Lack of Methylation Changes in GJB2 and RB1 Non-coding Regions of Cochlear Implant Patients with Sensorineural Hearing Loss.

Objective: Recent advances in epigenetic studies continue to reveal novel mechanisms of gene regulation and control, however little is known on the role of epigenetics in sensorineural hearing loss (SNHL) in humans. We aimed to investigate the methylation patterns of two regions, one in RB1 and another in GJB2 in Filipino patients with SNHL compared to hearing control individuals. Methods: We investigated an RB1 promoter region that was previously identified as differentially methylated in children with SNHL and lead exposure. Additionally, we investigated a sequence in an enhancer-like region within GJB2 that contains four CpGs in close proximity. Bisulfite conversion was performed on salivary DNA samples from 15 children with SNHL and 45 unrelated ethnically-matched individuals. We then performed methylation-specific real-time PCR analysis (qMSP) using TaqMan® probes to determine percentage methylation of the two regions. Results: Using qMSP, both our cases and controls had zero methylation at the targeted GJB2 and RB1 regions. Conclusion: Our study showed no changes in methylation at the selected CpG regions in RB1 and GJB2 in the two comparison groups with or without SNHL. This may be due to a lack of environmental exposures to these target regions. Other epigenetic marks may be present around these regions as well as those of other HL-associated genes.

Audiologic Measures in an Indigenous Community with A2ML1- and FUT2-Related Otitis Media.

Background: Many indigenous peoples are at elevated risk for otitis media, however there is limited information on hearing loss due to OM in these communities. An Indigenous Filipino community that has previously been described with an elevated prevalence of OM that is due to rare A2ML1 variants and a common FUT2 variant underwent additional phenological testing. In this study, we describe the audiologic profiles in A2ML1- and FUT2-related otitis media and the validity of otoscopy and genotyping for A2ML1 and FUT2 variants in screening for otitis media and hearing loss. Method: We analyzed A2ML1 and FUT2 genotypes together with demographic, otologic and audiologic data from tympanometry and hearing level assessments of 109 indigenous individuals. Results: We confirmed previous findings of a spectrum of nonsyndromic otitis media as associated with A2ML1 variants. A2ML1 and FUT2 variants were associated with high-frequency hearing loss at 4000 Hz. As expected, young age was associated with flat tympanograms, and eardrum perforations due to chronic otitis media were associated with severe-to-profound hearing loss across frequencies. Adding A2ML1 or FUT2 genotypes improved the validity of otoscopy as a screening test to rule out moderate-to-profound hearing loss. Conclusion: Continued multi-disciplinary management and audiologic follow-up using tympanometry and screening audiometry are needed to document and treat otitis media and prevent permanent hearing loss in the indigenous community.

Estilos de aprendizaje en estudiantes de la licenciatura en enfemeria de tres instituciones de educación superior en México / Learning styles in nursing degree students from three higher education institutions in Mexico

INTRODUCCIÓN. La sociedad actual demanda de enfermeros que desarrollen la autonomía necesaria para la resolución de problemas, la planificación, el seguimiento y la evaluación de su propio desempeño. Esta autonomía proviene del aprendizaje permanente. OBJETIVO. Determinar los Estilos de Aprendizaje predominantes entre los estudiantes de primer año matriculados en tres instituciones de educación superior en México para cursar la carrera de enfermería. METODOLOGÍA: Estudio cuantitativo y multicéntrico con un diseño descriptivo, y una muestra no probabilística. Para identificar los Estilos de aprendizaje de los estudiantes se utilizó el cuestionario VARK, con coeficiente alfa de Cronbach osciló entre 0.77 y 0.85. La escala fue digitalizada y programada mediante la herramienta Formulario de Google Drive. Se obtuvo un dictamen favorable por el comité de ética de las instituciones. Los resultados se procesaron en el programa estadístico SPSS versión 25.0. RESULTADOS: Se aplicaron 305 cuestionarios, donde 88,63 % fueron mujeres. El estilo de aprendizaje más preponderante fue el Quinestésico (30.39 %), seguido por el Lectura/Escritura (27.42 %), auditivo (26,58 %) y visual (15.61 %). De acuerdo con el estilo modal más del 50 % son multimodales. CONCLUSIÓN: Los resultados muestran que es fundamental contar con datos tanto individuales como grupales de los estudiantes para pensar estrategias de enseñanza y aprendizaje que tengan en cuenta las preferencias de aprendizaje de los estudiantes y la orientación temática del orden disciplinario, desde su ingreso a la universidad.

