thirty-three and sixty-four patients were included in the training and test set, respectively. Initially we derived and validated a 4-gene expression clusterization that was independently associated with lower survival in 20% of patients. This pattern included the following genes: TNFRSF9, BIRC3, BCL2L1 and G3BP2. Thereafter, we applied machine-learning models to predict survival. A set of 102 genes was highly predictive of disease outcome, outperforming available clinical information and COO classification. The final best model integrated clinical information, COO classification, 4-gene-based clusterization and the expression levels of 50 individual genes (training set c-index, 0.8404, test set c-index, 0.7942). CONCLUSION: Our results indicate that DLBCL survival models based on the application of machine learning algorithms to gene expression and clinical data can largely outperform other important prognostic variables such as disease stage and COO. Head-to-head comparisons with other risk stratification models are needed to compare its usefulness.

Structural Health Monitoring for Jacket-Type Offshore Wind Turbines: Experimental Proof of Concept.

Structural health monitoring for offshore wind turbines is imperative. Offshore wind energy is progressively attained at greater water depths, beyond 30 m, where jacket foundations are presently the best solution to cope with the harsh environment (extreme sites with poor soil conditions). Structural integrity is of key importance in these underwater structures. In this work, a methodology for the diagnosis of structural damage in jacket-type foundations is stated. The method is based on the criterion that any damage or structural change produces variations in the vibrational response of the structure. Most studies in this area are, primarily, focused on the case of measurable input excitation and vibration response signals. Nevertheless, in this paper it is assumed that the only available excitation, the wind, is not measurable. Therefore, using vibration-response-only accelerometer information, a data-driven approach is developed following the next steps: (i) the wind is simulated as a Gaussian white noise and the accelerometer data are collected; (ii) the data are pre-processed using group-reshape and column-scaling; (iii) principal component analysis is used for both linear dimensionality reduction and feature extraction; finally, (iv) two different machine-learning algorithms, k nearest neighbor (k-NN) and quadratic-kernel support vector machine (SVM), are tested as classifiers. The overall accuracy is estimated by 5-fold cross-validation. The proposed approach is experimentally validated in a laboratory small-scale structure. The results manifest the reliability of the stated fault diagnosis method being the best performance given by the SVM classifier.

Perinuclear Lamin A and Nucleoplasmic Lamin B2 Characterize Two Types of Hippocampal Neurons through Alzheimer's Disease Progression.

BACKGROUND: Recent reports point to a nuclear origin of Alzheimer's disease (AD). Aged postmitotic neurons try to repair their damaged DNA by entering the cell cycle. This aberrant cell cycle re-entry involves chromatin modifications where nuclear Tau and the nuclear lamin are involved. The purpose of this work was to elucidate their participation in the nuclear pathological transformation of neurons at early AD. METHODOLOGY: The study was performed in hippocampal paraffin embedded sections of adult, senile, and AD brains at I-VI Braak stages. We analyzed phospho-Tau, lamins A, B1, B2, and C, nucleophosmin (B23) and the epigenetic marker H4K20me3 by immunohistochemistry. RESULTS: Two neuronal populations were found across AD stages, one is characterized by a significant increase of Lamin A expression, reinforced perinuclear Lamin B2, elevated expression of H4K20me3 and nuclear Tau loss, while neurons with nucleoplasmic Lamin B2 constitute a second population. CONCLUSIONS: The abnormal cell cycle reentry in early AD implies a fundamental neuronal transformation. This implies the reorganization of the nucleo-cytoskeleton through the expression of the highly regulated Lamin A, heterochromatin repression and building of toxic neuronal tangles. This work demonstrates that nuclear Tau and lamin modifications in hippocampal neurons are crucial events in age-related neurodegeneration.

First steps in the formulation of praziquantel nanosuspensions for pharmaceutical applications.

