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12 microRNA expression profiling platforms are compared for their reproducibility, sensitivity, accuracy and specificity, and the strengths and weaknesses of each platform are discussed. MicroRNAs are important negative regulators of protein-coding gene expression and have been studied intensively over the past years. Several measurement platforms have been developed to determine relative miRNA abundance in biological samples using different technologies such as small RNA sequencing, reverse transcription–quantitative PCR (RT-qPCR) and (microarray) hybridization. In this study, we systematically compared 12 commercially available platforms for analysis of microRNA expression. We measured an identical set of 20 standardized positive and negative control samples, including human universal reference RNA, human brain RNA and titrations thereof, human serum samples and synthetic spikes from microRNA family members with varying homology. We developed robust quality metrics to objectively assess platform performance in terms of reproducibility, sensitivity, accuracy, specificity and concordance of differential expression. The results indicate that each method has its strengths and weaknesses, which help to guide informed selection of a quantitative microRNA gene expression platform for particular study goals.

Recent progress in the understanding of neurodegenerative diseases revealed that multiple molecular mechanisms contribute to pathological changes in neurons. A large fraction of these alterations can be linked to dysfunction in the endoplasmic reticulum (ER) and mitochondria, affecting metabolism and secretion of lipids and proteins, calcium homeostasis, and energy production. Remarkably, these organelles are interacting with each other at specialized domains on the ER called mitochondria-associated membranes (MAMs). These membrane structures rely on the interaction of several complexes of proteins localized either at the mitochondria or at the ER interface and serve as an exchange platform of calcium, metabolites, and lipids, which are critical for the function of both organelles. In addition, recent evidence indicates that MAMs also play a role in the control of mitochondria dynamics and autophagy. MAMs thus start to emerge as a key element connecting many changes observed in neurodegenerative diseases. This review will focus on the role of MAMs in amyotrophic lateral sclerosis (ALS) and hereditary motor and sensory neuropathy, two neurodegenerative diseases particularly affecting neurons with long projecting axons. We will discuss how defects in MAM signaling may impair neuronal calcium homeostasis, mitochondrial dynamics, ER function, and autophagy, leading eventually to axonal degeneration. The possible impact of MAM dysfunction in glial cells, which may affect the capacity to support neurons and/or axons, will also be described. Finally, the possible role of MAMs as an interesting target for development of therapeutic interventions aiming at delaying or preventing neurodegeneration will be highlighted.

Birthweight is an important predictor of newborn health and has been linked to maternal psychological stress during pregnancy. However, it is unclear whether prenatal stress affects birthweight similarly for both male and female infants. We used a well-established pregnancy cohort to investigate the impact of high maternal psychological stress during pregnancy on birthweight as a function of infant sex. Overall, 5702 mother-newborn pairs were analysed. Of these, 198 mothers reported high levels of stress using the Psychological Stress Measure (nine-items version; PSM-9). Maternal psychological stress was assessed between the 24 th and 28 th week of gestation and analyses were performed jointly and independently as a function of neonatal sex (separate analyses for male and female infants). Newborns exposed to high maternal psychological stress during pregnancy (a score above 26 measured using the PSM-9 questionnaire, corresponding to >97.5 th percentile) were compared to newborns of mothers who reported lower stress. ANCOVAs revealed that high levels of maternal stress during pregnancy were linked to infant birthweight as a function of infant sex. Male infants of mothers who reported high levels of stress had a greater birthweight whereas female infants had a lower birthweight under the same conditions, in comparison to mothers who did not report greater levels of stress. Although the effect size is small, these results underline the possibility that male and female fetuses may use different strategies when adapting to maternal adversity and highlight the need to consider infant sex as a moderator of the association between maternal psychological stress during pregnancy and infant birthweight.

