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The article discusses pharmacological treatment recommendations for hyperglycaemia in type 2 diabetes in Spain. It provides an overview of type 2 diabetes which is a disease characterized by chronic hyperglycaemia. It focuses on the commission of a working group by the Spanish diabetes society (SED) to produce a document to draw up consensus documents with recommendations regarding control targets, but there are discrepancies between these documents due to lack of extensive randomized trials.

Diarylamidines are a group of widely used small molecule drugs. One common use of diarylamidines is their pharmacological inhibition of ligand-gated cation channels, including tetrameric ionotropic glutamate receptors and trimeric degenerin/epithelial sodium channel channel/acid-sensing ion channels (DEG/ENaC/ASICs). Here, we discover a DEG/ENaC/ASIC channel from the brachiopod (lamp shell) Novocrania anomala, at which diarylamidines act as agonists. The channel is closely related to bile acid-gated, pH-gated, and peptide-gated channels but is not activated by such stimuli. We describe activation of the channel by diminazene, DAPI, and pentamidine, examine several biophysical and pharmacological properties, and briefly explore the molecular determinants of channel activity with site-directed mutagenesis. We term this channel the diarylamidine-activated sodium channel (DiaaNaC)., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nervous systems are endowed with rapid chemosensation and intercellular signaling by ligand-gated ion channels (LGICs). While a complex, bilaterally symmetrical nervous system is a major innovation of bilaterian animals, the employment of specific LGICs during early bilaterian evolution is poorly understood. We therefore questioned bilaterian animals' employment of acid-sensing ion channels (ASICs), LGICs that mediate fast excitatory responses to decreases in extracellular pH in vertebrate neurons. Our phylogenetic analysis identified an earlier emergence of ASICs from the overarching DEG/ENaC (degenerin/epithelial sodium channel) superfamily than previously thought and suggests that ASICs were a bilaterian innovation. Our broad examination of ASIC gene expression and biophysical function in each major bilaterian lineage of Xenacoelomorpha, Protostomia, and Deuterostomia suggests that the earliest bilaterian ASICs were probably expressed in the periphery, before being incorporated into the brain as it emerged independently in certain deuterostomes and xenacoelomorphs. The loss of certain peripheral cells from Ecdysozoa after they separated from other protostomes likely explains their loss of ASICs, and thus the absence of ASICs from model organisms Drosophila and Caenorhabditis elegans . Thus, our use of diverse bilaterians in the investigation of LGIC expression and function offers a unique hypothesis on the employment of LGICs in early bilaterian evolution., Competing Interests: JM, AB, PB, AH, TL No competing interests declared, (© 2023, Martí-Solans et al.)

Gene loss is a pervasive source of genetic variation that influences species evolvability, biodiversity and the innovation of evolutionary adaptations. To better understand the evolutionary patterns and impact of gene loss, here we investigate as a case study the evolution of the wingless (Wnt) family in the appendicularian tunicate Oikopleura dioica , an emergent EvoDevo model characterized by its proneness to lose genes among chordates. Genome survey and phylogenetic analyses reveal that only four of the thirteen Wnt subfamilies have survived in O. dioica -Wnt5, Wnt10, Wnt11, and Wnt16,-representing the minimal Wnt repertoire described in chordates. While the loss of Wnt4 and Wnt8 likely occurred in the last common ancestor of tunicates, representing therefore a synapomorphy of this subphylum, the rest of losses occurred during the evolution of appendicularians. This work provides the first complete Wnt developmental expression atlas in a tunicate and the first insights into the evolution of Wnt developmental functions in appendicularians. Our work highlights three main evolutionary patterns of gene loss: (1) conservation of ancestral Wnt expression domains not affected by gene losses; (2) function shuffling among Wnt paralogs accompanied by gene losses; and (3) extinction of Wnt expression in certain embryonic directly correlated with gene losses. Overall our work reveals that in contrast to "conservative" pattern of evolution of cephalochordates and vertebrates, O. dioica shows an even more radical "liberal" evolutionary pattern than that described ascidian tunicates, stretching the boundaries of the malleability of Wnt family evolution in chordates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Martí-Solans, Godoy-Marín, Diaz-Gracia, Onuma, Nishida, Albalat and Cañestro.)

