Exploring Blue Spaces' Effects on Childhood Leukaemia Incidence: A Population-Based Case-Control Study in Spain

Background: Blue spaces have been a key part of human evolution, providing resources and helping economies develop. To date, no studies have been carried out to explore how they may be linked to paediatric oncological diseases. Objectives: To explore the possible relationship of residential proximity to natural and urban blue spaces on childhood leukaemia. Methods: A population-based case–control study was conducted in four regions of Spain across the period 2000–2018. A total of 936 incident cases and 5616 controls were included, individually matched by sex, year of birth and place of residence. An exposure proxy with four distances (250 m, 500 m, 750 m, and 1 km) to blue spaces was built using the geographical coordinates of the participants’ home residences. Odds ratios (ORs) and 95% confidence intervals (95%CIs) for blue-space exposure were calculated for overall childhood leukaemia, and the acute lymphoblastic (ALL) and acute myeloblastic leukaemia (AML) subtypes, with adjustment for socio-demographic and environmental covariates. Results: A decrease in overall childhood leukaemia and ALL-subtype incidence was found as we came nearer to children’s places of residence, showing, for the study as a whole, a reduced incidence at 250 m (odds ratio (OR) = 0.77; 95%CI = 0.60–0.97), 500 m (OR = 0.78; 95%CI = 0.65–0.93), 750 m (OR = 0.80; 95%CI = 0.69–0.93), and 1000 m (OR = 0.84; 95%CI = 0.72–0.97). AML model results showed an increasing incidence at closest to subjects’ homes (OR at 250m = 1.06; 95%CI=0.63–1.71). Conclusions: Our results suggest a possible association between lower childhood leukaemia incidence and blue-space proximity. This study is a first approach to blue spaces’ possible effects on childhood leukaemia incidence; consequently, it is necessary to continue studying these spaces—while taking into account more individualised data and other possible environmental risk factors.This study was funded by Carlos III Institute of Health, Spain (grant numbers PI19CIII/00025, PI16CIII/00009, EPY-505/19-PFIS), and Spain’s Health Research Fund (Fondo de Investigación Sanitaria-FIS grant number 12/01416). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.S

Specialized Pro-Resolving Lipid Mediators: The Future of Chronic Pain Therapy?

Chronic pain (CP) is a severe clinical entity with devastating physical and emotional consequences for patients, which can occur in a myriad of diseases. Often, conventional treatment approaches appear to be insufficient for its management. Moreover, considering the adverse effects of traditional analgesic treatments, specialized pro-resolving lipid mediators (SPMs) have emerged as a promising alternative for CP. These include various bioactive molecules such as resolvins, maresins, and protectins, derived from ω-3 polyunsaturated fatty acids (PUFAs); and lipoxins, produced from ω-6 PUFAs. Indeed, SPMs have been demonstrated to play a central role in the regulation and resolution of the inflammation associated with CP. Furthermore, these molecules can modulate neuroinflammation and thus inhibit central and peripheral sensitizations, as well as long-term potentiation, via immunomodulation and regulation of nociceptor activity and neuronal pathways. In this context, preclinical and clinical studies have evidenced that the use of SPMs is beneficial in CP-related disorders, including rheumatic diseases, migraine, neuropathies, and others. This review integrates current preclinical and clinical knowledge on the role of SPMs as a potential therapeutic tool for the management of patients with CP

