Abstract
Background
Antibiotic use is associated with collateral damage to the healthy microbiota. Afabicin is a first-in-class prodrug inhibitor of the FabI enzyme that, when converted to the ...pharmacologically active agent afabicin desphosphono, demonstrates a staphylococcal-specific spectrum of activity. An expected benefit of highly targeted antibiotics such as afabicin is microbiome preservation.
Objectives
To compare the effects of oral treatment with afabicin and standard-of-care antibiotics upon the murine gut microbiota, and to assess the effects of oral afabicin treatment on the human gut microbiota.
Methods
Gut microbiota effects of a 10 day oral course of afabicin treatment were monitored in mice and compared with clindamycin, linezolid and moxifloxacin at human-equivalent dose levels using 16S rDNA sequencing. Further, the gut microbiota of healthy volunteers was longitudinally assessed across 20 days of oral treatment with afabicin 240 mg twice daily.
Results
Afabicin treatment did not significantly alter gut microbiota diversity (Shannon H index) or richness (rarefied Chao1) in mice. Only limited changes to taxonomic abundances were observed in afabicin-treated animals. In contrast, clindamycin, linezolid and moxifloxacin each caused extensive dysbiosis in the murine model. In humans, afabicin treatment was not associated with alterations in Shannon H or rarefied Chao1 indices, nor relative taxonomic abundances, supporting the findings from the animal model.
Conclusions
Oral treatment with afabicin is associated with preservation of the gut microbiota in mice and healthy subjects.
Endometriosis-related infertility remains a therapeutic challenge. A burning issue in this field of research is determining whether pre-assisted reproductive technology (ART) surgery may be of some ...benefit in terms of reproductive outcomes. This systematic review and meta-analysis aimed at comparing ongoing pregnancy rates (OPR) and/or live birth rates (LBR) in patients who underwent endometriosis surgery before ART (IVF/ICSI) in comparison with patients who underwent first-line ART (IVF/ICSI). Searches were conducted from January 1990 to June 2021 on PubMed, Embase, and Cochrane Library using the following search terms: endometriosis, surgery, reproductive outcomes, and IVF/ICSI. The primary outcomes were OPR or LBR. A total of 19 studies were included in the meta-analysis. No statistically significant differences in LBR 0.910.63, 1.30; I
= 66%; n = 11, OPR 1.280.66, 2.49; I
= 60%; n = 3, and early pregnancy loss rate 0.880.62, 1.25; I
= 0%; n = 7 per cycle were found when comparing patients who underwent endometriosis surgery before IVF/ICSI and those who did not. After the exclusion of the studies with high risks of bias, the LBR per cycle was significantly reduced in the case of surgical treatment before IVF/ICSI 0.530.33, 0.86; I
= 30%; n = 4. These data urge the clinician to carefully weigh the pros and cons before referring infertile patients with endometriosis to surgery before IVF, highlighting the key role of multidisciplinary referral centers.
Highlights ► We focus on several biological systems which are impaired with age in grey mouse lemurs, as in humans. ►Similarities between human and mouse lemur are demonstrated in both normal and ...pathological ageing process. ►This smaller, rapidly developed and shorter-lived non-human primate could be a suitable model for human ageing research. ►This non-human primate model offer predictive biomarkers of longevity and neuropathological ageing.
Converging evidence shows that the non-human primate gray mouse lemur (Microcebus murinus) is ideal for the study of the aging process and for testing the effects of new therapies and dietary ...interventions on age-associated pathologies. One such dietary supplement is resveratrol (RSV), a dietary polyphenolic compound with several positive effects on metabolic functions and longevity. However, little is known about the effect of RSV on the lemur sleep-wake cycle, which reflects mammalian brain function and health. In the present study, the authors investigated this effect by comparing sleep-wake cycles in adult lemurs based on electroencephalographic (EEG) rhythms. The effect of short-term RSV supplementation on the sleep-wake cycle of mouse lemurs was evaluated in entrained conditions (long-day photoperiods, light:dark 14:10). After 3 wks of RSV supplementation, the animals exhibited a significantly increased proportion of active-wake time, occurring mainly during the resting phase of the sleep-wake cycle (+163%). The increase in active-wake time with RSV supplementation was accompanied by a significant reduction of both paradoxical sleep (−95%) and slow-wave sleep (−38%). These changes mainly occurred during the resting phase of the sleep-wake cycle (RSV supplementation induced negligible changes in active-wake time during the active phase of the sleep-wake cycle). The present data suggest that RSV may be a potent regulator of sleep-wake rhythms and could be of major interest in the study of sleep perturbations associated with aging and neuropathology. (Author correspondence: aujard@mnhn.fr)
Abstract
Study question
Do Gonadotropin-releasing hormone agonists (GnRHa) triggering improves oocyte maturation, clinical outcomes, and safety compared to human chorionic gonadotropin (hCG) ...triggering during controlled ovarian stimulation with an antagonist protocol?