The urochordate Oikopleura dioica is emerging as a nonclassical animal model in the field of evolutionary developmental biology (a.k.a. evo-devo) especially attractive for investigating the impact of gene loss on the evolution of mechanisms of development. This is because this organism fulfills the requirements of an animal model (i.e., has a simple and accessible morphology, a short generation time and life span, and affordable culture in the laboratory and amenable experimental manipulation), but also because O. dioica occupies a key phylogenetic position to understand the diversification and origin of our own phylum, the chordates. During its evolution, O. dioica genome has suffered a drastic process of compaction, becoming the smallest known chordate genome, a process that has been accompanied by exacerbating amount of gene losses. Interestingly, however, despite the extensive gene losses, including entire regulatory pathways essential for the embryonic development of other chordates, O. dioica retains the typical chordate body plan. This unexpected situation led to the formulation of the so-called inverse paradox of evo-devo, that is, when a genetic diversity is able to maintain a phenotypic unity. This chapter reviews the biological features of O. dioica as a model animal, along with the current data on the evolution of its genes and genome. We pay special attention to the numerous examples of gene losses that have taken place during the evolution of this unique animal model, which is helping us to understand to which the limits of evo-devo can be pushed off.

Investigating environmental hazards than could affect appendicularians is of prime ecological interest because they are among the most abundant components of the mesozooplankton. This work shows that embryo development of the appendicularian Oikopleura dioica is compromised by diatom bloom-derived biotoxins, even at concentrations in the same range as those measured after blooms. Developmental gene expression analysis of biotoxin-treated embryos uncovers an aberrant golf ball-like phenotype affecting morphogenesis, midline convergence, and tail elongation. Biotoxins induce a rapid upregulation of defensome genes, and considerable delay and silencing of zygotic transcription of developmental genes. Upon a possible future intensification of blooms associated with ocean warming and acidification, our work puts an alert on the potential impact that an increase of biotoxins may have on marine food webs, and points to defensome genes as molecular biosensors that marine ecologists could use to monitor the genetic stress of natural populations exposed to microalgal blooms., Competing Interests: The authors declare no competing interests.

Background: What impact gene loss has on the evolution of developmental processes, and how function shuffling has affected retained genes driving essential biological processes, remain open questions in the fields of genome evolution and EvoDevo. To investigate these problems, we have analyzed the evolution of the Wnt ligand repertoire in the chordate phylum as a case study., Results: We conduct an exhaustive survey of Wnt genes in genomic databases, identifying 156 Wnt genes in 13 non-vertebrate chordates. This represents the most complete Wnt gene catalog of the chordate subphyla and has allowed us to resolve previous ambiguities about the orthology of many Wnt genes, including the identification of WntA for the first time in chordates. Moreover, we create the first complete expression atlas for the Wnt family during amphioxus development, providing a useful resource to investigate the evolution of Wnt expression throughout the radiation of chordates., Conclusions: Our data underscore extraordinary genomic stasis in cephalochordates, which contrasts with the liberal and dynamic evolutionary patterns of gene loss and duplication in urochordate genomes. Our analysis has allowed us to infer ancestral Wnt functions shared among all chordates, several cases of function shuffling among Wnt paralogs, as well as unique expression domains for Wnt genes that likely reflect functional innovations in each chordate lineage. Finally, we propose a potential relationship between the evolution of WntA and the evolution of the mouth in chordates.

The bloom of genomics is revealing gene loss as a pervasive evolutionary force generating genetic diversity that shapes the evolution of species. Outside bacteria and yeast, however, the understanding of the process of gene loss remains elusive, especially in the evolution of animal species. Here, using the dismantling of the retinoic acid metabolic gene network (RA-MGN) in the chordate Oikopleura dioica as a case study, we combine approaches of comparative genomics, phylogenetics, biochemistry, and developmental biology to investigate the mutational robustness associated to biased patterns of gene loss. We demonstrate the absence of alternative pathways for RA-synthesis in O. dioica, which suggests that gene losses of RA-MGN were not compensated by mutational robustness, but occurred in a scenario of regressive evolution. In addition, the lack of drastic phenotypic changes associated to the loss of RA-signaling provides an example of the inverse paradox of Evo-Devo. This work illustrates how the identification of patterns of gene coelimination-in our case five losses (Rdh10, Rdh16, Bco1, Aldh1a, and Cyp26)-is a useful strategy to recognize gene network modules associated to distinct functions. Our work also illustrates how the identification of survival genes helps to recognize neofunctionalization events and ancestral functions. Thus, the survival and extensive duplication of Cco and RdhE2 in O. dioica correlated with the acquisition of complex compartmentalization of expression domains in the digestive system and a process of enzymatic neofunctionalization of the Cco, while the surviving Aldh8 could be related to its ancestral housekeeping role against toxic aldehydes., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The genome sequencing and the development of RNAi knockdown technologies in the urochordate Oikopleura dioica are making this organism an attractive emergent model in the field of EvoDevo. To succeed as a new animal model, however, an organism needs to be easily and affordably cultured in the laboratory. Nowadays, there are only two facilities in the world capable to indefinitely maintain Oikopleura dioica, one in the SARS institute (Bergen, Norway) and the other in the Osaka University (Japan). Here, we describe the setup of a new facility in the University of Barcelona (Spain) in which we have modified previously published husbandry protocols to optimize the weekly production of thousands of embryos and hundreds of mature animals using the minimum amount of space, human resources, and technical equipment. This optimization includes novel protocols of cryopreservation and solid cultures for long-term maintenance of microalgal stocks-Chaetoceros calcitrans, Isochrysis sp., Rhinomonas reticulate, and Synechococcus sp.-needed for Oikopleura dioica feeding. Our culture system maintains partially inbred lines healthy with similar characteristics to wild animals, and it is easily expandable to satisfy on demand the needs of any laboratory that may wish to use Oikopleura dioica as a model organism., (© 2014 Wiley Periodicals, Inc.)

