The antibody response magnitude and kinetics may impact clinical severity, serological diagnosis and long-term protection of COVID-19, which may play a role in why children experience lower ...morbidity. We therefore tested samples from 122 children in Hong Kong with symptomatic (n = 78) and asymptomatic (n = 44) SARS-CoV-2 infections up to 200 days post infection, relative to 71 infected adults (symptomatic n = 61, and asymptomatic n = 10), and negative controls (n = 48). We assessed serum IgG antibodies to a 14-wide antigen panel of structural and accessory proteins by Luciferase Immuno-Precipitation System (LIPS) assay and circulating cytokines. Infected children have lower levels of Spike, Membrane, ORF3a, ORF7a, ORF7b antibodies, comparable ORF8 and elevated E-specific antibodies than adults. Combination of two unique antibody targets, ORF3d and ORF8, can accurately discriminate SARS-CoV-2 infection in children. Principal component analysis reveals distinct pediatric serological signatures, and the highest contribution to variance from adults are antibody responses to non-structural proteins ORF3d, NSP1, ORF3a and ORF8. From a diverse panel of cytokines that can modulate immune priming and relative inflammation, IL-8, MCP-1 and IL-6 correlate with the magnitude of pediatric antibody specificity and severity. Antibodies to SARS-CoV-2 internal proteins may become an important sero surveillance tool of infection with the roll-out of vaccines in the pediatric population.
Endoscopic therapy of upper gastrointestinal bleeding remains challenging with conventional endoscopic devices. Use of Hemospray, where a nanopowder with clotting abilities is sprayed onto the ...bleeding site, had been highly effective for management of arterial bleeding in a heparizined animal model. The safety and effectiveness of Hemospray for hemostasis of active peptic ulcer bleeding in humans was evaluated.
In a prospective, single-arm, pilot clinical study, consecutive adults with confirmed peptic ulcer bleeding (Forrest score Ia or Ib), who had all given informed consent to participation, underwent upper gastrointestinal endoscopy and application of Hemospray within 24 hours of hospital admission once hemodynamically stable. Up to two applications of Hemospray, not exceeding a total of 150 g were allowed. Bleeding recurrence was monitored post procedurally, by second-look endoscopy (72 hours post treatment), and by phone at 30 days. Rate of hemostasis, recurrent bleeding, mortality, need for surgical intervention, and treatment-related complications were assessed.
20 patients were recruited (18 men, 2 women; mean age 60.2 years). Acute hemostasis was achieved in 95 % (19 / 20) of patients; 1 patient had a pseudoaneurysm requiring arterial embolization. Bleeding recurred in 2 patients within 72 hours (shown by hemoglobin drop); neither had active bleeding identified at the 72-hour endoscopy. No mortality, major adverse events, or treatment- or procedure-related serious adverse events were reported during 30-day follow-up.
These pilot results indicate that Hemospray is safe in humans. Hemospray was effective in achieving acute hemostasis in active peptic ulcer bleeding.
This systematic review and meta-analysis is to evaluate the risk of development of concomitant strabismus due to refractive errors. Eligible studies published from 1946 to April 1, 2016 were ...identified from MEDLINE and EMBASE that evaluated any kinds of refractive errors (myopia, hyperopia, astigmatism and anisometropia) as an independent factor for concomitant exotropia and concomitant esotropia. Totally 5065 published records were retrieved for screening, 157 of them eligible for detailed evaluation. Finally 7 population-based studies involving 23,541 study subjects met our criteria for meta-analysis. The combined OR showed that myopia was a risk factor for exotropia (OR: 5.23, P = 0.0001). We found hyperopia had a dose-related effect for esotropia (OR for a spherical equivalent SE of 2-3 diopters D: 10.16, P = 0.01; OR for an SE of 3-4D: 17.83, P < 0.0001; OR for an SE of 4-5D: 41.01, P < 0.0001; OR for an SE of ≥5D: 162.68, P < 0.0001). Sensitivity analysis indicated our results were robust. Results of this study confirmed myopia as a risk for concomitant exotropia and identified a dose-related effect for hyperopia as a risk of concomitant esotropia.
Background
Basophils and mast cells contribute to the development of allergic reactions. Whereas these mature effector cells are extensively studied, the differentiation trajectories from ...hematopoietic progenitors to basophils and mast cells are largely uncharted at the single‐cell level.
Methods
We performed multicolor flow cytometry, high‐coverage single‐cell RNA sequencing analyses, and cell fate assays to chart basophil and mast cell differentiation at single‐cell resolution in mouse.
