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Physical and emotional pain deteriorates the quality of well-being. Also, numerous non-invasive and invasive treatments for diagnosed diseases such as cancer medications and surgical procedures cause various types of pain. Despite the multidisciplinary approaches available to manage pain, the unmet needs for medication with minimal side effects are substantial. Especially with the surge of opioid crisis during the last decades, non-opioid analgesics may reduce life-threatening overdosing and addictive liability. Although many clinical trials supported the potential potency of cannabis and cannabidiol (CBD) in pain management or treatment, the long-term benefits of cannabis or CBD are still not evident. At the same time, growing evidence shows the risk of overusing cannabis and CBD. Therefore, it is urgent to develop novel analgesic medications that minimize side effects. All four well-identified adenosine receptors, A 1 , A 2A , A 2B , and A 3 , are implicated in pain. Recently, a report demonstrated that an adenosine A 1 R-specific positive allosteric modulator (PAM) is a potent analgesic without noticeable side effects. Also, several A 3 R agonists are being considered as promising analgesic agent. However, the importance of adenosine in pain is relatively underestimated. To help readers understand, first, we will summarize the historical perspective of the adenosine system in preclinical and clinical studies. Then, we will discuss possible interactions of adenosine and opioids or the cannabis system focusing on pain. Overall, this review will provide the potential role of adenosine and adenosine receptors in pain treatment., Competing Interests: D-S Choi is a scientific advisory board member to Peptron Inc. Peptron had no role in preparing, reviewing, or approving the manuscript. All the other authors declare no biomedical financial interests or potential conflicts of interest., (© 2022 The Authors.)

Background: This study aims to allow the development of efficient measures to improve occupational health of shift-working nurses focusing on job stress, health promotion behavior, resilience, and sleep disturbance., Methods: It was conducted on a subject panel of 137 nurses who were aware of the purpose of the study and agreed to participate. They worked three shifts at a tertiary hospital or a general hospital located in metropolitan city B. The collected data were analyzed by the independent t test and one-way analysis of variance and post-tested by Scheffe's test, Pearson's correlation coefficients, and multiple linear regression analysis using SPSS/WIN 25.0., Results: The significant influencing factors on sleep disturbance were of those whose subjective health status was 'normal' (β = 0.29,  p  < .001), 'not healthy' (β = .40,  p  < .001), who have job stress (β = .22,  p  = .003), and who have health promotion behavior (β = -0.17,  p  = .023). The overall explanatory power was 31.1% (F = 16.31,  p  < .001)., Conclusion: Through this study, nurses' subjective health status and job stress of working shifts were found to be important factors influencing the sleep disturbance level, and the most influencing factor was identified as the subjective health status., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

Background Concerns over the neurotoxic potential of retained gadolinium in brain tissues after intravenous gadolinium-based contrast agent (GBCA) administration have led to pronounced worldwide use changes, yet the clinical sequelae of gadolinium retention remain undefined. Purpose To assess clinical and neurologic effects and potential neurotoxicity of gadolinium retention in rats after administration of various GBCAs. Materials and Methods From March 2017 through July 2018, 183 male Wistar rats received 20 intravenous injections of 2.5 mmol per kilogram of body weight (80 human equivalent doses) of various GBCAs (gadodiamide, gadobenate, gadopentetate, gadoxetate, gadobutrol, gadoterate, and gadoteridol) or saline over 4 weeks. Rats were evaluated 6 and 34 weeks after injection with five behavioral tests, and inductively coupled plasma mass spectrometry, transmission electron microscopy, and histopathology were performed on urine, serum, cerebrospinal fluid (CSF), basal ganglia, dentate nucleus, and kidney samples. Dunnett post hoc test and Wilcoxon rank sum test were used to compare differences between treatment groups. Results No evidence of differences in any behavioral test was observed between GBCA-exposed rats and control animals at either 6 or 34 weeks ( P = .08 to P = .99). Gadolinium concentrations in both neuroanatomic locations were higher in linear GBCA-exposed rats than macrocyclic GBCA-exposed rats at 6 and 34 weeks ( P < .001). Gadolinium clearance over time varied among GBCAs, with gadobutrol having the largest clearance (median: 62% for basal ganglia, 70% for dentate) and gadodiamide having no substantial clearance. At 34 weeks, gadolinium was largely cleared from the CSF and serum of gadodiamide-, gadobenate-, gadoterate-, and gadobutrol-exposed rats, especially for the macrocyclic agents (range: 70%-98% removal for CSF, 34%-94% removal for serum), and was nearly completely removed from urine (range: 96%-99% removal). Transmission electron microscopy was used to detect gadolinium foci in linear GBCA-exposed brain tissue, but no histopathologic differences were observed for any GBCA. Conclusion In this rat model, no clinical evidence of neurotoxicity was observed after exposure to linear and macrocyclic gadolinium-based contrast agents at supradiagnostic doses. © RSNA, 2022 Online supplemental material is available for this article.

