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© 2020 Wiley Periodicals, Inc.Missense mutations of the RET gene have been identified in both multiple endocrine neoplasia (MEN) type 2A/B and Hirschsprung disease (HSCR congenital absence of the enteric nervous system, ENS). Current consensus holds that MEN2A/B and HSCR are respectively caused by activating and inactivating RET mutations. However, the biological significance of RET missense mutations in vivo has not been fully elucidated. In the present study, we introduced one MEN2B-associated (M918T) and two HSCR-associated (N394K and Y791F) RET missense mutations into the corresponding regions of the mouse Ret gene by genome editing (RetM919T , RetN396K and RetY792F ) and performed histological examinations of Ret-expressing tissues to understand the pathogenetic impact of each mutant in vivo. RetM919T/+ mice displayed MEN2B-related phenotypes, including C cell hyperplasia and abnormal enlargement of the primary sympathetic ganglia. Similar sympathetic phenotype was observed in RetM919T/- mice, demonstrating a strong pathogenetic effect of the Ret M918T by a single allele expression. In contrast, no abnormality was found in the ENS of mice harboring the Ret N394K or Y791F mutation. Most surprisingly, single allele expression of RET N394K or Y791F was sufficient for normal ENS development, indicating that these RET mutants exert largely physiological function in vivo. This study reveals contrasting pathogenetic effects between MEN2B- and HSCR-associated RET missense mutations, and suggests that some of HSCR-associated RET missense mutations are by themselves neither inactivating nor pathogenetic and require involvement of other gene mutations for disease expressivity. This article is protected by copyright. All rights reserved.BACKGROUND AND OBJECTIVES Stroke is a chronic, complex condition that disproportionally affects older adults. Health systems are evaluating innovative transitional care (TC) models to improve outcomes in these patients. The Comprehensive Post-Acute Stroke Services (COMPASS) Study, a large cluster-randomized pragmatic trial, tested a TC model for patients with stroke or transient ischemic attack discharged home from the hospital. The implementation of COMPASS-TC in complex real-world settings was evaluated to identify successes and challenges with integration into the clinical workflow. RESEARCH DESIGN AND METHODS We conducted a concurrent process evaluation of COMPASS-TC implementation during the first year of the trial. Qualitative data were collected from 4 sources across 19 intervention hospitals. We analyzed transcripts from 43 conference calls with hospital clinicians, individual and group interviews with leaders and clinicians from 9 hospitals, and 2 interviews with the COMPASS-TC Director of Implementacal Society of America. All rights reserved. For permissions, please e-mail [email protected] A new concept has come to light recently, that is, Mycoplasma-induced rash and mucositis (MIRM). Here, we report the first case of recurrent rash, mucositis, and conjunctivitis involving Mycoplasma pneumoniae and C. pneumoniae that fits under the criteria of what is currently defined as MIRM. CASE PRESENTATION A patient aged 12 years with a history of recurrent aphthous ulcers presented in 2013 with worsening oral lesions, conjunctivitis, and vesicular rash. Her respiratory polymerase chain reaction (PCR) panel was positive for M. pneumoniae. She was diagnosed with Stevens-Johnson syndrome (SJS) secondary to M. pneumoniae and treated with a macrolide, acyclovir, and intravenous immunoglobulin (IVIG). The same patient returned 3 years later with an identical constellation of symptoms, at which time her PCR was positive for C. pneumoniae. In addition to IVIG and a macrolide, a corticosteroid treatment was administered. DISCUSSION Here, we present the case of a pediatric patient with a recurrence of mucocutaneous disease that is more consistent with MIRM than the proposed SJS or erythema multiforme (EM) documented via histology. Our patient's symptoms were controlled with azithromycin and IVIG and, in the second episode, with corticosteroids as well. This case adds to that of Mayor-Ibarguren et al, providing further evidence that C. pneumonia may also be a trigger for MIRM. Patients will benefit from expanding the definition of MIRM, as the pathogenesis differs from SJS and EM and could result in more specific treatment options. © The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail [email protected] sympathetic nervous system plays critical roles in the differentiation, maturation, and recruitment of immune cells under homeostatic conditions, and in responses to environmental stimuli, although its role in the migratory control of immune cells during acute inflammation remains unclear. In this study, using an advanced intravital bone imaging system established in our laboratory, we demonstrated that the sympathetic nervous system locally regulates neutrophil egress from the bone marrow for mobilization to inflammatory foci. We found that sympathetic neurons were located close to blood vessels in the bone marrow cavity; moreover, upon lipopolysaccharide (LPS) administration, local sympathectomy delayed neutrophil egress from the bone marrow and increased the proportion of neutrophils that remained in place. We also showed that vascular endothelial cells produced C-X-C motif chemokine ligand 1 (CXCL1), which is responsible for neutrophil egress out of the bone marrow. Its expression was upregulated during acute inflammation, and was suppressed by β-adrenergic receptor blockade, which was accompanied with inhibition of neutrophil egress into the systemic circulation. Furthermore, systemic β-adrenergic signaling blockade decreased the recruitment of neutrophils in the lung under conditions of acute systemic inflammation. Taken together, the results of this study first suggested a new regulatory system, wherein local sympathetic nervous activation promoted neutrophil egress by enhancing Cxcl1 expression in bone marrow endothelial cells in a β-adrenergic signaling-dependent manner, contributing to the recruitment of neutrophils at the onset of inflammation in vivo. © The Japanese Society for Immunology. 