Polymorphisms of CD16A and CD32 Fcγ receptors and circulating immune complexes in Ménière's disease: a case-control study

<p>Abstract</p> <p>Background</p> <p>Autoimmune diseases with elevated circulating autoantibodies drive tissue damage and the onset of disease. The Fcγ receptors bind IgG subtypes modulating the clearance of circulating immune complexes (CIC). The inner ear damage in Ménière's disease (MD) could be mediated by an immune response driven by CIC. We examined single-nucleotide polymorphism (SNPs) in the CD16A and CD32 genes in patients with MD which may determine a Fcγ receptor with lower binding to CIC.</p> <p>Methods</p> <p>The functional CD16A (FcγRIIIa*559A > C, rs396991) and CD32A (FcγRIIa*519A > G, rs1801274) SNPs were analyzed using PCR-based TaqMan Genotyping Assay in two cohorts of 156 mediterranean and 112 Galicia patients in a case-control study. Data were analyzed by χ²with Fisher's exact test and Cochran-Armitage trend test (CATT). CIC were measured by ELISA for C1q-binding CIC.</p> <p>Results</p> <p>Elevated CIC were found in 7% of patients with MD during the intercrisis period. No differences were found in the allelic frequency for rs396991 or rs1801274 in controls subjects when they were compared with patients with MD from the same geographic area. However, the frequency of AA and AC genotypes of CD16A (rs396991) differed among mediterranean and Galicia controls (Fisher's test, corrected p = 6.9 × 10^-4for AA; corrected p = 0.02 for AC). Although genotype AC of the CD16A receptor was significantly more frequent in mediterranean controls than in patients, [Fisher's test corrected p = 0.02; OR = 0.63 (0.44-0.91)], a genetic additive effect for the allele C was not observed (CATT, p = 0.23). Moreover, no differences were found in genotype frequencies for rs396991 between patients with MD and controls from Galicia (CATT, p = 0.14). The allelic frequency of CD32 (rs1801274) was not different between patients and controls either in mediterranean (p = 0.51) or Galicia population (p = 0.11).</p> <p>Conclusions</p> <p>Elevated CIC are not found in most of patients with MD. Functional polymorphisms of CD16A and CD32 genes are not associated with onset of MD.</p

Regulation of Fn14 Receptor and NF-κB Underlies Inflammation in Meniere’s Disease

Meniere’s disease (MD) is a rare disorder characterized by episodic vertigo, sensorineural hearing loss, tinnitus, and aural fullness. It is associated with a fluid imbalance between the secretion of endolymph in the cochlear duct and its reabsorption into the subarachnoid space, leading to an accumulation of endolymph in the inner ear. Epidemiological evidence, including familial aggregation, indicates a genetic contribution and a consistent association with autoimmune diseases (AD). We conducted a case–control study in two phases using an immune genotyping array in a total of 420 patients with bilateral MD and 1,630 controls. We have identified the first locus, at 6p21.33, suggesting an association with bilateral MD [meta-analysis leading signal rs4947296, OR = 2.089 (1.661–2.627); p = 1.39 × 10−09]. Gene expression profiles of homozygous genotype-selected peripheral blood mononuclear cells (PBMCs) demonstrated that this region is a trans-expression quantitative trait locus (eQTL) in PBMCs. Signaling analysis predicted several tumor necrosis factor-related pathways, the TWEAK/Fn14 pathway being the top candidate (p = 2.42 × 10−11). This pathway is involved in the modulation of inflammation in several human AD, including multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. In vitro studies with genotype-selected lymphoblastoid cells from patients with MD suggest that this trans-eQTL may regulate cellular proliferation in lymphoid cells through the TWEAK/Fn14 pathway by increasing the translation of NF-κB. Taken together; these findings suggest that the carriers of the risk genotype may develop an NF-κB-mediated inflammatory response in MD

Industrias audiovisuales: tendencias de producción y consumo

La digitalización de la creación cultural y su difusión online ha supuesto la entrada en los mercados de poderosos y novedosos agentes que se han convertido en los líderes no sólo de la industria tecnológica, sino de toda la producción cultural y de la economía. Dicha digitalización de los medios, además de la convergencia de las pantallas y la ruptura de la linealidad vertical y unidireccional de los medios convencionales ha conllevado un profundo cambio de paradigmas que atañe directamente a la creación audiovisual. Este volumen de la serie iniciada en el año 2012 a partir de las investigaciones de los estudiantes de la asignatura Estructura del mercado audiovisual del grado de Comunicación Audiovisual en la Universidad de Málaga nos lleva al análisis de la recepción y del consumo de diversas industrias del audiovisual, pero también al análisis de la producción condicionada por el contexto económico y por la demanda, así como a diversas cuestiones relacionadas con el marketing y los modelos de negocio de aquellas industrias. En una disciplina en la que no abundan los trabajos académicos actualizados, los autores y autoras de este volumen ofrecen con sus aportaciones estudios de casos significativos y paradigmáticos del estado de los diversos sectores de las industrias audiovisuales. Presentados aquí a modo de capítulos, estos textos suponen la iniciación en la investigación de estudiantes que combinan su formación académica e investigadora con su formación como profesionales en el área de la Comunicación Audiovisual. Ofrecemos aquí una selección de aquellas investigaciones que destacan por su interés, su capacidad analítica y crítica, su actualidad, su pertinencia y su disciplinada adecuación a una metodología de investigación apropiada para unos estudios que forman parte de las Ciencias Sociales. https://www.eumed.net/libros/1851/index.htm