As the bioaccumulation of microplastics (MPs) is considered as a potential health risk, many efforts have been made to understand the cellular dynamics and cytotoxicity of MPs. Here, we demonstrate that label-free multicolor coherent anti-Stokes Raman scattering (CARS) microscopy enables separate vibrational imaging of internalized MPs and lipid droplets (LDs) with indistinguishable shapes and sizes in live cells. By simultaneously obtaining polystyrene (PS)- and lipid-specific CARS images at two very different frequencies, 1000 and 2850 cm -1 , respectively, we successfully identify the local distribution of ingested PS beads and native LDs in Caenorhabditis elegans . We further show that the movements of PS beads and LDs in live cells can be separately tracked in real time, which allows us to characterize their individual intracellular dynamics. We thus anticipate that our multicolor CARS imaging method could be of great use to investigate the cellular transport and cytotoxicity of MPs without additional efforts for pre-labeling to MPs.

Rationale: Withdrawal from chronic alcohol exposure produces various physical and mental withdrawal symptoms. Activation of adenosine receptors is known to inhibit withdrawal-induced excitation. However, limited studies investigate how adenosine analogs may prove helpful tools to alleviate alcohol withdrawal-related affective behaviors., Objectives: This study aimed to investigate the effects of J4 compared with saline using the mice vapor or voluntary ethanol drinking model on behavioral endpoints representing ethanol-withdrawal negative emotionality commonly observed during abstinence from chronic alcohol use., Methods: We subjected C57BL/6 J mice to chronic intermittent ethanol (CIE) exposure schedule to investigate how 72-h withdrawal from alcohol alters affective-like behavior. Next, we determined how treatment with J4, a second-generation adenosine analog, influenced affective behaviors produced by alcohol withdrawal. Finally, we determined how J4 treatment alters voluntary ethanol drinking using the two-bottle-choice drinking paradigm., Results: Our results show that 72-h withdrawal from chronic intermittent ethanol exposure produces limited affective-like disturbances in male C57BL/6 J mice exposed to 4 cycles ethanol vapor. Most importantly, J4 treatment irrespective of ethanol exposure decreases innate anxiety-like behavior in mice., Conclusions: Withdrawal from chronic intermittent ethanol exposure and subsequent behavioral testing 72 h later produces minimal affective-like behavior. J4 treatment did however reduce marble-burying behavior and increased time spent in open arms of the elevated plus maze, suggesting J4 may be useful as a general anxiolytic., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To determine the performance of quantification of liver extracellular volume fraction (fECV) using dual-energy CT (DECT) compared with CT imaging for ruling out high-riskesophageal varices(HRV) in cirrhotic patients., Methods: We retrospectively analyzed 229 cirrhotic patients (training [n = 159] and internal validation cohorts [n = 70]) who underwent dual-source DECT, serum marker assessment, and esophagogastroduodenoscopy (EGD) from 2017 to 2020. The fECV score was measured using iodine maps from 3-minute delayed, equilibrium-phase images at 100/140 Sn kVp. The association of CT parameters and serum markers with HRV was investigated. Criteria combining the fECV score (≤ 25.1%) or CT imaging with platelet count (> 150,000/mm 3 ) were created and compared to rule out HRV., Results: In the training cohort, the fECV score (odds ratio (OR), 1.20; 95% confidence interval (CI), 1.09, 1.32) and CT imaging (OR, 28.21; 95% CI, 9.31, 85.93) were independent predictors of HRV, along with platelet count (OR, 0.85 and 0.78). Criteria combining the fECV score with platelet count showed significantly better performance than those combining CT imaging with platelet count in ruling out HRV (p < 0.001). Applying the criteria could have safely avoided an additional 10.7% and 8.6% of EGDs in the training and validation cohorts, respectively, achieving a final value of 36.5% and 35.7% spared EGDs (0 HRV missed) compared to CT imaging with platelet count., Conclusions: The combined DECT-based fECV score with platelet count is useful for ruling out HRV and can safely avoid more EGDs than CT imaging with platelet count., (Copyright © 2022. Published by Elsevier B.V.)

