Terkelsenjensby8330

Background & aims An efficient cell culture system for hepatitis B virus (HBV) is indispensable for research on viral characteristics and anti-viral reagents. Currently, for the HBV infection assay in cell culture, viruses derived from HBV genome-integrated cell lines of HepG2.2.15 or HepAD-38 are commonly used. However, these viruses are not suitable for the evaluation of polymorphism dependent-viral characteristics or resistant mutations against anti-viral reagents. HBV obtained by the transient transfection of the ordinary HBV molecular clone has limited infection efficiencies in cell culture. Approach & results We found that an 11 amino acid deletion (d11) in the preS1 region enhances the infectivity of cell culture-generated HBV (HBVcc) to sodium taurocholate co-transporting polypeptide-transduced HepG2 (HepG2/NTCP) cells. Infection of HBVcc derived from a d11-introduced genotype C strain (GTC-d11) was approximately 10-fold more efficient than infection of wild-type GTC (GTC-wt), and the number of infected cells was comparable between GTC-d11- and HepG2.2.15-derived viruses when inoculated with the same genome equivalents. A time-dependent increase in pre-genomic RNA and efficient synthesis of covalently closed circular DNA were detected after infection with the GTC-d11 virus. The involvement of d11 in the L-HBs protein in the enhanced infectivity was confirmed by an HBV reporter virus and hepatitis D virus infection system. The binding step of the GTC-d11 virus onto the cell surface was responsible for this efficient infection. Conclusions This system provides a powerful tool for studying the infection and propagation of HBV in cell culture, and also for developing the anti-viral strategy against HBV infection.Perineal descent is the result of the reduction in muscle strength mainly due to previous pregnancy. It leads to a modification in force vectors during defecation. This condition is frequently associated with other anatomical abnormalities within the posterior compartment andcan lead to the obstructive defecation syndrome (ODS). Patients affected by perineal descent complain mainly of the need for perineal manual support during defecation [1] .For the suitably selected middle 1/3 tongue cancer treated by the TORS, philosophy is to undertake simultaneous neck dissection, TORS primary resection, and reconstruction with the Sternomastoid flap Bilateral tongue base involvement requiring ligation of both lingual arteries, extension to vallecula, significant lateral pharyngeal wall involvement, mandibular invasion or close proximity to the mandible necessitating a marginal mandibulectomy were not considered appropriately resectable by a per-oral TORS approach 2 of 20 excisions in this experience led to close resections at the deep margin and subsequent recurrences, and extra care with deeply infiltrating tumors seems currently warranted The low morbidity and good swallowing outcomes observed are ascribed to preservation of co-ordinated swallowing when resections are undertaken per-orally In properly selected patients, this technique can circumvent the need for mandibulotomy or a lingual release pull-through, and also the need for free tissue transfer repair.Background IgG-autoantibodiesagainst the high affinity IgE-receptor,FcεRIα, contribute the pathogenesis of autoimmune chronic spontaneous urticaria (CSU). However, it is not known if such patients also exhibit IgM or IgA autoantibodies against FcεRIα. Objectives To develop an ELISAto assess serum levels of IgG, IgM andIgA autoantibodies against FcεRIα, and to investigateif their presence is linked to clinical features of CSU including the response to autologous serum skin testing (ASST). Methods Serum samples of 35 CSU patients (25 ASST-positive) and 52 healthy controlindividuals were analyzed using a newly developed competitive ELISA for IgG, IgM and IgAautoantibodies to FcεRIα. Results One in four CSU patients (8/35, 24%) had elevated serum levels of IgG-anti-FcεRIα compared with(3/52, 6%) in healthy controls. More than half of patients had IgM (21/35, 60%) and IgA (20/35, 57%) vs (3/52, 5%) each in healthy controls. read more ElevatedIgM, but not IgG or IgA autoantibodies, were significantly more frequent in ASST-positive CSU patients (18/25, 72%) compared with ASST-negative patients (3/10, 33%, P =0.022).Also, elevated levels of IgM-anti-FcεRIα, but not of IgG or IgA against FcεRIα, were linked to low blood basophil(r = 0.414, P = 0.021) and eosinophil(r = 0.623, P less then 0.001) counts. Conclusions Increased serum levels of IgM-anti-FcεRIα are common in patients with CSU and linked to features of autoimmune CSU. The role and relevance of autoantibodies to FcεRIα in CSU can and should be further characterized in future studies, and our novel assay can help with this.The emergence and evolution of the complement system and mast cells (MCs) can be traced back to sea urchins and the ascidian Styela plicata, respectively. Acting as a cascade of enzymatic reactions, complement is activated through the classical (CP), the alternative (AP) and the lectin pathway (LP) based on the recognized molecules. The system's main biological functions include lysis, opsonization and recruitment of phagocytes. MCs, beyond their classic role as master cells of allergic reactions, play a role in other settings, as well. Thus, MCs are considered as extrahepatic producers of complement proteins. They express various complement receptors, including those for C3a and C5a. C3a and C5a not only activate the C3aR and C5aR expressing MCs but also act as chemoattractants for MCs derived from different anatomic sites, such as from the bone marrow, human umbilical cord blood or skin in vitro. Crosstalk between MCs and complement is facilitated by the production of complement proteins by MCs and their activation by the MC tryptase. The