Search

Arsenic (As) and heavy metals (Cd, Hg, Pb, and Cu) and pesticide residues in 14 edible insects were investigated. The maximum levels of elements were 6.15 for As, 0.82 for Cd, 0.50 for Hg, 0.67 for Pb, and 297.7 ppm for Cu. Fenobucarb (or BPMC) has been quantified through GC- and LC-MS/MS analysis at a concentration of approximately 3 ppm. Further studies of the contaminants may help ensure the safety of edible insect consumption.

The authors conducted droplet evaporation experiments of light cycle oil (LCO) at various ambient temperatures and pressures. Five kinds of LCO and three kinds of arranged fuels were used. We investigated the evaporation characteristics of LCO and the relationships between the evaporation characteristics and the cetane index. In addition to that, a surrogate fuel composed of four chemical species, which can simulate the droplet evaporation characteristics of LCO, was suggested. Experimental results show that the differences in droplet lifetime between fuel species become larger with decreasing ambient temperature. This is because the low volatile component made the evaporation rate outstandingly slow at a low ambient temperature. It was found that the relationship between droplet lifetime and the late-stage distillation temperature becomes stronger at low ambient temperature and high ambient pressure. By an analysis employing the properties of chemical species in LCO surrogate fuel, it is clarified that the mass evaporation rate becomes smaller than the internal diffusion, which is the condition similar to that in the distillation test. Finally, the relationship between the droplet lifetime and the cetane index was investigated. It can be concluded that the droplet lifetime is independent of the cetane index under all conditions tested in this study. The experimental data obtained by this research can be utilized for the validation of multicomponent fuel droplet evaporation models in the future.

Daikenchuto (DKT) is one of the most widely used “Kampo” in Japan as a representative of herbal medicine. Because DKT is made from a natural product like food, it requires the management of pesticides; therefore, an analysis of residual pesticides in Kampo is required. The World Health Organization (WHO) indicates that pesticide residue analysis by the U.S. Pharmacopeia (USP) is required. USP defines 107 compounds containing organochlorine pesticides and organophosphorus pesticides and their metabolites, which have a high residual risk. Accordingly, to guarantee the safety of herbal medicines according to global standards is a very important issue. In this study, we developed an analytical method for 91 compounds, which are listed in USP, using DKT as the subject. The method could extract pesticides from DKT with acetone, elute pesticides with acetonitrile using a SepPak C18 column (5 g) and with ethyl acetate using a DSC-NH2 column (2 g), and perform simultaneous analyses by gas chromatography–tandem mass spectrometry (GC–MS/MS). This method, which could quantify 88 compounds, was validated according to USP. A pesticide residue analysis method that meets USP requirements enables the analysis of pesticide residues with a high residue risk and contributes to improving the safety of “Kampo” and other herbal medicines.

Background Glyphosate and its salt formulations are nonselective herbicides that have been extensively used worldwide, both for residential and agricultural purposes. The possible carcinogenicity and teratogenicity of glyphosate remain to be elucidated. We developed a sensitive and high-throughput analytical method for urinary glyphosate using liquid chromatography-tandem mass spectrometry with the aim of contributing to glyphosate exposure assessment in epidemiological studies. Methods After urine dilution (creatinine matching dilution to 0.05 g creatinine/L), glyphosate was extracted using two types of solid phase extraction columns (SCX and NH2) with automated sample preparation instruments. The eluate was dried and dissolved in the mobile phase, followed by liquid chromatography-tandem mass spectrometry analysis. The optimized method was applied to urine samples obtained from 54 Japanese adults and children. Results The results from the validation study demonstrated good recoveries (91.0-99.6%), within- and between-run precisions (< 15%), low detection limits (0.1 μg/L), and lower limit of quantification (0.3 μg/L). The detection frequency and median concentration of the urinary glyphosate in Japanese subjects were 59% and 0.25 μg/L (0.34 μg/g creatinine). Conclusions Our reliable determination method was successful in measuring urinary glyphosate concentration. Moreover, this is the first biomonitoring report of urinary glyphosate levels in the Japanese general population.

The comorbidity of chronic pain and mental dysfunctions such as depression and anxiety disorders has long been recognized, but the underlying mechanisms remain poorly understood. Here, using a mouse model of neuropathic pain, we demonstrated neuronal plasticity in the bed nucleus of the stria terminalis (BNST), which plays a critical role in chronic pain–induced maladaptive anxiety. Electrophysiology demonstrated that chronic pain increased inhibitory inputs to lateral hypothalamus (LH)–projecting BNST neurons. Chemogenetic manipulation revealed that sustained suppression of LH-projecting BNST neurons played a crucial role in chronic pain–induced anxiety. Furthermore, using a molecular genetic approach, we demonstrated that chronic pain elevated the excitability of a specific subpopulation of BNST neurons, which express cocaine- and amphetamine-regulated transcript (CART). The elevated excitability of CART-positive neurons caused the increased inhibitory inputs to LH-projecting BNST neurons, thereby inducing anxiety-like behavior. These findings shed light on how chronic pain induces psychiatric disorders, characterized by maladaptive anxiety.

