Effects of postnatal handling on adult behavior and brain mRNA expression of serotonin receptor, brain-derived neurotrophic factor and GABA-A receptor subunit

Development of brain and behavior is influenced by the interaction of genetic and environmental factors. Postnatal handling, a manipulation that briefly separates mouse offspring from their mother during the postnatal period, has been reported to yield beneficial effects on the behavior of adult offspring. However, brain mechanisms underlying the effects on the behavior have not been well understood. Here we first examined effects of postnatal handling on the behavior of adult male BALB/c mice. Offspring were separated for 15 min every day between postnatal day 1 (P1) and P14 and then various behaviors were tested in the adulthood. Postnatal handling reduced anxiety-like behavior in elevated plus maze and improved spatial learning and memory in Morris water maze without effects on depression-like behavior in forced swim test. Next, to elucidate mechanisms underlying the behavioral effects, we evaluated mRNA expression of the serotonin 1A (5-HT1A) receptor, brain-derived neurotrophic factor (BDNF), and GABA-A receptor subunits in the medial prefrontal cortex, amygdala, dorsal and ventral hippocampi, and dorsal raphe nucleus by quantitative RT-PCR, since these genes and brain regions have been shown to be involved in cognition and emotion. Postnatal handling up-regulated mRNA expression of the 5-HT1A receptor in the dorsal raphe nucleus and down-regulated 5-HT1A receptor mRNA expression in the amygdala on P15 and P71. In adulthood, mRNA expression of BDNF was up-regulated in the amygdala and dorsal hippocampus and down-regulated in the dorsal raphe nucleus, whereas that of GABA-A receptor α2 subunit was down-regulated in the amygdala. Taken together, the present study suggests that postnatal handling reduced anxiety-like behavior and improved learning and memory, which were accompanied by changes in mRNA expression of 5-HT1A receptor, BDNF and GABA-A receptor α2 subunit in the amygdala, 5-HT1A receptor in the dorsal raphe nucleus and BDNF in the dorsal hippocampus

Roles of 5-HT1A receptor in the expression of AMPA receptor and BDNF in developing mouse cortical neurons

The possible interactions between serotonergic and glutamatergic systems during neural development and under the pathogenesis of depression remain unclear. We now investigated roles of 5-HT1A receptor in the mRNA expression of AMPA receptor subunits (GluR1 and GluR2) and brain-derived neurotrophic factor (BDNF) using primary culture of cerebral cortex of mouse embryos. Neurons at embryonic day 18 were cultured for 3 days or 14 days and then treated with 5-HT1A receptor agonist (8-OH-DPAT) for 3 h or 24 h. In neurons cultured for 3 days, 8-OH-DPAT treatment for both 3 h and 24 h increased the mRNA levels of BDNF and GluR1, but not GluR2. In neurons cultured for 14 days, however, 8-OH-DPAT had no effects on these mRNA levels. Next, we examined in vivo roles of 5-HT1A receptor by administration of 8-OH-DPAT to newborn mice. Twenty-four hours after the oral administration of 8-OH-DPAT, the mRNA expression of BDNF was decreased in the frontal cortex, but had no effects on the mRNA expression of GluR1 and GluR2. Taken together, the present study suggests that 5-HT1A receptor activation modulates mRNA expression of AMPA receptor subunit and BDNF in cortical neurons, and the effects are different between in vitro and in vivo

Association between mitral annulus calcification and subtypes of heart failure rehospitalization

Background: Mitral annulus calcification (MAC) has been associated with cardiovascular diseases, including heart failure (HF); however, the associations between MAC and both the category and etiology of HF have not been fully elucidated. The aim of this study was to investigate the relationship between MAC and three types of HF rehospitalization: HF with preserved ejection fraction (HFpEF), HF with mid-range EF (HFmrEF), and HF with reduced EF (HFrEF). Methods: We enrolled consecutive patients undergoing echocardiography, who were admitted to our hospital for clinically indicated congestive HF between April 2014 and March 2018. Cox proportional-hazards models were used after adjusting for age, gender, and hypertension. Results: Of 353 patients, 40 (11.3%) had MAC. With a median follow-up of 2.8 years, 100 (28%) patients were rehospitalized for congestive HF (HFpEF 40%, HFmrEF 16%, HFrEF 44%, respectively). According to the Kaplan-Meier method, the estimated incidence of HFpEF rehospitalization in the MAC group was significantly greater than that in the non-MAC group (p < 0.001) whereas the incidences of HFmrEF and HFrEF rehospitalization were comparable between the groups (p = 0.101 and p = .291, respectively). In a multivariate analysis, MAC remained significantly associated with HFpEF rehospitalization (hazard ratio: 3.379; 95% confidence interval: 1.651–6.597). At initial HF hospitalization, E/e’ was significantly higher in the MAC group (both septum and lateral, p < 0.05), suggesting a possible relationship between MAC and left ventricular diastolic function. Conclusions: Mitral annulus calcification was associated with increased HFpEF rehospitalization and might be a cause of left ventricular diastolic dysfunction

