Overflow microfluidic networks for open and closed cell cultures on chip

Microfluidics have a huge potential in biomedical research, in particular for studying interactions among cell populations that are involved in complex diseases. Here, we present "overflow" microfluidic networks (oMFNs) for depositing, culturing, and studying cell populations, which are plated in a few microliters of cell suspensions in one or several open cell chambers inside the chip and subsequently cultured for several days in vitro (DIV). After the cells have developed their phenotype, the oMFN is closed with a lid bearing microfluidic connections. The salient features of the chips are (1) overflow zones around the cell chambers for drawing excess liquid by capillarity from the chamber during sealing the oMFN with the lid, (2) flow paths from peripheral pumps to cell chambers and between cell chambers for interactive flow control, (3) transparent cell chambers coated with cell adhesion molecules, and (4) the possibility to remove the lid for staining and visualizing the cells after, for example, fixation. Here, we use a two-chamber oMFN to show the activation of purinergic receptors in microglia grown in one chamber, upon release of adenosine triphosphate (ATP) from astrocytes that are grown in another chamber and challenged with glutamate. These data validate oMFNs as being particularly relevant for studying primary cells and dissecting the specific intercellular pathways involved in neurodegenerative and neuroinflammatory brain diseases

Perrault syndrome with neurological features in a compound heterozygote for two TWNK mutations : Overlap of TWNK-related recessive disorders

Altres ajuts: This research was supported with cofounding from the European Regional Development Fund (ERDF), "A way to make Europe") (to IdC); S2017/BMD‑3721‑RAREGENOMICS‑CM from the Consejería de Educación e Investigación de la Comunidad de Madrid (to MAMP).Background: Perrault syndrome is a rare autosomal recessive disorder that is characterized by the association of sensorineural hearing impairment and ovarian dysgenesis in females, whereas males have only hearing impairment. In some cases, patients present with a diversity of neurological signs. To date, mutations in six genes are known to cause Perrault syndrome, but they do not explain all clinically-diagnosed cases. In addition, the number of reported cases and the spectra of mutations are still small to establish conclusive genotype-phenotype correlations. Methods: Affected siblings from family SH19, who presented with features that were suggestive of Perrault syndrome, were subjected to audiological, neurological and gynecological examination. The genetic study included genotyping and haplotype analysis for microsatellite markers close to the genes involved in Perrault syndrome, whole-exome sequencing, and Sanger sequencing of the coding region of the TWNK gene. Results: Three siblings from family SH19 shared similar clinical features: childhood-onset bilateral sensorineural hearing impairment, which progressed to profound deafness in the second decade of life; neurological signs (spinocerebellar ataxia, polyneuropathy), with onset in the fourth decade of life in the two females and at age 20 years in the male; gonadal dysfunction with early cessation of menses in the two females. The genetic study revealed two compound heterozygous pathogenic mutations in the TWNK gene in the three affected subjects: c.85C>T (p.Arg29∗), previously reported in a case of hepatocerebral syndrome; and a novel missense mutation, c.1886C>T (p.Ser629Phe). Mutations segregated in the family according to an autosomal recessive inheritance pattern. Conclusions: Our results further illustrate the utility of genetic testing as a tool to confirm a tentative clinical diagnosis of Perrault syndrome. Studies on genotype-phenotype correlation from the hitherto reported cases indicate that patients with Perrault syndrome caused by TWNK mutations will manifest neurological signs in adulthood. Molecular and clinical characterization of novel cases of recessive disorders caused by TWNK mutations is strongly needed to get further insight into the genotype-phenotype correlations of a phenotypic continuum encompassing Perrault syndrome, infantile-onset spinocerebellar ataxia, and hepatocerebral syndrome

Topo-Iberia Project: CGPS crustal velocity field in the Iberian Peninsula and Morocco

A new continuous GPS network was installed under the umbrella of a research project called 'Geociencias en Iberia: Estudios integrados de topografı´a y evolución 4D (Topo-Iberia)', to improve understanding of kinematic behavior of the Iberian Peninsula region. Here we present a velocity field based on the analysis of the 4 years of data from 25 stations constituting the network, which were analyzed by three different analysis groups contributing to the project. Different geodetic software packages (GIPSY-OASIS, Bernese and GAMIT) as well as different approaches were used to estimate rates of present day crustal deformation in the Iberian Peninsula and Morocco. In order to ensure the consistency of the velocity fields determined by the three groups, the velocities obtained by each analysis center were transformed into a common Eurasia Reference Frame. After that, the strain rate field was calculated. The results put in evidence more prominent residual motions in Morocco and southernmost part of the Iberian Peninsula. In particular, the dilatation and shear strain rates reach their maximum values in the Central Betics and northern Alboran Sea. A small region of high shear strain rate is observed in the east-central part of the peninsula and another deformation focus is located around the Strait of Gibraltar and the Gulf of Cadiz

