Safety and Efficacy of Endovascular Coils and Non-Flow-Diverting Stents for Management of Unruptured Intracranial Aneurysms: A Location-Specific Outcomes Analysis.

INTRODUCTION: The relationship between the anatomical location of an unruptured saccular aneurysm, the efficacy, and the potential complications associated with coil and non-flow-diverting stents remains poorly documented. Therefore, the aim of this study is to evaluate the efficacy and safety of endovascular treatment based on the anatomical position of the unruptured intracranial aneurysm (UIA). METHODS: A retrospective cohort study was conducted using an anonymized database of patients who underwent endovascular therapy for UIAs between 2014 and 2021. RESULTS: A total of 138 patients with 147 UIAs were included. Immediate Raymond-Roy occlusion class I or II was achieved in 99.2% of patients in all anatomical locations, with a 96.2% occlusion rate at the 12-month follow-up. Complications occurred more frequently in the anterior cerebral artery (35%) and internal carotid artery in its ophthalmic segment (25%). However, the difference was not statistically significant. CONCLUSIONS: Our study shows that endovascular treatment with stents and coils is effective and safe for managing UIAs in various anatomical locations. The incidence of thromboembolic complications was significantly higher for UIAs located in the anterior cerebral artery.

The mouse fetal-placental arterial connection: A paradigm involving the primitive streak and visceral endoderm with implications for human development.

In Placentalia, the fetus depends upon an organized vascular connection with its mother for survival and development. Yet, this connection was, until recently, obscure. Here, we summarize how two unrelated tissues, the primitive streak, or body axis, and extraembryonic visceral endoderm collaborate to create and organize the fetal-placental arterial connection in the mouse gastrula. The primitive streak reaches into the extraembryonic space, where it marks the site of arterial union and creates a progenitor cell pool. Through contact with the streak, associated visceral endoderm undergoes an epithelial-to-mesenchymal transition, contributing extraembryonic mesoderm to the placental arterial vasculature, and to the allantois, or pre-umbilical tissue. In addition, visceral endoderm bifurcates into the allantois where, with the primitive streak, it organizes the nascent umbilical artery and promotes allantoic elongation to the chorion, the site of fetal-maternal exchange. Brachyury mediates streak extension and vascular patterning, while Hedgehog is involved in visceral endoderm's conversion to mesoderm. A unique CASPASE-3-positive cell separates streak- and non-streak-associated domains in visceral endoderm. Based on these new insights at the posterior embryonic-extraembryonic interface, we conclude by asking whether so-called primordial germ cells are truly antecedents to the germ line that segregate within the allantois, or whether they are placental progenitor cells. Incorporating these new working hypotheses into mutational analyses in which the placentae are affected will aid understanding a spectrum of disorders, including orphan diseases, which often include abnormalities of the umbilical cord, yolk sac, and hindgut, whose developmental relationship to each other has, until now, been poorly understood. This article is categorized under: Birth Defects > Associated with Preimplantation and Gastrulation Early Embryonic Development > Gastrulation and Neurulation.

Epigenetic Priming of Human Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Accelerates Cardiomyocyte Maturation.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) exhibit a fetal phenotype that limits in vitro and therapeutic applications. Strategies to promote cardiomyocyte maturation have focused interventions on differentiated hPSC-CMs, but this study tests priming of early cardiac progenitor cells (CPCs) with polyinosinic-polycytidylic acid (pIC) to accelerate cardiomyocyte maturation. CPCs were differentiated from hPSCs using a monolayer differentiation protocol with defined small molecule Wnt temporal modulation, and pIC was added during the formation of early CPCs. pIC priming did not alter the expression of cell surface markers for CPCs (>80% KDR+/PDGFRα+), expression of common cardiac transcription factors, or final purity of differentiated hPSC-CMs (∼90%). However, CPC differentiation in basal medium revealed that pIC priming resulted in hPSC-CMs with enhanced maturity manifested by increased cell size, greater contractility, faster electrical upstrokes, increased oxidative metabolism, and more mature sarcomeric structure and composition. To investigate the mechanisms of CPC priming, RNAseq revealed that cardiac progenitor-stage pIC modulated early Notch signaling and cardiomyogenic transcriptional programs. Chromatin immunoprecipitation of CPCs showed that pIC treatment increased deposition of the H3K9ac activating epigenetic mark at core promoters of cardiac myofilament genes and the Notch ligand, JAG1. Inhibition of Notch signaling blocked the effects of pIC on differentiation and cardiomyocyte maturation. Furthermore, primed CPCs showed more robust formation of hPSC-CMs grafts when transplanted to the NSGW mouse kidney capsule. Overall, epigenetic modulation of CPCs with pIC accelerates cardiomyocyte maturation enabling basic research applications and potential therapeutic uses. Stem Cells 2019;37:910-923.