Over the past two decades, domestic shipments of glyphosate (Gly), in the form of an ionic salt, have been increasing steadily in Japan. This increase has raising concerns about the effects of chemical exposure on children. The International Agency for Research on Cancer classified Gly as a "probably carcinogenic to humans (Group 2A)" in 2015. The purpose of the current study was to analyze Gly in urine samples of Japanese children to determine temporal changes, seasonal changes, and gender differences.First-morning urine samples were obtained from 50 Japanese children (4-6-year-old) in October of 2006, 2011, and 2015 (total = 150) to investigate the temporal trends in urinary Gly concentrations. Additionally, first-morning urine samples were collected from 3-year-old children in August-September of 2012 (summer; n = 42) and in February of 2013 (winter; n = 42) to investigate the seasonal and gender differences, and the correlations between urinary Gly concentrations and insecticide exposure biomarkers. Urine samples were analyzed to measure for Gly using a liquid chromatography with tandem mass spectrometry (LC-MS/MS).Detectable Gly concentrations were found in 41% of the 234 children. The 75th percentile and maximum concentrations of urinary Gly were 0.20 and 1.33 μg/L, respectively. The urinary Gly concentration in 2015 was significantly higher than in 2006, suggesting that the Gly exposure levels have been increasing. No seasonal or gender-specific differences in urinary Gly concentrations were observed, and no correlation with insecticide exposure biomarkers was found.This study revealed that Gly exposure trends show an increase between 2006 and 2015, and that season and gender were not the exposure-determining factors. Overall, urinary concentrations of Gly were comparable with studies from other countries.

Although dysfunction of the mesolimbic dopaminergic system has been implicated in chronic pain, the underlying mechanisms remain to be elucidated. We hypothesized that increased inhibitory inputs to the neuronal pathway from the dorsolateral bed nucleus of the stria terminalis (dlBNST) to the ventral tegmental area (VTA) during chronic pain may induce tonic suppression of the mesolimbic dopaminergic system. To test this hypothesis, male Sprague Dawley rats were subjected to spinal nerve ligation to induce neuropathic pain and then spontaneous IPSCs (sIPSCs) were measured in this neuronal pathway. Whole-cell patch-clamp electrophysiology of brain slices containing the dlBNST revealed that the frequency of sIPSCs significantly increased in VTA-projecting dlBNST neurons 4 weeks after surgery. Next, the role of corticotropin-releasing factor (CRF) signaling within the dlBNST in the increased sIPSCs was examined. CRF increased the frequency of sIPSCs in VTA-projecting dlBNST neurons in sham-operated controls, but not in chronic pain rats. By contrast, NBI27914, a CRF type 1 receptor antagonist, decreased the frequency of sIPSCs in VTA-projecting dlBNST neurons in the chronic pain rats, but not in the control animals. In addition, histological analyses revealed the increased expression of CRF mRNA in the dlBNST. Finally, bilateral injections of NBI27914 into the dlBNST of chronic pain rats activated mesolimbic dopaminergic neurons and induced conditioned place preference. Together, these results suggest that the mesolimbic dopaminergic system is tonically suppressed during chronic pain by enhanced CRF signaling within the dlBNST via increased inhibitory inputs to VTA-projecting dlBNST neurons.SIGNIFICANCE STATEMENTThe comorbidity of chronic pain and depression has long been recognized. Although dysfunction of the mesolimbic dopaminergic system has been implicated in both chronic pain and depression, the underlying mechanisms remain to be elucidated. Here, we show that the inhibitory inputs to the neuronal pathway from the dorsolateral bed nucleus of the stria terminalis (dlBNST) to the ventral tegmental area increase during chronic pain. This neuroplastic change is mediated by enhanced corticotropin-releasing factor signaling within the dlBNST that leads to tonic suppression of the mesolimbic dopaminergic system, which may be involved in the depressive mood and anhedonia under the chronic pain condition.