Longitudinal acquisition of endotracheal intubation skills in novice physicians

Little is known about the acquisition of intubation skills among novice physicians during their one-year clinical training. Our primary objective was to determine the changes in the intubation skills of novice physicians between prior to the clinical training and after completion of the clinical training. We used data of a prospective longitudinal multicenter data registry developed to investigate factors associated with the improvement of intubation skills among novice physicians. The study participants included 90 postgraduate year 1 physicians in 2015–2016. We used 4 simulation scenarios based on the devices used (direct laryngoscope [DL] and Airway scope [AWS]) and difficulty of intubation (normal and difficult scenarios). As a marker of the intubation skills, we used the force applied on the maxillary incisors and the tongue with each intubation. We compared the data obtained prior to clinical training with those obtained after completion of one-year clinical training. When using DL, compared to prior, significantly less force were applied on the maxillary incisors and the tongue after clinical training in the normal scenario (28.0 N vs 19.5 N, p < 0.001, and 11.1 N vs 8.4 N, p = 0.004). Likewise, when using AWS, compared to prior, significantly less force were applied on the tongue after clinical training in the normal scenario (22.0 N vs 0 N, p < 0.001). The force on the tongue decreased after clinical training but not significant. These associations persisted in the difficult airway scenario. These findings suggest that force applied on oral structures can be quantified as a marker of intubation skills by using high-fidelity simulators, and the assessment of procedural competency is recommended for all novice physicians prior to performing intubation in the clinical setting to improve the quality of emergency care

Runx3-regulated expression of two Ntrk3 transcript variants in dorsal root ganglion neurons

Somatosensation is divided into proprioception and cutaneous sensation. Dorsal root ganglion (DRG) neurons project their fibers toward peripheral targets including muscles and skin, and centrally to the spinal cord. Proprioceptive DRG neurons transmit information from muscle spindles and Golgi tendon organs to the spinal cord. We previously showed that Runt‐related transcription factor 3 (Runx3) is expressed in these neurons and their projections to the ventral spinal cord and muscle spindles are lost in Runx3‐deficient (Runx3−/−) mouse embryos. Although Runx3 is likely to contribute to the fate decision and projection of proprioceptive DRG neurons, the precise roles for Runx3 in these phenomena are unknown. To identify genes regulated by Runx3 in embryonic DRGs, we performed microarray analyses using cDNAs isolated from wild‐type and Runx3−/− DRGs of embryonic day (E) 12.5 and selected two transcript variants of the tyrosine kinase receptor C (TrkC) gene. These variants, Ntrk3 variant 1 (Ntrk3‐v1) and variant 2 (Ntrk3‐v2), encode full‐length and truncated receptors of neurotrophin‐3, respectively. Using double in situ hybridization, we found that most of Ntrk3‐v1 mRNA expression in E14.5 DRGs depended on Runx3 but that more than half of Ntrk3‐v2 mRNA one were expressed in a Runx3‐independent manner. Furthermore, our data revealed that the rate of Ntrk3‐v1 and Ntrk3‐v2 colocalization in DRGs changed from E14.5 to E18.5. Together, our data suggest that Runx3 may play a crucial role in the development of DRGs by regulating the expression of Ntrk3 variants and that DRG neurons expressing Ntrk3‐v1 but not Ntrk3‐v2 may differentiate into proprioceptive ones. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 313–322, 201

Noise robust automatic charge state recognition in quantum dots by machine learning and pre-processing, and visual explanations of the model with Grad-CAM

Charge state recognition in quantum dot devices is important in preparation of quantum bits for quantum information processing. Towards auto-tuning of larger-scale quantum devices, automatic charge state recognition by machine learning has been demonstrated. In this work, we propose a simpler method using machine learning and pre-processing. We demonstrate the operation of the charge state recognition and evaluated an accuracy high as 96%. We also analyze the explainability of the trained machine learning model by gradient-weighted class activation mapping (Grad-CAM) which identifies class-discriminative regions for the predictions. It exhibits that the model predicts the state based on the change transition lines, indicating human-like recognition is realized.Comment: 15 pages, 6 figure