INTRODUCTION. Today's society demands that nurses develop the necessary autonomy to solve problems, plan, monitor and evaluate their own performance. This autonomy comes from lifelong learning. AIM. To determine the predominant learning styles among first-year nursing students enrolled in three higher education institutions in Mexico. METHODOLOGY: Quantitative and multicenter study with a descriptive designand a non-probabilistic sample. To identify the learning styles of the students, the VARK questionnaire was used, with Cronbach's alpha coefficient ranging between 0.77 and 0.85. The scale was digitized and programmed using the Google Drive Form tool. A favorable opinion was obtained by the ethics committee of each institution. The results were processed in the statistical program SPSS, version 25.0. RESULTS: 305 questionnaires were completed by respondents, 88.63% of which were women. The most predominant learning style was kinesthetic (30.39%), followed by reading/writing (27.42%), auditory (26.58%) and visual (15.61%). As to the modal style, more than 50% were multimodal. CONCLUSION: The results show that it is essential to have both individual and group data related to students so that teaching and learning strategies can take into account their learning preferences, as well as the thematic orientation of the discipline of nursing, from the time of their admission to the university.

Emotional intelligence characterization in university students at a nutrition bachelor's degree / Caracterización de la inteligencia emocional en estudiantes universitarios del área de nutrición

Abstract Objective: Identify the levels of emotional intelligence possessed by students of a Bachelor of Nutrition degree at a university in southeastern Mexico. Materials and methods: According to reviewed documental sources this is a quantitative study, with a descriptive non-experimental approach. In this research, a validated Salovery and Meyer TMMS-24, adapted to Spanish, was applied; this instrument consists of 24 items, subdivided into three subscales or dimensions of the Likert type made up of five items. The sampling was non- probabilistic, including 172 university students, who accepted the terms of the informed consent. For data analysis, the SPSS v.25 program was executed to assembly the information obtained through descriptive statistics (frequency, mean, median and percentage) and variability measures (range, standard deviation and variance). A t-Student test was performed for the analysis of means according to the levels, with a p value <0.005 to determine statistically significant differences. Results: 52.91% of the students are located at a level of "adequate attention", but 47.1% must improve. In relation to the level of understanding, 43.60% have adequate clarity in this sphere of emotional intelligence, while 56.60% must improve this component and 52.33% have adequate regulation, while 47.67% must improve. No statistically significant differences were found; as well as there were no differences in the means between both genders (p = ≥0.05). Conclusions: The study population showed an adequate management level of their emotional intelligence, being emotional perception the one that is presented more frequently as adequate, however, the clarity of feelings presents the lowest levels, so It is evident the need to carry out intervention programs in university students to promote further development of the dimensions that make up emotional intelligence.

Resumen Objetivo: Identificar los niveles de inteligencia emocional en estudiantes de la Licenciatura en Nutrición de una universidad en el sureste de México. Materiales y método: Es un estudio cuantitativo, no experimental descriptivo. En la investigación se aplicó el TMMS-24 de Salovery y Mayer, adaptada al español; dicho instrumento consta de 24 ítems, subdividida en tres subescalas o dimensiones, de tipo Likert conformado por cinco ítems. El muestreo fue no probabilístico, incluyendo a 172 estudiantes universitarios, quienes aceptaron los términos del consentimiento informado. Para el análisis de los resultados se ejecuta el programa SPSS v.25 para agrupar la información obtenida mediante la estadística descriptiva (frecuencia, media, mediana y porcentaje) y medidas de variabilidad (rango, desviación estándar y varianza). Se realizó una prueba de t-Student para el análisis de medias según los niveles, con valor p < 0.005 para determinar diferencias estadísticamente significativas. Resultados: El 52.91 % de los estudiantes se ubican en un nivel de "adecuada atención", pero el 47.1% debe mejorar. En relación con el nivel de comprensión el 43.60 % tiene una adecuada claridad en esta esfera de la inteligencia emocional, mientras el 56.60 % debe mejorar este componente y el 52.33 % tiene una adecuada regulación, mientras 47.67 % debe mejorar. No se encontraron diferencias estadísticamente significativas; así como tampoco hubo diferencias de las medias entre ambos géneros (p=≥0.05). Conclusiones: La población de estudio se ubica en un adecuado manejo de su inteligencia emocional, siendo la percepción emocional la que se presenta con mayor frecuencia como adecuada, sin embargo, la claridad de sentimientos es la que presenta los niveles más bajos, por lo que es evidente la necesidad de llevar a cabo programas de intervención en universitarios que fomenten el desarrollo de las dimensiones que conforman la inteligencia emocional.

