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Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. [https://www.selleckchem.com/products/FK-506-(Tacrolimus).html selleck products] Government Works.BACKGROUND Fatigue is a very common and debilitating symptom in patients with systemic lupus erythematosus (SLE), even among those with a mild or inactive disease. The objective of this study is to define fatigue determinants and describe the impact of fatigue on health-related quality of life (HRQoL) and illness perception in a monocentric cohort of patients with SLE. METHODS This is a cross-sectional study. Adult patients with SLE were included. For each patient, demographics, medications, comorbidities, organ damage (Systemic Lupus International Collaborating Clinics Damage Index), active disease manifestations and Systemic Lupus Disease Activity Index scores were collected. It was evaluated if each patient met the definitions of remission and low disease activity. At enrolment, each patient completed the Short Form-36 (SF-36), Functional Assessment Chronic Illness Therapy-Fatigue (FACIT-F), Lupus Impact Tracker (LIT), Systemic Lupus Activity Questionnaire (SLAQ) and Brief Index of Lupus Damage (BILD). Theeir employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES We used an in-house molecular assay for the detection of Klebsiella granulomatis in ulcer specimens collected over a 12-year surveillance period in order to determine whether a diagnosis of donovanosis could be ascribed to genital ulcer disease (GUD) of unknown aetiology in our setting. METHODS Between 2007 and 2018, a total of 974 genital ulcer specimens with no previously identified sexually transmitted (STI) pathogens were selected from STI aetiological surveys conducted in all nine provinces of South Africa. Giemsa-stained ulcer smears from the same participants had previously been routinely analysed for the presence of typical Donovan bodies within large mononuclear cells. A Klebsiella screening assay targeting the phoE (phosphate porin) gene was used in combination with restriction digest analysis and sequencing to confirm the presence of K. granulomatis. RESULTS The Klebsiella screening assay tested positive in 19/974 (2.0%) genital ulcer specimens. Restriction digest analysis and nucleotide sequencing of the phoE gene confirmed that none of these specimens was positive for K. granulomatis DNA. Similarly, Donovan bodies were not identified in the Giemsa stained ulcer smears of these specimens. CONCLUSIONS This is the first study to assess K. granulomatis as a cause of genital ulceration in South Africa over a 12-year surveillance period using molecular methods. The results demonstrate that K. granulomatis is no longer a prevalent cause of GUD in our population. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.The respiratory epithelium comprises polarized cells at the interface between the environment and airway tissues. Polarized apical and basolateral protein secretions are a feature of airway epithelium homeostasis. Human respiratory syncytial virus (hRSV) is a major human pathogen that primarily targets the respiratory epithelium. However, the consequences of hRSV infection on epithelium secretome polarity and content remain poorly understood. To investigate the hRSV-associated apical and basolateral secretomes, a proteomics approach was combined with an ex-vivo pediatric human airway epithelial (HAE) model &nbsp;of hRSV infection (data are available via ProteomeXchange with identifier PXD013661). Following infection, a skewing of apical/basolateral abundance ratios was identified for several individual proteins. Novel modulators of neutrophil and lymphocyte activation (CXCL6, CSF3, SECTM1 or CXCL16), and antiviral proteins (BST2 or CEACAM1) were detected in infected, but not in uninfected cultures. Importantly, CXCL6, CXCL16, CSF3 were also detected in nasopharyngeal aspirates (NPA) from hRSV-infected infants but not healthy controls. Furthermore, the antiviral activity of CEACAM1 against RSV was confirmed in vitro using BEAS-2B cells.hRSV infection disrupted the polarity of the pediatric respiratory epithelial secretome and was associated with immune modulating proteins (CXCL6, CXCL16, CSF3) never linked with this virus before. In addition, the antiviral activity of CEACAM1 against hRSV had also never been previously characterized. This study, therefore, provides novel insights into RSV pathogenesis and endogenous antiviral responses in pediatric airway epithelium. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Eosinophilic gastrointestinal diseases (EGIDs) are a diverse group of intestinal diseases involving the infiltration of eosinophils into the bowel wall. EGID can present with a variety of clinical conditions, which are largely dependent on the location of eosinophils in the intestinal wall. We describe the first reported pediatric cases of EGID presenting with symptomatic partial bowel obstruction from intestinal masses due to isolated focal mural involvement. Both patients subsequently responded favorably to therapy with exclusive elemental nutrition in the first case and exclusive elemental nutrition with steroids in the second case. These cases reveal the wide-ranging clinical manifestations of EGID, expand on the differential diagnosis of focal intestinal masses, and provide guidance on the evaluation of ambiguous cases. Copyright © 2020 by the American Academy of Pediatrics.When parents or guardians hope for a miracle for their child who is critically ill, ethical and professional challenges can arise. Often, although not always, the parent or guardian's hope for a miracle entails a request for continued life-sustaining interventions. Striking a balance between the pediatrician's conception of good medicine and the parent or guardian's authority requires a response that is sensitive, practical, and ethically sound. In this article, we recommend 3 cumulative steps that promote such a response. First, we recommend ways of exploring essential issues through open inquiry, interdisciplinary dialogue, and self-reflection. As part of this exploration, pediatricians will discover that parents or guardians often have unique ideas about what a miracle might be for their child. The second step includes analyzing this diversity and seeking understanding. We classify the hope for a miracle into 3 distinct categories integrated, seeking, and adaptive. After the pediatrician has categorized the parent or guardian's hope, they can consider specific recommendations.