Background A method that promotes the retrieval of lost long-term memories has not been well established. Histamine in the central nervous system is implicated in learning and memory, and treatment with antihistamines impairs learning and memory. Because histamine H3 receptor inverse agonists upregulate histamine release, the inverse agonists may enhance learning and memory. However, whether the inverse agonists promote the retrieval of forgotten long-term memory has not yet been determined. Methods Here, we employed multidisciplinary methods, including mouse behavior, calcium imaging, and chemogenetic manipulation, to examine whether and how the histamine H3 receptor inverse agonists, thioperamide and betahistine, promote the retrieval of a forgotten long-term object memory in mice. In addition, we conducted a randomized double-blind, placebo-controlled crossover trial in healthy adult participants to investigate whether betahistine treatment promotes memory retrieval in humans. Results The treatment of H3 receptor inverse agonists induced the recall of forgotten memories even 1 week and 1 month after training in mice. The memory recovery was mediated by the disinhibition of histamine release in the perirhinal cortex, which activated the histamine H2 receptor. Histamine depolarized perirhinal cortex neurons, enhanced their spontaneous activity, and facilitated the reactivation of behaviorally activated neuronal ensembles. A human clinical trial revealed that treatment of H3 receptor inverse agonists is specifically more effective for items that are more difficult to remember and subjects with poorer performance. Conclusions These results highlight a novel interaction between the central histamine signaling and memory engrams.

BACKGROUND: The authors sought to quantify the results of clinical and radiological analyses of extreme lateral interbody fusion (XLIF) plus percutaneous pedicle screw (PPS) fixation for patients with lumbar spinal stenosis (LSS) by focusing on the distinct mechanism of indirect decompression. METHODS: Data obtained from a total of 37 patients with 47 surgical sites were retrospectively analyzed. Clinical outcomes for all patients were evaluated using the Japanese Orthopaedic Association (JOA) score and the improvement rate of the JOA score. Preoperative and postoperative magnetic resonance images were used to measure the transverse areas of both the dural sac (DS area) and ligamentous flavum (LF area) in the axial sections and the length of the intervertebral disc bulge (DB length) in sagittal sections. Then, the rate of change (RC) of the DS area (RC-DS), the RC of the LF area (RC-LF), and the RC of the DB length (RC-DB) from the preoperative period to the postoperative period were calculated. Furthermore, we divided all surgical sites into the small expansion group (SE group; RC-DS

Information from direct experience and observation of others is integrated in the brain to enable appropriate responses to environmental stimuli. Fear memory can be acquired by observing a conspecific’s distress. However, it remains unclear how prior fear observation affects self-experienced fear learning. In this study, we tested whether prior observation of a conspecific receiving contextual fear conditioning affects subsequent self-experienced fear conditioning and how neuronal ensembles represent the integration of the observation and self-experience. Test mice observed demonstrator mice experiencing fear conditioning on day 1 and directly experienced fear conditioning on day 2. Contextual fear memory was tested on day 3. The prior observation of fear conditioning promoted subsequent self-experienced fear conditioning in a hippocampus-dependent manner. We visualized hippocampal neurons that were activated during the observation and self-experience of fear conditioning and found that self-experienced fear conditioning preferentially activated dorsal CA1 neurons that were activated during the observation. When mice observed and directly experienced fear conditioning in different contexts, preferential reactivation was not observed in the CA1, and fear memory was not enhanced. These findings indicate that dorsal CA1 neuronal ensembles that were activated during both the observation and self-experience of fear learning are implicated in the integration of observation and self-experience for strengthening fear memory.

In pharmacological studies conducted on animals over the last four decades, histamine was determined to be a strong modulator of learning and memory. Activation of histamine signaling enhances memory consolidation and retrieval. Even long after learning and forgetting, it can still restore the retrieval of forgotten memories. These findings based on animal studies led to human clinical trials with histamine H3 receptor antagonists/inverse agonists, which revealed their positive effects on learning and memory. Therefore, histamine signaling is a promising therapeutic target for improving cognitive impairments in patients with various neuropsychiatric disorders, including Alzheimer’s disease. While the memory-modulatory effects of histamine receptor agonists and antagonists have been confirmed by several research groups, the underlying mechanisms remain to be elucidated. This review summarizes how the activation and inhibition of histamine signaling influence memory processes, introduces the cellular and circuit mechanisms, and discusses the relationship between the human histaminergic system and learning and memory.

