486 research outputs found

    The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study

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    <p>Introduction: Children presenting for the first time with inflammatory bowel disease (IBD) offer a unique opportunity to study aetiological agents before the confounders of treatment. Microaerophilic bacteria can exploit the ecological niche of the intestinal epithelium; Helicobacter and Campylobacter are previously implicated in IBD pathogenesis. We set out to study these and other microaerophilic bacteria in de-novo paediatric IBD.</p> <p>Patients and Methods: 100 children undergoing colonoscopy were recruited including 44 treatment naïve de-novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to microaerophilic culture with Gram-negative isolates then identified by sequencing. Biopsies were also PCR screened for the specific microaerophilic bacterial groups: Helicobacteraceae, Campylobacteraceae and Sutterella wadsworthensis.</p> <p>Results: 129 Gram-negative microaerophilic bacterial isolates were identified from 10 genera. The most frequently cultured was S. wadsworthensis (32 distinct isolates). Unusual Campylobacter were isolated from 8 subjects (including 3 C. concisus, 1 C. curvus, 1 C. lari, 1 C. rectus, 3 C. showae). No Helicobacter were cultured. When comparing IBD vs. normal colon control by PCR the prevalence figures were not significantly different (Helicobacter 11% vs. 12%, p = 1.00; Campylobacter 75% vs. 76%, p = 1.00; S. wadsworthensis 82% vs. 71%, p = 0.312).</p> <p>Conclusions: This study offers a comprehensive overview of the microaerophilic microbiota of the paediatric colon including at IBD onset. Campylobacter appear to be surprisingly common, are not more strongly associated with IBD and can be isolated from around 8% of paediatric colonic biopsies. S. wadsworthensis appears to be a common commensal. Helicobacter species are relatively rare in the paediatric colon.</p&gt

    Association between the mood stabilizing treatment of bipolar disorder and risk of suicide attempts: A self-controlled case series study

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    Bipolar disorder (BPD) is associated with high rates of suicide attempts but the anti-suicidal effect of mood stabilizing agents remains unclear. This study aimed to examine the association between mood stabilizing agents (lithium, valproate, lamotrigine, carbamazepine or antipsychotics) and risk of suicide attempts in patients with BPD using self-controlled case series study design. Among 14,087 patients with BPD who received mood stabilizing agents from 2001 to 2020 in Hong Kong, 1316 patients had at least one suicide attempts during the observation period. An increased risk of suicide attempts was observed 14 days before treatment initiation compared to non-exposed period. Following treatment initiation, an increased risk with smaller magnitude was found with the use of mood stabilizing agents. A lower risk was observed with lithium and antiepileptics while the risk remained attenuated with decreasing magnitude with antipsychotics. During 30-day post-treatment period, the risk was elevated. Therefore, this study suggests that use of mood stabilizing agents is not causally associated with an increased risk of suicide attempts. Indeed, there are potential protective effects of lithium and antiepileptics against suicide attempts. Assiduous monitoring of symptoms relapse and warning signs of suicide should be part of the management plan and discussed between clinicians, caregivers and patients

    Id1 Interacts and Stabilizes the Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) in Nasopharyngeal Epithelial Cells

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    The EBV-encoded latent membrane protein 1 (LMP1) functions as a constitutive active form of tumor necrosis factor receptor (TNFR) and activates multiple downstream signaling pathways similar to CD40 signaling in a ligand-independent manner. LMP1 expression in EBV-infected cells has been postulated to play an important role in pathogenesis of nasopharyngeal carcinoma. However, variable levels of LMP1 expression were detected in nasopharyngeal carcinoma. At present, the regulation of LMP1 levels in nasopharyngeal carcinoma is poorly understood. Here we show that LMP1 mRNAs are transcribed in an EBV-positive nasopharyngeal carcinoma (NPC) cell line (C666-1) and other EBV-negative nasopharyngeal carcinoma cells stably re-infected with EBV. The protein levels of LMP1 could readily be detected after incubation with proteasome inhibitor, MG132 suggesting that LMP1 protein is rapidly degraded via proteasome-mediated proteolysis. Interestingly, we observed that Id1 overexpression could stabilize LMP1 protein in EBV-infected cells. In contrary, Id1 knockdown significantly reduced LMP1 levels in cells. Co-immunoprecipitation studies revealed that Id1 interacts with LMP1 by binding to the CTAR1 domain of LMP1. N-terminal region of Id1 is required for the interaction with LMP1. Furthermore, binding of Id1 to LMP1 suppressed polyubiquitination of LMP1 and may be involved in stabilization of LMP1 in EBV-infected nasopharyngeal epithelial cells

    Impact of analyzing fewer image frames per segment during offline volumetric radiofrequency-based intravascular ultrasound measurements of target lesions prior to percutaneous coronary interventions

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    In the present study, we evaluated the impact of a 50% reduction in number of image frames (every second frame) on the analysis time and variability of offline volumetric radiofrequency-based intravascular ultrasound (RF-IVUS) measurements in target lesions prior to percutaneous coronary interventions (PCI). Volumetric RF-IVUS data of vessel geometry and plaque composition are generally obtained by a semi-automated analysis process that includes time-consuming manual contour editing. A reduction in the number of frames used for volumetric analysis may speed up the analysis, but could increase measurement variability. We repeatedly performed offline volumetric analyses in RF-IVUS image sets of 20 mm-long coronary segments that contained 30 de novo lesions prior to PCI. A 50% reduction in frames decreased the analysis time significantly (from 57.5 ± 7.3 to 35.7 ± 3.7 min; P < 0.0001) while geometric and compositional RF-IVUS measurements did not differ significantly from measurements obtained from all frames. The variability between measurements on the reduced number of frames versus all frames was comparable to the intra-observer measurement variability. In target lesions prior to PCI, offline volumetric RF-IVUS analyses can be performed using a reduced number of image frames (every second frame). This reduces the time of analysis without substantially increasing measurement variability

    The sudden change phenomenon of quantum discord

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    Even if the parameters determining a system's state are varied smoothly, the behavior of quantum correlations alike to quantum discord, and of its classical counterparts, can be very peculiar, with the appearance of non-analyticities in its rate of change. Here we review this sudden change phenomenon (SCP) discussing some important points related to it: Its uncovering, interpretations, and experimental verifications, its use in the context of the emergence of the pointer basis in a quantum measurement process, its appearance and universality under Markovian and non-Markovian dynamics, its theoretical and experimental investigation in some other physical scenarios, and the related phenomenon of double sudden change of trace distance discord. Several open questions are identified, and we envisage that in answering them we will gain significant further insight about the relation between the SCP and the symmetry-geometric aspects of the quantum state space.Comment: Lectures on General Quantum Correlations and their Applications, F. F. Fanchini, D. O. Soares Pinto, and G. Adesso (Eds.), Springer (2017), pp 309-33

    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
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