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Cualificación docente en el uso de herramientas TIC para el fortalecimiento de prácticas pedagógicas en el aula de la Institución Educativa Celmira Bueno de Orejuela en la básica secundaria.

Este proyecto tiene como objeto brindar a los docentes las competencias que necesitan para utilizar eficazmente las TIC en el aula. Para garantizar una educación de alta calidad, es imperativo abordar esta brecha de cualificación. Para abordar este problema se utilizó una estrategia de investigación mixta. Para medir el conocimiento de los docentes sobre herramientas TIC, se aplicó una prueba de diagnóstico preliminar. Seguidamente, se examinaron las herramientas que los profesores conocían y utilizaban en su práctica.Este estudio demuestra la importancia de la formación docente en herramientas TIC para mejorar las estrategias de instrucción. Este proyecto sienta una base sólida para futuras iniciativas de desarrollo profesional destinadas a mejorar el dominio de los profesores con las herramientas TIC.MaestríaMagíster en Recursos Digitales Aplicados a la Educació

Clinical Subgroups in Bilateral Meniere Disease.

Journal Article;Meniere disease (MD) is a heterogeneous clinical condition characterized by sensorineural hearing loss, episodic vestibular symptoms, and tinnitus associated with several comorbidities, such as migraine or autoimmune disorders (AD). The frequency of bilateral involvement may range from 5 to 50%, and it depends on the duration of the disease. We have performed a two-step cluster analysis in 398 patients with bilateral MD (BMD) to identify the best predictors to define clinical subgroups with a potential different etiology to improve the phenotyping of BMD and to develop new treatments. We have defined five clinical variants in BMD. Group 1 is the most frequently found, includes 46% of patients, and is defined by metachronic hearing loss without migraine and without AD. Group 2 is found in 17% of patients, and it is defined by synchronic hearing loss without migraine or AD. Group 3, with 13% of patients, is characterized by familial MD, while group 4, that includes 12% of patients, is associated by the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by AD. This approach can be helpful in selecting patients for genetic and clinical research. However, further studies will be required to improve the phenotyping in these clinical variants for a better understanding of the diverse etiological factors contributing to BMD.This study was funded by a PI13/1242 Grant from ISCIII by FEDER funds from the EUYe

Pottery from the interstage of Neolithic and Bronze Age and from later epochs

<div><p>Meniere's disease is an episodic vestibular syndrome associated with sensorineural hearing loss (SNHL) and tinnitus. Patients with MD have an elevated prevalence of several autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and psoriasis), which suggests a shared autoimmune background. Functional variants of several genes involved in the NF-κB pathway, such as <i>REL</i>, <i>TNFAIP3</i>, <i>NFKB1</i> and <i>TNIP1</i>, have been associated with two or more immune-mediated diseases and allelic variations in the <i>TLR10</i> gene may influence bilateral affectation and clinical course in MD. We have genotyped 716 cases of MD and 1628 controls by using the ImmunoChip, a high-density genotyping array containing 186 autoimmune loci, to explore the association of immune system related-loci with sporadic MD. Although no single nucleotide polymorphism (SNP) reached a genome-wide significant association (p<10⁻⁸), we selected allelic variants in the NF-kB pathway for further analyses to evaluate the impact of these SNPs in the clinical outcome of MD in our cohort. None of the selected SNPs increased susceptibility for MD in patients with uni or bilateral SNHL. However, two potential regulatory variants in the <i>NFKB1</i> gene (rs3774937 and rs4648011) were associated with a faster hearing loss progression in patients with unilateral SNHL. So, individuals with unilateral MD carrying the C allele in rs3774937 or G allele in rs4648011 had a shorter mean time to reach hearing stage 3 (>40 dB HL) (log-rank test, corrected p values were p = 0.009 for rs3774937 and p = 0.003 for rs4648011, respectively). No variants influenced hearing in bilateral MD. Our data support that the allelic variants rs3774937 and rs4648011 can modify hearing outcome in patients with MD and unilateral SNHL.</p></div

Linkage disequilibrium plot showing the haploblocks with the rs3774937 and rs4648011 (r² = 0.67, D' = 0.95).

<p>Linkage disequilibrium plot showing the haploblocks with the rs3774937 and rs4648011 (r² = 0.67, D' = 0.95).</p