Mutations in the MFN2 gene encoding Mitofusin 2 lead to the development of Charcot–Marie–Tooth type 2A (CMT2A), a dominant axonal form of peripheral neuropathy. Mitofusin 2 is localized at both the outer membrane of mitochondria and the endoplasmic reticulum and is particularly enriched at specialized contact regions known as mitochondria-associated membranes (MAM). We observed that expression of MFN2R94Q induces distal axonal degeneration in the absence of overt neuronal death. The presence of mutant protein leads to reduction in endoplasmic reticulum and mitochondria contacts in CMT2A patient-derived fibroblasts, in primary neurons and in vivo, in motoneurons of a mouse model of CMT2A. These changes are concomitant with endoplasmic reticulum stress, calcium handling defects, and changes in the geometry and axonal transport of mitochondria. Importantly, pharmacological treatments reinforcing endoplasmic reticulum–mitochondria cross-talk, or reducing endoplasmic reticulum stress, restore the mitochondria morphology and prevent axonal degeneration. These results highlight defects in MAM as a cellular mechanism contributing to CMT2A pathology mediated by mutated MFN2.

Background We investigated the association between antidepressant and anxiolytic exposure during the first and early second trimester of pregnancy (< 16 weeks), and hypertensive disorders of pregnancy (including preeclampsia and gestational hypertension) in women with singleton pregnancy. Methods This study is based on a large prospective cohort of 7866 pregnant women. We included pregnant women aged 18 years or older without chronic hepatic or renal disease at the time of recruitment. Participants lost to the follow-up, with multiple pregnancies and pregnancy terminations, miscarriages or fetal deaths before 20 weeks of gestation were excluded from the study, as well as women with no data on the antidepressant/anxiolytic medication use during pregnancy. Information concerning antidepressant or anxiolytic medication use was extracted from hospital records after delivery. The associations between their use and the risk of gestational hypertension or preeclampsia were calculated. Results The final sample for analysis included 6761 participants including 218 (3.2%) women who were exposed to antidepressant and/or anxiolytic medication before the 16th week of gestation. Forty-one women had a non-medicated depression or anxiety during the pregnancy. Moreover, 195 (2.9%) and 122 (1.8%) women developed gestational hypertension and preeclampsia respectively. When compared to women unexposed to antidepressant/anxiolytic medication, depression and anxiety, those using antidepressant and/or anxiolytic drugs before the 16th week of gestation were at increased risk of preeclampsia (adjusted odd ratio (aOR) 3.09 [CI 95% 1.56–6.12]), especially if they continued their medication after the 16th week (aOR 3.41 [CI 95% 1.66–7.02]) compared to those who did not (1.60 [CI 95% 0.21–12.34]). Conclusions Women exposed to antidepressant and/or anxiolytic medication before the 16th week of pregnancy have a 3-fold increased risk for preeclampsia when compared to women unexposed to antidepressant/anxiolytic medication, depression and anxiety. Also, our results suggested that women who stopped their medication before the 16th week of pregnancy could be benefit from reduced preeclampsia risk.

Agomelatine is a novel antidepressant acting as a melatonergic receptor agonist and serotonergic (5-HT 2C ) receptor antagonist. In adult rats, chronic agomelatine treatment enhanced cell proliferation and neurogenesis in the ventral hippocampus (VH), a region pertinent to mood disorders. This study compared the effects of agomelatine on cell proliferation, maturation, and survival and investigated the cellular mechanisms underlying these effects. Agomelatine increased the ratio of mature vs immature neurons and enhanced neurite outgrowth of granular cells, suggesting an acceleration of maturation. The influence of agomelatine on maturation and survival was accompanied by a selective increase in the levels of BDNF (brain-derived neurotrophic factor) vs those of VEGF (vascular endothelial factor) and IGF-1 (insulin-like growth factor 1), which were not affected. Agomelatine also activated several cellular signals (extracellular signal-regulated kinase1/2, protein kinase B, and glycogen synthase kinase 3 β ) known to be modulated by antidepressants and implicated in the control of proliferation/survival. Furthermore, as agomelatine possesses both melatonergic agonist and serotonergic (5-HT 2C ) antagonist properties, we determined whether melatonin and 5-HT 2C receptor antagonists similarly influence cell proliferation and survival. Only the 5-HT 2C receptor antagonists, SB243,213 or S32006, but not melatonin, mimicked the effects of agomelatine on cell proliferation in VH. The promoting effect of agomelatine on survival was not reproduced by the 5-HT 2C receptor antagonists or melatonin alone. However, it was blocked by a melatonin antagonist, S22153. These results show that agomelatine treatment facilitates all stages of neurogenesis and suggest that a joint effect of melatonin agonism and 5HT 2C antagonism may be involved in promotion by agomelatine of survival in the hippocampus.