Mitochondria are essential organelles central to various cellular functions such as energy production, metabolic pathways, signaling transduction, lipid biogenesis, and apoptosis. In the central nervous system, neurons depend on mitochondria for energy homeostasis to maintain optimal synaptic transmission and integrity. Deficiencies in mitochondrial function, including perturbations in energy homeostasis and mitochondrial dynamics, contribute to aging, and Alzheimer's disease. Chronic and heavy alcohol use is associated with accelerated brain aging, and increased risk for dementia, especially Alzheimer's disease. Furthermore, through neuroimmune responses, including pro-inflammatory cytokines, excessive alcohol use induces mitochondrial dysfunction. The direct and indirect alcohol-induced neuroimmune responses, including pro-inflammatory cytokines, are critical for the relationship between alcohol-induced mitochondrial dysfunction. In the brain, alcohol activates microglia and increases inflammatory mediators that can impair mitochondrial energy production, dynamics, and initiate cell death pathways. Also, alcohol-induced cytokines in the peripheral organs indirectly, but synergistically exacerbate alcohol's effects on brain function. This review will provide recent and advanced findings focusing on how alcohol alters the aging process and aggravates Alzheimer's disease with a focus on mitochondrial function. Finally, we will contextualize these findings to inform clinical and therapeutic approaches towards Alzheimer's disease., Competing Interests: D-SC is a scientific advisory board member to Peptron Inc. Peptron Inc had no role in the preparation, review, or approval of the manuscript; nor the decision to submit the manuscript for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 León, Kang, Franca-Solomon, Shang and Choi.)

Alzheimer's disease is the most common neurodegenerative disease, affecting more than 6 million US citizens and representing the most prevalent cause for dementia. Neurogenesis has been repeatedly reported to be impaired in AD mouse models, but the reason for this impairment remains unclear. Several key factors play a crucial role in AD including Aβ accumulation, intracellular neurofibrillary tangles accumulation, and neuronal loss (specifically in the dentate gyrus of the hippocampus). Neurofibrillary tangles have been long associated with the neuronal loss in the dentate gyrus. Of note, Aβ accumulation plays an important role in the impairment of neurogenesis, but recent studies started to shed a light on the role of APP gene expression on the neurogenesis process. In this review, we will discuss the recent approaches to neurogenesis in Alzheimer disease and update the development of therapeutic methods.

Delivery of automatic electrical defibrillator (AED) by unmanned aerial vehicle (UAV) was suggested for out-of-hospital cardiac arrest (OHCA). The goal of this study is to assess the effect of topographic and weather conditions on call to AED attach time by UAV-AED. We included OHCA patients from 2013 to 2016 in Seoul, South Korea. We developed a UAV-AED flight simulator using topographic information of Seoul for Euclidean and topographic flight pathway including vertical flight to overcome high-rise structures. We used 4 kinds of UAV flight scenarios according to weather conditions or visibility. Primary outcome was emergency medical service (EMS) call to AED attach time. Secondary outcome was pre-arrival rate of UAV-AED before current EMS based AED delivery. Call to AED attach time in topographic pathway was 7.0 min in flight and control advanced UAV and 8.0 min in basic UAV model. Pre-arrival rate in Euclidean pathway was 38.0% and 16.3% for flight and control advanced UAV and basic UAV. Pre-arrival rate in the topographic pathway was 27.0% and 11.7%, respectively. UAV-AED topographic flight took longer call to AED attach time than Euclidean pathway. Pre-arrival rate of flight and control advanced UAV was decreased in topographic flight pathway compared to Euclidean pathway., (© 2021. The Author(s).)

