Expression of Inducible Nitric Oxide Synthase (iNOS) in Microglia of the Developing Quail Retina

Inducible nitric oxide synthase (iNOS), which produce large amounts of nitric oxide (NO), is induced in macrophages and microglia in response to inflammatory mediators such as LPS and cytokines. Although iNOS is mainly expressed by microglia that become activated in different pathological and experimental situations, it was recently reported that undifferentiated amoeboid microglia can also express iNOS during normal development. The aim of this study was to investigate the pattern of iNOS expression in microglial cells during normal development and after their activation with LPS by using the quail retina as model. iNOS expression was analyzed by iNOS immunolabeling, western-blot, and RT-PCR. NO production was determined by using DAR-4M AM, a reliable fluorescent indicator of subcellular NO production by iNOS. Embryonic, postnatal, and adult in situ quail retinas were used to analyze the pattern of iNOS expression in microglial cells during normal development. iNOS expression and NO production in LPS-treated microglial cells were investigated by an in vitro approach based on organotypic cultures of E8 retinas, in which microglial cell behavior is similar to that of the in situ retina, as previously demonstrated in our laboratory. We show here that amoeboid microglia in the quail retina express iNOS during normal development. This expression is stronger in microglial cells migrating tangentially in the vitreal part of the retina and is downregulated, albeit maintained, when microglia differentiate and become ramified. LPS treatment of retina explants also induces changes in the morphology of amoeboid microglia compatible with their activation, increasing their lysosomal compartment and upregulating iNOS expression with a concomitant production of NO. Taken together, our findings demonstrate that immature microglial cells express iNOS during normal development, suggesting a certain degree of activation. Furthermore, LPS treatment induces overactivation of amoeboid microglia, resulting in a significant iNOS upregulation.This work was supported by grants from Ministerio de Economía y Competitividad, Spain (BFU2010-19981) and Junta de Andalucía, Spain (P07-CVI-03008)

Educar para la transparencia y una ciudadanía informada: diseño, aplicación y evaluación del programa IRIS para alumnado de Bachillerato de la Región de Murcia (España)

In order to develop a validated model to teach key conceptsand values on the right to information and transparency to young people, the "IRIS" program was designed during the 2017-2018 academic year, which was applied as part of the "Philosophy" course of the First Year of High School students of six Secondary Education Institutes of five municipalities of the Region of Murcia. Its objectives were: a) Prepare and teach a Learning Unit on Transparency and Right to Information, in accordance with the standards of the Philosophy curriculum of the Region of Murcia. b) Identify initial perceptions of the students of the Region regarding concepts as Transparency and Open Government. c) Design a Contest on dissertations and videos on transparency and good governance, aimed at the students participating in the project. e) Evaluate results and identify recommendations to improve the program. After the evaluation we concluded that objectives had been achieved, and have proposed some recommendations to generalize and consolidate the acquisition of this citizen competence: a specific training plan for teachers, the inclusion of this standard on transparency in the autonomic curriculum, and that is necessary to develop a set of materials, texts and practical tasks to make easier the application to the teaching staff

Educar para la transparencia y una ciudadanía informada: diseño, aplicación y evaluación del programa IRIS para alumnado de Bachillerato de la Región de Murcia (España)

In order to develop a validated model to teach key conceptsand values on the right to information and transparency to young people, the "IRIS" program was designed during the 2017-2018 academic year, which was applied as part of the "Philosophy" course of the First Year of High School students of six Secondary Education Institutes of five municipalities of the Region of Murcia. Its objectives were: a) Prepare and teach a Learning Unit on Transparency and Right to Information, in accordance with the standards of the Philosophy curriculum of the Region of Murcia. b) Identify initial perceptions of the students of the Region regarding concepts as Transparency and Open Government. c) Design a Contest on dissertations and videos on transparency and good governance, aimed at the students participating in the project. e) Evaluate results and identify recommendations to improve the program. After the evaluation we concluded that objectives had been achieved, and have proposed some recommendations to generalize and consolidate the acquisition of this citizen competence: a specific training plan for teachers, the inclusion of this standard on transparency in the autonomic curriculum, and that is necessary to develop a set of materials, texts and practical tasks to make easier the application to the teaching staff

