Summary
Background
TCS (topical corticosteroids) are the first‐line drug in the treatment of oral lichen planus (OLP). However, the value of topical calcineurin inhibitors (TCI) including tacrolimus, ...pimecrolimus and ciclosporin for OLP is still controversial.
Objectives
To compare the efficacy and safety of TCI vs. TCS for OLP.
Methods
The authors searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and four Chinese databases from 1950 to May 2018. The randomized controlled trials comparing TCI and TCS for OLP reported at least one of the following outcomes: improvement of clinical signs and/or symptoms, relapse, blood levels of TCI and adverse events.
Results
Twenty‐one trials involving 965 patients were included in the analysis. For the treatment of OLP (3–8 weeks), TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy. Tacrolimus–TCS resulted in similar outcomes, with relapse at 3 weeks to 6 months. Blood levels of TCI were usually undetectable. In addition, tacrolimus showed a statistically higher incidence of local adverse events than TCS for short‐term treatment. A few systemic adverse events occurred in the tacrolimus and ciclosporin groups, but they were not serious.
Conclusions
The evidence for tacrolimus (n = 12), pimecrolimus (n = 3) and ciclosporin (n = 6) demonstrated that treatment with TCI may be an alternative approach when OLP does not respond to the standard protocols. Tacrolimus 0·1% should be the first drug of choice when selecting TCI for short‐term treatment in recalcitrant OLP. Further well‐designed trials are warranted to evaluate the long‐term efficacy and safety of TCI.
What's already known about this topic?
The main topical drug for oral lichen planus (OLP) is topical corticosteroids (TCS).
Patients with OLP who are not responsive to TCS or are at risk of adverse events from TCS need other alternative drugs.
Topical calcineurin inhibitors (TCI), including tacrolimus, pimecrolimus and ciclosporin, have become a hot topic in a variety of mucocutaneous immune‐mediated diseases.
What does this study add?
TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy for the short‐term treatment of OLP.
The local adverse events of tacrolimus were higher than with TCS. A few systemic adverse events were reported with TCI, but they were all tolerable and not serious.
The limited evidence for pimecrolimus (three trials) and ciclosporin (six trials) requires further studies to evaluate the short‐term and long‐term efficacy and safety of TCI compared with TCS.
Linked Comment: Thongprasom. Br J Dermatol 2019; 181:1120.
Plain language summary available online
The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This ...Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross sections for WIMP masses above 9 GeV/c^{2}. The most stringent limit is set for spin-independent scattering at 36 GeV/c^{2}, rejecting cross sections above 9.2×10^{-48} cm at the 90% confidence level.
Magnetic reconnection is important to the dynamics of many astrophysical and fusion plasmas but our understanding of it is incomplete. Petaflop-scale simulations of the evolution of turbulent ...magnetic reconnection in a three-dimensional plasma indicate that it proceeds in a way that is dramatically different from classical theory. PUBLICATION ABSTRACT
The brain endothelium is an important therapeutic target for the inhibition of cerebrovascular dysfunction in ischemic stroke. Previously, we documented the important regulatory roles of microRNAs in ...the cerebral vasculature, in particular the cerebral vascular endothelium. However, the functional significance and molecular mechanisms of other classes of non-coding RNAs in the regulation of cerebrovascular endothelial pathophysiology after stroke are completely unknown.
