Implicaciones clínicas, resultados obstétrico-perinatales y complicaciones fetales en gestantes portadoras de anticuerpos anti-Ro/SS-A y anti-LA/SS-B

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Obstetricia y Ginecología. Fecha de lectura: 27-09-2017Esta tesis tiene embargado el acceso al texto completo hasta el 27-03-201

Enhancing metabarcoding efficiency and ecological insights through integrated taxonomy and DNA reference barcoding: A case study on beach meiofauna

Molecular techniques like metabarcoding, while promising for exploring diversity of communities, are often impeded by the lack of reference DNA sequences available for taxonomic annotation. Our study explores the benefits of combining targeted DNA barcoding and morphological taxonomy to improve metabarcoding efficiency, using beach meiofauna as a case study. Beaches are globally important ecosystems and are inhabited by meiofauna, microscopic animals living in the interstitial space between the sand grains, which play a key role in coastal biodiversity and ecosystem dynamics. However, research on meiofauna faces challenges due to limited taxonomic expertise and sparse sampling. We generated 775 new cytochrome c oxidase I DNA barcodes from meiofauna specimens collected along the Netherlands' west coast and combined them with the NCBI GenBank database. We analysed alpha and beta diversity in 561 metabarcoding samples from 24 North Sea beaches, a region extensively studied for meiofauna, using both the enriched reference database and the NCBI database without the additional reference barcodes. Our results show a 2.5-fold increase in sequence annotation and a doubling of species-level Operational Taxonomic Units (OTUs) identification when annotating the metabarcoding data with the enhanced database. Additionally, our analyses revealed a bell-shaped curve of OTU richness across the intertidal zone, aligning more closely with morphological analysis patterns, and more defined community dissimilarity patterns between supralittoral and intertidal sites. Our research highlights the importance of expanding molecular reference databases and combining morphological taxonomy with molecular techniques for biodiversity assessments, ultimately improving our understanding of coastal ecosystems

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

The Human Rev Interacting Protein (hRIP) is Required for Rev Function and HIV-1 Replication: a Dissertation

Retroviruses have evolved sophisticated mechanisms to ensure timely export of incompletely spliced viral messenger ribonucleic acids (mRNAs) for gene expression and for viral packaging. For example, the Human Immunodeficiency Virus type 1 (HIV-1) encodes the Rev regulatory protein, a sequence-specific RNA-binding protein that is responsible for the cytoplasmic accumulation of intron-containing viral mRNAs. The HIV-1 Rev protein contains an amino terminal (N-terminal) Arginine-Rich Motif (ARM) RNA-binding domain (RBD) and a carboxy terminal (C-terminal) leucine-rich activation domain which functions as a Nuclear Export Signal (NES). The Rev ARM interacts in a sequence-specific manner with a cis-acting viral RNA stem-loop structure, the Rev Responsive Element (RRE), located in all incompletely spliced viral mRNAs. This initial interaction is followed by the recruitment of additional Rev molecules to form a RiboNucleoProtein (RNP) complex involving the RRE and Rev molecules. The cytoplasmic accumulation of the Rev:RRE RNP complex is dependent on the interaction of Rev with key cellular cofactors. Rev activation domain mutants exhibit a trans-dominant negative phenotype, suggesting that this domain of Rev interacts with cellular proteins required for Rev function. Biochemical and genetic studies have identified several cellular proteins that bind to the activation domain of Rev and are therefore candidate cofactors for Rev function. Amongst these is the human Rev Interacting Protein [hRIP, 79], which is also known as the Rev/Rex activation domain-binding protein [Rab, 18]. hRIP was identified in a yeast two-hybrid assay with the HIV-1 Rev and its functionally equivalent Human T-cell Leukemia Virus type-1 (HTLV-1) Rex protein as baits. The interaction between hRIP and HIV-1 Rev is dependent on a functional Rev NES, as predicted for a bona fide Rev cellular cofactor, and the Nucleoporin-like (Nup-like) repeats in the C-terminus of hRIP (18, 79]. Additional genetic studies indicated that the interaction between hRIP and Rev is indirect and is most likely mediated by the cellular export receptor CRM1 (Chromosomal Region Maintenance 1) [1, 153]. A role for hRIP in Rev function or HIV-1 replication has remained elusive. The goal of this dissertation was to determine whether hRIP is required for Rev function and HIV-1 replication. We used two approaches, a dominant-negative mutant and RNA interference (RNAi), to ablate hRIP activity and analyzed Rev function and HIV-1 replication using standard assays. The results of this dissertation demonstrate that hRIP is required for Rev function and HIV-1 replication. We show that Rev function is inhibited upon ablation of hRIP activity by either a trans-dominant negative mutant or RNAL Furthermore, we find that depletion of endogenous hRIP by RNAi results in the loss of viral replication in human cell lines and primary human macrophages. Unexpectedly, in the absence of functional hRIP, RRE-containing viral RNAs accumulate in the nuclear periphery where hRIP is localized. Comparable ablation of hRIP activity did not affect the intracellular localization or trafficking of a variety of proteins or cellular poly (A+ mRNA, suggesting that the inhibition of Rev-directed RNA export is specific. In conclusion, the results of this dissertation demonstrate that hRIP is involved in the movement of Rev-directed RNAs from the nuclear periphery to the cytoplasm. Therefore, hRIP is required for Rev function and HIV-1 replication. The hRIP protein is not essential for the maintenance of cell viability and thus might represent a novel target for the development of antiviral agents for HIV-1