Emerging Roles for Immune Cells and MicroRNAs in Modulating the Response to Cardiac Injury.

Stimulating cardiomyocyte regeneration after an acute injury remains the central goal in cardiovascular regenerative biology. While adult mammals respond to cardiac damage with deposition of rigid scar tissue, adult zebrafish and salamander unleash a regenerative program that culminates in new cardiomyocyte formation, resolution of scar tissue, and recovery of heart function. Recent studies have shown that immune cells are key to regulating pro-inflammatory and pro-regenerative signals that shift the injury microenvironment toward regeneration. Defining the genetic regulators that control the dynamic interplay between immune cells and injured cardiac tissue is crucial to decoding the endogenous mechanism of heart regeneration. In this review, we discuss our current understanding of the extent that macrophage and regulatory T cells influence cardiomyocyte proliferation and how microRNAs (miRNAs) regulate their activity in the injured heart.

Visceral endoderm and the primitive streak interact to build the fetal-placental interface of the mouse gastrula.

Hypoblast/visceral endoderm assists in amniote nutrition, axial positioning and formation of the gut. Here, we provide evidence, currently limited to humans and non-human primates, that hypoblast is a purveyor of extraembryonic mesoderm in the mouse gastrula. Fate mapping a unique segment of axial extraembryonic visceral endoderm associated with the allantoic component of the primitive streak, and referred to as the "AX", revealed that visceral endoderm supplies the placentae with extraembryonic mesoderm. Exfoliation of the AX was dependent upon contact with the primitive streak, which modulated Hedgehog signaling. Resolution of the AX's epithelial-to-mesenchymal transition (EMT) by Hedgehog shaped the allantois into its characteristic projectile and individualized placental arterial vessels. A unique border cell separated the delaminating AX from the yolk sac blood islands which, situated beyond the limit of the streak, were not formed by an EMT. Over time, the AX became the hindgut lip, which contributed extensively to the posterior interface, including both embryonic and extraembryonic tissues. The AX, in turn, imparted antero-posterior (A-P) polarity on the primitive streak and promoted its elongation and differentiation into definitive endoderm. Results of heterotopic grafting supported mutually interactive functions of the AX and primitive streak, showing that together, they self-organized into a complete version of the fetal-placental interface, forming an elongated structure that exhibited A-P polarity and was composed of the allantois, an AX-derived rod-like axial extension reminiscent of the embryonic notochord, the placental arterial vasculature and visceral endoderm/hindgut.

Generation of multipotent induced cardiac progenitor cells from mouse fibroblasts and potency testing in ex vivo mouse embryos.

Here we describe a protocol to generate expandable and multipotent induced cardiac progenitor cells (iCPCs) from mouse adult fibroblasts using forced expression of Mesp1, Tbx5, Gata4, Nkx2.5 and Baf60c (MTGNB) along with activation of Wnt and JAK/STAT signaling. This method does not use iPS cell factors and thus differs from cell activation and signaling-directed (CASD) reprogramming to cardiac progenitors. Our method is specific to direct CPC reprogramming, whereas CASD reprogramming can generate various cell types depending on culture conditions and raises the possibility of transitioning through a pluripotent cell state. The protocol describes how to isolate and infect primary fibroblasts; induce reprogramming and observe iCPC colonies; expand and characterize reprogrammed iCPCs by immunostaining, flow cytometry and gene expression; differentiate iCPCs in vitro into cardiac-lineage cells; and test the embryonic potency of iCPCs via injection into the cardiac crescent of mouse embryos. A scientist experienced in molecular cell biology and embryology can reproduce this protocol in 12-16 weeks. iCPCs can be used for studying cardiac biology, drug discovery and regenerative medicine.

