Molecular control of neuromuscular junction development

Skeletal muscle innervation is a multi-step process leading to the neuromuscular junction (NMJ) apparatus formation. The transmission of the signal from nerve to muscle occurs at the NMJ level. The molecular mechanism that orchestrates the organization and functioning of synapses is highly complex, and it has not been completely elucidated so far. Neuromuscular junctions are assembled on the muscle fibers at very precise locations called end plates (EP). Acetylcholine receptor (AChR) clusterization at the end plates is required for an accurate synaptic transmission. This review will focus on some mechanisms responsible for accomplishing the correct distribution of AChRs at the synapses. Recent evidences support the concept that a dual transcriptional control of AChR genes in subsynaptic and extrasynaptic nuclei is crucial for AChR clusterization. Moreover, new players have been discovered in the agrin-MuSK pathway, the master organizer of postsynaptical differentiation. Mutations in this pathway cause neuromuscular congenital disorders. Alterations of the postynaptic apparatus are also present in physiological conditions characterized by skeletal muscle wasting. Indeed, recent evidences demonstrate how NMJ misfunctioning has a crucial role at the onset of age-associated sarcopenia

Who has a better auditory gaydar? Sexual orientation categorization by heterosexual and lesbian, gay and bisexual people

Lesbian, gay and bisexual (LGB) people are supposed to be better at gaydar than heterosexual. Across two studies we examined auditory gaydar performed by LGB and heterosexual listeners. In Study 1 participants (n = 127) listened to male and female speakers (n = 10) and judged their sexual orientation on a binary choice (gay/lesbian vs. heterosexual). In Study 2, participants (n = 192) judged speakers’ (n = 31) sexual orientation on a Kinsey-like scale (1 = exclusively heterosexual, 7 = exclusively gay/lesbian). Results showed gaydar judgments differences in relative terms that did not indicate an overall gaydar accuracy. Moreover, LGB participants were not better at gaydar than heterosexual participants but rather showed a shift in criterion when making auditory gaydar judgments, namely they report a weaker straight categorization bias. Overall, these findings contribute to the understanding of sexual orientation categorization among heterosexual majority and LGB minority groups.info:eu-repo/semantics/publishedVersio

Early amniotomy after cervical ripening for induction of labor: a systematic review and meta-analysis of randomized controlled trials

OBJECTIVE DATA: Timing of artificial rupture of membranes (ie, amniotomy) in induction of labor is controversial, because it has been associated not only with shorter labors, but also with fetal nonreassuring testing, at times necessitating cesarean delivery. The aim of this systematic review and metaanalysis of randomized trials was to evaluate the effectiveness of early amniotomy vs late amniotomy or spontaneous rupture of membranes after cervical ripening. STUDY: The search was conducted with the use of electronic databases from inception of each database through February 2019. Review of articles included the abstracts of all references that were retrieved from the search. STUDY APPRAISAL AND SYNTHESIS METHODS: Selection criteria included randomized clinical trials that compared early amniotomy vs control (ie, late amniotomy or spontaneous rupture of membranes) after cervical ripening with either Foley catheter or prostaglandins at any dose. The primary outcome was the incidence of cesarean delivery. The summary measures were reported as summary relative risk with 95% of confidence interval with the use of the random effects model of DerSimonian and Laird. RESULTS: Four trials that included 1273 women who underwent cervical ripening with either Foley catheter or prostaglandins and then were assigned randomly to either early amniotomy, late amniotomy, or spontaneous rupture of membranes (control subjects) were included in the review. Women who were assigned randomly to early amniotomy had a similar risk of cesarean delivery (31.1% vs 30.9%; relative risk, 1.05; 95% confidence interval, 0.71-1.56) compared with control subjects and had a shorter interval from induction to delivery of approximately 5 hours (mean difference, -4.95 hours; 95% confidence interval, -8.12 to -1.78). Spontaneous vaginal delivery was also reduced in the early amniotomy group, but only 1 of the included trials reported this outcome (67.5% vs 69.1%; relative risk, 0.78; 95% confidence interval, 0.66-0.93). No between-group differences were reported in the other obstetrics or perinatal outcomes. CONCLUSION: After cervical ripening, routine early amniotomy does not increase the risk of cesarean delivery and reduces the interval from induction to delivery

Pessary versus cerclage versus expectant management for cervical dilation with visible membranes in the second trimester.