Praziquantel (PZQ), a broad spectrum anthelmintic drug, cannot be found in acceptable dosage forms for elderly patients, paediatric patients, and for veterinary use. In fact, very little has been done up to now in the formulation of liquid dosage forms, being they always formulated for parenteral administration. To beat this important challenge, it was accomplished a comprehensive analysis of the influence of two elementary physicochemical aspects, i.e. surface thermodynamic and electrokinetic properties, on the colloidal stability of PZQ nanosuspensions. The hydrophobic character of the drug, intensely determining the flocculation curves, was confirmed by the thermodynamic characterization. The electrophoretic characterization, in combination with the sedimentation and relative absorbance versus time curves, highlighted that the electrical double layer thickness and the surface charge can play an essential role in the stability of the pharmaceutical colloid. Finally, it was demonstrated that controlling the pH values and the incorporation of electrolytes can help in formulating PZQ aqueous nanosuspensions with appropriate stability and redispersibility behaviours for pharmaceutical use.

The association of germline variants with chronic lymphocytic leukemia outcome suggests the implication of novel genes and pathways in clinical evolution.

BACKGROUND: Chronic Lymphocytic Leukemia (CLL) is the most frequent lymphoproliferative disorder in western countries and is characterized by a remarkable clinical heterogeneity. During the last decade, multiple genomic studies have identified a myriad of somatic events driving CLL proliferation and aggressivity. Nevertheless, and despite the mounting evidence of inherited risk for CLL development, the existence of germline variants associated with clinical outcomes has not been addressed in depth. METHODS: Exome sequencing data from control leukocytes of CLL patients involved in the International Cancer Genome Consortium (ICGC) was used for genotyping. Cox regression was used to detect variants associated with clinical outcomes. Gene and pathways level associations were also calculated. RESULTS: Single nucleotide polymorphisms in PPP4R2 and MAP3K4 were associated with earlier treatment need. A gene-level analysis evidenced a significant association of RIPK3 with both treatment need and survival. Furthermore, germline variability in pathways such as apoptosis, cell-cycle, pentose phosphate, GNα13 and Nitric oxide was associated with overall survival. CONCLUSION: Our results support the existence of inherited conditionants of CLL evolution and points towards genes and pathways that may results useful as biomarkers of disease outcome. More research is needed to validate these findings.

Carcinogenesis: the cancer cell-mast cell connection.

BACKGROUND: In mammals, inflammation is required for wound repair and tumorigenesis. However, the events that lead to inflammation, particularly in non-healing wounds and cancer, are only partly understood. FINDINGS: Mast cells, due to their great plasticity, could orchestrate the inflammatory responses inducing the expression of extraembryonic programs of normal and pathological tissue formation. This heterogeneity of mast cells could allow a microenvironment to be recreated similar to the extraembryonic structures, i.e., amnion and yolk sac, which are needed for embryonic development. Mast cells could provide a framework for understanding the connection between inflammation and tumor growth, invasion and metastasis. In this way, the mast cells could express inflammatory phenotypes, which would enable the cancer stem cells to develop. Thus, the cancer cell uses mast cells to express the extraembryonic functions that are needed to allow the cancer stem cell to proliferate and invade. If so, then by using this appropriate inflammatory interstitial microenvironment, a cancer stem cell can reach maximum levels of growth and invasion inside the host. CONCLUSION: Therefore, the comparison of tumors with wounds that do not heal would be supported since both pathological processes use extraembryonic mechanisms by mast cells. The adoption of these mechanisms warrants tumor survival in an embryonic-like state.

Vesomni improves the quality of life in men with lower urinary tract symptoms in routine clinical practice in Europe.