Background: Childhood adversity is a global health problem affecting 25-50% of children worldwide. Few prior studies have examined the underlying neurochemistry of adversity in adolescents. This cross-sectional study examined spectroscopic markers of trauma in a cohort of adolescents with major depressive disorder (MDD) and healthy controls. We hypothesized that historical adversity would have a negative relationship with spectroscopic measures of glutamate metabolites in anterior cingulate cortex., Methods: Adolescent participants (aged 13-21) underwent a semi-structured diagnostic interview and clinical assessment, which included the self-report Childhood Trauma Questionnaire (CTQ), a 28-item assessment of childhood adversity. Proton magnetic resonance spectroscopy ( 1 H-MRS) scans at 3 Tesla of an anterior cingulate cortex (ACC) voxel (8 cm 3 ) encompassing both hemispheres were collected using a 2-dimensional J -averaged sequence to assess N -acetylaspartate (NAA), Glx (glutamate+glutamine) and [NAA]/[Glx] concentrations. Generalized linear models assessed the relationships between CTQ scores and metabolite levels in ACC., Results: Thirty-nine participants (17 healthy controls, 22 depressed participants) underwent 1 H-MRS and completed the CTQ measures. There were decrements in [NAA]/[Glx] ratio in the ACC of participants with childhood adversity while no significant relationship between CTQ total score and any of the ACC metabolites was found in the combined sample. Exploratory results revealed a positive association between Glx levels and CTQ scores in depressed participants. Conversely the [NAA]/[Glx] ratio had a negative association with total CTQ scores in the depressed participants. Emotional Abuse Scale showed a significant negative relationship with [NAA]/[Glx] ratio in the combined sample when adjusted for depression severity., Conclusions: Our findings suggest that childhood adversity may impact brain neurochemical profiles. Further longitudinal studies should examine neurochemical correlates of childhood adversity throughout development and in populations with other psychiatric disorders., Competing Interests: Statement of Interest Dr. Lewis. received grant support from the Brain & Behavior Research Foundation as the Alan G. Ross Memorial Investigator. He has been a site investigator for multicenter trials funded by Neuronetics, Inc. and NeoSync, Inc. Dr. Port has served as an imaging consultant for Takeda Pharmaceutical Company, Ltd., Biomedical Systems Corp., and Neuronetics, Inc. Dr. Choi is a scientific advisory board member for Peptron Inc. Dr Croarkin has received research grant support from Pfizer, Inc; equipment support from Neuronetics, Inc; equipment support from MagVenture, Inc; and supplies and genotyping services from Assurex Health, Inc for investigator-initiated studies. He was the primary investigator for a multicenter study funded by Neuronetics, Inc and a site primary investigator for a study funded by NeoSync, Inc. Dr Croarkin has served as a consultant for Engrail Therapeutics, Myriad Neuroscience, Procter & Gamble Companyand Sunovion. The other authors report no financial relationships with commercial interests.

Recently, spotted wing Drosophila, Drosophila suzukii , is globally prevalent and causes agricultural losses to many fruits. To export Korean strawberry, methyl bromide fumigation is required to remove D. suzukii infestations, but Korean strawberry farmers are worried about fruit damage because methyl bromide can cause phytotoxicity on fresh commodities. In this report, we assessed the efficacy and phytotoxicity of single and successive application of methyl bromide and cold treatment on an export variety of strawberry to reduce fruit damage. The currently recommended dosage of methyl bromide, 40 g/m 3 for 3 h at 18 °C, was enough to control all stages of D. suzukii without phytotoxicity. A dosage of 20 g/m 3 of methyl bromide treatment for 3 h, followed by 1 d of cold (0 °C) treatment, showed 100% mortality in all growth stages of D. suzukii without fruit damage. Successive application of methyl bromide and cold treatment shows potential as a method of decreasing phytotoxicity and reducing the use of methyl bromide for environmental considerations.

