How new technologies can promote an active and healthy city. Digital platform to identify areas of informal sport practise in the city of Malaga

La investigación realizada se ha llevado a cabo en el marco de la Cátedra Tecnologías Emergentes para la Ciudadanía, Red de Cátedras Estratégicas del Vicerrectorado de Proyectos Estratégicos, Universidad de Málaga, y el Polo Digital, Ayuntamiento de Málaga.In recent years the urban public space has become the largest casual sports infrastructure in cities and suburbs. WHO establishes a direct relationship between the Active Healthy City, social cohesion of communities and public space. This approach provides a framework for research and work on the design of the city and urban space as support for this sport practice. Moreover, new technologies provide an opportunity to promote the sport in the city. “Malaga Activa” digital platform project is an initiative that wants to promote the informal sport practice on the urban public space (outside the regulated sports facilities) and healthy living in the neighborhoods of the city of Malaga. This paper presents the results of the first phase of the project identifying the active sport areas -those in which physical and casual sport activities take place-. It also includes a methodology and a performance test of the created digital platform, as well as an assessment of the experience and possible improvements to be incorporated in the successive phases of the project.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Mali : Interessen, Intrigen, Interventionen

Volume: 71Start Page: 27End Page: 4

Isatuximab plus atezolizumab in patients with advanced solid tumors: results from a phase I/II, open-label, multicenter study

Atezolizumab; Isatuximab; Solid tumorsAtezolizumab; Isatuximab; Tumores sólidosAtezolizumab; Isatuximab; Tumors sòlidsBackground The anti-CD38 antibody isatuximab is approved for the treatment of relapsed/refractory multiple myeloma, but there are no data on its efficacy in solid tumors. This phase I/II study (NCT03637764) assessed the safety and activity of isatuximab plus atezolizumab (Isa + Atezo), an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with immunotherapy-naive solid tumors: epithelial ovarian cancer (EOC), glioblastoma (GBM), hepatocellular carcinoma (HCC), and squamous cell carcinoma of the head and neck (SCCHN). Patients and methods Phase I assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and the recommended phase II dose (RP2D) of isatuximab 10 mg/kg intravenously (i.v.) every week for 3 weeks followed by once every 3 weeks + atezolizumab 1200 mg i.v. every 3 weeks. Phase II used a Simon’s two-stage design to assess the overall response rate or progression-free survival rate at 6 months (GBM cohort). Interim analysis was carried out at 6 months following first dose of the last enrolled patient in each cohort. Pharmacodynamic biomarkers were tested for CD38, PD-L1, tumor-infiltrating immune cells, and FOXP3+ regulatory T cells (Tregs) in the tumor microenvironment (TME). Results Overall, 107 patients were treated (EOC, n = 18; GBM, n = 33; HCC, n = 27; SCCHN, n = 29). In phase I, Isa + Atezo showed an acceptable safety profile, no dose-limiting toxicities were observed, and RP2D was confirmed. Most patients experienced ≥1 treatment-emergent adverse event (TEAE), with ≤48.5% being grade ≥3. The most frequent TEAE was infusion reactions. The study did not continue to stage 2 based on prespecified targets. Tumor-infiltrating CD38+ immune cells were reduced and almost cleared after treatment. Isa + Atezo did not significantly modulate Tregs or PD-L1 expression in the TME. Conclusions Isa + Atezo had acceptable safety and tolerability. Clinical pharmacodynamic evaluation revealed efficient target engagement of isatuximab via treatment-mediated reduction of CD38+ immune cells in the TME. Based on clinical data, CD38 inhibition does not improve responsiveness to PD-L1 blockade in these patients.This work was sponsored by Sanofi (no grant number)

Forkhead Box P3 Methylation and Expression in Men with Obstructive Sleep Apnea

BACKGROUND: Epigenetic changes in obstructive sleep apnea (OSA) have been proposed as a mechanism for end-organ vulnerability. In children with OSA, Forkhead Box P3 (FOXP3) DNA methylation were associated with inflammatory biomarkers; however, the methylation pattern and its effect in the expression of this gene have not been tested in adults with OSA. METHODS: Plasma samples from subjects without comorbid conditions other than OSA were analyzed (the Epigenetics Status and Subclinical Atherosclerosis in Obstructive Sleep Apnea (EPIOSA) Study: NCT02131610). In 16 patients with severe OSA (Apnea-Hypopnea Index-AHI- > 30 events/h) and seven matched controls (AHI 10) and 31 controls, we quantified FOXP3 protein expression by ELISA and gene expression by quantitative real-time PCR. C-reactive protein (CRP) and plasma Treg cells were also evaluated. RESULTS: Neither the levels of the promoter nor the TSDR demethylated region were different between controls and patients with OSA, whether they were grouped by normal or high CRP. FOXP3 protein and mRNA expression did not differ between groups. CONCLUSIONS: FOXP3 methylation or its expression is not altered in adults with OSA, whatever their inflammatory status

