Nervous system function is mediated by a precisely patterned network of synaptic connections. While several cell-adhesion and secreted molecules promote the assembly of synapses, the contribution of ...signals that negatively regulate synaptogenesis is not well understood. We examined synapse formation in the
Caenorhabditis elegans motor neuron DA9, whose presynapses are restricted to a specific segment of its axon. We report that the Wnt
lin-44 localizes the Wnt receptor
lin-17/Frizzled (Fz) to a subdomain of the DA9 axon that is devoid of presynaptic specializations. When this signaling pathway, composed of the Wnts
lin-44 and
egl-20,
lin-17/Frizzled and
dsh-1/Dishevelled, is compromised, synapses develop ectopically in this subdomain. Conversely, overexpression of LIN-44 in cells adjacent to DA9 is sufficient to expand LIN-17 localization within the DA9 axon, thereby inhibiting presynaptic assembly. These results suggest that morphogenetic signals can spatially regulate the patterning of synaptic connections by subdividing an axon into discrete domains.
Glucocorticoids for croup in children Aregbesola, Alex; Aregbesola, Alex; Tam, Clara M ...
Cochrane database of systematic reviews,
01/2023, Letnik:
2023, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background
Glucocorticoids are the mainstay for the treatment of croup. The existing evidence demonstrates that glucocorticoids are effective in the treatment of croup in children. However, updating ...the evidence on their clinical relevance in croup is imperative. This is an update to a review first published in 1999, and updated in 2004, 2011, and 2018.
Objectives
To investigate the effects and safety of glucocorticoids in the treatment of croup in children aged 18 years and below.
Search methods
We searched the Cochrane Library, which includes the Cochrane Central Register of Controlled Trials (CENTRAL; 2022 Issue 9), Ovid MEDLINE Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations and Ovid MEDLINE (1946 to 4 March 2022), Embase (Ovid) (1974 to 4 March 2022). We also searched the WHO ICTRP and ClinicalTrials.gov on 4 March 2022.
Selection criteria
We included randomised controlled trials (RCTs) in children (aged 18 years and below) with croup. We assessed the effect of glucocorticoids compared to the following: placebo, any other pharmacologic agents, any other glucocorticoids, any combination of other glucocorticoids, given by different modes of administration, or given in different doses. The included studies must have assessed at least one of our primary outcomes (defined as the change in croup score or return visits, (re)admissions to the hospital or both) or secondary outcomes (defined as the length of stay in hospital or emergency departments, patient improvement, use of additional treatments, or adverse events).
Data collection and analysis
Review authors independently extracted data, with another review author verified. We entered the data into Review Manager 5 for meta‐analysis. Two review authors independently assessed studies for risk of bias using the Cochrane risk of bias tool. Two review authors assessed the certainty of the evidence for the primary outcomes using the GRADE approach.
Main results
This updated review includes 45 RCTs with a total of 5888 children, an increase of two RCTs with 1323 children since the last update. We also identified one ongoing study and one study awaiting classification. We assessed most studies (98%) as at high or unclear risk of bias.
Any glucocorticoid compared to placebo
Compared to placebo, glucocorticoids may result in greater reductions in croup score after two hours (standardised mean difference (SMD) −0.65, 95% confidence interval (CI) −1.13 to −0.18; 7 RCTs, 426 children; low‐certainty evidence); six hours (SMD −0.76, 95% CI −1.12 to −0.40; 11 RCTs, 959 children; low‐certainty evidence); and 12 hours (SMD −1.03, 95% CI −1.53 to ‐0.53; 8 RCTs, 571 children; low‐certainty evidence). The evidence for change in croup score after 24 hours is very uncertain (SMD −0.86, 95% CI −1.40 to −0.31; 8 RCTs, 351 children; very low‐certainty evidence).