AIM: To evaluate the impact of Vesomni/Urizia/Volutsa, a fixed-dose combination tablet containing 6 mg solifenacin (antimuscarinic) and 0.4 mg tamsulosin (α-blocker), on health-related quality of life (HRQoL) and treatment satisfaction in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) in routine clinical practice. METHODS: EUROPA was a noninterventional study of men with LUTS/BPH not responding to monotherapy who were prescribed Vesomni in routine clinical practice. Data were collected retrospectively (1 year) and prospectively (1 year). Assessments were performed at baseline, weeks 4 to 8, weeks 9 to 18 (optional), weeks 19 to 39 (optional), and Weeks 40 to 52. The primary endpoint was change from baseline in HRQoL, as assessed by the Overactive Bladder Questionnaire (OAB-q) symptom bother subscale score. Change from baseline in OAB-q total and coping, sleep, and social interaction subscale scores, treatment satisfaction-visual analog scale (TS-VAS), International Prostate Symptom Score (IPSS), and European Quality of Life 5-Dimension-5-Level (EQ-5D-5L) questionnaire were also evaluated. RESULTS: Five hundred and eighty-nine patients were enrolled. The mean changes in adjusted mean (95% confidence interval [CI]) OAB-q symptom bother subscale scores were -16.40 (-24.31, -8.49) at weeks 4 to 8 and -19.59 (-28.26, -10.92) at weeks 40 to 52; at weeks 40 to 52, changes were clinically meaningful in 84.6% of patients. Adjusted mean (95% CI) change from baseline to weeks 40 to 52 were 15.02 (7.35, 22.69), 19.37 (10.86, 27.89), 18.65 (7.44, 29.86), 9.85 (3.90, 15.81), and 16.09 (9.07, 23.11) for concern, coping, sleep, social interaction, and total, respectively. TS-VAS, IPSS, and EQ-5D-5L all improved, and treatment persistence at weeks 40 to 52 was 77.1%. Urinary retention was reported in four (0.7%) patients. CONCLUSIONS: Vesomni was well-tolerated and improved HRQoL and treatment satisfaction in patients with LUTS/BPH.

Melatonin decreases in vitro viability and migration of spheres derived from CF41.Mg canine mammary carcinoma cells.

BACKGROUND: Mammary cancer is a common disease affecting female dogs, where approximately 50% of the cases are malignant. There is a subpopulation of cancer cells with stem cell-like features within the tumour microenvironment, which can form in vitro spheres, cell structures that grow in anchor-free conditions. This cell population shows resistance to conventional antitumor treatments explaining in part the recurrence of some type of cancers. It has been previously reported that spheres derived from CF41.Mg canine mammary carcinoma cells exhibit several stemness features. Melatonin has shown antitumor effects on cancer mammary cells; nevertheless, its effects have been poorly evaluated on canine mammary cancer stem-like cells. In this regard, it has described that melatonin decreases the expression of OCT-4 in CMT-U2229 mammary cancer cells, a transcription factor that participates in the modulation of self-renewal and drug resistance in cancer stem-like cells. The aim of this study was to compare the effects of melatonin on viability and migration of canine mammary carcinoma CF41.Mg-spheres, and CF41.Mg-parental cells. CF41.Mg cells were grown in DMEM high-glucose medium containing 10% bovine foetal serum. CF41.Mg-spheres were cultured in ultra-low attachment plates with serum-free DMEM/F12 containing several growth factors. Cell viability (MTS reduction) and migration (transwell) assays were conducted in presence of melatonin (0.01, 0.1 or 1 mM). RESULTS: Melatonin decreased cell viability at 1 mM (P < 0.05), with a significant reduction in spheres compared to parental cells at 24 and 48 h (P < 0.05). Cell migration was inhibited in response to non-cytotoxic concentration of melatonin (0.1 mM) (P < 0.05) in spheres and monolayer of cells, no significant differences were detected between both cell subtypes. CONCLUSIONS: These results indicate that melatonin reduces viability and migration of CF41.Mg cells, where spheres exhibit greater sensitivity to the hormone. Thus, melatonin represents a valuable potential agent against mammary cancer cells, especially cancer stem-like cells.

Influence of Phyllosilicate Structure on Performance of Polypropylene Nanocomposites Prepared via In-Situ Polymerization.

This work explores the use of two different phyllosilicate structures (muscovite mica and bentonite) as co-support for in situ polymerization of propylene using Ziegler-Natta catalyst based on MgCl2/TiCl4 with electron donor for isotacticity control. It was observed along the experiments that the mass ratio MgCl2:mica needs to be at least 3:1 in order to maintain a feasible catalyst activity. It was found through XRD, TEM, SEM and DMA that crystallinity of polypropylene composites is different according to the nature of phyllosilicates used and the mechanical performance of mica composites, as long as wettability and thermal stability were in general higher than those of PP/bentonite composites. Moreover, activity of MgCl2:mica supported catalyst was higher than that co-supported on bentonite. Chemical modification in mica showed to improve in more than 500% the elastic modulus of PP/mica composites.