After surgery, patients reported the delay in receiving help as the primary factor for poorly controlled pain. This study aimed to compare the effectiveness of patient management through two communication modalities: remote transmission (RT) versus bedside control (BC). We hypothesized that using remote technology for pump programming may provide the best postoperative infusion regimen for the patient's self-assessment of pain and adverse events. A multicenter, randomized, parallel-group, controlled trial. Anesthesiology department and orthopedic surgery ward at three university hospitals. Eighty patients undergoing orthopedic surgery with postoperative perineural patient-controlled analgesia were included. Two groups (n = 40 for each group) were formed by randomization. In the postoperative period, perineural analgesia was followed up via an RT system or BC for 72 h. A nurse assessed daily pain, sensory and motor blocks and adverse events. Patients completed a questionnaire three times a day and alerted for any problem according to the group (RT system or nurses' follow-up). On the third postoperative day, the nurse removed the catheter, completed the final assessment, and collected the historical data from the pump. A physician's shorter response time to change the patient control analgesia (PCA) program was the primary endpoint. Of the 80 patients, 71 were analyzed (34 were randomized to the RT group and 37 to the BC group). Fifty-eight pump setting changes were noted. Analysis of repeated evaluations shows that mean time (SD) to change the PCA pump settings was significantly lower in the RT group (20 min (22.3 min)) than in the BC group (55.9 min (71.1 min)); mean difference [95% CI], −35.9 min [−74.3 to 2.4]); β estimation [95% CI], −34 [−63 to −6], p = 0.011). Pain relief, sensory and motor blocks did not differ between the groups: β estimation [95% CI], 0.1 [−0.4 to 0.6], p = 0.753; 0.5 [−0.4 to 1.4], p = 0.255; 0.9 [−0.04 to 1.8], p = 0.687, respectively. β = −34 [−63 to −6], p = 0.011). The consumption of ropivacaine, nurse workload and the cost of the analgesia regimen decreased in the RT group. No differences were noted in satisfaction scores or complication rates. The response time for the physician to change the PCA program when necessary was shorter for patients using RT and alerts to the physician were more frequent compared with spot checks by nurses. RT helps to decrease nurses' workload, ropivacaine consumption, and costs but did not affect postoperative pain relief, complication rate, or patient-reported satisfaction score. Comité de Protection des Personnes, Sud Méditerranée III, Montpellier-Nîmes, France, registration number EudraCT A01698-35. ClinicalTrials.gov ID:NCT02018068 The full trial protocol can be accessed at Department of Anesthesiology and Critical Care Medicine, Medical Research and Statistics Unit, Lapeyronie University Hospital, Avenue Doten G Giraud, Montpellier, France. s-bringuierbranchereau@chu-montpellier.fr •Forty percent of patients experienced moderate to severe pain after orthopedic surgery.•Patients reported the delay in receiving help for pain relief improvement as the primary factor for poorly controlled pain.•RT for perineural analgesia may provide the best infusion regimen for patient self-assessment of pain.•RT decreased the time to change pump programs.•RT allowed the patients to self-report adverse events more easily compared to bedside care.•RT helped to decrease nurse workload , ropivacaine consumption and costs.