One glucocorticoid compared to another glucocorticoid
There was little to no difference between prednisolone and dexamethasone for reduction in croup score at two‐hour post‐baseline score (SMD 0.06, 95% CI −0.06 to 0.18; 1 RCT, 1231 children; high‐certainty evidence). There was likely little to no difference between prednisolone and dexamethasone for reduction in croup score at six‐hour post‐baseline score (SMD 0.21, 95% CI −0.21 to 0.62; 1 RCT, 99 children; moderate‐certainty evidence). However, dexamethasone probably reduced the return visits or (re)admissions for croup by almost half (risk ratio (RR) 0.55, 95% CI 0.28 to 1.11; 4 RCTs, 1537 children; moderate‐certainty evidence), and showed a 28% reduction in the use of supplemental glucocorticoids as an additional treatment (RR 0.72, 95% CI 0.53 to 0.97; 2 RCTs, 926 children).
Dexamethasone given in different doses
Compared to 0.15 mg/kg, 0.60 mg/kg dexamethasone probably reduced the severity of croup as assessed by the croup scoring scale at 24‐hour postbaseline score (SMD 0.63, 95% CI 0.16 to 1.10; 1 RCT, 72 children; moderate‐certainty evidence); however, this was not the case at two hours (SMD −0.27, 95% CI −0.76 to 0.22; 2 RCTs, 861 children; high‐certainty evidence). There was probably no reduction at six hours (SMD −0.45, 95% CI −1.26 to 0.35; 3 RCTs, 178 children; moderate‐certainty evidence), and the evidence at 12 hours is very uncertain (SMD −0.60, 95% CI −4.39 to 3.19; 2 RCTs, 113 children; very low‐certainty evidence). There was little to no difference between doses of dexamethasone in return visits or (re)admissions of children or both (RR 0.91, 95% CI 0.71 to 1.17; 3 RCTs, 949 children; high‐certainty evidence) or length of stay in the hospital or emergency department (mean difference 0.12, 95% CI −0.32 to 0.56; 2 RCTs, 892 children). The need for additional treatments, such as epinephrine (RR 0.78, 95% CI 0.34 to 1.75; 2 RCTs, 885 children); intubation (risk difference 0.00, 95% CI −0.00 to 0.00; 2 RCTs, 861 children); or use of supplemental glucocorticoids (RR 0.77, 95% CI 0.51 to 1.15; 2 RCTs, 617 children), also did not differ between doses of dexamethasone.
There were moderate to high levels of heterogeneity in the analyses for most comparisons. Adverse events were observed for some of the comparisons reported in the review.
Authors' conclusions
The evidence that glucocorticoids reduce symptoms of croup at two hours, shorten hospital stays, and reduce the rate of return visits or (re)admissions has not changed in this update. A smaller dose of 0.15 mg/kg of dexamethasone may be as effective as the standard dose of 0.60 mg/kg. More RCTs are needed to strengthen the evidence for effectiveness of low‐dose dexamethasone at 0.15 mg/kg to treat croup.
Infrared fluorescent proteins (IFPs) provide an additional color to GFP and its homologs in protein labeling. Drawing on structural analysis of the dimer interface, we identified a ...bacteriophytochrome in the sequence database that is monomeric in truncated form and engineered it into a naturally monomeric IFP (mIFP). We demonstrate that mIFP correctly labels proteins in live cells, Drosophila and zebrafish. It should be useful in molecular, cell and developmental biology.