A physico-genetic module for the polarisation of auxin efflux carriers PIN-FORMED (PIN).

Intracellular polarisation of auxin efflux carriers is crucial for understanding how auxin gradients form in plants. The polarisation dynamics of auxin efflux carriers PIN-FORMED (PIN) depends on both biomechanical forces as well as chemical, molecular and genetic factors. Biomechanical forces have shown to affect the localisation of PIN transporters to the plasma membrane. We propose a physico-genetic module of PIN polarisation that integrates biomechanical, molecular, and cellular processes as well as their non-linear interactions. The module was implemented as a discrete Boolean model and then approximated to a continuous dynamic system, in order to explore the relative contribution of the factors mediating PIN polarisation at the scale of single cell. Our models recovered qualitative behaviours that have been experimentally observed and enable us to predict that, in the context of PIN polarisation, the effects of the mechanical forces can predominate over the activity of molecular factors such as the GTPase ROP6 and the ROP-INTERACTIVE CRIB MOTIF-CONTAINING PROTEIN RIC1.

Peripheral Neuroimmunoendocrine Interactions: Contribution of TNFRp55 to the Circadian Synchronization of Progesterone and Cytokine Production in Joints of Mice in Late Pregnancy.

OBJECTIVE: Circadian rhythms are generated by the suprachiasmatic nucleus of the hypothalamus and involve rhythmic expression of clock genes and proteins. This rhythmicity is transferred to peripheral tissues by neural and hormonal signals. Late pregnancy is considered a state of inflammation which impacts on peripheral tissues such as joints. Tumor necrosis factor (TNF) mediates inflammatory and circadian responses through its p55 receptor (TNFRp55). Neuroimmunoendocrine interactions in joints have not been studied completely. The purpose of this study was to analyze these interactions, investigating the circadian rhythms of progesterone (Pg) and pro- and anti-inflammatory cytokines in the joints at the end of pregnancy (gestational day 18). Moreover, the impact of TNFRp55 deficiency on these temporal oscillations was explored. METHODS: Wild-type and TNFRp55-deficient (KO) C57BL/6 mice were kept under constant darkness in order to study their endogenous circadian rhythms. The expression of the clock genes Bmal1 and Per1 at circadian time 7 was studied by reverse transcription polymerase chain reaction in the ankle joints of nonpregnant and pregnant (gestational day 18) mice. In late pregnancy, Pg and the cytokines interleukin 17 (IL-17), IL-6, and IL-10 were measured in the joints throughout a 24-h period by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. RESULTS: A significant increase in Bmal1 and Per1 mRNA expression was detected in the joints of pregnant KO mice. Furthermore, KO mice displayed a desynchronization of articular Pg and cytokine production. CONCLUSIONS: Our results show that TNF, via TNFRp55 signaling, modulates articular Pg and cytokine circadian rhythms in late pregnancy. These findings suggest a temporal neuroimmunoendocrine association in peripheral tissues in late pregnancy.

Intersection Intelligence: Supporting Urban Platooning with Virtual Traffic Lights over Virtualized Intersection-Based Routing.

The advent of the autonomous car is paving the road to the realization of ideas that will help optimize traffic flows, increase safety and reduce fuel consumption, among other advantages. We present one proposal to bring together Virtual Traffics Lights (VTLs) and platooning in urban scenarios, leaning on vehicle-to-vehicle (V2V) communication protocols that turn intersections into virtual containers of data. Newly-introduced protocols for the combined management of VTLs and platoons are validated by simulation, comparing a range of routing protocols for the vehicular networks with the baseline given by common deployments of traditional traffic lights ruled by state-of-the-art policies. The simulation results show that the combination of VTLs and platoons can achieve significant reductions in travel times and fuel consumption, provided that proper algorithms are used to handle the V2V communications.