Electric shock causes a fleeing-like persistent behavioral response in the nematode Caenorhabditis elegans.

Behavioral persistency reflects internal brain states, which are the foundations of multiple brain functions. However, experimental paradigms enabling genetic analyses of behavioral persistency and its associated brain functions have been limited. Here, we report novel persistent behavioral responses caused by electric stimuli in the nematode Caenorhabditis elegans. When the animals on bacterial food are stimulated by alternating current, their movement speed suddenly increases 2- to 3-fold, persisting for more than 1 minute even after a 5-second stimulation. Genetic analyses reveal that voltage-gated channels in the neurons are required for the response, possibly as the sensors, and neuropeptide signaling regulates the duration of the persistent response. Additional behavioral analyses implicate that the animal's response to electric shock is scalable and has a negative valence. These properties, along with persistence, have been recently regarded as essential features of emotion, suggesting that C. elegans response to electric shock may reflect a form of emotion, akin to fear.

Robotic endoscope with double-balloon and double-bend tube for colonoscopy.

The insertion of conventional colonoscopes can sometimes cause patients to experience pain during the procedure owing to the stretching of the mesentery. In this study, a prototype of a robotic colonoscope with a double-balloon and double-bend tube based on the conventional double-balloon endoscope was developed to simplify insertion and prevent the overstretching of the colon. Both the outer and inner tubes were confirmed to be free from interference from wires and sheaths. Additionally, all functions such as tip bending, inflation and deflation of the balloons, and actuator-driven pulling and pushing of the inner tube were operated properly. During the insertion test, the device could be reached the cecum of a colon model in approximately 442 s when operated by a non-medical operator. In addition, the device did not overstretch the colon model, thereby suggesting that the insertion mechanism can follow the shape of the colon model. As a result, the developed mechanism has the potential to navigate through a highly-bent colon without overstretching.

Neural mechanism of experience-dependent sensory gain control in C. elegans.

Animals' sensory systems adjust their responsiveness to environmental stimuli that vary greatly in their intensity. Here we report the neural mechanism of experience-dependent sensory adjustment, especially gain control, in the ASH nociceptive neurons in Caenorhabditis elegans. Using calcium imaging under gradual changes in stimulus intensity, we find that the ASH neurons of naive animals respond to concentration increases in a repulsive odor 2-nonanone regardless of the magnitude of the concentration increase. However, after preexposure to the odor, the ASH neurons exhibit significantly weak responses to a small gradual increase in odor concentration while their responses to a large gradual increase remain strong. Thus, preexposure changes the slope of stimulus-response relationships (i.e., gain control). Behavioral analysis suggests that this gain control contributes to the preexposure-dependent enhancement of odor avoidance behavior. Mathematical analysis reveals that the ASH response consists of fast and slow components, and that the fast component is specifically suppressed by preexposure for the gain control. In addition, genetic analysis suggests that G protein signaling may be required for the regulation of fast component. We propose how prior experience dynamically and specifically modulates stimulus-response relationships in sensory neurons, eventually leading to adaptive modulation of behavior.

Cis-Selective Double Spirocyclization via Dearomatization and Isomerization under Thermodynamic Control.

Spiro compounds have been considered key scaffolds for pharmaceutical applications. Although many synthetic methods exist for monospirocycles, fewer approaches are known for dispirocycles. Here, we report a highly cis-selective method for constructing a 5/6/5-dispirocyclic structure containing pyrrolidine and γ-lactam rings with various substituents from a series of N-arylpropiolamides. The high cis-selectivity would result from isomerization under thermodynamic control. Cis- and trans-diastereomers can be in equilibrium, favoring cis-adducts.

Activating Nitrogen-doped Graphene Oxygen Reduction Electrocatalysts in Acidic Electrolytes using Hydrophobic Cavities and Proton-conductive Particles.

Although pyridinic-nitrogen (pyri-N) doped graphene is highly active for the oxygen reduction reaction (ORR) of fuel cells in alkaline media, the activity critically decreases under acidic conditions. We report on how to prevent the deactivation based on the mechanistic understanding that O 2 + p y r i - N H + + e - → O 2 , a + p y r i - N H ${{{\rm O}}_{2}+{\rm p}{\rm y}{\rm r}{\rm i}{\rm { -}}{\rm N}{{\rm H}}^{+}+{{\rm e}}^{-}{\to }_{\ }^{{\rm \ }}{{\rm O}}_{2,{\rm a}}+{\rm p}{\rm y}{\rm r}{\rm i}{\rm { -}}{\rm N}{\rm H}}$ governs the ORR kinetics. First, we considered that the deactivation is due to the hydration of pyri-NH+ , leading to a lower shift of the redox potential. Introducing the hydrophobic cavity prevented the hydration of pyri-NH+ but inhibited the proton transport. We then increased proton conductivity in the hydrophobic cavity by introducing SiO2 particles coated with ionic liquid polymer/Nafion® which kept the high onset potentials with an increased current density even in acidic media.

Predicting the complexity of head-and-neck volumetric-modulated arc therapy planning using a radiation therapy planning quality assurance software.