Sistema de Documentación Virtual del Patrimonio para la gestión y difusión del Patrimonio Cultural de la Universidad de Cantabria

Desde el Vicerrectorado de Cultura de la Universidad de Cantabria se propuso la virtualización del Campus Universitario para la gestión y difusión del patrimonio cultural de la Universidad. Se empezó por el edifico más simbólico, que recoge parte del patrimonio artístico de la institución, como es el Paraninfo de la Universidad, donde se ubica la instalación escultórica de Agustín Ibarrola, Nubes de Papel. Dentro de esta parte del proyecto se procedió a la consolidación, limpieza y reintegración de materiales en dicha obra, lo que permitió la documentación geométrica y virtualización integral de las piezas. Este hecho hizo posible la difusión íntegra de esta obra, conjuntamente con el resto de los bienes artísticos presentes dentro del edificio

Flexible Approach to <i>Stemona</i> Alkaloids: Total Syntheses of (−)-Stemospironine and Three New Diastereoisomeric Analogs

Total syntheses of (−)-stemospironine and three new diastereoisomeric analogs have been completed through a flexible strategy devised for <i>Stemona</i> alkaloids. The azabicycle <b>7</b> is the pivotal intermediate, from which the sequence splits according to each particular target. The most remarkable differential feature for stemospironine is the installation of the spiranic γ-lactone through an intramolecular Horner–Wadsworth–Emmons olefination. The configuration of the stereogenic center at C-11 was controlled by fine-tuning of the synthetic sequence

Flexible Approach to <i>Stemona</i> Alkaloids: Total Syntheses of (−)-Stemospironine and Three New Diastereoisomeric Analogs

Total syntheses of (−)-stemospironine and three new diastereoisomeric analogs have been completed through a flexible strategy devised for <i>Stemona</i> alkaloids. The azabicycle <b>7</b> is the pivotal intermediate, from which the sequence splits according to each particular target. The most remarkable differential feature for stemospironine is the installation of the spiranic γ-lactone through an intramolecular Horner–Wadsworth–Emmons olefination. The configuration of the stereogenic center at C-11 was controlled by fine-tuning of the synthetic sequence

Influence of Gelatin Hydrogel Porosity on the Crystallization of CaCO₃

We investigated the influence of the porosity of the growth medium on the crystallization of calcium carbonate in hydrogels with different gelatin solid contents (2.5, 5, and 10 wt %). In all experiments, the precipitate consisted of calcite with occasional occurrences of some vaterite and aragonite. The calcite grew as compact radial intergrowths of crystals that show rhombohedral external faces. The crystal surfaces consist of identical 1–10 μm sized rhombohedral sub-blocks. Electron backscatter diffraction (EBSD) uncovered the radial intergrowth structure of the aggregates. EBSD also documented the internal microscale mosaicity and mesocrystal-like constitution of the gel-grown calcite. Raman spectroscopy and thermogravimetric analysis confirmed the presence of gelatin within the crystals. It reached up to ∼2 mass % in the calcite-gelatin composites that formed in hydrogels with 10 wt % gelatin content. Calcite morphology and mosaicity varied with the gelatin content of the hydrogel, such that an increase in gelatin content initiated the growth of smaller crystal aggregates having progressively rougher surfaces, increasing amounts of incorporated gel, and increasing degrees of misorientation in the internal mosaic structure. Apart from biospecific morphology, the gel growth experiment successfully mimics many characteristics of calcite biomineralization such as formation of a hierarchical hybrid composite, crystal mosaicity, and mesocrystal-like constitution

Effects of Mg and Hydrogel Solid Content on the Crystallization of Calcium Carbonate in Biomimetic Counter-diffusion Systems

Carbonate biominerals are nanocomposites with an intimate association of organic and mineral components. Here we investigate the crystallization of CaCO₃ in gelatin hydrogels (2.5 and 10 wt % solid content) in the presence of Mg (0.01 M) in the growth medium. The precipitate consisted mainly of calcite in all experiments. A wide variety of morphologies and incorporated Mg contents (up to 26 mol % in sphere-like aggregates grown in 10 wt % gelatin) was observed. Etching experiments uncovered an intimate relationship between the inorganic component and a polymeric network in the calcite crystal aggregates. The characteristics of this network varied for hydrogels with different solid contents. When Mg was not present in the growth medium, we obtained 200 nm to 1 μm thick incorporations that were bordered on both sides by a delicate gelatin network. As Mg was added, the incorporations became thinner (∼50–60 nm), and the gelatin network became compact. Electron backscatter diffraction evidenced that the calcite usually consists of aggregates of mutually misoriented crystals with an internal mosaic spread. Crystals with high lattice co-orientation, which occur rather rarely, are terminated by regular rhombohedral (104)-type faces. The irregular-shaped and mosaic-structured aggregates occasionally have a rim of such rhombohedral crystallites. In the experiment with 10 wt % solid gelatin content and Mg in the growth medium, the calcite consisted of crystallites with fan-like small-angle misorientations (split growth), leading to spherulitic microstructures. We attribute these frequent and characteristic small-angle boundaries to dislocations that relax misfit strain, which is associated with selective Mg incorporation at acute growth steps. We ascribe our observations to the acidic functional groups of the gelatin promoting the desolvation of the hydrated Mg²⁺ ions, leading to an increased incorporation of Mg into calcite and a reduced inhibition of calcite nucleation and growth