21 research outputs found

    A real-life glucose tolerance test in children to screen for CFRD

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    Електрофізичні властивості системи політетрафторетилен – вуглецеві нанотрубки

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    Проведено дослідження комплексної діелектричної проникності та електропровідності в надвисокочастотному діапазоні (9 ГГц) і на низьких частотах (0,1; 1 та 10 кГц) двох систем політетрафторетилен – багатошарові вуглецеві нанотрубки з вихідними та диспергованими у водному середовищі . Введення диспергованих нанотрубок в полімер знижує поріг перколяції з 4,5 % до 2,6 % (мас.) за рахунок рівномірного розподілу наповнювача у полімері, що призводить до зростання міжфазної поверхні взаємодії полімер – вуглецеві нанотрубки, яка проявляється в збільшенні значень дійсної та уявної складової комплексної діелектричної проникності.Проведены исследования комплексной диэлектрической проницаемости и электропроводности в сверхвысокочастотном диапазоне (9 ГГц) и на низких частотах (0,1; 1; 10 кГц) двух систем политетрафторэтилен–многослойные углеродные нанотрубки с исходными и диспергированными у водной среде. Введение диспергированных нанотрубок в полимер снижает порог перколяции с 4,5% до 2,6 % (масс.) за счет равномерного распределения наполнителя в полимере, что приводит к возрастанию межфазной поверхности взаимодействия полимер – углеродные нанотрубки, которая проявляется в увеличении значений действительной и мнимой составляющей комплексной диэлектрической проницаемости.Complex dielectric permeability and conductivity of two systems, namely polytetrafluorethylene – intact carbon nanotubes and polytetrafluorethylene – carbon nanotubes dispersed in aqueous media, has been studied in super high-frequency range (9 GHz) and at low frequencies (0,1; 1 and 10 kHz). Doping of the polymer with the dispersed nanotubes decreases percolation threshold (limit ) from 4,5 wt. % to 2,6 wt. % due to uniform distribution of the filler in the polymer. This results to increase of interface interaction polymer - carbon nanotubes that is demonstrated by increase of value of real and imaginary component of complex dielectric permeability

    Sars-cov-2 entry into human airway organoids is serine protease-mediated and facilitated by the multibasic cleavage site

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    Coronavirus entry is mediated by the spike protein that binds the receptor and mediates fusion after cleavage by host proteases. The proteases that mediate entry differ between cell lines, and it is currently unclear which proteases are relevant in vivo. A remarkable feature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is the presence of a multibasic cleavage site (MBCS), which is absent in the SARS-CoV spike. Here, we report that the SARS-CoV-2 spike MBCS increases infectivity on human airway organoids (hAOs). Compared with SARS-CoV, SARS-CoV-2 entered faster into Calu-3 cells and, more frequently, formed syncytia in hAOs. Moreover, the MBCS increased entry speed and plasma membrane serine protease usage relative to cathepsin-mediated endosomal entry. Blocking serine proteases, but not cathepsins, effectively inhibited SARS-CoV-2 entry and replication in hAOs. Our findings demonstrate that SARS-CoV-2 enters relevant airway cells using serine proteases, and suggest that the MBCS is an adaptation to this viral entry strategy

    Partial recovery of exocrine pancreatic function and intestinal fat absorption after ivacaftor treatment

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    Objectives: Ivacaftor treatment results in rapid improvement of lung function and weight gain. We hypothesize that the reported ivacaftor induced weight gain is related to recovery of exocrine pancreatic function and improved intestinal fat absorption. Methods: We measured fecal elastase-1 (FE), FEV1 and body height and weight, in a 13-year old girl with CF (dF508/S1251N) with proven pancreatic insufficiency (F

