Does oral alprazolam affect ventilation? a randomised, double-blind, placebo-controlled trial

The respiratory effects of benzodiazepines have been controversial. This investigation aimed to study the effects of oral alprazolam on ventilation. In a randomised, double-blind cross-over protocol, 20 healthy men ingested 1 mg of alprazolam or placebo in random order, 1 week apart. Ventilation was unobtrusively monitored by inductance plethysmography along with end-tidal PCO2 and pulse oximetry 60-160 min after drug intake. Subjects were encouraged to keep eyes open. Meanï¿(1/2)+/- was similar (6.21 +/- 0.71 vs 6.41 +/- 1.12 L/min, P = NS). End-tidal PCO2 and oxygen saturation did also not differ between treatments. However, coefficients of variation of minute ventilation after alprazolam exceeded those after placebo (43 +/- 23% vs 31 +/- 13%, P < 0.05). More encouragements to keep eyes open were required after alprazolam than after placebo (5.2 +/- 5.7 vs 1.3 +/- 2.3 calls, P < 0.05). In a multiple regression analysis, higher coefficients of variation of minute ventilation after alprazolam were related to a greater number of calls. Oral alprazolam in a mildly sedative dose has no clinically relevant effect on ventilation in healthy, awake men. The increased variability of ventilation on alprazolam seems related to vigilance fluctuations rather than to a direct drug effect on ventilation

CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo that segregate across generations

CRISPR-Cas9 can introduce unintended off-target effects. Here authors show that unintended mutations produced by in vivo of zebrafish can be inherited by their off-spring.CRISPR-Cas9 genome editing has potential to cure diseases without current treatments, but therapies must be safe. Here we show that CRISPR-Cas9 editing can introduce unintended mutations in vivo, which are passed on to the next generation. By editing fertilized zebrafish eggs using four guide RNAs selected for off-target activity in vitro, followed by long-read sequencing of DNA from >1100 larvae, juvenile and adult fish across two generations, we find that structural variants (SVs), i.e., insertions and deletions >= 50 bp, represent 6% of editing outcomes in founder larvae. These SVs occur both at on-target and off-target sites. Our results also illustrate that adult founder zebrafish are mosaic in their germ cells, and that 26% of their offspring carries an off-target mutation and 9% an SV. Hence, pre-testing for off-target activity and SVs using patient material is advisable in clinical applications, to reduce the risk of unanticipated effects with potentially large implications

CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo that segregate across generations

CRISPR-Cas9 can introduce unintended off-target effects. Here authors show that unintended mutations produced by in vivo of zebrafish can be inherited by their off-spring.CRISPR-Cas9 genome editing has potential to cure diseases without current treatments, but therapies must be safe. Here we show that CRISPR-Cas9 editing can introduce unintended mutations in vivo, which are passed on to the next generation. By editing fertilized zebrafish eggs using four guide RNAs selected for off-target activity in vitro, followed by long-read sequencing of DNA from >1100 larvae, juvenile and adult fish across two generations, we find that structural variants (SVs), i.e., insertions and deletions >= 50 bp, represent 6% of editing outcomes in founder larvae. These SVs occur both at on-target and off-target sites. Our results also illustrate that adult founder zebrafish are mosaic in their germ cells, and that 26% of their offspring carries an off-target mutation and 9% an SV. Hence, pre-testing for off-target activity and SVs using patient material is advisable in clinical applications, to reduce the risk of unanticipated effects with potentially large implications.Genome Instability and Cance

Popular Snore Aids: Do They Work?

Objective The study goal was to critically evaluate 3 popular noninvasive treatments for snoring: an oral spray lubricant applied before bedtime, a nasal strip designed to maintain nasal valve patency, and a head-positioning pillow. Study design Prospective, randomized blinded clinical trial of 3 popular noninvasive snore aids using objective acoustic snoring analysis and subjective patient and bed-partner questionnaires in 40 snoring patients. A digital recorder allowed snoring analysis with data collected in the home environment over 1 week. Results There is neither objective nor subjective benefit to the use of tested popular noninvasive snore aids. Palatal snoring, palatal loudness, average loudness of snoring, averaged palatal flutter frequency, and respiratory disturbance index did not significantly change when comparing the 3 snoring aids with no treatment. Subjective comments and complications are reviewed as well. Conclusion This is the first prospective comparison trial of popular noninvasive snoring aids. There is no significant objective or subjective snoring improvement in the anti-snoring aids studied compared with the use of no aid. Significance Outcome studies aid in verifying or refuting claims made by popular noninvasive snore aids