Neurodegeneration in patients with Type 2 Diabetes Mellitus without Diabetic Retinopathy

Purpose. To evaluate neurodegeneration in patients with type 2 diabetes mellitus (DM2) without diabetic retinopathy and to assess the possible role of systemic vascular complications in retinal changes. Methods. Sixty eyes of 60 patients with DM2 and without any signs of diabetic retinopathy and 60 eyes of 60 healthy controls underwent retinal evaluation using Spectralis optical coherence tomography. Macular ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL) were evaluated. Peripapillary RNFL thickness was assessed using Glaucoma and Axonal Analytics applications. Comparison between patients with the presence/absence of systemic vascular complications and different disease duration was made. Results. Macular GCL was reduced in patients compared to controls (p < 0.001). Differences in the macular RNFL thickness were only observed in the outer inferior sector (p = 0.033). A reduction in the peripapillary RNFL (average, inferior, and inferotemporal thickness, p < 0.05 for all three) was observed in patients using both applications. Patients with chronic systemic vascular complications presented a reduction in the temporal RNFL (p = 0.019) compared to patients without complications. The superotemporal RNFL thickness was thinner in patients with longer disease duration. Conclusions. Patients with type 2 DM without diabetic retinopathy and good metabolic control present neurodegeneration affecting neurons in the macular area and axons in different sectors of the optic disc. Systemic vascular complications contributed to further axonal damage in these patients, suggesting a possible role of subclinical ischaemia to retinal neurodegeneration in type 2 DM

Detection and characterization of staphylococcus aureus and methicillin-resistant s. aureus in foods confiscated in EU borders

Producción CientíficaThe aim of the study was to evaluate the potential role of the illegal entry of food in UE in the Methicillin-resistant S. aureus (MRSA) spread. We studied the prevalence and characteristics of Staphylococcus aureus and MRSA isolated from foods of animal origin confiscated from passengers on flights from 45 non-EU countries from 2012 to 2015 by the Border Authorities at Bilbao International Airport (Spain) and Vienna International Airport (Austria), as well as foods from open markets close to EU land borders. Of 868 food samples tested (diverse meat samples including antelope, duck, guinea pig, pork, rodents, turkey, dairy products, and eggs), 136 (15.7%) were positive for S. aureus and 26 (3.0%) for MRSA. All MRSA strains were mecA-positive. The prevalence of S. aureus-positive dairy samples among food confiscated at Bilbao International Airport was 64.6%, and this airport also had the highest value (11.8%) for MRSA-positive samples. The predominant sequence type was ST5 (30.8%), followed by ST8, ST1649, ST1, and other lineages were found to a lesser extent (ST7, ST22, ST72, ST97, and ST398). Six isolates tested positive for luk-PVL genes (SCCmec IV subtypes IVc and IVe). Enterotoxin profiling revealed that 19 MRSA strains were enterotoxigenic, harboring one or more se genes. The MRSA isolates positive for luk-PVL genes were not enterotoxigenic, and none of the isolates tested positive for enterotoxin E. We found 14 resistance profiles, and more than 69% of the MRSA isolates were resistant to three or more types of antimicrobial agents. This finding reveals both the wide diversity of the antimicrobial resistance found in the strains and the capacity to resist not only to beta-lactam drugs. One MRSA strain showed unusual characteristics: it was oxacillin-susceptible, harbored SCCmec V, and was positive for sed, seg, and sej but negative for PVL virulence factors. This study shows the presence of enterotoxigenic HA-, CA-, and LA-MRSA in foods illegally entering the EU, and highlights illegal importation of food as route of enterotoxigenic MRSA spread. Uncontrolled entry of food stuffs into the EU can be a relevant neglected route of MRSA dissemination.Séptimo Programa Marco de la UE Proyecto PROMISE (proyecto n. 265877)Ministerio de Economía y Competitividad (AGL2016- 74882-C3-3