We recently showed that the mesolimbic dopaminergic system was tonically suppressed during chronic pain by enhanced corticotropin releasing factor (CRF) signaling within the dorsolateral bed nucleus of the stria terminalis (dlBNST), and that inhibition of intra-dlBNST CRF signaling restored the mesolimbic dopaminergic system function. Specifically, bilateral intra-dlBNST injections of the CRF type 1 receptor antagonist NBI27914 increased intra-nucleus accumbens dopamine release and induced reward-related behaviors in rats with chronic pain. Here, we used a conditioned place preference (CPP) test to explore whether intra-dlBNST injections of neuropeptide Y (NPY) restored the mesolimbic reward system function in chronic pain rats, because we previously showed that NPY had an effect opposite to that of CRF in dlBNST neurons. Specifically, CRF depolarized type II dlBNST neurons whereas NPY hyperpolarized them. However, unexpectedly, intra-dlBNST NPY injections had no effect on CPP test outcomes. Then, we compared the effects of NPY on the membrane potentials of type II dlBNST neurons of sham-operated control rats and those of chronic pain animals. Whole-cell patch-clamp electrophysiology revealed that NPY hyperpolarized type II dlBNST neurons in the sham-operated group. By contrast, in the chronic pain group, NPY did not hyperpolarize, but rather depolarized, type II dlBNST neurons. These results indicate that NPY no longer hyperpolarizes type II dlBNST neurons in rats with chronic pain, therefore it does not reverse the excitatory effects of CRF. This may be why intra-dlBNST injections of NPY into chronic pain rats did not exhibit a rewarding effect in the CPP test, whereas intra-dlBNST injections of NBI27914 did. This is the first study to demonstrate a chronic pain-induced neuroplastic change in NPY signaling in the dlBNST. Such a change may be involved in the dysfunction of the mesolimbic reward system under the chronic pain condition.

Motivational states are complex and consist of cognitive, emotional, and physiological components controlled by a network across multiple brain regions. An integral component of this neural circuitry is the bed nucleus of the stria terminalis (BNST). Here, we identified a subpopulation of neurons within BNST expressing the gene prepronociceptin (PnocBNST), that can modulate the rapid changes in physiological arousal that occur upon exposure to stimuli with motivational salience. Using in vivo two-photon calcium imaging we found that excitatory responses from individual PnocBNST neurons directly corresponded with rapid increases in pupillary size and occurred upon exposure to both aversive and rewarding odors. Furthermore, optogenetic activation of these neurons increased pupillary size, but did not alter approach/avoidance or locomotor behaviors. These findings suggest that excitatory responses in PnocBNST neurons encode rapid arousal responses irrespective of tested behaviors. Further histological, electrophysiological, and single-cell RNA sequencing data revealed that PnocBNST neurons are composed of genetically and anatomically identifiable subpopulations that can be further investigated. Taken together, our findings demonstrate a key role for a PnocBNST neuronal ensemble in encoding the rapid arousal responses that are triggered by motivational stimuli.

Even after memories fade they may persist latently in the brain. However, there are no clinically applicable methods for reactivating memory traces and promoting memory retrieval. In the brain histamine modulates learning and memory, sleep and wakefulness, feeding, drinking, and neuroendocrine functions. Animal studies demonstrated that histamine H

Aims Thermoregulatory responses in homeothermic animals, including humans, are classified into involuntary autonomous and voluntary behavioral thermoregulatory responses. Although behavioral thermoregulatory responses are probably driven by positive (pleasant) and/or negative (unpleasant) emotions, the neuronal mechanisms underlying the induction of negative emotions by hot and cold environments remain poorly understood. The bed nucleus of the stria terminalis is a brain region implicated in stress responses and negative emotions, such as fear, anxiety, and aversion. Various stimuli that cause negative emotions, such as immobilization stress, fox odor, gastric distension, and inflammatory pain, increase noradrenaline release in the rat bed nucleus of the stria terminalis, especially in the ventral bed nucleus of the stria terminalis. It has been reported that the negative emotional component of pain is mediated by noradrenergic neurotransmission in the ventral bed nucleus of the stria terminalis. However, the role of intra‐ventral bed nucleus of the stria terminalis noradrenergic neurotransmission in the induction of negative emotion by exposure to hot and cold environments remains to be elucidated. For the first step to address this issue, the effects of hot and cold environments on noradrenaline release in the ventral bed nucleus of the stria terminalis were examined. Methods In vivo microdialysis analyses in unanesthetized, freely moving male Sprague‐Dawley rats were performed to examine hot and cold environments‐induced noradrenaline release in the ventral bed nucleus of the stria terminalis. Results Exposure to hot (38°C) and cold (8°C) environments significantly increased noradrenaline release in the ventral bed nucleus of the stria terminalis. Conclusions The results suggest that exposure to hot and cold environments enhances noradrenergic neurotransmission in the ventral bed nucleus of the stria terminalis, which may induce negative emotion, and thereby drive avoidance behaviors, that is, escape from hot and cold environments., Intra‐ventral bed nucleus of the stria terminalis noradrenergic transmission is reported to mediate negative emotions. In the present study using an in vivo microdialysis technique, we demonstrated that hot (38°C) and cold (8°C) environments increased noradrenaline release in the ventral bed nucleus of the stria terminalis. Noradrenergic transmission may drive escape behaviors from hot and cold environments.