Brachyury drives formation of a distinct vascular branchpoint critical for fetal-placental arterial union in the mouse gastrula.

How the fetal-placental arterial connection is made and positioned relative to the embryonic body axis, thereby ensuring efficient and directed blood flow to and from the mother during gestation, is not known. Here we use a combination of genetics, timed pharmacological inhibition in living mouse embryos, and three-dimensional modeling to link two novel architectural features that, at present, have no status in embryological atlases. The allantoic core domain (ACD) is the extraembryonic extension of the primitive streak into the allantois, or pre-umbilical tissue; the vessel of confluence (VOC), situated adjacent to the ACD, is an extraembryonic vessel that marks the site of fetal-placental arterial union. We show that genesis of the fetal-placental connection involves the ACD and VOC in a series of steps, each one dependent upon the last. In the first, Brachyury (T) ensures adequate extension of the primitive streak into the allantois, which in turn designates the allantoic-yolk sac junction. Next, the streak-derived ACD organizes allantoic angioblasts to the axial junction; upon signaling from Fibroblast Growth Factor Receptor-1 (FGFR1), these endothelialize and branch, forming a sprouting VOC that unites the umbilical and omphalomesenteric arteries with the fetal dorsal aortae. Arterial union is followed by the appearance of the medial umbilical roots within the VOC, which in turn designate the correct axial placement of the lateral umbilical roots/common iliac arteries. In addition, we show that the ACD and VOC are conserved across Placentalia, including humans, underscoring their fundamental importance in mammalian biology. We conclude that T is required for correct axial positioning of the VOC via the primitive streak/ACD, while FGFR1, through its role in endothelialization and branching, further patterns it. Together, these genetic, molecular and structural elements safeguard the fetus against adverse outcomes that can result from vascular mispatterning of the fetal-placental arterial connection.

STELLA collaborates in distinct mesendodermal cell subpopulations at the fetal-placental interface in the mouse gastrula.

The allantois-derived umbilical component of the chorio-allantoic placenta shuttles fetal blood to and from the chorion, thereby ensuring fetal-maternal exchange. The progenitor populations that establish and supply the fetal-umbilical interface lie, in part, within the base of the allantois, where the germ line is claimed to segregate from the soma. Results of recent studies in the mouse have reported that STELLA (DPPA-3, PGC7) co-localizes with PRDM1 (BLIMP1), the bimolecular signature of putative primordial germ cells (PGCs) throughout the fetal-placental interface. Thus, if PGCs form extragonadally within the posterior region of the mammal, they cannot be distinguished from the soma on the basis of these proteins. We used immunohistochemistry, immunofluorescence, and confocal microscopy of the mouse gastrula to co-localize STELLA with a variety of gene products, including pluripotency factor OCT-3/4, mesendoderm-associated T and MIXl1, mesendoderm- and endoderm-associated FOXa2 and hematopoietic factor Runx1. While a subpopulation of cells localizing OCT-3/4 was always found independently of STELLA, STELLA always co-localized with OCT-3/4. Despite previous reports that T is involved in specification of the germ line, co-localization of STELLA and T was detected only in a small subset of cells in the base of the allantois. Slightly later in the hindgut lip, STELLA+/(OCT-3/4+) co-localized with FOXa2, as well as with RUNX1, indicative of definitive endoderm and hemangioblasts, respectively. STELLA was never found with MIXl1. On the basis of these and previous results, we conclude that STELLA identifies at least five distinct cell subpopulations within the allantois and hindgut, where they may be involved in mesendodermal differentiation and hematopoiesis at the posterior embryonic-extraembryonic interface. These data provide a new point of departure for understanding STELLA's potential roles in building the fetal-placental connection.

Symbiotic association between Salix purpurea L. and Rhizophagus irregularis: modulation of plant responses under copper stress.