Results
Analysis of flow cytometry data reconstructed a detailed map of basophil and mast cell differentiation, including a bifurcation of progenitors into two specific trajectories. Molecular profiling and pseudotime ordering of the single cells revealed gene expression changes during differentiation. Cell fate assays showed that multicolor flow cytometry and transcriptional profiling successfully predict the bipotent phenotype of a previously uncharacterized population of peritoneal basophil‐mast cell progenitors.
Conclusions
A combination of molecular and functional profiling of bone marrow and peritoneal cells provided a detailed road map of basophil and mast cell development. An interactive web resource was created to enable the wider research community to explore the expression dynamics for any gene of interest.
Flow cytometry and single‐cell gene expression data reconstruct a road map of mouse basophil and mast cell differentiation. Cell fate assays show that previously uncharacterized peritoneal progenitors can differentiate into both basophils and mast cells. An interactive web resource enables the wider research community to explore the gene expression dynamics of differentiating cells.
Abbreviations: Ba, basophil; FACS, fluorescence‐activated cell sorting; MC, mast cell; Prog, progenitor; scRNA‐seq, single‐cell RNA sequencing.
This study compared the effectiveness of tai chi (TC) muscle power training (MPT), TC alone, MPT alone, and no training for improving the limits of stability (LOS) and motor and leg muscular ...performance and decreasing falls in children with developmental coordination disorder (DCD). One hundred and twenty-one children with DCD were randomly assigned to the TC-MPT, TC, MPT, or control group. The three intervention groups received TC-MPT, TC, or MPT three times per week for 3 months. Measurements were taken before and after the intervention period. The primary outcomes were the LOS completion time and dynamic LOS scores. The secondary outcomes included the Movement Assessment Battery for Children-Second Edition total test score and percentile rank, knee muscle peak force and time to peak force, and the number of falls. None of the interventions affected the LOS test scores. Improvements in the peak forces of the knee extensors and flexors were demonstrated in the TC (p = 0.006) and MPT groups (p = 0.032), respectively. The number of falls also decreased in these two groups (p < 0.001). Thus, clinicians may prescribe TC or MPT for children with DCD to increase their knee muscle strength and reduce their risk of falls.
Women with atrial fibrillation are at a higher risk of stroke, despite treatment with warfarin. It is unclear if women treated with direct oral anticoagulants (DOACs) have better clinical outcomes, ...especially when considering the quality of anticoagulation control of warfarin.
This study compared the effectiveness and safety outcomes of DOACs versus warfarin in men and women with stratifications for anticoagulation control.
Patients newly diagnosed with atrial fibrillation and prescribed oral anticoagulants during 2010 to 2015 were identified using the Hong Kong clinical database. Propensity score matching was performed in men and women separately. Further analysis was conducted to stratify warfarin users according to their anticoagulation control. Cox regression was used to compare the risk of ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), gastrointestinal bleeding, and all-cause mortality in the specific sex.
There were 4,972 men and 4,834 women successfully matched in our cohort. Compared with warfarin, DOAC use was associated with a lower risk of ICH (hazard ratio HR: 0.16; 95% confidence interval CI: 0.06 to 0.40) and all-cause mortality (HR: 0.55; 95% CI: 0.39 to 0.77) in women but not in men. The treatment by sex interaction was significant for ICH only, and a significantly lower risk of ICH remained in the DOAC group when compared with warfarin users with good anticoagulation control (HR: 0.13; 95% CI: 0.02 to 1.00) among women only. The risks of ischemic stroke or systemic embolism and gastrointestinal bleeding with DOACs versus warfarin were comparable in both sexes.
DOACs were associated with a lower risk of ICH and all-cause mortality in women only, where the association of lower ICH risk remained when compared with warfarin users with good anticoagulation control.
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Polypyridyl and related ligands have been widely used for the development of water oxidation catalysts. Supposedly these ligands are oxidation‐resistant and can stabilize high‐oxidation‐state ...intermediates. In this work a series of ruthenium(II) complexes Ru(qpy)(L)22+ (qpy=2,2′:6′,2′′:6′′,2′′′‐quaterpyridine; L=substituted pyridine) have been synthesized and found to catalyze CeIV‐driven water oxidation, with turnover numbers of up to 2100. However, these ruthenium complexes are found to function only as precatalysts; first, they have to be oxidized to the qpy‐N,N′′′‐dioxide (ONNO) complexes Ru(ONNO)(L)23+ which are the real catalysts for water oxidation.
