Microarray analyses demonstrate the involvement of type i interferons in psoriasiform pathology development in D6-deficient mice

The inflammatory response is normally limited by mechanisms regulating its resolution. In the absence of resolution, inflammatory pathologies can emerge, resulting in substantial morbidity and mortality. We have been studying the D6 chemokine scavenging receptor, which played an indispensable role in the resolution phase of inflammatory responses and does so by facilitating removal of inflammatory CC chemokines. In D6-deficient mice, otherwise innocuous cutaneous inflammatory stimuli induce a grossly exaggerated inflammatory response that bears many similarities to human psoriasis. In the present study, we have used transcriptomic approaches to define the molecular make up of this response. The data presented highlight potential roles for a number of cytokines in initiating and maintaining the psoriasis-like pathology. Most compellingly, we provide data indicating a key role for the type I interferon pathway in the emergence of this pathology. Neutralizing antibodies to type I interferons are able to ameliorate the psoriasis-like pathology, confirming a role in its development. Comparison of transcriptional data generated from this mouse model with equivalent data obtained from human psoriasis further demonstrates the strong similarities between the experimental and clinical systems. As such, the transcriptional data obtained in this preclinical model provide insights into the cytokine network active in exaggerated inflammatory responses and offer an excellent tool to evaluate the efficacy of compounds designed to therapeutically interfere with inflammatory processes

Efficacy and safety of a hexanic extract of Serenoa repens (Permixon (R)) for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH): systematic review and meta-analysis of randomised controlled trials and observational studies

Objectives To comprehensively evaluate the efficacy and safety of the hexanic extract of Serenoa repens (HESr, Permixon (R); Pierre Fabre Medicament, Castres, France), at a dose of 320 mg daily, as monotherapy for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Materials and methods We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) and prospective observational studies in patients with LUTS/BPH identified through searches in Medline, Web of Knowledge (Institute for Scientific Information), Scopus, the Cochrane Library, and bibliographic references up to March 2017. Articles studying S. repens extracts other than Permixon were excluded. Data were collected on International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), nocturia, quality of life, prostate volume, sexual function, and adverse drug reactions (ADRs). Data obtained from RCTs and observational studies were analysed jointly and separately using a random effects model. A sub-group analysis was performed of studies that included patients on longer-term treatment (= 1 year). Results Data from 27 studies (15 RCTs and 12 observational studies) were included for meta-analysis (total N = 5 800). Compared with placebo, the HESr was associated with 0.64 (95% confidence interval [CI] -0.98 to -0.31) fewer voids/ night (P < 0.001) and an additional mean increase in Q(max) of 2.75 mL/s (95% CI 0.57 to 4.93; P = 0.01). When compared with a-blockers, the HESr showed similar improvements on IPSS (weighted mean difference [WMD] 0.57, 95% CI -0.27 to 1.42; P = 0.18) and a comparable increase in Q(max) to tamsulosin (WMD -0.02, 95% CI -0.71 to 0.66; P = 0.95). Efficacy assessed using the IPSS was similar after 6 months of treatment between the HESr and 5a-reductase inhibitors (5ARIs). Analysis of all available published data for the HESr showed a mean improvement in IPSS from baseline of -5.73 points (95% CI -6.91 to -4.54; P < 0.001). HESr did not negatively affect sexual function and no clinically relevant effect was observed on prostate-specific antigen. Prostate volume decreased slightly. Similar efficacy results were seen in patients treated for = 1 year (n = 447). The HESr had a favourable safety profile, with gastrointestinal disorders being the most frequent ADR (mean incidence of 3.8%). Conclusion The present meta-analysis, which includes all available RCTs and observational studies, shows that the HESr (Permixon) reduced nocturia and improved Q(max) compared with placebo and had a similar efficacy to tamsulosin and short-term 5ARI in relieving LUTS. HESr (Permixon) appears to be an efficacious and well-tolerated therapeutic option for the longterm medical treatment of LUTS/BPH

An iterative method to design traffic flow models

Existing traffic flow modeling theory lacks of guidelines to construct traffic flow models from scratch. In addition, traffic flow models are mainly analyzed with computer simulation then computer programs are involved in the test of the model. Different methods have been proposed not just from traffic flow but for modeling in general, however, existing methods do not rely on iterative process, which is widely used for designing software. In this paper a methodology to generate traffic models is presented. The methodology proposes an agile iterative process to design traffic flow models. The method has been validated with a real life case study; a model for a sector of the traffic flow in Puebla City. Data were gathered from the city and used to validate the model. In addition, an algorithm to modify the traffic lights' control accordingly to the global traffic conditions was developed and tested with the collected data. The results show a reduction in traffic density during peak hour for traffic.Anglai

WHICH FACTORS CONTROL THE PICOPLANKTON COMMUNITY STRUCTURE IN THE OCEAN?