Nucleotides in neuroregeneration and neuroprotection

AbstractBrain injury generates the release of a multitude of factors including extracellular nucleotides, which exhibit bi-functional properties and contribute to both detrimental actions in the acute phase and also protective and reparative actions in the later recovery phase to allow neuroregeneration. A promising strategy toward restoration of neuronal function is based on activation of endogenous adult neural stem/progenitor cells. The implication of purinergic signaling in stem cell biology, including regulation of proliferation, differentiation, and cell death has become evident in the last decade. In this regard, current strategies of acute transplantation of ependymal stem/progenitor cells after spinal cord injury restore altered expression of P2X4 and P2X7 receptors and improve functional locomotor recovery. The expression of both receptors is transcriptionally regulated by Sp1 factor, which plays a key role in the startup of the transcription machinery to induce regeneration-associated genes expression. Finally, general signaling pathways triggered by nucleotide receptors in neuronal populations converge on several intracellular kinases, such as PI3K/Akt, GSK3 and ERK1,2, as well as the Nrf-2/heme oxigenase-1 axis, which specifically link them to neuroprotection. In this regard, regulation of dual specificity protein phosphatases can become novel mechanism of actions for nucleotide receptors that associate them to cell homeostasis regulation.This article is part of the Special Issue entitled ‘Purines in Neurodegeneration and Neuroregeneration’

The novel desmopressin analogue [V4Q5]dDAVP inhibits angiogenesis, tumour growth and metastases in vasopressin type 2 receptor-expressing breast cancer models

Desmopressin (dDAVP) is a safe haemostatic agent with previously reported antitumour activity. It acts as a selective agonist for the V2 vasopressin membrane receptor (V2r) present on tumour cells and microvasculature. The purpose of this study was to evaluate the novel peptide derivative [V4Q5]dDAVP in V2r-expressing preclinical mouse models of breast cancer. We assessed antitumour effects of [V4Q5]dDAVP using human MCF-7 and MDA‑MB‑231 breast carcinoma cells, as well as the highly metastatic mouse F3II cell line. Effect on in vitro cancer cell growth was evaluated by cell proliferation and clonogenic assays. Cell cycle distribution was analysed by flow cytometry. In order to study the effect of intravenously administered [V4Q5]dDAVP on tumour growth and angiogenesis, breast cancer xenografts were generated in athymic mice. F3II cells were injected into syngeneic mice to evaluate the effect of [V4Q5]dDAVP on spontaneous and experimental metastatic spread. In vitro cytostatic effects of [V4Q5]dDAVP against breast cancer cells were greater than those of dDAVP, and associated with V2r-activated signal transduction and partial cell cycle arrest. In MDA‑MB‑231 xenografts, [V4Q5]dDAVP (0.3 µg/kg, thrice a week) reduced tumour growth and angiogenesis. Treatment of F3II mammary tumour-bearing immunocompetent mice resulted in complete inhibition of metastatic progression. [V4Q5]dDAVP also displayed greater antimetastatic efficacy than dDAVP on experimental lung colonisation by F3II cells. The novel analogue was well tolerated in preliminary acute toxicology studies, at doses ≥300-fold above that required for anti-angiogenic/antimetastatic effects. Our data establish the preclinical activity of [V4Q5]dDAVP in aggressive breast cancer, providing the rationale for further clinical trials.Fil: Garona, Juan. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pifano, Marina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Orlando, Ulises Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Pastrian, María Belén. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Iannucci, Nancy Beatriz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ortega, Hugo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Ciencias Veterinarias del Litoral; Argentina. Universidad Nacional del Litoral; ArgentinaFil: Podesta, Ernesto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ripoll, Giselle Vanina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Evaluación ambiental estratégica de la explotación petrolera costa afuera en la Región Caribe Colombiana

La propuesta de investigación doctoral consiste en la realización de una Evaluación Ambiental Estratégica a la explotación petrolera costa afuera en la región del caribe colombiano, guiado por la necesidad de los planes gubernamentales de realizar estas actividades y la oposición generada por los accidentes ambientales ocurridos en Colombia y alrededor del mundo; la investigación buscara generar una guía que permita fortalecer el plan de desarrollo desde los marco institucionales y políticos. Empresas vinculadas al sector petrolero y gasífero, tales como la Agencia Nacional de Hidrocarburos (ANH), Comisión de Regulación de Energía y Gas (CREG), la Unidad de Planeación Minero-Energética (UPME), empresas operadoras de campos costa afuera, además del Ministerio de Minas y Energía. En términos generales, las entidades encargadas de la regulación, planeación y control del mercado del gas y el petróleo. Los eventuales resultados de esta tesis doctoral implicarían un cambio en los esquemas para la exploración y explotación de los campos petroleros costa afuera en la región caribe de Colombia. La Evaluación Ambiental Estratégica permitirá tener un modelo de evaluación para generar propuestas y recomendaciones para la formulación de una política petrolera adaptada a la problemática ambiental y social del país