Heme oxygenase 1 and 2 common genetic variants and risk for essential tremor

Varios informes sugirieren que una función hemo oxigenasa 1 y 2 de los genes HMOX HMOX1 y 2 modifican el riesgo de desarrollar la enfermedad de Parkinson (EP). Porque el temblor esencial (ET) y PD comparten fenotipo y, probablemente, unos factores etiológicos semejantes, analizamos si tales genes están relacionados con el riesgo de desarrollar ET. Se analizó la distribución de las frecuencias genotípicas y alélicas de los HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363 y rs1051308 HMOX2 polimorfismos de nucleótido único, así como la presencia de variaciones de número de copias de estos genes en 202 sujetos con ET familiar y 747 controles sanos. Las frecuencias alélicas de rs2071746T y R1051308G ET fueron significativamente menores en los pacientes que en los controles. Ninguno de los polimorfismos estudiados influyeron en el comienzo de la enfermedad. El presente estudio sugiere una débil asociación entre HMOX1 rs2071746 y rs1051308 HMOX2 polimorfismo y el riesgo de desarrollar ET en la población española.Several reports suggested a role of heme oxygenase genes 1 and 2 (HMOX1 and HMOX2) in modifying the risk to develop Parkinson disease (PD). Because essential tremor (ET) and PD share phenotypical and, probably, etiologic factors of the similarities, we analyzed whether such genes are related with the risk to develop ET. We analyzed the distribution of allelic and genotype frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 single nucleotide polymorphisms, as well as the presence of copy number variations of these genes in 202 subjects with familial ET and 747 healthy controls. Allelic frequencies of rs2071746T and rs1051308G were significantly lower in ET patients than in controls. None of the studied polymorphisms influenced the disease onset. The present study suggests a weak association between HMOX1 rs2071746 and HMOX2 rs1051308 polymorphisms and the risk to develop ET in the Spanish population.T• Instituto de Salud Carlos III, Fondo de Investigación Sanitaria: Ayudas PI12/00241, PI12/00324 y RETICS RD12/0013/0002 • Junta de Extremadura: Ayuda GR10068 • Ministerio de Ciencia e Innovación: Ayudas SAF2006-10126 (2006–2009) y SAF2010-22329-C02-01 (2011–2013) • Parcialmente financiado Fondos FEDER – Fondo Europeo de Desarrollo RegionalpeerReviewe

Is hospital discharge administrative data an appropriate source of information for cancer registries purposes? Some insights from four Spanish registries

<p>Abstract</p> <p>Background</p> <p>The use of hospital discharge administrative data (HDAD) has been recommended for automating, improving, even substituting, population-based cancer registries. The frequency of false positive and false negative cases recommends local validation.</p> <p>Methods</p> <p>The aim of this study was to detect newly diagnosed, false positive and false negative cases of cancer from hospital discharge claims, using four Spanish population-based cancer registries as the gold standard. Prostate cancer was used as a case study.</p> <p>Results</p> <p>A total of 2286 incident cases of prostate cancer registered in 2000 were used for validation. In the most sensitive algorithm (that using five diagnostic codes), estimates for Sensitivity ranged from 14.5% (CI95% 10.3-19.6) to 45.7% (CI95% 41.4-50.1). In the most predictive algorithm (that using five diagnostic and five surgical codes) Positive Predictive Value estimates ranged from 55.9% (CI95% 42.4-68.8) to 74.3% (CI95% 67.0-80.6). The most frequent reason for false positive cases was the number of prevalent cases inadequately considered as newly diagnosed cancers, ranging from 61.1% to 82.3% of false positive cases. The most frequent reason for false negative cases was related to the number of cases not attended in hospital settings. In this case, figures ranged from 34.4% to 69.7% of false negative cases, in the most predictive algorithm.</p> <p>Conclusions</p> <p>HDAD might be a helpful tool for cancer registries to reach their goals. The findings suggest that, for automating cancer registries, algorithms combining diagnoses and procedures are the best option. However, for cancer surveillance purposes, in those cancers like prostate cancer in which care is not only hospital-based, combining inpatient and outpatient information will be required.</p

COVID-19 vaccine effectiveness against hospitalization due to SARS-CoV-2: A test-negative design study based on Severe Acute Respiratory Infection (SARI) sentinel surveillance in Spain