Using RNA sequencing (RNA-seq) technology, we profiled long non-coding RNA (lncRNA) expressional signatures in primary brain microvascular endothelial cells (BMECs) after oxygen–glucose deprivation (OGD), an in vitro mimic of ischemic stroke conditions. After 16h of OGD exposure, the expression levels for 362 of the 10,677 lncRNAs analyzed changed significantly, including a total of 147 lncRNAs increased and 70 lncRNAs decreased by more than 2-fold. Among them, the most highly upregulated lncRNAs include Snhg12, Malat1, and lnc-OGD 1006, whereas the most highly downregulated lncRNAs include 281008D09Rik, Peg13, and lnc-OGD 3916. Alteration of the most highly upregulated/downregulated ODG-responsive lncRNAs was further confirmed in cultured BMECs after OGD as well as isolated cerebral microvessels in mice following transient middle cerebral artery occlusion (MCAO) and 24h reperfusion by the quantitative real-time PCR approach. Moreover, promoter analysis of altered ODG-responsive endothelial lncRNA genes by bioinformatics showed substantial transcription factor binding sites on lncRNAs, implying potential transcriptional regulation of those lncRNAs. These findings are the first to identify OGD-responsive brain endothelial lncRNAs, which suggest potential pathological roles for these lncRNAs in mediating endothelial responses to ischemic stimuli. Endothelial-selective lncRNAs may function as a class of novel master regulators in cerebrovascular endothelial pathologies after ischemic stroke.
•A first study to profile ischemic-responsive brain endothelial long non-coding RNAs•Total 217 lncRNAs were classified as ischemic-responsive endothelial lncRNAs.•The most highly altered lncRNAs were confirmed in brain microvessels after stroke.•Identified key transcription factors that regulate ischemic-responsive lncRNAs
Purpose
Patients with type 2 diabetes (T2D) have demonstrated a higher risk for developing more severe cases of COVID-19, but the complex genetic mechanism between them is still unknown. The aim of ...the present study was to untangle this relationship using genetically based approaches.
Methods
By leveraging large-scale genome-wide association study (GWAS) summary statistics of T2D and COVID-19 severity, linkage disequilibrium score regression and Mendelian randomization (MR) analyses were utilized to quantify the genetic correlations and causal relationships between the two traits. Gene-based association and enrichment analysis were further applied to identify putative functional pathways shared between T2D and COVID-19 severity.
Results
Significant, moderate genetic correlations were detected between T2D and COVID-19 hospitalization (
r
g
= 0.156, SE = 0.057,
p
= 0.005) or severe disease (
r
g
= 0.155, SE = 0.057,
p
= 0.006). MR analysis did not support evidence for a causal effect of T2D on COVID-19 hospitalization (OR 1.030, 95% CI 0.979, 1.084,
p
= 0.259) or severe disease (OR 0.999, 95% CI 0.934, 1.069,
p
= 0.982). Genes having
p
gene
< 0.05 for both T2D and COVID-19 severe were significantly enriched for biological pathways, such as response to type I interferon, glutathione derivative metabolic process and glutathione derivative biosynthetic process.
Conclusions
Our findings further confirm the comorbidity of T2D and COVID-19 severity, but a non-causal impact of T2D on severe COVID-19. Shared genetically modulated molecular mechanisms underlying the co-occurrence of the two disorders are crucial for identifying therapeutic targets.
Background. Seven persons in one family living in eastern China developed fever and thrombocytopenia during May 2007, but the initial investigation failed to identify an infectious etiology. In ...December 2009, a novel bunyavirus (designated severe fever with thrombocytopenia syndrome bunyavirus SFTSV) was identified as the cause of illness in patients with similar clinical manifestations in China. We reexamined this family cluster for SFTSV infection. Methods. We analyzed epidemiological and clinical data for the index patient and 6 secondary patients. We tested stored blood specimens from the 6 secondary patients using real time reverse transcription polymerase chain reaction (RT-PCR), viral culture, genetic sequencing, micro-neutralization assay (MNA), and indirect immunofluorescence assay (IFA). Results. An 80-year-old woman with fever, leucopenia, and thrombocytopenia died on 27 April 2007. Between 3 and 7 May 2007, another 6 patients from her family were admitted to a local county hospital with fever and other similar symptoms. Serum specimens collected in 2007 from these 6 patients were positive for SFTS viral RNA through RT-PCR and for antibody to SFTSV through MNA and IFA. SFTSV was isolated from 1 preserved serum specimen. The only shared characteristic between secondary patients was personal contact with the index patient; none reported exposure to suspected animals or vectors. Conclusions. Clinical and laboratory evidence confirmed that the patients of fever and thrombocytopenia occurring in a family cluster in eastern China in 2007 were caused by a newly recognized bunyavirus, SFTSV. Epidemiological investigation strongly suggests that infection of secondary patients was transmitted to family members by personal contact.
