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Photocatalytic destruction regarding tetracycline by metal-organic frameworks modified using Bi2WO6 nanosheet below the sunlight.
. 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 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. We detail context-specific responses for each kind of hope. 1-NM-PP1 mouse By attending to these nuances, not only will the parent or guardian's perspective be heard but also the pediatrician's recommendation can strike a balance between advocating for their conception of good medicine and respecting the parent or guardian's beliefs. Copyright © 2020 by the American Academy of Pediatrics.Glucagon-like peptide-2 (GLP-2) agonists have therapeutic potential in clinical indications where the integrity of the intestinal mucosa or its absorptive function are compromised, such as in short bowel syndrome (SBS). Native hGLP-2, a 33-amino acid peptide secreted from the small intestine, contributes to nutritional absorption but its very short half-life due to enzymatic cleavage and renal clearance severely limits its therapeutic value. The GLP-2 analog teduglutide (Revestive®/Gattex®, Shire Inc) has been approved for use in SBS since 2012 but has a once-daily injection regimen. Pharmacokinetic (PK) and pharmacodynamic studies confirm that apraglutide, a novel GLP-2 analog, has very low clearance, long elimination half-life and high plasma protein binding compared with GLP-2 analogs teduglutide and glepaglutide. Apraglutide and teduglutide retain potency and selectivity at the GLP-2 receptor comparable to native hGLP 2 while glepaglutide was less potent and less selective. In rat intravenous PK studies, s of apraglutide will benefit patients by enabling a reduced dosing frequency and removing the need for daily injections. The American Society for Pharmacology and Experimental Therapeutics.The molecular mechanisms governing normal neurodevelopment are tightly regulated by the action of transcription factors. Repressor element 1 (RE1) silencing transcription factor (REST) is widely documented as a regulator of neurogenesis that acts by recruiting corepressor proteins and repressing neuronal gene expression in non-neuronal cells. The REST corepressor 1 (CoREST1), CoREST2, and CoREST3 are best described for their role as part of the REST complex. However, recent evidence has shown the proteins have the ability to repress expression of distinct target genes in a REST-independent manner. These findings indicate that each CoREST paralogue may have distinct and critical roles in regulating neurodevelopment and are more than simply "REST corepressors," whereby they act as independent repressors orchestrating biological processes during neurodevelopment. Copyright © 2020 Maksour et al.Perceptual performance in a visual task can be enhanced by simultaneous multisensory information, but can also be enhanced by a symbolic or amodal cue inducing a specific expectation. That similar benefits can arise from multisensory information and within-modality expectation raises the question of whether the underlying neurophysiological processes are the same or distinct. We investigated this by comparing the influence of the following three types of auxiliary probabilistic cues on visual motion discrimination in humans (1) acoustic motion, (2) a premotion visual symbolic cue, and (3) a postmotion symbolic cue. Using multivariate analysis of the EEG data, we show that both the multisensory and preceding visual symbolic cue enhance the encoding of visual motion direction as reflected by cerebral activity arising from occipital regions ∼200-400 ms post-stimulus onset. This suggests a common or overlapping physiological correlate of cross-modal and intramodal auxiliary information, pointing to a neural mechanism susceptive to both multisensory and more abstract probabilistic cues. We also asked how prestimulus activity shapes the cue-stimulus combination and found a differential influence on the cross-modal and intramodal combination while alpha power modulated the relative weight of visual motion and the acoustic cue, it did not modulate the behavioral influence of a visual symbolic cue, pointing to differences in how prestimulus activity shapes the combination of multisensory and abstract cues with task-relevant information. Copyright © 2020 Kayser and Kayser.Johnson and Degeling have recently enquired whether one health (OH) requires a comprehensive normative framework, concluding that such a framework, while not necessary, may be helpful. In this commentary, we provide a context for this debate, and describe how pragmatism has been predominant in the OH literature. We nevertheless argue that articulating a comprehensive normative theory to ground OH practice might clear existing vagueness and provide stronger guidance in relevant health dilemmas. A comprehensive theory will also be needed eventually to ground notions such as universal good. We, thus, call for the systematic articulation of a comprehensive, metaethical theory, concomitantly with already ongoing normative work. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Animals used in biological research and testing have become integrated into the trajectories of modern biomedicine, generating increased expectations for and connections between human and animal health. Animal research also remains controversial and its acceptability is contingent on a complex network of relations and assurances across science and society, which are both formally constituted through law and informal or assumed. In this paper, we propose these entanglements can be studied through an approach that understands animal research as a nexus spanning the domains of science, health and animal welfare. We introduce this argument through, first, outlining some key challenges in UK debates around animal research, and second, reviewing the way nexus concepts have been used to connect issues in environmental research. Third, we explore how existing social sciences and humanities scholarship on animal research tends to focus on different aspects of the connections between scientific research, human health and animal welfare, which we suggest can be combined in a nexus approach.
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