Abstract Objective To conduct a systematic review of the efficacy and safety of exogenous melatonin in managing secondary sleep disorders and sleep disorders accompanying sleep restriction, such as ...jet lag and shiftwork disorder. Data sources 13 electronic databases and reference lists of relevant reviews and included studies; Associated Professional Sleep Society abstracts (1999 to 2003). Study selection The efficacy review included randomised controlled trials; the safety review included randomised and non-randomised controlled trials. Quality assessment Randomised controlled trials were assessed by using the Jadad Scale and criteria by Schulz et al, and non-randomised controlled trials by the Downs and Black checklist. Data extraction and synthesis One reviewer extracted data and another reviewer verified the data extracted. The inverse variance method was used to weight studies and the random effects model was used to analyse data. Main results Six randomised controlled trials with 97 participants showed no evidence that melatonin had an effect on sleep onset latency in people with secondary sleep disorders (weighted mean difference −13.2 (95% confidence interval −27.3 to 0.9) min). Nine randomised controlled trials with 427 participants showed no evidence that melatonin had an effect on sleep onset latency in people who had sleep disorders accompanying sleep restriction (−1.0 (−2.3 to 0.3) min). 17 randomised controlled trials with 651 participants showed no evidence of adverse effects of melatonin with short term use (three months or less). Conclusions There is no evidence that melatonin is effective in treating secondary sleep disorders or sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder. There is evidence that melatonin is safe with short term use.
To conduct a pilot study to compare the frequency of errors that accompany single vs. double data extraction, compare the estimate of treatment effect derived from these methods, and compare the time ...requirements for these methods.
Reviewers were randomized to the role of data extractor or data verifier, and were blind to the study hypothesis. The frequency of errors associated with each method of data extraction was compared using the McNemar test. The data set for each method was used to calculate an efficacy estimate by each method, using standard meta-analytic techniques. The time requirement for each method was compared using a paired
t-test.
Single data extraction resulted in more errors than double data extraction (relative difference: 21.7%,
P = .019). There was no substantial difference between methods in effect estimates for most outcomes. The average time spent for single data extraction was less than the average time for double data extraction (relative difference: 36.1%,
P = .003).
In the case that single data extraction is used in systematic reviews, reviewers and readers need to be mindful of the possibility for more errors and the potential impact these errors may have on effect estimates.
Hypnotics have a role in the management of acute insomnia; however, the efficacy and safety of pharmacological interventions in the management of chronic insomnia is unclear.
The objective of this ...paper is to conduct a systematic review of the efficacy and safety of drug treatments for chronic insomnia in adults.
Twenty-one electronic databases were searched, up to July 2006.
Randomized double-blind, placebo-controlled trials were eligible. Quality was assessed using the Jadad scale. Data were pooled using the random effects model.
One hundred and five studies were included in the review. Sleep onset latency, as measured by polysomnography, was significantly decreased for benzodiazepines (BDZ), (weighted mean difference: -10.0 minutes; 95% CI: -16.6, -3.4), non-benzodiazepines (non-BDZ) (-12.8 minutes; 95% CI: -16.9, -8.8) and antidepressants (ADP) (-7.0 minutes; 95% CI: -10.7, -3.3). Sleep onset latency assessed by sleep diaries was also improved (BDZ: -19.6 minutes; 95% CI: -23.9, -15.3; non-BDZ: -17.0 minutes; 95% CI: -20.0, -14.0; ADP: -12.2 minutes; 95% CI: -22.3, -2.2). Indirect comparisons between drug categories suggest BDZ and non-BDZ have a similar effect. All drug groups had a statistically significant higher risk of harm compared to placebo (BDZ: risk difference RD: 0.15; non-BDZ RD: 0.07; and ADP RD: 0.09), although the most commonly reported adverse events were minor. Indirect comparisons suggest that non-BDZ are safer than BDZ.
Benzodiazepines and non-benzodiazepines are effective treatments in the management of chronic insomnia, although they pose a risk of harm. There is also some evidence that antidepressants are effective and that they pose a risk of harm.
The central nervous system (CNS) loses the ability to regenerate early during development, but it is not known why. The retina has long served as a simple model system for study of CNS regeneration. ...Here we show that amacrine cells signal neonatal rat retinal ganglion cells (RGCs) to undergo a profound and apparently irreversible loss of intrinsic axon growth ability. Concurrently, retinal maturation triggers RGCs to greatly increase their dendritic growth ability. These results suggest that adult CNS neurons fail to regenerate not only because of CNS glial inhibition but also because of a loss of intrinsic axon growth ability.
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