An ultra-sensitive electrochemical biosensor using the Spike protein for capturing antibodies against SARS-CoV-2 in point-of-care.

This work presents an innovative ultra-sensitive biosensor having the Spike protein on carbon-based screen-printed electrodes (SPEs), for monitoring in point-of-care antibodies against SARS-CoV-2, a very important tool for epidemiological monitoring of COVID-19 infection and establishing vaccination schemes. In an innovative and simple approach, a highly conductive support is combined with the direct adsorption of Spike protein to enable an extensive antibody capture. The high conductivity was ensured by using carboxylated carbon nanotubes on the carbon electrode, by means of a simple and quick approach, which also increased the surface area. These were then modified with EDC/NHS chemistry to produce an amine layer and undergo Spike protein adsorption, to generate a stable layer capable of capturing the antibodies against SARS-CoV-2 in serum with great sensitivity. Electrochemical impedance spectroscopy was used to evaluate the analytical performance of this biosensor in serum. It displayed a linear response between 1.0 â€‹pg/mL and 10 â€‹ng/mL, with a detection limit of ∼0.7 â€‹pg/mL. The analysis of human positive sera containing antibody in a wide range of concentrations yielded accurate data, correlating well with the reference method. It also offered the unique ability of discriminating antibody concentrations in sera below 2.3 â€‹µg/mL, the lowest value detected by the commercial method. In addition, a proof-of-concept study was performed by labelling anti-IgG antibodies with quantum dots to explore a new electrochemical readout based on the signal generated upon binding to the anti-S protein antibodies recognised on the surface of the biosensor. Overall, the alternative serologic assay presented is a promising tool for assessing protective immunity to SARS-CoV-2 and a potential guide for revaccination.

Improvement of Glycaemia and Endothelial Function by a New Low-Dose Curcuminoid in an Animal Model of Type 2 Diabetes.

Curcumin has been suggested as a promising treatment for metabolic diseases, but the high doses required limit its therapeutic use. In this study, a new curcuminoid is synthesised to increase curcumin anti-inflammatory and antioxidant potential and to achieve hypoglycaemic and protective vascular effects in type 2 diabetic rats in a lower dose. In vitro, the anti-inflammatory effect was determined through the Griess reaction, and the antioxidant activity through ABTS and TBARS assays. In vivo, Goto-Kakizaki rats were treated for 2 weeks with the equimolar dose of curcumin (40 mg/kg/day) or curcuminoid (52.4 mg/kg/day). Fasting glycaemia, insulin tolerance, plasma insulin, insulin signalling, serum FFA, endothelial function and several markers of oxidative stress were evaluated. Both compounds presented a significant anti-inflammatory effect. Moreover, the curcuminoid had a marked hypoglycaemic effect, accompanied by higher GLUT4 levels in adipose tissue. Both compounds increased NO-dependent vasorelaxation, but only the curcuminoid exacerbated the response to ascorbic acid, consistent with a higher decrease in vascular oxidative and nitrosative stress. SOD1 and GLO1 levels were increased in EAT and heart, respectively. Altogether, these data suggest that the curcuminoid developed here has more pronounced effects than curcumin in low doses, improving the oxidative stress, endothelial function and glycaemic profile in type 2 diabetes.

Otologic and vestibular symptoms in COVID-19: A scoping review.