OBJECTIVE: We evaluated pessary for dilated cervix and exposed membranes for prolonging pregnancy compared to cerclage or expectant management. METHODS: Multicenter retrospective cohort study of women, 15-24 weeks, singleton pregnancies, dilated cervix ≥2 cm and exposed membranes. Women received pessary, cerclage or expectant management. Primary outcome was gestational age (GA) at delivery. Secondary outcomes were time until delivery, preterm premature rupture of membranes (PPROM) and neonatal survival. RESULTS: About 112 women met study criteria; 9 - pessary, 85 - cerclage and 18 - expectant management. Mean GA at delivery was 22.9 ± 4.5 weeks with pessary, 29.2 ± 7.5 weeks with cerclage and 25.6 ± 6.7 weeks with expectant management (p = 0.015). Time until delivery was 16.1 ± 18.9 days in the pessary group, 61.7 ± 48.2 days in the cerclage group and 26.8 ± 33.4 days in the expectant group (p \u3c 0.001). PPROM occurred less frequently and neonatal survival increased in women with cerclage. There was a significant difference in all the perinatal outcomes with cerclage compared with either pessary or expectant management. CONCLUSIONS: Perinatal outcomes with pessary were not superior to expectant management in women with dilated cervix with exposed membranes in the second trimester in this small retrospective cohort

Faf1 is expressed during neurodevelopment and is involved in Apaf1-dependent caspase-3 activation in proneural cell

Fas-associated factor 1 (Faf1) has been described as a Fas-binding pro-apoptotic protein and as a component of the death-inducing signaling complex (DISC) in Fas-mediated apoptosis. Faf1 is able to potentiate Fas-induced apoptosis in several cell lines, although its specific functions are still not clear. Here we show that Faf1 is highly expressed in several areas of the developing telencephalon. Its expression pattern appears to be dynamic at different embryonic stages and to be progressively confined within limited territories. To decipher the specific role of Faf1 in developing brain, we used cDNA over-expression and mRNA down-regulation experiments to modulate Faf1 expression in telencephalic neural precursor cells, and we showed that in neural cell death Faf1 acts as a Fas-independent apoptotic enhancer. Moreover, we found that Faf1 protein level is down-regulated during apoptosis in a caspase- and Apaf1-dependent manner

Fetal brain hemodynamics in pregnancies at term: correlation with gestational age, birthweight and clinical outcome

Introduction: The primary aim of this study was to ascertain the strength of association between cerebral blood flow assessed in anterior (ACA), middle (MCA), and posterior (PCA) cerebral arteries and the following clinical outcomes: small for gestational age (SGA), induction of labor (IOL) for oligohydramnios and caesarean section (CS) for nonreassuring fetal status (NRFS) during labor. Material and methods: Retrospective analysis of prospectively collected data on consecutive singleton pregnancies from 40 0/7 to 41 6/7 week of gestation. UA, ACA, MCA, PCA pulsatility index (PI) were measured from 40 weeks of gestations. Furthermore, the ratios between cerebral blood flow and UA (CPR, ACA/UA and PCA/UA) were calculated and correlated with the observed outcomes. Results: Two hundred twenty-four singleton pregnancies were included in the study. Mean PI of either ACA (p = .04), MCA (p = .008), and PCA (p = .003) were lower in the SGA compared to non-SGA group; furthermore, mean PCA PI was significantly lower than MCA PI (p = .04). Furthermore, CPR (p = .016), ACA/UA (p = .02), and PCA/UA (p = .003) were significantly lower in the SGA group compared to controls. UA, ACA, MCA, and PCA PI were higher in women undergoing IOL for oligohydramnios compared to controls. Logistic regression analysis showed that CPR and PCA/UA ratio were independently associated with SGA. SGA, ACA PI, and ACA/UA were independently associated with CS for NRFS. Finally, birthweight centile, were independently associated with IOL oligohydramnios. Despite this, the predictive accuracy of Doppler in detecting any of the explored outcome was only poor to moderate. Conclusion: Redistribution of cerebral blood flow at term is significantly associated with SGA, IOL for oligohydramnios and CS for NRFS in labor. However, the predictive accuracy of Doppler at term is only poor to moderate, thus advising against its use in clinical practice as a standalone screening test for adverse perinatal outcome in pregnancies at term. Key Message Redistribution of cerebral blood flow at term is significantly associated with SGA, IOL for oligohydramnios and CS for NRFS in labor