Histological caracterization of experimental urethroplasties with oral mucosa

Introducción: Diferentes técnicas quirúrgicas se han utilizado para la reconstrucción uretral, entre ellas la utilización de injertos de mucosa oral. El objetivo del trabajo es estudiar las modificaciones estructurales y ultraestructurales en los tejidos injertados sometidos a condiciones ambientales diferentes a las del tejido original. Material y métodos: 20 ratas Wistar macho de 300 g sometidas a anestesia general. Al grupo control se seccionó longitudinalmente la uretra peneana suturándola posteriormente. Grupos estudio, se realizó uretroplastia con injertos de mucosa oral autóloga y análisis (fijación con formaldehido y tinción H&E) tras sacrificio a los 7, 14 y 30 días. Resultados: La técnica empleada fue factible. El análisis de los tejidos orales implantados mostró adecuada integración, que fue completa a los 30 días presentando 5-6 capas de células planas estructura semejante al epitelio uretral. Conclusiones: La mucosa oral como injerto heterotópico se diferencia de forma adecuada generando un tejido estructuralmente similar a la uretra nativa.Introduction: Several surgical techniques have been used for urethral reconstruction. In this context, oral mucosa grafts are currently required. The aim of this study was to analyze the structural and ultraestructural modifications of grafted tissues exposed to different environmental conditions. Material and methods: 20 male Wistar rats under general anesthesia were used. Control group was set, and groups of study were set, and underwent an urethroplasty with oral mucosa graft analyzed at 7, 14 and 30 days. Results: The technique used was feasible. The analysis in oral grafted tissues showed an adequate integration level, with a shrinking interphase formation between the oral and urethral mucosa. At 30 days, the integration was completed and the oral mucosa showed 5-6 flat cell layers, with a similar structure to the urethral epithelium. Conclusions: The oral mucosa used as heterologous graft was able to differentiate in an adequate way to generate a structurally similar tissue to the native urethra.Financiado por: FIS expediente P 107061

Usual dietary intake, nutritional adequacy and food sources of calcium, phosphorus, magnesium and vitamin D of spanish children aged one to dagger

Bone problems in the population begin to be establish in childhood. The present study aims to assess the usual calcium, phosphorus, magnesium, and vitamin D intakes, along with the food sources of these nutrients, in Spanish children participating in the EsNuPI (Estudio Nutricional en Población Infantil Española) study. Two 24 h dietary recalls were applied to 1448 children (1 to <10 years) divided into two sub-samples: one reference sample (RS) of the general population [n = 707] and another sample which exclusively included children consuming enriched or fortified milks, here called “adapted milks” (AMS) [n = 741]. Estimation of the usual intake shows that nutrient intake increased with age for all nutrients except vitamin D. Using as reference the Dietary Reference Values from the European Food Safety Authority (EFSA), calcium and magnesium intakes were found to be below the average requirement (AR) and adequate intake (AI), respectively, in a considerable percentage of children. Furthermore, phosphorus exceeded the AI in 100% of individuals and vitamin D was lower than the AI in almost all children studied. The results were very similar when considering only plausible reporters. When analyzing the food sources of the nutrients studied, milk and dairy products contributed the most to calcium, phosphorus, magnesium, and vitamin D. Other sources of calcium were cereals and vegetables; for phosphorus: meat, meat products, and cereals; for magnesium: cereals and fruits; and, for vitamin D: fish and eggs. These results highlight the desirability of improving the intake concerning these nutrients, which are involved in bone and metabolic health in children. The AMS group appeared to contribute better to the adequacy of those nutrients than the RS group, but both still need further improvement. Of special interest are the results of vitamin D intakes, which were significantly higher in the AMS group (although still below the AI), independent of age

The role of retinal fluid location in atrophy and fibrosis evolution of patients with neovascular age-related macular degeneration long-term treated in real world

Purpose: To assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age-related macular degeneration (nAMD) receiving long-term treatment in the real world. Methods: An ambispective 36-month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinal fluid, on best-corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed. Results: After 36 months of follow-up and an average of 13.8 anti-VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85-12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09-3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23-0.71) and its progression (OR = 0.44, 95% CI = 0.26-0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14-0.83). Fibrosis development and progression were related to IRF at any visit (p < 0.001). In contrast, 36-month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29-0.81) and its progression (OR = 0.50, 95% CI = 0.31-0.81). Conclusion: Atrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice

Agenda de investigación: smart cities y seguridad en Andalucía = Research agenda: smart cities and security in Andalusia, Spain