The G protein-coupled receptor kinase (GRK) family member protein GRK3 has been linked to the pathophysiology of schizophrenia and bipolar disorder. Expression, as well as protein levels, of GRK3 are reduced in post-mortem prefrontal cortex of schizophrenia subjects. Here, we investigate functional behavior and neurotransmission related to immune activation and psychosis using mice lacking functional Grk3 and utilizing a variety of methods, including behavioral, biochemical, electrophysiological, molecular, and imaging methods. Compared to wildtype controls, the Grk3 -/- mice show a number of aberrations linked to psychosis, including elevated brain levels of IL-1β, increased turnover of kynurenic acid (KYNA), hyper-responsiveness to D-amphetamine, elevated spontaneous firing of midbrain dopamine neurons, and disruption in prepulse inhibition. Analyzing human genetic data, we observe a link between psychotic features in bipolar disorder, decreased GRK expression, and increased concentration of CSF KYNA. Taken together, our data suggest that Grk3 -/- mice show face and construct validity relating to the psychosis phenotype with glial activation and would be suitable for translational studies of novel immunomodulatory agents in psychotic disorders., (© 2021. The Author(s).)

Purpose: To assess patient radiation doses during diagnostic and therapeutic neurointerventional procedures from multiple centers and propose dose reference level (RL)., Materials and Methods: Consecutive neurointerventional procedures, performed in 22 hospitals from December 2020 to June 2021, were retrospectively studied. We collected data from a sample of 429 diagnostic and 731 therapeutic procedures. Parameters including dose-area product (DAP), cumulative air kerma (CAK), fluoroscopic time (FT), and total number of image frames (NI) were obtained. RL were calculated as the 3rd quartiles of the distribution., Results: Analysis of 1160 procedures from 22 hospitals confirmed the large variability in patient dose for similar procedures. RLs in terms of DAP, CAK, FT, and NI were 101.6 Gy·cm2, 711.3 mGy, 13.3 minutes, and 637 frames for cerebral angiography, 199.9 Gy·cm2, 3,458.7 mGy, 57.3 minutes, and 1,000 frames for aneurysm coiling, 225.1 Gy·cm2, 1,590 mGy, 44.7 minutes, and 800 frames for stroke thrombolysis, 412.3 Gy·cm2, 4,447.8 mGy, 99.3 minutes, and 1,621.3 frames for arteriovenous malformation (AVM) embolization, respectively. For all procedures, the results were comparable to most of those already published. Statistical analysis showed male and presence of procedural complications were significant factors in aneurysmal coiling. Male, number of passages, and procedural combined technique were significant factors in stroke thrombolysis. In AVM embolization, a significantly higher radiation dose was found in the definitive endovascular cure group., Conclusion: Various RLs introduced in this study promote the optimization of patient doses in diagnostic and therapeutic interventional neuroradiology procedures. Proposed 3rd quartile DAP (Gy·cm2) values were 101.6 for diagnostic cerebral angiography, 199.9 for aneurysm coiling, 225.1 for stroke thrombolysis, and 412.3 for AVM embolization. Continual evolution of practices and technologies requires regular updates of RLs.

The purpose of this study was to investigate and evaluate balance ability, isokinetic moments, and physical fitness according to the growth period from middle school to university in male taekwondo players. Thirty-five taekwondo players (middle school, n=11; high school, n=15; university, n=9) participated in this study. The anteriorposterior and medial-lateral CoP displacement at balance ability was better in university players than in high school and middle school players. The isokinetic knee joint muscle strength of the right extension and flexion % body weight (BW) at 60°/s was higher in university players than in high school players. The average power of right flexion BW at 180°/sec was higher in middle school players than in high school players. Back strength was higher in university players than in middle and high school players. The repeated jump was higher in high school players than in middle school players. The standing broad jump was higher in university players than in middle school players. The side-step was higher in university players than in high school players. The average power and total energy of anaerobic power were higher in university and high school players than in middle school players. The peak drop in anaerobic power was higher in middle school players than in high school players. Based on the results of the present study, the growth period should be considered when applying training such as balance, isokinetic moments, and physical fitness to male taekwondo players., Competing Interests: CONFLICT OF INTEREST No potential conflicts of interest relevant to this article were reported., (Copyright © 2021 Korean Society of Exercise Rehabilitation.)