Background: Otologic and vestibular symptoms have been seen in patients confirmed to have COVID-19 disease. Further discussion of these symptoms may provide insight into short- and long-term management for these patients. Objective: The aim of this review was to describe the otologic and vestibular symptoms that present in patients with COVID-19. The primary outcomes of this review were onset, duration and clinical outcomes of these symptoms. Sources of Evidence: Pub Med, APAMed Central, Herdin, CINAHL, Scopus, Springer Link, ProQuest Coronavirus Research Database, and Google Scholar were searched for the articles to be included. Eligibility Criteria: Studies included were those involving adult patients diagnosed with COVID-19 who experienced hearing loss, ear pain, ear discharge, otitis media, vertigo, or tinnitus. Studies were eligible for inclusion if there was a description of the otologic dysfunction, specifically onset, duration, or clinical outcomes. Results: The majority of patients who experienced hearing loss (68%), tinnitus (88%), vertigo/dizziness (30%), ear pain (8%), and discharge (100%) did so within a month of experiencing the typical symptoms of COVID-19. A majority also experienced complete resolution of their symptoms within 2 weeks. Standard treatment for COVID-19 was usually provided but when specific diagnoses are made for these symptoms (e.g., sudden sensorineural hearing loss, otitis media, vestibular neuritis), they are treated in the same manner as one would for non-COVID-19 cases, in addition to the management for COVID-19. In certain cases, there may be a need for additional work-up to rule out other causes. Conclusions: Otologic and vestibular symptoms were present in COVID-19 patients, majority as part of the systemic nature of the disease. The onset, duration, and course were consistent with the natural history of a systemic viral infection. COVID-19 should be considered in any patient with a new-onset hearing loss, tinnitus, or vertigo/dizziness, even in the absence of infectious or respiratory symptoms.

Elemental Chemometrics as Tools to Depict Stalked Barnacle (Pollicipes pollicipes) Harvest Locations and Food Safety.

The stalked barnacle Pollicipes pollicipes is an abundant species on the very exposed rocky shore habitats of the Spanish and Portuguese coasts, constituting also an important economical resource, as a seafood item with high commercial value. Twenty-four elements were measured by untargeted total reflection X-ray fluorescence spectroscopy (TXRF) in the edible peduncle of stalked barnacles sampled in six sites along the Portuguese western coast, comprising a total of 90 individuals. The elemental profile of 90 individuals originated from several geographical sites (N = 15 per site), were analysed using several chemometric multivariate approaches (variable in importance partial least square discriminant analysis (VIP-PLS-DA), stepwise linear discriminant analysis (S-LDA), linear discriminant analysis (LDA), random forests (RF) and canonical analysis of principal components (CAP)), to evaluate the ability of each approach to trace the geographical origin of the animals collected. As a suspension feeder, this species introduces a high degree of background noise, leading to a comparatively lower classification of the chemometric approaches based on the complete elemental profile of the peduncle (canonical analysis of principal components and linear discriminant analysis). The application of variable selection approaches such as the VIP-PLS-DA and S-LDA significantly increased the classification accuracy (77.8% and 84.4%, respectively) of the samples according to their harvesting area, while reducing the number of elements needed for this classification, and thus the background noise. Moreover, the selected elements are similar to those selected by other random and non-random approaches, reinforcing the reliability of this selection. This untargeted analytical procedure also allowed to depict the degree of risk, in terms of human consumption of these animals, highlighting the geographical areas where these delicacies presented lower values for critical elements compared to the standard thresholds for human consumption.

Establishing a governance threshold in small-scale fisheries to achieve sustainability.

The lack of effective governance is a major concern in small-scale fisheries. The implementation of governance that encompasses the three pillars of sustainability (social, economic, and ecological) is still a worldwide challenge. We examined nine stalked barnacle fisheries (Pollicipes pollicipes) across Southwest Europe to better understand the relationship between governance elements and sustainability. Our results show that nested spatial scales of management, the access structure, co-management, and fisher's participation in monitoring and surveillance promote sustainability. However, it is not the mere presence of these elements but their level of implementation that drives sustainability. Efforts should be placed in the accomplishment of a minimum combination of local scales of management, access rights through individual quotas, instructive-consultative co-management and functional participation. Surpassing this threshold in future governance structures will start to adequately promote social, economic and ecologically sustainability in small-scale fisheries.