A 84 year-old patient, in therapy with androgen deprivation during the last 5 years due a prostate cancer, is presented with a osteoporotic fracture of the first lumbar vertebra. The pivotal role of the primary care physician, in the prevention of the osteoporosis secondary to the hypogonadism in these patients, is highlighted., (Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.)

A case is presented of a 75 year-old patient with chronic kidney failure, atrial fibrillation, diabetes mellitus, and hypertension. She had regularly been admitted to hospital due to episodes of rapid atrial fibrillation that were not well tolerated in relation to the concomitant hypotension and dyspnea. An adverse drug reaction was deduced from the clinical course, and the relative importance of this in daily medical practice is emphasized., (Copyright © 2011 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.)

Objective: Monocyte recruitment and interaction with the endothelium is imperative to vascular recovery. Tie2 plays a key role in endothelial health and vascular remodeling. We studied monocyte-mediated Tie2/angiopoietin signaling following interaction of primary monocytes with endothelial cells and its role in endothelial cell survival., Methods and Results: The direct interaction of primary monocytes with subconfluent endothelial cells resulted in transient secretion of angiopoietin-1 from monocytes and the activation of endothelial Tie2. This effect was abolished by preactivation of monocytes with tumor necrosis factor-α. Although primary monocytes contained high levels of both angiopoietin 1 and 2, endothelial cells contained primarily angiopoietin 2. Seeding of monocytes on serum-starved endothelial cells reduced caspase-3 activity by 46 ± 5.1%, and 52 ± 5.8% after tumor necrosis factor-α treatment and decreased detected single-stranded DNA levels by 41 ± 4.2% and 40 ± 3.5%, respectively. This protective effect of monocytes on endothelial cells was reversed by Tie2 silencing with specific short interfering RNA. The antiapoptotic effect of monocytes was further supported by the activation of cell survival signaling pathways involving phosphatidylinositol 3-kinase, STAT3, and AKT., Conclusions: Monocytes and endothelial cells form a unique Tie2/angiopoietin-1 signaling system that affects endothelial cell survival and may play critical a role in vascular remodeling and homeostasis.

Direct interaction of unactivated primary monocytes with endothelial cells induces a mitogenic effect in subconfluent, injured endothelial monolayers through activation of endothelial Met. We now report that monocytes' contact-dependent mitogenicity is controlled by activation-mediated regulation of hepatocyte growth factor. Direct interaction of unactivated monocytes with subconfluent endothelial cells for 12 hours resulted in 9- and 120-fold increase in monocyte tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) mRNA levels and bitemporal spike in hepatocyte growth factor that closely correlates with endothelial Met and extracellular signal-related kinase (ERK) phosphorylation. Once activated, monocytes cannot induce a second wave of endothelial cell proliferation and endothelial Met phosphorylation and soluble hepatocyte growth factor levels fall off. Monocyte-induced proliferation is dose dependent and limited to the induction of a single cell cycle. Monocytes retain their ability to activate other endothelial cells for up to 8 hours after initial interaction, after which they are committed to the specific cell. There is therefore a profoundly sophisticated mode of vascular repair. Confluent endothelial cells ensure vascular quiescence, whereas subconfluence promotes vessel activation. Simultaneously, circulating monocytes stimulate endothelial cell proliferation, but lose this potential once activated. Such a system provides for the fine balance that can restore vascular and endothelial homeostasis with minimal overcompensation.

Objectives: Ethical, social, or civic banks, constitute a secondary source of financing, which is particularly relevant in Southern and Central Europe. However there is no information on the scientific literature on this source of health care financing., Method: We review the characteristics of saving banks in Spain and illustrate the contribution of one institution "Obra Social Caixa Catalunya" (OS-CC) to the health care financing in Spain., Results: Savings bank health care funding was equivalent to 3 percent of the public health expenditure for 2008. The programs developed by OS-CC illustrate the complex role of savings banks in health financing, provision, training, and policy, particularly in the fields of integrated care and innovation., Conclusions: Financing is a basic tool for health policy. However, the role of social banking in the development of integrated care networks has been largely disregarded, in spite of its significant contribution to complementary health and social care in Southern and Central Europe. Decision makers both at the public health agencies and at the social welfare departments of savings banks should become aware of the policy implications and impact of savings bank activities in the long-term care system.