188 research outputs found

    Паравертебральная блокада при лечении пациентов с закрытой травмой груди

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    The study was conducted in the Thoracoabdominal Department of the N.V. Sklifosovsky Research Institute for Emergency Medicine to explore the role of paravertebral block in the treatment of blunt chest trauma. The study included 715 patients with isolated chest trauma hospitalized between January 1, 2020 and August 2021. 55 patients received analgesic therapy in the form of paravertebral block. The comparison group included 660 patients who did not undergo paravertebral block, in their case pain relief was provided by systemic administration of analgesics. The compared groups did not differ significantly in sex and age composition. There were also no differences in the frequency of chronic diseases and interpleural complications. There were no significant complications during the block. The comparison revealed a significant decrease in the incidence of pleurisy and a shorter length of stay in hospital. Paravertebral block is an effective and safe method of pain management for patients with blunt chest trauma. The use of this technique reduces the incidence of post-traumatic pleurisy and duration of hospitalization.Исследование проведено в торакоабдоминальном отделении НИИ СП им. Н.В. Склифосовского с целью изучения значения паравертебральной блокады. Было включено 715 пациентов с изолированной травмой груди, госпитализированных в экстренном порядке в период с 1 января 2020 по август 2021 года; 55 пациентов в ходе лечения получили обезболивающую терапию в виде паравертебральной блокады. В группу сравнения включили 660 пациентов, которым не выполняли проводниковую блокаду, обезболивание обеспечивали системным введением анальгетиков. Сравниваемые группы значимо не отличались по половому и возрастному составу. Отличий в частоте хронических заболеваний и интраплевральных осложнений также не было. Значимых осложнений при выполнении блокады не отмечалось. При сравнении выявлено достоверное уменьшение частоты плеврита и более короткое время нахождения в стационаре. Паравертебральная блокада является эффективным и безопасным методом обезболивания пациентов с закрытой травмой груди. Использование этой методики снижает частоту развития посттравматического плеврита и ускоряет выписку больных

    Circuit dissection of the role of somatostatin in itch and pain

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    Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide somatostatin. We find that in the periphery, somatostatin is exclusively expressed in Nppb+ neurons, and we demonstrate that Nppb+somatostatin+ cells function as pruriceptors. Employing chemogenetics, pharmacology and cell-specific ablation methods, we demonstrate that somatostatin potentiates itch by inhibiting inhibitory dynorphin neurons, which results in disinhibition of GRPR+ neurons. Furthermore, elimination of somatostatin from primary afferents and/or from spinal interneurons demonstrates differential involvement of the peptide released from these sources in itch and pain. Our results define the neural circuit underlying somatostatin-induced itch and characterize a contrasting antinociceptive role for the peptide

    Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis

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    Abnormal development of multiciliated cells is a hallmark of a variety of human conditions associated with chronic airway diseases, hydrocephalus and infertility. Multiciliogenesis requires both activation of a specialized transcriptional program and assembly of cytoplasmic structures for large-scale centriole amplification that generates basal bodies. It remains unclear, however, what mechanism initiates formation of these multiprotein complexes in epithelial progenitors. Here we show that this is triggered by nucleocytoplasmic translocation of the transcription factor E2f4. After inducing a transcriptional program of centriole biogenesis, E2f4 forms apical cytoplasmic organizing centres for assembly and nucleation of deuterosomes. Using genetically altered mice and E2F4 mutant proteins we demonstrate that centriole amplification is crucially dependent on these organizing centres and that, without cytoplasmic E2f4, deuterosomes are not assembled, halting multiciliogenesis. Thus, E2f4 integrates nuclear and previously unsuspected cytoplasmic events of centriole amplification, providing new perspectives for the understanding of normal ciliogenesis, ciliopathies and cancer

    Generation of NSE-MerCreMer Transgenic Mice with Tamoxifen Inducible Cre Activity in Neurons