coordinated activity between MCs and the complement system plays a key role e.g. in a number of allergic, cutaneous and vascular diseases. At a molecular level, MCs and complement system interactions are based on the production of several complement zymogens by MCs and their activation by MC-released proteases. Additionally, at a cellular level, MCs act as potent effector cells of complement activation by expressing receptors for C3a and C5a through which their chemoattraction and activation are mediated by anaphylatoxins in a paracrine and autocrine fashion.Objective To summarize evidence on the efficacy and safety of the use of extensively hydrolyzed formulas (EHFs) for the treatment of children with cow's milk allergy (CMA). Design Systematic review of randomized controlled trials (RCTs) per PRISMA guidelines. The risk of bias of included RCTs was assessed using the Cochrane Collaboration's risk of bias tool. In general, a narrative synthesis of the findings was performed. When sufficient data were available, a meta-analysis using the random-effect model was performed. Data sources The Cochrane Library, MEDLINE, and EMBASE databases were searched up to February 2020. Eligibility criteria RCTs, including cross-over trials, assessing children of any age with any type of CMA that compared use of a formula containing extensively hydrolyzed bovine proteins (whey and/or casein) with use of any other formula for CMA management were eligible for inclusion. Each type of EHF was evaluated separately. Outcome measures included allergic reactions (i.e., gastrointestinal, ement of CMA.Objective Due to their tropical location, development status and the limited capacity of health systems, Pacific island counties and territories are particularly susceptible to infectious disease outbreaks; but evidence as to the optimal way in which outbreaks are detected is scarce. In this review we synthesise evidence from literature about how outbreaks are detected in Pacific island countries and territories and critique factors identified as inhibiting surveillance practice. Method For this systematic review we searched electronic databases Embase, Global Health, MEDLINE and MEDLINE Epub from 1-January-2010 and 31-March-2019 for reports describing infectious disease outbreaks occurring in the Pacific islands. Reports were included if they reported the method by which an outbreak was detected or the time between an outbreak's onset and its detection. We extracted information about the report type and authors, the outbreak and its method/s of detection, and pertinent issues inhibiting surveillance practice. Results Of 860 articles identified, 37 reports describing 39 outbreaks met the inclusion criteria. Most outbreaks (n=30) were identified through formal event-based surveillance; six through syndromic surveillance; and two by ad-hoc notification from the community. Barriers to early outbreak detection included population isolation; lack of resources and infrastructure to support surveillance implementation and signal investigation; and broader health system factors such as preparedness planning and availability of laboratory services. Conclusion Most surveillance-related gain in the Pacific islands may be made through building formal event-based surveillance systems and streamlining reporting processes to facilitate outbreak notification. This observation is pertinent given the focus on establishing and expanding syndromic surveillance approaches for outbreak detection in the islands over the last decade.Background and purpose Non-alcoholic fatty liver disease (NAFLD) is considered to be one of the most common chronic liver diseases across worldwide. Astaxanthin (Ax) is a type of carotenoid,and beneficial effects of Ax,including anti-oxidative, anti-inflammatory, and anti-tumor activity, have been identified. The present study aimed to elucidate the protective effect of Ax against NAFLD and its underlying mechanism. Experimental approach Mice were fed either a high fat or chow diet, with or without AX, for up to 12 weeks. L02 cells were treated with free fatty acids combined with different doses of Ax for 48 h. Histopathology, expression of lipid metabolism, inflammation, apoptosis, and fibrosis-related gene expression were assessed. And the function of mitochondria were also evaluated. Key results The results indicated that Ax attenuated HFD- and FFA-induced lipid accumulation and its associated oxidative stress, cell apoptosis, inflammation, and fibrosis both in vivo and in vitro. Ax upregulated FGF21 and PGC-1α expression in damaged hepatocytes, which suggested an unrecognized mechanism of Ax on ameliorating NAFLD. Conclusion and implications Ax attenuated hepatocyte damage and mitochondrial dysfunction in NAFLD by upregulating FGF21/PGC-1α pathway. Our studies verified that Ax may become a promising drug to treat or relieve NAFLD.The importance of oxygen for the survival of multicellular and aerobic organisms is well established and documented. Over the years, increased knowledge of its use for bioenergetics has placed oxygen at the centre of research on mitochondria and ATP-generating processes. Understanding the molecular mechanisms governing cellular oxygen sensing and response has allowed for the discovery of novel pathways oxygen is involved in, culminating with the award of the Nobel prize for Medicine and Physiology in 2019 to the pioneers of this field, Greg Semenza, Peter Ratcliffe and William Kaelin. However, it is now beginning to be appreciated that oxygen can be a signalling molecule involved in a vast array of molecular processes, most of which impinge on gene expression control. This review will focus on the knowns and unknowns of oxygen as a signalling molecule, highlighting the role of 2-oxoglutarate-dependent dioxygenases as central players in the cellular response to deviations in oxygen tension.