2020. All rights reserved. For permissions, please e-mail [email protected], linalool was found to be the most abundant component among the volatile cocktails released from flowers of Freesia hybrida, which was catalyzed by a monoterpene synthase FhTPS1. However, the regulatory network developmentally modulating the expression of FhTPS1 gene remains unexplored. In this study, three regulators, FhMYB21L1, FhMYB21L2 and FhMYC2, were screened from 52 candidate regulatory genes. Selleck Trichostatin A The two MYB regulators were synchronously expressed with FhTPS1 and could activate its expression significantly when overexpressed, and the binding of FhMYB21L2 to the MYBCORE sites in FhTPS1 promoter was further confirmed, indicating its direct activation roles. FhMYC2 showed an adverse expression pattern compared with FhTPS1, it could decrease the binding of FhMYB21 against FhTPS1 promoter to counteract its activation capacity when co-expressed, indicating roles of the MYB-bHLH complex in the regulation of FhTPS1 gene. In Arabidopsis thaliana, both MYB21 and MYC2 regulators were proved to activate the expression of sesquiterpene synthase genes, and the regulation roles of AtMYB21 and AtMYC2 on linalool synthase gene was also confirmed, implying conserved functions of the MYB-bHLH complex in these two evolutionarily divergent plants. Moreover, the expression ratio between MYB21 and MYC2 orthologous might be determinant factor for the flower linalool emission. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email [email protected] The prevalence of diabetes mellitus (DM) in patients with primary aldosteronism (PA) is higher than in those with essential hypertension and the general population. Although DM is a common major risk factor for the cardio-cerebrovascular (CCV) diseases and renal complications, details of its effects in PA have not been demonstrated. OBJECTIVE The aim of this study was to determine the effects of co-existent DM on the risk of CCV events and progression of renal complications in PA patients. DESIGN Multi-institutional cross-sectional study. PATIENTS AND METHODS PA patients experienced between January 2006 and October 2016 and with available data of CCV events and DM were enrolled from the Japan PA registry of the JPAS/JRAS (n=2,524). CCV events and renal complications were compared between DM group and non-DM group by logistic and liner-regression analysis. RESULTS DM significantly increased the odds ratio of CCV events (OR 1.59, 95% CI 1.05-2.41) and that of proteinuria (OR 2.25, 95% CI 1.59-3.16). DM correlated significantly with the declines in eGFR (β=0.05, p=0.02). CONCLUSIONS This the first report to demonstrate the presence of DM as an independent risk factor for CCV events and renal complications even in PA patients. Management of DM should be considered in addition to the specific treatment of PA. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail [email protected] authors informed the journal that an error occurred in their manuscript.Figure 3C was mistakenly merged by the authors.The new version of the Figure 3C is as below.Reference1. Meng Zhang, Xiuxiu Tan, Junjie Huang, Zekai Ke, Yukun Ge, Hu Xiong, Wei Lu, Lu Fang, Zhiming Cai, Song Wu Association of 3 Common Polymorphisms of IL-27 Gene with Susceptibility to Cancer in Chinese Evidence From an Updated Meta-Analysis of 27 Studies. Med Sci Monit 2015; 21 2505-2513. DOI 10.12659/MSM.895032.We describe the management, focusing on the anesthetic preparedness, of a 44-year-old man who presented with impalement of a 1 m long serrated rod through the right supraclavicular fossa extending up to the right iliac fossa, along with rib fractures and laceration of the liver and diaphragm.In patients with critical tracheal stenosis, particularly involving the lower part of trachea, a highly experienced team of anesthesiologists to tackle the difficulties of securing and maintaining the ventilation, cardiac surgeon who can swiftly establish cardiopulmonary bypass, an experienced surgeon for tracheal reconstruction are a prerequisite for managing these highly complex cases. The present paper describes three patients suffering from severe tracheal narrowing wherein spontaneous bag-mask ventilation was used for establishing cardiopulmonary bypass via mid-sternotomy as a rare life-saving procedure for urgent tracheal reconstructive surgery. A highly experienced team of anesthesiologists to tackle the difficulties of securing and maintaining the ventilation, cardiac surgeon who can swiftly establish CPB, and an experienced surgeon for tracheal reconstruction are a prerequisite for managing these highly complex cases. The present paper describes three patients suffering from severe tracheal narrowing wherein spontaneous bag-mask ventilation was used for establishing CPB via mid-sternotomy as a rare life-saving procedure for urgent tracheal reconstructive surgery.
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