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    To establish a genetic tool for conditional deletion or expression of gene in neurons in a temporally controlled manner, we generated a transgenic mouse (NSE-MerCreMer), which expressed a tamoxifen inducible type of Cre recombinase specifically in neurons. The tamoxifen inducible Cre recombinase (MerCreMer) is a fusion protein containing Cre recombinase with two modified estrogen receptor ligand binding domains at both ends, and is driven by the neural-specific rat neural specific enolase (NSE) promoter. A total of two transgenic lines were established, and expression of MerCreMer in neurons of the central and enteric nervous systems was confirmed. Transcript of MerCreMer was detected in several non-neural tissues such as heart, liver, and kidney in these lines. In the background of the Cre reporter mouse strain Rosa26R, Cre recombinase activity was inducible in neurons of adult NSE-MerCreMer mice treated with tamoxifen by intragastric gavage, but not in those fed with corn oil only. We conclude that NSE-MerCreMer lines will be useful for studying gene functions in neurons for the conditions that Cre-mediated recombination resulting in embryonic lethality, which precludes investigation of gene functions in neurons through later stages of development and in adult

    Estrogen receptor transcription and transactivation: Structure-function relationship in DNA- and ligand-binding domains of estrogen receptors

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    Estrogen receptors are members of the nuclear receptor steroid family that exhibit specific structural features, ligand-binding domain sequence identity and dimeric interactions, that single them out. The crystal structures of their DNA-binding domains give some insight into how nuclear receptors discriminate between DNA response elements. The various ligand-binding domain crystal structures of the two known estrogen receptor isotypes (α and β) allow one to interpret ligand specificity and reveal the interactions responsible for stabilizing the activation helix H12 in the agonist and antagonist positions

    Uplifting manhood to wonderful heights? News coverage of the human costs of military conflict from world war I to Gulf war Two

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    Domestic political support is an important factor constraining the use of American military power around the world. Although the dynamics of war support are thought to reflect a cost-benefit calculus, with costs represented by numbers of friendly war deaths, no previous study has examined how information about friendly, enemy, and civilian casualties is routinely presented to domestic audiences. This paper establishes a baseline measure of historical casualty reporting by examining New York Times coverage of five major wars that occurred over the past century. Despite important between-war differences in the scale of casualties, the use of conscription, the type of warfare, and the use of censorship, the frequency of casualty reporting and the framing of casualty reports has remained fairly consistent over the past 100 years. Casualties are rarely mentioned in American war coverage. When casualties are reported, it is often in ways that minimize or downplay the human costs of war

    Neural Crest Cell Survival Is Dependent on Rho Kinase and Is Required for Development of the Mid Face in Mouse Embryos

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    Neural crest cells (NCC) give rise to much of the tissue that forms the vertebrate head and face, including cartilage and bone, cranial ganglia and teeth. In this study we show that conditional expression of a dominant-negative (DN) form of Rho kinase (Rock) in mouse NCC results in severe hypoplasia of the frontonasal processes and first pharyngeal arch, ultimately resulting in reduction of the maxilla and nasal bones and severe craniofacial clefting affecting the nose, palate and lip. These defects resemble frontonasal dysplasia in humans. Disruption of the actin cytoskeleton, which leads to abnormalities in cell-matrix attachment, is seen in the RockDN;Wnt1-cre mutant embryos. This leads to elevated cell death, resulting in NCC deficiency and hypoplastic NCC-derived craniofacial structures. Rock is thus essential for survival of NCC that form the craniofacial region. We propose that reduced NCC numbers in the frontonasal processes and first pharyngeal arch, resulting from exacerbated cell death, may be the common mechanism underlying frontonasal dysplasia

    Cell Cycle-Dependent Induction of Homologous Recombination by a Tightly Regulated I-SceI Fusion Protein

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    Double-strand break repair is executed by two major repair pathways: non-homologous end joining (NHEJ) and homologous recombination (HR). Whereas NHEJ contributes to the repair of ionizing radiation (IR)-induced double strand breaks (DSBs) throughout the cell cycle, HR acts predominantly during the S and G2 phases of the cell cycle. The rare-cutting restriction endonuclease, I-SceI, is in common use to study the repair of site-specific chromosomal DSBs in vertebrate cells. To facilitate analysis of I-SceI-induced DSB repair, we have developed a stably expressed I-SceI fusion protein that enables precise temporal control of I-SceI activation, and correspondingly tight control of the timing of onset of site-specific chromosome breakage. I-SceI-induced HR showed a strong, positive linear correlation with the percentage of cells in S phase, and was negatively correlated with the G1 fraction. Acute depletion of BRCA1, a key regulator of HR, disrupted the relationship between S phase fraction and I-SceI-induced HR, consistent with the hypothesis that BRCA1 regulates HR during S phase
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