Nutritional and educational intervention to reduce malnutrition due to excess in university students / Intervención educativa nutricional para la reducción de malnutrición por exceso en estudiantes universitarios

Abstract Objective: To assess the effect of a nutritional/educational intervention over malnutrition due to excess in university students. Materials & Methods: A quantitative study with a descriptive approach. Intervention was conducted through the implementation of educational strategies promoting healthy lifestyles, nutritional status of participants was monitored throughout the entire scholar cycle (16 weeks). Non-probabilistic sampling was used including 52 university students who willingly accepted to participate. Data was processed using descriptive statistics (frequency, category variable percentages, measures of central tendency, dispersion for numerical variables). Nutritional profiles of the participants were evaluated based on the normality of the data through the use Kolmogorv Smirnov test, averages, T tests for related samples and the Wilcoxon test to evaluate the intervention effects. Results: Weight average before intervention stage was 74.7 kg and 68.2 kg after intervention. Before intervention 42.31% presented malnutrition due to excess, after intervention 17.3% presented malnutrition due to excess which signifies a decrease of 25. 01 % was recorded (p value < 0.001) Conclusions: Educational intervention had an impact on the nutritional status of university students in relation with the percentage of malnutrition due to excess normal weight students ratio was increased.

Resumen Objetivo: Evaluar el efecto de una intervención educativa nutricional sobre la reducción de la malnutrición por exceso en estudiantes universitarios. Materiales y método: Es un estudio cuantitativo con alcance descriptivo. La intervención se basó en la implementación de estrategias educativas que incidieran en estilos de vida saludables y se monitoreó el estado nutricional durante un ciclo escolar (16 semanas). El muestreo fue de tipo no probabilístico, incluyendo a 52 estudiantes universitarios, quienes aceptaron los términos del consentimiento informado. Para el procesamiento de datos se empleó estadística descriptiva (frecuencias, porcentajes para las variables categóricas, medidas de tendencia central y dispersión para las variables numéricas). El perfil nutricional de los participantes se evalúo en función de la normalidad de los datos mediante la prueba Kolmogorv Smirnov, se calcularon promedios, prueba t para muestras relacionadas y la prueba de Wilcoxon para evaluar el efecto de la intervención. Resultados: El peso promedio antes de la intervención fue 74.7 kg y después de la intervención fue 68.2 kg. Antes de la intervención el 42.31 %, presentaron malnutrición por exceso y al final de la intervención el 17.3 %, evidenciándose una disminución de 25.01% al finalizar la intervención (p valor< 0.001). Conclusiones: La intervención educativa incidió en el estado nutricional de los participantes, con relación a la malnutrición por exceso, se incrementó el porcentaje de estudiantes con estado nutricional normal.

Antifungal and Anti-Inflammatory Potential of Bupleurum rigidum subsp. paniculatum (Brot.) H.Wolff Essential Oil.

Fungal infections remain a major health concern with aromatic plants and their metabolites standing out as promising antifungal agents. The present study aims to assess, for the first time, the antifungal and anti-inflammatory potential of Bupleurum subsp. paniculatum (Brot.) H.Wolff essential oil from Portugal. The oil obtained by hydrodistillation and characterized by GC-MS, showed high amounts of monoterpene hydrocarbons, namely α-pinene (29.0-36.0%), ß-pinene (26.1-30.7%) and limonene (10.5-13.5%). The antifungal potential was assessed, according to CLSI guidelines, against several clinical and collection strains. The essential oil showed a broad fungicidal effect being more potent against Cryptococcus neoformans and dermatophytes. Moreover, a significant germ tube inhibition was observed in Candida albicans as well as a disruption of mature biofilms, thus pointing out an effect of the oil against relevant virulent factors. Furthermore, fungal ultrastructural modifications were detected through transmission electron microscopy, highlighting the nefarious effect of the oil. Of relevance, the oil also evidenced anti-inflammatory activity through nitric oxide inhibition in macrophages activated with lipopolysaccharide. In addition, the essential oil's bioactive concentrations did not present toxicity towards macrophages. Overall, the present study confirmed the bioactive potential of B. rigidum subsp. paniculatum essential oil, thus paving the way for the development of effective drugs presenting concomitantly antifungal and anti-inflammatory properties.

Identification of Novel Candidate Genes and Variants for Hearing Loss and Temporal Bone Anomalies.