In daily medical practice, scapular pain associated with cervical radiculopathy is commonly seen prior to the onset of pain of the upper extremity; however, the cause of the scapular pain is uncertain. We report a case of herpes zoster with simultaneous skin rash in both the upper extremity and interscapular region, which corresponds to the painful scapular region in case of C8 cervical radiculopathy. A 71-year-old healthy woman complained of shoulder and scapular pain followed by a blistering skin rash on both the ulnar side of her upper extremity and intrascapular region on the right side. She was diagnosed with herpes zoster and was prescribed amenamevir as oral treatment with vidarabine ointment. After 1 year, she still had mild causalgia on her III–V fingers and needed oral treatment with pregabalin. To our knowledge, this is the first case report of a herpes zoster rash in the upper extremity and intrascapular region simultaneously. We speculate that the rash in the two regions is caused by the varicella zoster virus (VZV) traveling from the same ganglion, probably the C8 ganglion, considering the dermatome of the rash area in the upper extremity and the intrascapular region correspond to the innervation zone of the medial branches of the dorsal ramus of the cervical nerve root, which resembles the scapular region in case of cervical radiculopathy. This phenomenon implies the mechanism of scapular pain is related to cervical radiculopathy. Further case reports are needed to confirm this.

The usefulness of carperitide in patients with acute heart failure (AHF) has not been confirmed; carperitide is expensive, and thus, its routine use has not been shown to add much value in clinical settings. We analyzed the impact of carperitide usage on the outcome and cost of hospitalization in AHF patients.Data obtained from the Diagnosis Procedure Combination (DPC) database from July 2014 until June 2015 from 371 hospitals were analyzed. Emergent patients with acute heart failure (ICD code I50* and DPC code 050130) who did not undergo any surgical procedures were enrolled. We compared the outcomes and cost between the carperitide group and non-carperitide group using propensity score matched analysis.In 37,891 heart failure patients (52.2% male; 79.2±11.9years), 13,421 pairs were selected according to the propensity score matching. In-hospital death occurred more frequently in the carperitide group (n=997; 7.4%) than in the non-carperitide group (n=844; 6.3%; p0.01). Carperitide use was also related with higher costs of hospitalizations, and total dose of carperitide administered during hospitalization decreased with the increasing case volume (p0.01). On the other hand, carperitide usage was frequently recognized in hospitals with larger annual case volumes (32.1%, Q1; 37.3%, Q2; 40.7%, Q3, p-value0.01).Carperitide usage negatively affected patient outcomes and cost of hospitalization. In hospitals with lower annual case volume, clinicians should pay attention to the total dose and duration of carperitide. On the other hand, in hospitals with larger annual case volumes, clinicians should pay attention to the thresholds/indications to prescribe carperitide in AHF patients.

Droplet evaporation in sub- and supercritical environments has been studied experimentally under microgravity conditions. A single suspended droplet of n-hexadecane was employed for the experiments. The initial droplet diameter was 0.4 mm. A pair of alumina/silica fibers of 7 µm in diameter was applied to suspend a droplet. The ambient pressure was varied in the range of 1.0–3.0 MPa, and the ambient temperature was set at 773 K. Sequential backlit images of an evaporating droplet were recorded using a high-speed digital video camera. Temporal variations in the droplet diameter were measured using a self-made computer-aided image analyzer. Microgravity conditions were produced by a 50-m drop tower. Temporal variations in the droplet diameter were successfully obtained for droplet evaporations in the supercritical environments. The normalized droplet lifetime increased with the ambient pressure. The evaporation rate constant increased with the ambient pressure, reached the maximum value at an ambient pressure slightly above the critical pressure of the fuel, and then decreased. The initial heat-up period linearly increased with the ambient pressure, reached the maximum value at an ambient pressure of 2.0 MPa, and then decreased. The ratio of the initial heat-up period to droplet lifetime increased with the ambient pressure, reached the maximum value of about 0.6 at an ambient pressure of 2.0 MPa, and then decreased. The droplet evaporation lifetime increased with the ambient pressure at subcritical ambient pressures even though the evaporation rate constant increased because the increase in the initial heat-up period overtook the decrease in the quasi-steady evaporation period. It was found that, in the case of fuels with a high critical temperature, the initial heat-up period determines the ambient pressure dependence of the droplet evaporation lifetime in the environments around the critical point of the fuel.