Disparate miRNA expression in serum and plasma of patients with acute myocardial infarction: a systematic and paired comparative analysis

Despite the promising value of miRNAs in the diagnostic and prognostic of cardiovascular disease (CVD), recent meta-analyses did not support their potential. Methodological variances in studies may interfere with miRNA profle and afect their results. This study determines if the blood starting material is a source of variance in miRNA profle by performing a paired comparison in plasma and serum of the expression of primary miRNAs associated with CVD. Circulating miRNA yield was similar in both plasma and serum, although a signifcant increase was observed in patients with Non-ST-elevation myocardial infarction (NSTEMI) compared to control volunteers. When normalized by the expression of miR-484, diferent patterns of miRNA expression between serum and plasma. Although NSTEMI modifed the expression of miR-1 and miR-208 in both serum and plasma, plasma displayed a higher variance than serum (Levene's test p<0.01). For miR-133a and miR-26a, diferences were only detected in serum (p=0.0240), and conversely, miR-499a showed diferences only in plasma of NSTEMI (p=0.001). Interestingly, miR-21 showed an opposite pattern of expression, being increased in serum (2−ΔΔCt : 5.7, p=0.0221) and decreased in plasma (2−ΔΔCt : 0.5, p=0.0107). Plasma and serum exhibit diferent patterns of circulating miRNA expression in NSTEMI and suggest that results from studies with diferent starting material could not be comparable

A three-dimensional printed customized bolus: adapting to the shape of the outer ear

Background: The skin-sparing effect of megavoltage-photon beams in radiotherapy (RT) reduces the target coverage of superficial tumours. Consequently, a bolus is widely used to enhance the target coverage for superficial targets. This study evaluates a three-dimensional (3D)-printed customized bolus for a very irregular surface, the outer ear. Materials and methods: We fabricated a bolus using a computed tomography (CT) scanner and evaluated its efficacy. The head of an Alderson Rando phantom was scanned with a CT scanner. Two 3D boluses of 5- and 10-mm thickness were designed to fit on the surface of the ear. They were printed by the Stratasys Objet260 Connex3 using the malleable “rubber-like” photopolymer Agilus. CT simulations of the Rando phantom with and without the 3D and commercial high density boluses were performed to evaluate the dosimetric properties of the 3D bolus. The prescription dose to the outer ear was 50 Gy at 2 Gy/fraction. Results: We observed that the target coverage was slightly better with the 3D bolus of 10 mm compared with the commercial one (D98% 98.2% vs. 97.6%).The maximum dose was reduced by 6.6% with the 3D bolus and the minimum dose increased by 5.2% when comparing with the commercial bolus. In addition, the homogeneity index was better for the 3D bolus (0.041 vs. 0.073). Conclusion: We successfully fabricated a customized 3D bolus for a very irregular surface. The target coverage and dosimetric parameters were at least comparable with a commercial bolus. Thus, the use of malleable materials can be considered for the fabrication of customized boluses in cases with complex anatomy

Guía docente común de las titulaciones de Ingeniero en Electrónica en las universidades andaluzas

El presente documento constituye el resultado del trabajo elaborado de acuerdo con la Convocatoria de Elaboración de Guías Docentes de Titulaciones Andaluzas conforme al Sistema de Créditos Europeos (años 2005/2006) de la Dirección General de Universidades, dependiente de la Secretaría General de Universidades, Investigación y Tecnología de la Consejería de Innovación, Ciencia y Empresa de la Junta de Andalucía