Background: Hearing loss remains an important global health problem that is potentially addressed through early identification of a genetic etiology, which helps to predict outcomes of hearing rehabilitation such as cochlear implantation and also to mitigate the long-term effects of comorbidities. The identification of variants for hearing loss and detailed descriptions of clinical phenotypes in patients from various populations are needed to improve the utility of clinical genetic screening for hearing loss. Methods: Clinical and exome data from 15 children with hearing loss were reviewed. Standard tools for annotating variants were used and rare, putatively deleterious variants were selected from the exome data. Results: In 15 children, 21 rare damaging variants in 17 genes were identified, including: 14 known hearing loss or neurodevelopmental genes, 11 of which had novel variants; and three candidate genes IST1, CBLN3 and GDPD5, two of which were identified in children with both hearing loss and enlarged vestibular aqueducts. Patients with variants within IST1 and MYO18B had poorer outcomes after cochlear implantation. Conclusion: Our findings highlight the importance of identifying novel variants and genes in ethnic groups that are understudied for hearing loss.

Otitis media susceptibility and shifts in the head and neck microbiome due to SPINK5 variants.

BACKGROUND: Otitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants that confer OM susceptibility. METHODS: We performed exome and Sanger sequencing of >1000 DNA samples from 551 multiethnic families with OM and unrelated individuals, RNA-sequencing and microbiome sequencing and analyses of swabs from the outer ear, middle ear, nasopharynx and oral cavity. We also examined protein localisation and gene expression in infected and healthy middle ear tissues. RESULTS: A large, intermarried pedigree that includes 81 OM-affected and 53 unaffected individuals cosegregates two known rare A2ML1 variants, a common FUT2 variant and a rare, novel pathogenic variant c.1682A>G (p.Glu561Gly) within SPINK5 (LOD=4.09). Carriage of the SPINK5 missense variant resulted in increased relative abundance of Microbacteriaceae in the middle ear, along with occurrence of Microbacteriaceae in the outer ear and oral cavity but not the nasopharynx. Eight additional novel SPINK5 variants were identified in 12 families and individuals with OM. A role for SPINK5 in OM susceptibility is further supported by lower RNA counts in variant carriers, strong SPINK5 localisation in outer ear skin, faint localisation to middle ear mucosa and eardrum and increased SPINK5 expression in human cholesteatoma. CONCLUSION: SPINK5 variants confer susceptibility to non-syndromic OM. These variants potentially contribute to middle ear pathology through breakdown of mucosal and epithelial barriers, immunodeficiency such as poor vaccination response, alteration of head and neck microbiota and facilitation of entry of opportunistic pathogens into the middle ear.

A2ML1 and otitis media: novel variants, differential expression, and relevant pathways.

A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media.

FUT2 Variants Confer Susceptibility to Familial Otitis Media.

Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154∗) is associated with either risk for autoimmune diseases or protection against viral diarrhea and HIV. We determined the role of FUT2 in otitis media susceptibility by obtaining DNA samples from 609 multi-ethnic families and simplex case subjects with otitis media. Exome and Sanger sequencing, linkage analysis, and Fisher exact and transmission disequilibrium tests (TDT) were performed. The common FUT2 c.604C>T (p.Arg202∗) variant co-segregates with otitis media in a Filipino pedigree (LOD = 4.0). Additionally, a rare variant, c.412C>T (p.Arg138Cys), is associated with recurrent/chronic otitis media in European-American children (p = 1.2 × 10-5) and US trios (TDT p = 0.01). The c.461G>A (p.Trp154∗) variant was also over-transmitted in US trios (TDT p = 0.01) and was associated with shifts in middle ear microbiota composition (PERMANOVA p < 10-7) and increased biodiversity. When all missense and nonsense variants identified in multi-ethnic US trios with CADD > 20 were combined, FUT2 variants were over-transmitted in trios (TDT p = 0.001). Fut2 is transiently upregulated in mouse middle ear after inoculation with non-typeable Haemophilus influenzae. Four FUT2 variants-namely p.Ala104Val, p.Arg138Cys, p.Trp154∗, and p.Arg202∗-reduced A antigen in mutant-transfected COS-7 cells, while the nonsense variants also reduced FUT2 protein levels. Common and rare FUT2 variants confer susceptibility to otitis media, likely by modifying the middle ear microbiome through regulation of A antigen levels in epithelial cells. Our families demonstrate marked intra-familial genetic heterogeneity, suggesting that multiple combinations of common and rare variants plus environmental factors influence the individual otitis media phenotype as a complex trait.