Background/Aim: The more complex the treatment plan, the higher the possibility of errors in dose verification. Recently, a treatment planning quality assurance (QA) software (PlanIQ) with a function to objectively evaluate the quality of volumetric-modulated arc therapy (VMAT) treatment plans by scoring and calculating the ideal dose-volume histogram has been marketed. This study aimed to assess the association between the scores of ideal treatment plans identified using PlanIQ and the results of dose verification and to investigate whether the results of dose verification can be predicted based on the complexity of treatment plans. Materials and methods: Dose verification was performed using an ionization chamber dosimeter, a radiochromic film, and a three-dimensional dose verification system, Delta4 PT. Correlations between the ideal treatment plan scores obtained by PlanIQ and the results of the absolute dose verification and dose distribution verification were obtained, and it was examined whether dose verifications could be predicted from the complexity of the treatment plans. Results: Even when the score from the ideal treatment plan was high, the results of absolute dose verification and dose distribution verification were sometimes poor. However, even when the score from the ideal treatment plan was low, the absolute volume verification and dose distribution verification sometimes yielded good results. Conclusions: Treatment plan complexity can be determined in advance from the ideal treatment plan score calculated by PlanIQ. However, it is difficult to predict the results of dose verification using an ideal treatment plan.

[Two cases of chronic upside down stomach with "reverse incarceration" in the abdominal cavity].

Upside down stomach (UDS) is a rare type of hiatal hernia. It is categorized by herniation of either the entire stomach or most of the gastric portion of the stomach into the posterior mediastinum. Acute UDS usually presents with abdominal and thoracic symptoms immediately after the stomach rotates, while chronic UDS often has either mild or no symptoms with the entire stomach rotated in the mediastinum. The first case was a 70-year-old female who was admitted with complaints of sudden vomiting and epigastric pain after eating. Computed tomography (CT) revealed UDS. Almost the entire stomach was twisted in the mediastinum, but the fornix was located in the abdominal cavity. After endoscopic reduction, the entire stomach was located in the mediastinum. Her symptoms disappeared and she was able to eat. The second case was another 70-year-old female with multiple hospitalizations due to frequent vomiting after eating. A review of previous CT scans showed a typical chronic UDS with the entire stomach located in the mediastinum. During her most current hospitalization, she was admitted with complaints of frequent vomiting and chest pain after overeating, and a CT showed UDS with only the fornix located in the abdominal cavity. Following hospitalization, the persistent vomiting disappeared and a CT scan at that point revealed that the fornix had returned to the mediastinum and she now had a normal UDS. These results indicate that chronic UDS caused acute symptoms due to "reverse incarceration" in the abdominal cavity through the diaphragmatic hiatus following eating. Chronic UDS is often either asymptomatic or only mildly symptomatic. However, these cases suggest that there is a mechanism whereby chronic UDS may cause acute UDS-like symptoms when the fornix becomes "reversely incarcerated" in the abdominal cavity following eating.

Over 1000 nm Near-Infrared Multispectral Imaging System for Laparoscopic In Vivo Imaging.

In this study, a laparoscopic imaging device and a light source able to select wavelengths by bandpass filters were developed to perform multispectral imaging (MSI) using over 1000 nm near-infrared (OTN-NIR) on regions under a laparoscope. Subsequently, MSI (wavelengths: 1000-1400 nm) was performed using the built device on nine live mice before and after tumor implantation. The normal and tumor pixels captured within the mice were used as teaching data sets, and the tumor-implanted mice data were classified using a neural network applied following a leave-one-out cross-validation procedure. The system provided a specificity of 89.5%, a sensitivity of 53.5%, and an accuracy of 87.8% for subcutaneous tumor discrimination. Aggregated true-positive (TP) pixels were confirmed in all tumor-implanted mice, which indicated that the laparoscopic OTN-NIR MSI could potentially be applied in vivo for classifying target lesions such as cancer in deep tissues.

Analysis of prostate intensity- and volumetric-modulated arc radiation therapy planning quality with PlanIQTM.

PURPOSE: The purpose of this study was to assess the quality of treatment planning using the PlanIQTM software and to investigate whether it is possible to improve the quality of treatment planning using the "Feasibility dose-volume histogram (DVH)TM " implemented in the PlanIQTM software. METHODS: Using the PlanIQTM software, we retrospectively analyzed the learning curve regarding the quality of the treatment plans for 148 patients of prostate intensity-modulated radiation therapy and volumetric-modulated radiation therapy performed at our institution over the past eight years. We also sought to examine the possibility of improving treatment planning quality by re-planning in 47 patients where the quality of the target dose and the dose limits for organs at risk (OARs) were inadequate. The re-planning treatment plans referred to the Feasibility DVHTM implemented in the PlanIQTM software and modified the treatment planning system based on the target dose and OAR constraints. RESULTS: Analysis of the learning curve of the treatment plans quality using PlanIQTM software retrospectively showed a trend of improvement in the treatment plan quality from year to year. The improvement in the treatment plans quality was more influenced by dose reduction in the OARs than by target coverage. In all cases where re-planning was performed, the improvement in the treatment plan's quality resulted in a better treatment plan than the one adopted for delivery to patients in the clinical plan. CONCLUSIONS: The PlanIQTM provided insights into the quality of the treatment plans at our institution and identified problems and areas for improvement in the treatment plans, allowing for the development of appropriate treatment plans for specific patients.

Rapid Access to Dispirocyclic Scaffolds Enabled by Diastereoselective Intramolecular Double Functionalization of Benzene Rings.

Here we describe the diastereoselective synthesis of (5r,8r)-1,9-diazadispiro[4.2.48 .25 ]tetradecatrienes via domino double spirocyclization of N-arylamide derivatives. This reaction can serve as a fast way to synthesize diazadispirocycles, which are found in the core structures of bioactive natural products. Product diversification via Suzuki-Miyaura cross coupling and application to the synthesis of 1-oxa-9-azadispiro[4.2.48 .25 ]tetradecatrienes were also conducted.