What is the real catalyst? A series of ruthenium(II) complexes Ru(qpy)(L)22+ (qpy=2,2′:6′,2′′:6′′,2′′′‐quaterpyridine; L=substituted pyridine) function as precatalysts for water oxidation using (NH4)2Ce(NO3)6 (CAN) as the terminal oxidant. In the presence of CAN, they are readily oxidized to the qpy‐N,N′′′‐dioxide complexes Ru(ONNO)(L)23+, which are the real catalysts for water oxidation.
Positive selection of high-affinity B cells within germinal centers (GCs) drives affinity maturation of antibody responses. Here, we examined the mechanism underlying the parallel transition from ...immunoglobulin M (IgM) to IgG. Early GCs contained mostly unswitched IgM+ B cells; IgG+ B cells subsequently increased in frequency, dominating GC responses 14–21 days after antigen challenge. Somatic hypermutation and generation of high-affinity clones occurred with equal efficiency among IgM+ and IgG+ GC B cells, and inactivation of Ig class-switch recombination did not prevent depletion of IgM+ GC B cells. Instead, high-affinity IgG+ GC B cells outcompeted high-affinity IgM+ GC B cells via a selective advantage associated with IgG antigen receptor structure but independent of the extended cytoplasmic tail. Thus, two parallel forms of GC B-cell-positive selection, based on antigen receptor variable and constant regions, respectively, operate in tandem to ensure high-affinity IgG antibodies predominate in mature serum antibody responses.
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•IgM+ and IgG+ GC B cells both undergo SHM and generate high-affinity variants•High-affinity IgG+ GC B cells are retained over high-affinity IgM+ GC B cells•Positive selection does not require the extended cytoplasmic domain of IgG•Rare, aberrant IgD+ GC B cells are also positively selected over IgM+ GC B cells
Early germinal centers (GCs) contain unswitched IgM+ and switched IgG+ B cells but ultimately support mature IgG antibody responses. Sundling et al. show that IgG+ B cells are enriched and IgM+ B cells depleted from GCs by a process of positive selection based on the antigen receptor constant region.
Accurately diagnosing indeterminate biliary strictures is challenging but important for patient prognostication and further management. Biopsy sampling under direct cholangioscopic vision might be ...superior to standard ERCP techniques such as brushing or biopsy sampling. Our aim was to investigate whether digital single-operator cholangioscopy (DSOC) compared with standard ERCP workup improves the diagnostic yield in patients with indeterminate biliary strictures.
Patients with an indeterminate biliary stricture on the basis of MRCP were randomized to standard ERCP visualization with tissue brushing (control arm CA) or DSOC visualization and DSOC-guided biopsy sampling (study arm SA). This was a prospective, international, multicenter trial with a procedure-blinded pathologist.
The first sample sensitivity of DSOC-guided biopsy samples was significantly higher than ERCP-guided brushing (SA 68.2% vs CA 21.4%, P < .01). The sensitivity of visualization (SA 95.5% vs CA 66.7%, P = .02) and overall accuracy (SA 87.1% vs CA 65.5%, P = .05) were significantly higher in the SA compared with the CA, whereas specificity, positive predictive value, and negative predictive value showed no significant difference. Adverse events were equally low in both arms.
DSOC-guided biopsy sampling was shown to be safe and effective with a higher sensitivity compared with standard ERCP techniques in the visual and histopathologic diagnosis of indeterminate biliary strictures. (Clinical trial registration number: NCT 03140007.)
Cortex Moutan (CM, root bark of
Paeonia suffruticosa Andr.) is one of the common herbs found in anti-diabetic traditional Chinese medicine formulae. To study the potential anti-diabetic mechanisms of ...CM, four
in vitro models (intestinal brush border membrane vesicles (BBMV), rat hepatoma cell line H4IIE, human skin fibroblasts cell line Hs68 and mouse adipocytes 3T3-L1) were used. CM showed significant
in vitro anti-diabetic effects by inhibiting glucose uptake of BBMV and enhancing glucose uptake into Hs68 and 3T3-L1 cells. Using bioassay-guided fractionation, paeonol was confirmed to be one of the active constituents for inhibiting BBMV glucose uptake. With neonatal-streptozotocin diabetic rats, paeonol (200 and 400
mg/kg
body wt.) was found to improve oral glucose tolerance
in vivo. To the best of our knowledge, this is the first report on the anti-diabetic effect of paeonol.
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