Perfil sociosanitario e información a donantes y receptores renales de vivo en tres hospitales andaluces / Socio-sanitary profile and information for living kidney donors and recipients in three Andalusian hospitals

ANTECEDENTES: La información suministrada por profesionales sanitarios a posibles donantes y receptores es fundamental para una decisión autónoma y objetiva de donar un riñón en vida. OBJETIVOS: Conocer las características de la información que reciben los donantes y receptores renales de vivo, averiguando su perfil sociosanitario, sus características sociodemográficas, económico-laborales, de salud y la actividad cuidadora de dichos donantes y receptores. MÉTODOS: Estudio observacional, descriptivo, transversal, de la población de donantes y receptores renales de vivo, de los Hospitales Universitarios Puerta del Mar (Cádiz), Virgen del Rocío (Sevilla) y Complejo Hospitalario Universitario de Granada, entre el 8 de abril de 2014 y el 8 de junio de 2015. RESULTADOS Y CONCLUSIONES: Según los 40 donantes y 40 receptores renales de vivo encuestados, los facultativos de nefrología son principalmente quienes dan a conocer e informan sobre la donación renal en vida. Casi la mitad de receptores demandan más información, por lo que se deberían actualizar los procesos de evaluación y de información antes de la donación. En general, el donante renal vivo es mujer, de 50 años, con estudios de Primaria/ESO, vive en pareja, está emparentado con el receptor del riñón, realiza un trabajo remunerado, tiene sobrepeso, percibe su salud como muy buena o buena, y no fuma ni consume alcohol. Sin embargo, el receptor renal tipo es hombre, con 44 años, tiene estudios de bachillerato/FP, no trabaja, percibe su salud como buena o regular, y son personas independientes para las actividades de la vida diaria

BACKGROUND: Information provided by health professionals to potential donors and recipients is essential for an autonomous and objective decision to make a living kidney donation. OBJECTIVES: To determine the characteristics of the information received by living kidney donors and recipients, to find out their socio-sanitary profile, their socio-demographics, financial and labour characteristics, health and the caregiving activity of these donors and recipients. METHODS: Observational, descriptive and cross-sectional study of the population of living kidney donors and recipients from the University Hospitals Puerta del Mar (Cádiz), Virgen del Rocío (Seville), and the University Hospital Complex of Granada, between 08/04/2014 and 08/06/2015. RESULTS AND CONCLUSIONS: According to the 40 living kidney donors and their 40 recipients surveyed, it is mainly nephrologists who make people aware and provide information about living kidney donation. Almost half of recipients require more information so the evaluation processes and pre-donation information should be updated. In general, the living kidney donor is female, aged 50, with primary/secondary education, lives with a partner and is related to the kidney recipient. Also, the living kidney donor is in paid employment, is overweight, perceives her health as very good or good, and does not smoke or drink alcohol. However, the typical living kidney recipient is male, aged 44 and has completed secondary school studies and vocational training. Furthermore, he does not work, perceives his health as good or regular, and he is an independent person for activities of daily living

Socio-sanitary profile and information for living kidney donors and recipients in three Andalusian hospitals. / Perfil sociosanitario e información a donantes y receptores renales de vivo en tres hospitales andaluces.

BACKGROUND: Information provided by health professionals to potential donors and recipients is essential for an autonomous and objective decision to make a living kidney donation. OBJECTIVES: To determine the characteristics of the information received by living kidney donors and recipients, to find out their socio-sanitary profile, their socio-demographics, financial and labour characteristics, health and the caregiving activity of these donors and recipients. METHODS: Observational, descriptive and cross-sectional study of the population of living kidney donors and recipients from the University Hospitals Puerta del Mar (Cádiz), Virgen del Rocío (Seville), and the University Hospital Complex of Granada, between 08/04/2014 and 08/06/2015. RESULTS AND CONCLUSIONS: According to the 40 living kidney donors and their 40 recipients surveyed, it is mainly nephrologists who make people aware and provide information about living kidney donation. Almost half of recipients require more information so the evaluation processes and pre-donation information should be updated. In general, the living kidney donor is female, aged 50, with primary/secondary education, lives with a partner and is related to the kidney recipient. Also, the living kidney donor is in paid employment, is overweight, perceives her health as very good or good, and does not smoke or drink alcohol. However, the typical living kidney recipient is male, aged 44 and has completed secondary school studies and vocational training. Furthermore, he does not work, perceives his health as good or regular, and he is an independent person for activities of daily living.