Summary answer
The final triggering using GnRHa allows a higher number of retrieved and mature oocytes to be obtained with comparable clinical outcomes and lower OHSS risk.
What is known already
GnRHa represent an alternative to hCG for ovulation triggering after controlled ovarian stimulation with an antagonist protocol for IVF/ICSI. GnRHa triggering is thought to be more physiological due to the endogenous surges in LH and FSH levels. However, the benefit of GnRHa over hCG triggering on oocyte maturation remains controversial.
Study design, size, duration
A systematic review and meta-analysis of randomised controlled clinical trials. Searches were conducted from 01 January 1990 to 15 April 2020 on MEDLINE, EMBASE, the Cochrane Library, ClinicalTrials.gov and EudraCT, using the following search terms: ‘GnRH agonist’, ‘hCG’, ‘triggering’. Two independent reviewers carried out the study selection, the bias assessment using the RoB2 tool, and the data extraction according to Cochrane methods.
Participants/materials, setting, methods
The primary outcomes were the total number of retrieved oocytes and the number of mature oocytes. The main secondary outcomes were the number of embryos obtained, the clinical pregnancy rate, the early pregnancy loss rate, the live birth rate, and the incidence of ovarian hyperstimulation syndrome (OHSS). Random-effects meta-analysis was performed followed by prespecified sensitivity and subgroup analyses.
Main results and the role of chance
A total of 29 randomised controlled trials were included. The mean number of retrieved oocytes difference in means (95% CI) 0.99 (0.21, 1.78); p = 0.01; n = 26 and of mature oocytes 0.68 (0.04, 1.33); p = 0.04; n = 12 were statistically significantly higher after GnRHa than after hCG triggering. A similar difference was observed for the number of embryos 0.94 (0.19, 1.68); p = 0.01; n = 10. No differences in the clinical pregnancy rate risk ratio 1.01 (0.90, 1.14); p = 0.83; n = 23, early pregnancy loss 1.27 (0.94, 1.71); p = 0.13; n = 16, and live birth rate 1.00 (0.77, 1.29); p = 0.97; n = 6 were noted. GnRHa was associated with a lower incidence of OHSS odds ratio 0.25 (0.08, 0.74); p = 0.012; n = 20.
Limitations, reasons for caution
The validity of meta-analysis results depends mainly on the quality and the number of the published studies available.
Wider implications of the findings: In light of its safety and effectiveness, GnRHa should be the new standard for triggering in antagonist cycles, with dual triggering with hCG when the risk of OHSS is low and a fresh embryo transfer approach is used.
Trial registration number
NA
Ontogenetic modification of an early memory is relatively poorly understood. And an important question is whether the memory output is more determined by the age at acquisition or at retention? Here ...we explore the expression of odor-shock conditioning in the rat pup. Acquisition at post-natal day 6 (P6) leads to an approach response and at post-natal day 12 (P12) to an avoidance response when the retention test is 24
h later. In both cases, anisomycin injected immediately post-acquisition induced a retrograde amnesia. Controls show that, in either case, short-term memory measured 4
h after acquisition is not impaired and that anisomycin given after a 4
h delay has no effect. Thus, at the two ages, memory involves a consolidation process. The main result is the spontaneous reversal of the conditioned response from approach acquired at P6 to avoidance when tested at P13. This phenomenon is robust as it is observed in three conditions. Moreover, amnesia induced at P6 is maintained at P13. Results are discussed in terms of maturation and/or competition of the memory traces.
The paper sets out to challenge the notions of 'affordable' private schools in the context of South Africa. It is guided by one main question: 'affordable private schools for whom?' It argues that, ...contrary to claims by its public and private proponents, affordable private schools in South Africa do not cater for poor children. Their rise has coincided with the emergence, in the post-apartheid period, of a-mostly black-middle class. However, despite its imprecision, the 'affordable' terminology can also be interpreted as a discursive device that obscures the class interests and distributional choices that actually shape South Africa's education system. It allows the social forces in favour of the expansion of private education-segments of the state and pro-market lobbyists-to frame their project in social justice terms. The paper concludes that the state's ambiguous position towards the so-called 'affordable' or 'low-fee' private schools reflects national leaders' delicate balancing act between contradictory objectives, which is overly determined by their embrace of an orthodox macro-economic model that constrains the fiscal space for public education.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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