There are increasing concerns about trace metal levels such as copper (Cu) in industrial sites and the broader environment. Different studies have highlighted the role of mycorrhizal associations in plant tolerance to trace metals, modulating some of the plant metabolic and physiological responses. In this study, we investigated the role of the symbiotic association betweenRhizophagus irregularisandSalix purpureaL. in modulating plant responses under Cu stress. We measured Cu accumulation, oxidative stress-related, photosynthetic-related and hydraulic traits, for non-inoculated (non-arbuscular mycorrhizal fungi) and inoculated saplings exposed to different Cu concentrations. We found thatS. purpureais a suitable option for phytoremediation of Cu, acting as a phytostabilizer of this trace metal in its root system. We observed that the symbiotic association modulates a broad spectrum of metabolic and physiological responses inS. purpureaunder Cu conditions, including (i) a reduction in gas exchange associated with chlorophyll content changes and (ii) the sequestration of Cu into the cell walls, modifying vessels anatomy and impacting leaf specific conductivity (KL) and root hydraulic conductance (LP). UpholdingKLandLPunder Cu stress might be related to a dynamic Aquaporin gene regulation ofPIP1;2along with an up-regulation ofTIP2;2in the roots of inoculatedS. purpurea.

Gene expression patterns underlying changes in xylem structure and function in response to increased nitrogen availability in hybrid poplar.

Nitrogen availability has a strong influence on plant growth and development. In this study, we examined the effect of nitrogen availability on xylogenesis in hybrid poplar (Populus trichocarpa x deltoides H11-11). Saplings of hybrid poplar were fertilized for 33 d with either high or adequate levels of ammonium nitrate. We observed enhanced radial growth, wider vessels and fibres and thinner fibre walls in the secondary xylem of high N relative to adequate N plants. These anatomical differences translated into altered hydraulic properties with xylem being more transport efficient but also more vulnerable to drought-induced cavitation in high N plants. The changes in xylem structure and function were associated with differences in gene expression as revealed by the transcriptome analysis of the developing xylem region. We found 388 genes differentially expressed (fold change ±1.5, P-value ≤ 0.05), including a number of genes putatively involved in nitrogen and carbohydrate metabolism and various aspects of xylem cell differentiation. Several genes encoding known transcriptional regulators of secondary cell wall deposition were down-regulated in high N plants, corresponding with thinner secondary cell walls in these plants. The results of this study provide us with gene candidates potentially affecting xylem hydraulic and structural traits.

Cellular localization of aquaporin mRNA in hybrid poplar stems.

PREMISE OF THE STUDY: Aquaporins (AQPs) are channel proteins, and their function is mostly associated with transmembrane water transport. While aquaporin genes are known to be expressed in woody poplar stems, little is known about AQP expression at the cellular level. Localization of AQP expression to particular cell and tissue types is a necessary prerequisite in understanding the biological role of these genes. METHODS: Subsets of plants were subjected to 6 wk of high nitrogen fertilization (high N plants) or to a controlled drought. Experimental treatments affected cambial activity and wood anatomy. RNA in situ hybridization was used to characterize spatial expression of three AQP genes in stem cross sections. KEY RESULTS: The strongest labeling consistently occurred in the cambial region and in adjacent xylem and phloem cells. Expression was also detected in rays. Contact cells exhibited high expression, while expression in other ray cells was more variable. High N plants exhibited a broader band of expression in the cambial region than plants receiving only adequate N fertilization (control plants) and plants subjected to drought. CONCLUSIONS: Water channels in stems were expressed in a manner that allows hydraulic coupling between xylem and other tissues that may serve as water reservoirs, including phloem and pith parenchyma. Expression of AQPs in rays may increase radial flow of water from xylem and phloem to the cambial region where AQPs may help sustain rapid cell division and expansion of developing vessel elements.

Influence of evaporative demand on aquaporin expression and root hydraulics of hybrid poplar.