Smart cities' security governance is a significant challenge that requires careful planning, design, and management. Unfortunately, the number of Andalusian researchers and research groups working on this topic is currently limited, which hinders scientific progress, international competitiveness, and knowledge transfer. To address this issue, this project aims to establish a research agenda to identify the most relevant topics, facilitate resource allocation, and encourage collaboration among researchers, industry, and the public sector. In the near future, effective security management in smart cities will require multidisciplinary approaches that bring together experts from various fields. By promoting coherent initiatives and establishing robust research programs, we can build a strong foundation for sustainable smart cities.P20-00941Security and Global Affair

Determinants and Differences in Satisfaction with the Inhaler Among Patients with Asthma or COPD

Satisfaction with the inhaler is an important determinant of treatment adherence in patients with asthma and chronic obstructive pulmonary disease (COPD). However, few studies have compared these 2 groups to identify the factors associated with satisfaction with the inhaler. To assess and compare satisfaction with the inhaler in patients with asthma or COPD and to determine the variables associated with high inhaler satisfaction. A multicenter, cross-sectional study of 816 patients (406 with asthma and 410 with COPD) was conducted. Satisfaction was assessed with the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire. All participants completed the Test of Adherence to Inhalers and either the Asthma Control Test (ACT) or the COPD Assessment Test (CAT). Overall, the asthma group was significantly more satisfied with the inhaler (mean [standard deviation] FSI-10 scores: 44.1 [6.5] vs 42.0 [7.7]; P <.001) and more satisfied on most (7 of 10; 70%) items. Patients with asthma were significantly more satisfied with the inhaler regardless of the adherence level or the type of nonadherence pattern. Younger age, good disease control (ACT ≥20 or CAT ≤10), previous inhaler training, and absence of unwitting nonadherence were all independently and significantly associated with high inhaler satisfaction. Age, disease control, and training in inhalation technique all play a more significant role than the specific diagnosis in explaining satisfaction with the device in patients with asthma and COPD. These findings underscore the need to provide better training and more active monitoring of the inhalation technique to improve patient satisfaction, treatment adherence, and clinical outcomes

Indigenous women managing pregnancy complications in rural Ecuador

Previous research has explored the potential use of digital health to support maternal health in the Global South highlighting the importance of understanding the socio-cultural context to inform system design. However, the experiences of indigenous women managing pregnancy complications in Latin America remain underexplored in HCI. We present a qualitative study with 25 indigenous pregnant women in an Ecuadorian rural community looking at their experiences during complications, their antenatal care visits and their access and use of technologies. Our findings highlight key barriers that hinder the use of antenatal care services and influence women's experiences managing complications. Based on the findings, we present opportunities for digital health centered on indigenous women to enhance antenatal care in rural Ecuador

Caracterización de la púrpura trombótica trombocitopénica congénita mediante técnicas inmunológicas y moleculares: resultados de la colección nacional del GEPTT

CO-093 Introducción: La Púrpura Trombótica Trombocitopénica congénita (PTTc) es una enfermedad ultra-rara caracterizada por un déficit severo de la enzima ADAMTS13 como consecuencia de mutaciones heredadas de forma autosómica recesiva en el gen ADAMTS13 (9q34). En este estudio, desarrollado dentro del Grupo Cooperativo Español de PTT (GEPTT), se ha llevado a cabo la creación de una colección centralizada de muestras biológicas y su caracterización inmunológica y molecular para mejorar el diagnóstico y el manejo clínico de los pacientes. Métodos: Se incluyeron en este estudio seis pacientes con diagnóstico clínico o sospecha de PTTc de diferentes hospitales españoles. Se estudió la actividad de ADAMTS13 e inhibidores mediante la técnica ELISA con el kit “TECHNOZYM® ADAMTS-13 Activity e INH” (Technoclone). Además, se realizó test Bethesda para descartar la presencia de inhibidores no IgG. Para el estudio genético, se implementó un panel de captura (SureSelect, Agilent) dirigido a la región genómica completa, incluyendo también las regiones no codificantes, del gen ADAMTS13 (chr9: 136278459 - 136325025, hg19). Las librerías de DNA se secuenciaron con la plataforma MiSeq (Illumina®) y el posible efecto patogénico de las variantes identificadas se estudió a nivel de i) proteína, utilizando predictores de cambio de aminoácido (SIFT) y de estructura de la proteína (SwissModel) y ii) splicing, con herramientas de análisis in silico (HSF) y validación funcional in vitro mediante minigenes. En 3 casos se realizó un cariotipo molecular utilizando array de SNPs (CytoScan HD, Affymetrix) para detectar regiones de pérdida de material genético y/o de heterocigosidad (LOH). Resultados: La mediana de actividad de ..