    Persistence and evolution of feline coronavirus in a closed cat-breeding colony

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    AbstractFeline coronavirus (FCoV) persistence and evolution were studied in a closed cat-breeding facility with an endemic serotype I FCoV infection. Viral RNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR) in the feces and/or plasma of 36 of 42 cats (86%) tested. Of 5 cats, identified as FCoV shedders during the initial survey, 4 had detectable viral RNA in the feces when tested 111 days later. To determine whether this was due to continuous reinfection or to viral persistence, 2 cats were placed in strict isolation and virus shedding in the feces was monitored every 2–4 days. In 1 of the cats, virus shedding continued for up to 7 months. The other animal was sacrificed after 124 days of continuous virus shedding in order to identify the sites of viral replication. Viral mRNA was detected only in the ileum, colon, and rectum. Also in these tissues, FCoV-infected cells were identified by immunohistochemistry. These findings provide the first formal evidence that FCoV causes chronic enteric infections. To assess FCoV heterogeneity in the breeding facility and to study viral evolution during chronic infection, FCoV quasispecies sampled from individual cats were characterized by RT-PCR amplification of selected regions of the viral genome followed by sequence analysis. Phylogenetic comparison of nucleotides 7–146 of ORF7b to corresponding sequences obtained for independent European and American isolates indicated that the viruses in the breeding facility form a clade and are likely to have originated from a single founder infection. Comparative consensus sequence analysis of the more variable region formed by residues 79–478 of the S gene revealed that each cat harbored a distinct FCoV quasispecies. Moreover, FCoV appeared to be subject to immune selection during chronic infection. The combined data support a model in which the endemic infection is maintained by chronically infected carriers. Virtually every cat born to the breeding facility becomes infected, indicating that FCoV is spread very efficiently. FCoV-infected cats, however, appear to resist superinfection by closely related FCoVs

    Assessment of controversial pediatric asthma management options using GRADE

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    OBJECTIVES: To develop explicit and transparent recommendations on controversial asthma management issues in children and to illustrate the usefulness of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach in rating the quality of evidence and strength of recommendations. METHODS: Health care questions were formulated for 3 controversies in clinical practice: what is the most effective treatment in asthma not under control with standard-dose inhaled corticosteroids (ICS; step 3), the use of leukotriene receptor antagonist for viral wheeze, and the role of extra fine particle aerosols. GRADE was used to rate the quality of evidence and strength of recommendations after performing systematic literature searches. We provide evidence profiles and considerations about benefit and harm, preferences and values, and resource use, all of which played a role in formulating final recommendations. RESULTS: By applying GRADE and focusing on outcomes that are important to patients and explicit other considerations, our recommendations differ from those in other international guidelines. We prefer to double the dose of ICS instead of adding a long-acting β-agonist in step 3; ICS instead of leukotriene receptor antagonist are the first choice in preschool wheeze, and extra fine particle ICS formulations are not first-line treatment in children with asthma. Recommendations are weak and based on low-quality evidence for critical outcomes. CONCLUSIONS: W

    The glycosylation status of the murine hepatitis coronavirus M protein affects the interferogenic capacity of the virus in vitro and its ability to replicate in the liver but not the brain

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    The coronavirus M protein, the most abundant coronaviral envelope component, is invariably glycosylated, which provides the virion with a diffuse, hydrophilic cover on its outer surface. Remarkably, while the group 1 and group 3 coronaviruses all have M proteins with N-linked sugars, the M proteins of the group 2 coronaviruses [e.g., mouse hepatitis virus (MHV)] are O-glycosylated. The conservation of the N- and O-glycosylation motifs suggests that each of these types of carbohydrate modifications is beneficial to their respective virus. Since glycosylation of the M protein is not required for virus assembly, the oligosaccharides are likely to be involved in the virus–host interaction. In order to investigate the role of the M protein glycosylation in the host, two genetically modified MHVs were generated by using targeted RNA recombination. The recombinant viruses carried M proteins that were either N-glycosylated or not glycosylated at all, and these were compared with the parental, O-glycosylated, virus. The M protein glycosylation state did not influence the tissue culture growth characteristics of the recombinant viruses. However, it affected their interferogenic capacity as measured using fixed, virus-infected cells. Viruses containing M proteins with N-linked sugars induced type I interferons to higher levels than viruses carrying M proteins with O-linked sugars. MHV with unglycosylated M proteins appeared to be a poor interferon inducer. In mice, the recombinant viruses differed in their ability to replicate in the liver, but not in the brain, whereas their in vivo interferogenic capacity did not appear to be affected by their glycosylation status. Strikingly, their abilities to replicate in the liver correlated with their in vitro interferogenic capacity. This apparent correlation might be explained by the functioning of lectins, such as the mannose receptor, which are abundantly expressed in the liver but also play a role in the induction of interferon-α by dendritic cells
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