When light levels and evaporative demand increase, dynamic physiological changes in roots may be required to restore the water balance at the whole plant level. We hypothesized that a dynamic increase in root hydraulic conductance (L(P)) and aquaporin (AQP) expression could moderate the transpiration-induced drop in water potential (Ψ), allowing continued gas exchange in hybrid poplar (Populus trichocarpa × deltoides) saplings. Fifty-six AQPs have been identified in poplar, but little information about their expression patterns in roots is available, especially from a whole-plant water relations perspective. We measured AQP expression and L(P) in plants subjected to different levels of light and evaporative demand. Shaded plants had only one-tenth the root area of plants growing at higher light levels. Shade-grown saplings experiencing a sudden increase in light exhibited a threefold higher L(P) than plants remaining in shade. This dynamic increase in L(P) corresponded with increased transcript abundance of 15 AQPs out of a total of 33 genes simultaneously assessed by quantitative RT-PCR. The tissue-level localization of transcripts of four AQPs was studied with in situ hybridization. Comprehensive expression profiling in conjunction with physiological and morphological measurements is a valuable reference for future studies on AQP function in poplar.

Functional characterization of drought-responsive aquaporins in Populus balsamifera and Populus simonii×balsamifera clones with different drought resistance strategies.

We have characterized poplar aquaporins (AQPs) to investigate their possible functions in differential drought responses of Populus balsamifera and Populus simonii×balsamifera leaves. Plants were exposed to mild and severe levels of drought stress and to drought stress recovery treatment, and their responses were compared with well-watered controls. Compared with P. balsamifera, P. simonii×balsamifera used drought avoidance as the main drought resistance strategy, and rapidly reduced stomatal conductance in response to stress. This strategy is correlated with growth rate reductions. Eleven AQPs were transcriptionally profiled in leaves from these experiments and five were functionally characterized for water channel activity. PIP1;3 and PIP2;5 were among the most highly expressed leaf AQPs that were responsive to drought. Expression of PIP1;3 and five other AQPs increased in response to drought in the leaves of P. simonii×balsamifera but not in P. balsamifera, suggesting a possible role of these AQPs in water redistribution in the leaf tissues. PIP2;5 was upregulated in P. balsamifera, but not in P. simonii×balsamifera, suggesting that this AQP supports the transpiration-driven water flow. Functional characterization of five drought-responsive plasma membrane intrinsic proteins (PIPs) demonstrated that three PIP2 AQPs (PIP2;2, PIP2;5, PIP2;7) functioned as water transporters in Xenopus laevis oocytes, while the two PIP1 AQPs (PIP1;2 and PIP1;3) did not, consistent with the notion that they may be functional only as heterotetramers.

Agenesia dental en pacientes jóvenes: [revisión] / Dental agenesia in young patients

La agenesia dental o ausencia dental congénita, es un síndrome que se manifiesta en diversas poblaciones del mundo y genera múltiples consecuencias si su diagnóstico no se realiza oportunamente. Para determinar su prevalencia en los pacientes de cuatro Instituciones Prestadores de Servicios de Salud (IPS) del sector privado de Santiago de Cali se realizó un estudio descriptivo a partir de la revisión de 1.440 historias clínicas con sus correspondientes radiografías panorámicas. Estos registros pertenecían a usuarios de las cuatro instituciones cuyas edades oscilaron entre 14 y 21 años. Determinada la agenesia dental en 141 de las radiografías, se procedió a verificar clínicamente el impacto de la anomalía para establecer la correlación de la falta de formación de los gérmenes dentales con algunas variables como género, edad, grupo de dientes afectado, tipos de dientes, cantidad de dientes faltantes por la patología de desarrollo, cuadrantes y arcadas involucradas. Además se tomó nota de la posible presencia de algún síndrome que pudiera estar relacionado con la falta genética. Se puso especial atención en la proporción de agenesia de terceros molares respecto a los otros grupos de dientes afectados.

Dental Ageneses or dental congenital absence is a syndrome seen in world diverse populations and generates a lot of consequences that could be avoided if its diagnosis were opportune done. To determine its prevalence among young between 14 to 21 years old users of four private or public health services providers located at Santiago de Cali city, a descriptive study was carried out by 1.440 dental stories and its correspondent panoramic x-ray revision in order to determine the number and ratio of dental ageneses present on the age groups. It was found that 141 patients (10) had been diagnosed at least one ageneses tooth. On this information basis a clinical examination was accorded whit each patient in order to determine relationships among some variables as young gender, age, dental group affected, type of tooth involved, quadrant an arches and, in addition if there were some kind of syndrome that could be related. Special attention was placed on a possible association among third molar and other teeth agenesis.