Picoplankton are the most abundant organisms in the ocean, often dominate planktonic biomass and primary production, and they could represent a substantial contribution to the global export of carbon. Nowadays, we have a limited understanding about the factors that control the picoplankton community structure. A recent analysis indicates that light and temperature are the main factors explaining Prochlorococcus and Synechococcus distributions, whereas nutrient concentrations play a minor role (Flombaum et al., PNAS 2013). Methodological difficulties to quantify mixing in the marine enviroments have motivated the use of indirect approaches to determine the input of nutrients into the euphotic zone, however, nutrient concentrations are not necessarily a proxy of nutrient supply. We present a large data set, including open-ocean and coastal regions, of simultaneous measurements of picoplankton abundance, temperature and irradiance, together with estimates of nutrient supply. The transport of nutrients across the nutricline was computed combining nutrient concentrations and small-scale turbulence observations collected with a microstructure profiler. Our preliminary results indicate that nutrient supply also plays a role in the distribution of functional groups of picoplankton in the ocean

Efficacy and tolerability of the hexanic extract of Serenoa repens compared to tamsulosin in moderate-severe LUTS-BPH patients

Altres ajuts: Pierre Fabre Ibérica S.A.In a subset analysis of data from a 6-month, multicenter, non-interventional study, we compared change in symptoms and quality of life (QoL), and treatment tolerability, in men with moderate to severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) receiving tamsulosin (TAM, 0.4 mg/day) or the hexanic extract of Serenoa repens (HESr, 320 mg/day) as monotherapy. Symptoms and QoL were assessed using the IPSS and BII questionnaires, respectively. Patients in the treatment groups were matched using two statistical approaches (iterative and propensity score matching). Within the iterative matching approach, data was available from a total of 737 patients (353 TAM, 384 HESr). After 6 months, IPSS scores improved by a mean (SD) of 5.0 (4.3) points in the TAM group and 4.5 (4.7) points in the HESr group (p = 0.117, not significant). Improvements in QoL were equivalent in the two groups. TAM patients reported significantly more adverse effects than HESr patients (14.7% vs 2.1%; p < 0.001), particularly ejaculation dysfunction and orthostatic hypotension. These results show that HESr is a valid treatment option for men with moderate/severe LUTS/BPH; improvements in urinary symptoms and QoL were similar to those observed for tamsulosin, but with considerably fewer adverse effects

Factors controlling the community structure of picoplankton in contrasting marine environments.

The effect of inorganic nutrients on planktonic assemblages has traditionally relied on concentrations rather than estimates of nutrient supply. We combined a novel dataset of hydrographic properties, turbulent mixing, nutrient concentration, and picoplankton community composition with the aims of (i) quantifying the role of temperature, light, and nitrate fluxes as factors controlling the distribution of autotrophic and heterotrophic picoplankton subgroups, as determined by flow cytometry, and (ii) describing the ecological niches of the various components of the picoplankton community. Data were collected at 97 stations in the Atlantic Ocean, including tropical and subtropical open-ocean waters, the northwestern Mediterranean Sea, and the Galician coastal upwelling system of the northwest Iberian Peninsula. A generalized additive model (GAM) approach was used to predict depth-integrated biomass of each picoplankton subgroup based on three niche predictors: sea surface temperature, averaged daily surface irradiance, and the transport of nitrate into the euphotic zone, through both diffusion and advection. In addition, niche overlap among different picoplankton subgroups was computed using nonparametric kernel density functions. Temperature and nitrate supply were more relevant than light in predicting the biomass of most picoplankton subgroups, except for Prochlorococcus and lownucleic-acid (LNA) prokaryotes, for which irradiance also played a significant role. Nitrate supply was the only factor that allowed the distinction among the ecological niches of all autotrophic and heterotrophic picoplankton subgroups. Prochlorococcus and LNA prokaryotes were more abundant in warmer waters ( > 20 ◦C) where the nitrate fluxes were low, whereas Synechococcus and high-nucleic-acid (HNA) prokaryotes prevailed mainly in cooler environments characterized by intermediate or high levels of nitrate supply. Finally, the niche of picoeukaryotes was defined by low temperatures and high nitrate supply. These results support the key role of nitrate supply, as it not only promotes the growth of large phytoplankton, but it also controls the structure of marine picoplankton communitie

Wich factors control the picoplankton community structure in the ocean?

Comunicación oralPicoplankton are the most abundant organisms in the ocean, often dominate planktonic biomass and primary production, and they could represent a substantial contribution to the global export of carbon. Nowadays, we have a limited understanding about the factors that control the picoplankton community structure. A recent analysis indicates that light and temperature are the main factors explaining Prochlorococcus and Synechococcus distributions, whereas nutrient concentrations play a minor role (Flombaum et al., PNAS 2013). Methodological difficulties to quantify mixing in the marine enviroments have motivated the use of indirect approaches to determine the input of nutrients into the euphotic zone, however, nutrient concentrations are not necessarily a proxy of nutrient supply. We present a large data set, including open-ocean and coastal regions, of simultaneous measurements of picoplankton abundance, temperature and irradiance, together with estimates of nutrient supply. The transport of nutrients across the nutricline was computed combining nutrient concentrations and small-scale turbulence observations collected with a microstructure profiler. Our preliminary results indicate that nutrient supply also plays a role in the distribution of functional groups of picoplankton in the ocean