LUX-ZEPLIN (LZ) is a second-generation direct dark matter experiment with spin-independent WIMP-nucleon scattering sensitivity above
1.4
×
10
-
48
cm
2
for a WIMP mass of
40
GeV
/
c
2
and a
1000
days
...exposure. LZ achieves this sensitivity through a combination of a large
5.6
t
fiducial volume, active inner and outer veto systems, and radio-pure construction using materials with inherently low radioactivity content. The LZ collaboration performed an extensive radioassay campaign over a period of six years to inform material selection for construction and provide an input to the experimental background model against which any possible signal excess may be evaluated. The campaign and its results are described in this paper. We present assays of dust and radon daughters depositing on the surface of components as well as cleanliness controls necessary to maintain background expectations through detector construction and assembly. Finally, examples from the campaign to highlight fixed contaminant radioassays for the LZ photomultiplier tubes, quality control and quality assurance procedures through fabrication, radon emanation measurements of major sub-systems, and bespoke detector systems to assay scintillator are presented.
•Study evaluating postoperative course after TORS oropharyngeal resection.•Clinical trial patients receiving deescalated adjuvant therapy for HPV(+)OPSCC.•Patients had acceptable post-operative ...bleeding rates requiring intervention (4.6%)•There were very low rates of postoperative complication.
Dose de-escalation of adjuvant therapy (DART) in patients with HPV(+)OPSCC was investigated in two prospective Phase II and III clinical trials (MC1273 and MC1675). We report the 30-day morbidity and mortality associated with primary TORS resection in patients enrolled in these trials.
Patients with HPV(+)OPSCC, who underwent TORS resection between 2013 and 2020 were considered in this analysis. The severity of postoperative transoral bleeding was graded using both the Hinni Grade (HG) transoral surgery bleeding scale and the Common Terminology for Adverse Events (CTCAE) v5.0. Post-surgical complications within 30 days of surgery, as well as rates of tracheostomy, PEG and nasogastric tube placement.
219 patients were included. A total of 7 (3.2 %) patients had a tracheostomy placed at the time of surgery, and all were decannulated within 26 days (median: 5, range: 2–26). There were 33 (15.1 %) returns to the emergency department (ED) with 10 (4.6 %) patients requiring readmission. Using the HG scale, 10 (4.6 %) patients experienced ≥ Grade 3 bleeding with no Grade 5 or 6 bleeds. In contrast, using the CTCAE scale, 15 patients (6.8 %) experienced ≥ Grade 3 bleeding with no Grade 5 bleeds. There was one post-operative death in a patient withdrawn from the trial, and no deaths related to hemorrhage.
TORS for HPV(+)OPSCC in carefully selected patients at a high volume center was associated with low morbidity and mortality.
Coronal heating is a big question for modern astronomy. Daily measurement of 985 solar spectral irradiances (SSIs) at the spectral intervals 1-39 and 116-2416 nm during 2003 March 1 to 2017 October ...28 is utilized to investigate characteristics of solar rotation in the solar atmosphere by means of the Lomb-Scargle periodogram method to calculate their power spectra. The rotation period of coronal plasma is determined to be 26.3 days, and that of the solar atmosphere at the bottom of the photosphere modulated by magnetic structures is 27.5 days. Here we report for the first time that, unexpectedly, the coronal atmosphere is found to rotate faster than the underlying photosphere. When time series of SSIs are divided into different cycles as well as the ascending and descending periods of a solar cycle, the rotation rate in the corona is also found to be larger than that in the photosphere, and this actually uncovers hidden evidence: it is small-scale magnetic activity that heats the corona.
PDF