A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patients

Oncolytic viruses represent a unique type of agents that combine self-amplification, lytic, and immunostimulatory properties against tumors. A local and locoregional clinical benefit has been demonstrated upon intratumoral injections of an oncolytic herpes virus in melanoma patients, leading to its approval in the United States and Europe for patients without visceral disease (up to stage IVM1a). However, in order to debulk and change the local immunosuppressive environment of tumors that cannot be injected directly, oncolyitc viruses need to be administered systemically. Among different viruses, adenovirus has been extensively used in clinical trials but with few evidences of activity upon systemic administration. Preclinical efficacy of a single intravenous administration of our oncolytic adenovirus ICOVIR5, an adenovirus type 5 responsive to the retinoblastoma pathway commonly deregulated in tumors, led us to use this virus in a dose-escalation phase 1 trial in metastatic melanoma patients. The results in 12 patients treated with a single infusion of a dose up to 1 × 1013 viral particles show that ICOVIR5 can reach melanoma metastases upon a single intravenous administration but fails to induce tumor regressions. These results support the systemic administration of armed oncolytic viruses to treat disseminated cancer

Macro- and micro-geographic variation of short-beaked common dolphin’s whistles in the Mediterranean Sea and Atlantic Ocean

Author Posting. © The Author(s), 20113. This is the author's version of the work. It is posted here by permission of Taylor & Francis for personal use, not for redistribution. The definitive version was published in Ethology Ecology & Evolution 26 (2014): 392-404, doi:10.1080/03949370.2013.851122.Genetic studies have shown that there are small but significant differences between the short-beaked common dolphin populations in the Atlantic Ocean and those in the Mediterranean Sea. The short-beaked common dolphin is a highly vocal species with a wide sound production repertoire including whistles. Whistles are continuous, narrowband, frequency-modulated signals that can show geographic variation in dolphin species. This study tests whether the differences, highlighted by genetic studies, are recognisable in the acoustic features of short-beaked common dolphin’s whistles in the two adjacent areas of the Atlantic Ocean and the Mediterranean Sea. From a selected sample of good quality whistles (514 recorded in the Atlantic and 193 in the Mediterranean) 10 parameters of duration, frequency and frequency modulation were measured. Comparing data among basins, differences were found for duration and all frequency parameters except for minimum frequency. Modulation parameters showed the highest coefficient of variation. Through discriminant analysis we correctly assigned 75.7% of sounds to their basins. Furthermore, micro-geographic analysis revealed similarity between the sounds recorded around the Azores and the Canary archipelagos and between the Bay of Biscay and the Mediterranean Sea. Results are in agreement with the hypothesis proposed by previous genetic studies that two distinct populations are present, still supposing a gene flow between the basins. This study is the first to compare shortbeaked common dolphin’s whistles of the Atlantic Ocean and the Mediterranean areas.Data collection and processing in the Azores was conducted under projects POCTI/BSE/38991/01, PTDC/MAR/74071/2006 and M2.1.2/F/012/2011, supported by FCT (Fundação para a Ciência e a Tecnologia) and DRCTC/SRCTE (Secretaria Regional de Ciência, Tecnologia e Equipamentos), FEDER funds, the Competitiveness Factors Operational (COMPETE), QREN European Social Fund and Proconvergencia Açores Program. We acknowledge funds provided by FCT to LARSyS Associated Laboratory & IMAR-University of the Azores/ the Thematic Area E of the Strategic Project (OE & Compete) and by the DRCTC – Government of the Azores pluriannual funding. M.A. Silva was supported by an FCT postdoctoral grant (SFRH/ BPD/29841/2006). I. Cascão and R. Prieto were supported by FCT doctoral grants (SFRH/BD/ 41192/2007 and SFRH/BD/32520/2006, respectively) and R. Prieto by a research grant from the Azores Regional Fund for Science and Technology (M3.1.5/F/115/2012). Data collection by SECAC (Society for the Study of Cetaceans in the Canary Archipelago) was funded by the U.E. LIFE programme – project LIFE INDEMARES (LIFE 07/NAT/E/000732)- and the Fundación Biodiversidad, under the Spanish Ministry of Environment, Rural and Marine Affairs (project ZEC-TURSIOPS).2014-11-0