Background: With the emergence of SARS-CoV-2, influenza surveillance systems in Spain were transformed into a new syndromic sentinel surveillance system. The Acute Respiratory Infection Surveillance System (SiVIRA in Spanish) is based on a sentinel network for acute respiratory infection (ARI) surveillance in primary care and a network of sentinel hospitals for severe ARI (SARI) surveillance in hospitals. Methods: Using a test-negative design and data from SARI admissions notified to SiVIRA between January 1 and October 3, 2021, we estimated COVID-19 vaccine effectiveness (VE) against hospitalization, by age group, vaccine type, time since vaccination, and SARS-CoV-2 variant. Results: VE was 89% (95% CI: 83-93) against COVID-19 hospitalization overall in persons aged 20 years and older. VE was higher for mRNA vaccines, and lower for those aged 80 years and older, with a decrease in protection beyond 3 months of completing vaccination, and a further decrease after 5 months. We found no differences between periods with circulation of Alpha or Delta SARS-CoV-2 variants, although variant-specific VE was slightly higher against Alpha. Conclusions: The SiVIRA sentinel hospital surveillance network in Spain was able to describe clinical and epidemiological characteristics of SARI hospitalizations and provide estimates of COVID-19 VE in the population under surveillance. Our estimates add to evidence of high effectiveness of mRNA vaccines against severe COVID-19 and waning of protection with time since vaccination in those aged 80 or older. No substantial differences were observed between SARS-CoV-2 variants (Alpha vs. Delta).The data of the study was originally collectedas part of the following projects run by the European Centre for Disease Prevention and Control:“Establishing Severe Acute Respiratory Infections (SARI) surveillance and performing hospital-based COVID-19 transmission studies”, “Developing an infrastructure and performing vaccine effectiveness studies for COVID-19 vaccines in the EU/EEA”, and the “Vaccine Effectiveness, Burden and Impact Studies(VEBIS) of COVID-19 and Influenza".S

Association between vitamin D receptor rs731236 (Taq1) polymorphism and risk for restless legs syndrome in the Spanish caucasian population

Varios trabajos recientes sugieren un posible papel de la deficiencia de vitamina D en la etiología o el síndrome de las piernas inquietas (RLS). Hemos analizado la posible relación de 2 polimorfismos de un solo nucleótido (SNP) en el receptor de la vitamina D3 (GEN VDR) con el riesgo de SPI. Hemos estudiado la variante alélica genotipo y frecuencias de VDR rs2228570 y rs731236 VDR SNPs en 205 RLS pacientes y 445 controles sanos mediante un ensayo TaqMan. Las frecuencias de los rs731236AAgenotype y la variante alélica rs731236un SPI fue significativamente inferior en los pacientes que en los controles (P<0,005 y 0,01, respectivamente). El síndrome de las piernas inquietas pacientes portadoras de la variante alélica rs731236G había una edad temprana en el inicio, y los portadores del genotipo GG731236rs tuvieron mayor severidad de RLS, aunque estos datos desaparecieron después de los análisis multivariados. Ninguno de los SNPs estudiados estaba relacionada con la positividad de la historia familiar de SPI. Estos resultados sugieren una modesta, pero significativa asociación entre rs731236 VDR SNP y el riesgo de síndrome de piernas inquietas.Several recent works suggest a possible role of vitamin D deficiency in the etiology or restless legs syndrome (RLS). We analyzed the possible relationship of 2 common single nucleotide polymorphisms (SNPs) in the vitamin D3 receptor (VDR) gene with the risk for RLS. We studied the genotype and allelic variant frequencies of VDR rs2228570 and VDR rs731236 SNPs in 205 RLS patients and 445 healthy controls using a TaqMan essay. The frequencies of the rs731236AAgenotype and the allelic variant rs731236A were significantly lower in RLS patients than in controls (P<0.005 and<0.01, respectively). Restless legs syndrome patients carrying the allelic variant rs731236G had an earlier age at onset, and those carrying the rs731236GG genotype had higher severity of RLS, although these data disappeared after multivariate analyses. None of the SNPs studied was related with the positivity of family history of RLS. These results suggest a modest, but significant association between VDR rs731236 SNP and the risk for RLS.• Instituto de Salud Carlos III, Madrid, Fondo de Investigación Sanitaria: Ayudas PI12/00241, PI12/00324, y RETICS RD12/0013/0002 • Junta de Extremadura: GR15026 y PRIS10016 • Ministerio de Ciencia e Innovación: Ayudas SAF2006-10126 (2006–2009) y SAF2010-22329-C02-01 (2011-2013) • Parciamente financiado con Fondos FEDERpeerReviewe