Galantamine Hydrobromide

32228651

Background
Mature sperm carry thousands of RNAs, including mRNAs, lncRNAs, tRNAs, rRNAs and sncRNAs, though their functional significance is still a matter of debate. Growing evidence suggests that sperm RNAs, especially sncRNAs, are selectively retained during spermiogenesis or specifically transferred during epididymis maturation, and are thus delivered to the oocyte at fertilization, providing resources for embryo development. However , a deep characterization of the sncRNA content of bull sperm and its expression profile across breeds is currently lacking. To fill this gap, we optimized a guanidinium-Trizol total RNA extraction protocol to prepare high-quality RNA from frozen bull sperm collected from 40 representative bulls from six breeds. Deep sequencing was performed (40 M single 50-bp reads per sample) to establish a comprehensive repertoire of cattle sperm sncRNA.

Results
Our study showed that it comprises mostly piRNAs (26%), rRNA fragments (25%), miRNAs (20%) and tRNA fragments (tsRNA, 14%). We identified 5p-halves as the predominant tsRNA subgroup in bull sperm, originating mostly from Gly and Glu isoacceptors. Our study also increased by ~ 50% the sperm repertoire of known miRNAs and identified 2022 predicted miRNAs. About 20% of sperm miRNAs were located within genomic clusters, expanding the list of known polycistronic pri-miRNA clusters and defining several networks of co-expressed miRNAs. Strikingly, our study highlighted the great diversity of isomiRs, resulting mainly from deletions and non-templated additions (A and U) at the 3p end. Substitutions within miRNA sequence accounted for 40% of isomiRs, with G>A, U>C and C>U substitutions being the most frequent variations. In addition, many sncRNAs were found to be differentially expressed across breeds.

Conclusions
Our study provides a comprehensive overview of cattle sperm sncRNA, and these findings will pave the way for future work on the role of sncRNAs in embryo development and their relevance as biomarkers of semen fertility.

sncRNA, miRNA, isomiR, piRNA, tRNA, Sperm, Bull

A comprehensive overview of bull sperm-borne small non-coding RNAs and their diversity across breeds

Eli Sellem,corresponding author1 Sylvain Marthey,2 Andrea Rau,2 Luc Jouneau,3,4 Aurelie Bonnet,1 Jean-Philippe Perrier,3,4 Sebastien Fritz,1,2 Chrystelle Le Danvic,1 Mekki Boussaha,2 Helene Kiefer,3,4 Helene Jammes,3,4 and Laurent Schibler1

2020

27306653

Background
Tension?type headache (TTH) affects about 1 person in 5 worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (two to 14 headaches per month), and chronic TTH (15 headache days a month or more). Paracetamol (acetaminophen) is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH.

Objectives
To assess the efficacy and safety of paracetamol for the acute treatment of frequent episodic TTH in adults.

Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (CRSO), MEDLINE, EMBASE, and the Oxford Pain Relief Database to October 2015, and also reference lists of relevant published studies and reviews. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers’ websites.

Selection criteria
We included randomised, double?blind, placebo?controlled studies (parallel?group or cross?over) using oral paracetamol for symptomatic relief of an acute episode of TTH. Studies had to be prospective, with participants aged 18 years or over, and include at least 10 participants per treatment arm.

Data collection and analysis
Two review authors independently assessed studies for inclusion and extracted data. We used the numbers of participants achieving each outcome to calculate the risk ratio (RR) and number needed to treat for one additional beneficial outcome (NNT) or one additional harmful outcome (NNH) for oral paracetamol compared to placebo or an active intervention for a range of outcomes, predominantly those recommended by the International Headache Society (IHS).

We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created ‘Summary of findings’ tables.

Main results
We included 23 studies, all of which enrolled adults with frequent episodic TTH. Twelve studies used the IHS diagnostic criteria or similar, six used the older classification of the Ad Hoc Committee, and five did not describe specific diagnostic criteria but generally excluded participants with migraines. Participants had moderate or severe pain at the start of treatment. While 8079 people with TTH participated in these studies, the numbers available for any analysis were lower than this because outcomes were inconsistently reported and because many participants received active comparators.

None of the included studies were at low risk of bias across all domains considered, although for most studies and domains this was likely to be due to inadequate reporting rather than poor methods. We judged five studies to be at high risk of bias for incomplete outcome reporting, and seven due to small size.

For the IHS preferred outcome of being pain free at two hours the NNT for paracetamol 1000 mg compared with placebo was 22 (95% confidence interval (CI) 15 to 40) in eight studies (5890 participants; high quality evidence), with no significant difference from placebo at one hour. The NNT was 10 (7.9 to 14) for pain?free or mild pain at two hours in five studies (5238 participants; high quality evidence). The use of rescue medication was lower with paracetamol 1000 mg than with placebo, with an NNTp to prevent an event of 7.8 (6.0 to 11) in six studies (1856 participants; moderate quality evidence). On limited data, the efficacy of paracetamol 500 mg to 650 mg was not superior to placebo, and paracetamol 1000 mg was not different from either ketoprofen 25 mg or ibuprofen 400 mg (low quality evidence).

Adverse events were not different between paracetamol 1000 mg and placebo (RR 1.1 (0.94 to 1.3); 5605 participants; 11 studies; high quality evidence). Studies reported no serious adverse events.

The quality of the evidence using GRADE comparing paracetamol 1000 mg with placebo was moderate to high. Where evidence was downgraded it was because a minority of studies reported the outcome. For comparisons of paracetamol 500 mg to 650 mg with placebo, and of paracetamol 1000 mg with active comparators, we downgraded the evidence to low quality or very low quality because of the small number of studies and events.

Authors’ conclusions
Paracetamol 1000 mg provided a small benefit in terms of being pain free at two hours for people with frequent episodic TTH who have an acute headache of moderate or severe intensity.

Adult, Humans, Acetaminophen, Acetaminophen/adverse effects, Acetaminophen/therapeutic use, Administration, Oral, Analgesics, Non?Narcotic, Analgesics, Non?Narcotic/adverse effects, Analgesics, Non?Narcotic/therapeutic use, Pain Measurement, Randomized Controlled Trials as Topic, Tension?Type Headache, Tension?Type Headache/diagnosis, Tension?Type Headache/drug therapy, Time Factors

Paracetamol (acetaminophen) for acute treatment of episodic tension?type headache in adults

Guy Stephens, Sheena Derry, R Andrew Moore

2016 Jun;