Prevalence and reasons for non-follow-up of newborns with "refer" results on initial hearing screening

OBJECTIVE: To determine the prevalence rate of follow-up among infants who had a "refer" result on initial newborn hearing screening and to identify reasons for default by parents or guardians.METHODS:Design: Cross-Sectional StudySetting: Tertiary National University HospitalParticipants: 79 parents or guardians whose newborns obtained a "refer" result on initial hearing screening were interviewed over the phone.RESULTS: Among those babies who had a "refer" result on initial hearing screening, 51% followed up for repeat testing. The most common reasons for non-follow up by parents or guardians include being busy, distance from the hospital and baby's health condition.CONCLUSIONS: The follow-up rate in this study is higher compared to previous figures (27%), but is still below target. The reasons for non-follow-up obtained suggest problems may exist on all levels of the healthcare system. Appropriate solutions to address these problems should be explored.

Middle ear microbiome differences in indigenous Filipinos with chronic otitis media due to a duplication in the A2ML1 gene.

BACKGROUND: Previously rare A2ML1 variants were identified to confer otitis media susceptibility in an indigenous Filipino community and in otitis-prone US children. The goal of this study is to describe differences in the middle ear microbiome between carriers and non-carriers of an A2ML1 duplication variant that increases risk for chronic otitis media among indigenous Filipinos with poor health care access. METHODS: Ear swabs were obtained from 16 indigenous Filipino individuals with chronic otitis media, of whom 11 carry the A2ML1 duplication variant. Ear swabs were submitted for 16S rRNA gene sequencing. RESULTS: Genotype-based differences in microbial richness, structure, and composition were identified, but were not statistically significant. Taxonomic analysis revealed that the relative abundance of the phyla Fusobacteria and Bacteroidetes, and genus Fusobacterium were nominally increased in carriers compared to non-carriers, but were non-significant after correction for multiple testing. We also detected rare bacteria including Oligella that was reported only once in the middle ear. CONCLUSIONS: These findings suggest that A2ML1-related otitis media susceptibility may be mediated by changes in the middle ear microbiome. Knowledge of middle ear microbial profiles according to genetic background can be potentially useful for therapeutic and prophylactic interventions for otitis media and can guide public health interventions towards decreasing otitis media prevalence within the indigenous Filipino community.

Genetic and Environmental Determinants of Otitis Media in an Indigenous Filipino Population.

OBJECTIVE: To identify genetic and environmental risk factors for otitis media in an indigenous Filipino population. STUDY DESIGN: Cross-sectional study. SETTING: Indigenous Filipino community. SUBJECTS AND METHODS: Clinical history and information on breastfeeding, tobacco smoke exposure, and swimming were obtained from community members. Heads of households were interviewed for family history and personal beliefs on ear health. Height and weight were measured. Otoscopic findings were described for the presence and character of perforation or discharge. An A2ML1 duplication variant that confers otitis media susceptibility was Sanger sequenced in all DNA samples. Co-occurrence of middle ear bacteria detected by 16S rRNA gene sequencing was determined according to A2ML1 genotype and social cluster. RESULTS: The indigenous Filipino population has a ~50% prevalence of otitis media. Young age was associated with otitis media (4 age strata; P = .004); however, age was nonsignificant as a bistratal or continuous variable. There was no association between otitis media and sex, body mass index, breastfeeding, tobacco exposure, or deep swimming. In multivariate analyses, A2ML1 genotype is the strongest predictor of otitis media, with an odds ratio of 3.7 (95% confidence interval: 1.3-10.8; P = .005). When otitis media diagnoses were plotted across ages, otitis media was observed within the first year of life, and chronic otitis media persisted up to adulthood, particularly in A2ML1-variant carriers. CONCLUSION: Among indigenous Filipinos, A2ML1 genotype is the primary risk factor for otitis media and main determinant of disease progression, although age, the middle ear microbiome, and social clusters might modulate the effect of the A2ML1 genotype.