Vibrational sum-frequency generation (VSFG) spectroscopy, a surface-specific technique, was shown to be useful even for characterizing the vibrational optical activity of chiral molecules in isotropic bulk liquids. However, accurately determining the spectroscopic parameters is still challenging because of the spectral congestion of chiroptical VSFG peaks with different amplitudes and phases. Here, we show that a time-variable infrared-visible chiroptical three-wave-mixing technique can be used to determine the spectroscopic parameters of second-order vibrational response signals from chiral chemical liquids. For varying the delay time between infrared and temporally asymmetric visible laser pulses, we measure the chiral VSFG, achiral VSFG, and their interference spectra of bulk R -(+)-limonene liquid and perform a global fitting analysis for those time-variable spectra to determine their spectroscopic parameters accurately. We anticipate that this time-variable VSFG approach will be useful for developing nearly background-free chiroptical characterization techniques with enhanced spectral resolution.

In the striatum, two main types of GABAergic medium spiny neurons (MSNs), denoted striatonigral (or direct-pathway MSNs, dMSNs) and striatopallidal neurons (indirect-pathway MSNs, iMSNs), form circuits with distinct pallidal nuclei, which sends "GO" or "NO-GO" signals through the thalamus. These striatopallidal circuits evaluate and execute reward-seeking and taking behaviors. Especially, the dorsal striatum can be further divided into the dorsomedial striatum (DMS, equivalent to caudate in primates and humans) and dorsolateral striatum (DLS, equivalent to putamen), which orchestrates goal-directed and habitual reward-seeking and taking behaviors, respectively. Using optogenetics, chemogenetics and in vivo calcium imaging technologies combined with electrophysiology and digitalized behavior phenotyping, recent studies have revealed cell-, circuit- and context-specific functions of these microcircuits in addictive behaviors. Also, region-specific astrocytes regulate the homeostatic activities of the dMSNs and iMSNs as well as the downstream circuits, which determine the net balance of cortico-striato-pallidal activities to the thalamic neurons. This review will summarize the recent progress of striatopallidal circuits focusing on astrocyte-neuron interaction and, reward- and alcohol-seeking behaviors. Our review will also discuss the translational and clinical implications of these microcircuit studies. This article is part of the special Issue on "Neurocircuitry Modulating Drug and Alcohol Abuse"., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

To infer the introduction sources of the oriental fruit fly, Bactrocera dorsalis , we used a mitochondrial marker to reconstruct the haplotype network and 15 microsatellite loci to reveal genetic structure and relationships between the geographically or temporally different collections from Asia. We performed Approximate Bayesian computations to infer a global origin and a source of the quarantine collections found in Korea. As a result, the 40 populations were divided into three groups, of which genetic similarity is not related to the geographic vicinity. Korean samples had a similar genetic structure to Taiwan and Thailand ones. Our results suggest that the place of origin of the B. dorsalis specimens found in Korea's border quarantine is likely to be Taiwan or Thailand. As the global origin of B. dorsalis , we estimated that Taiwan and Thailand were most likely the global origins of Southeast Asian populations by testing hypothetical scenarios by the approximate Bayesian computation analyses. Our results will allow easier identification of the source region of the forthcoming invasion of quarantined B. dorsalis specimens.

Tenebrio molitor larva (mealworms) has recently attracted attention as a protein source for food and feed. The larva is generally fed with wheat bran, which can be possibly contaminated with glyphosate. To establish food safe standards, a rugged and effective analytical method for glyphosate, aminomethylphosphonic acid, glufosinate, and their metabolites including 3-methylphosphinico-propionic acid, and N-acetyl glufosinate, in mealworms was optimized using liquid chromatography tandem mass spectrometry. An anionic polar pesticide column was used due to its high suitability for glyphosate. Acidified water and acetonitrile were used to extract the target compounds without contribution from various fatty and pigment interferences derived from brownish insects. Seven different clean-up procedures ((1) 50 mg C18 (2) 20 mg C18/Z-sep (3) PRiME hydrophilic-lipophilic balance (HLB) cartridge (4) 75 mg Z-sep, (5) 75 mg Z-sep+, (6) EMR-lipid cartridge, and (7) 50 mg ENVI-Carb) were compared. Due to its simplicity and cost-effectiveness, PRiME HLB was selected for clean-up. The recoveries of the target compounds were ranged from 86 to 96% with < 20% relative standard deviations. Therefore, this simple and effective method can be applied for the two pesticides and their metabolites in other edible insects or high-fat matrices., (© 2021. The Author(s).)

Parkinson's disease (PD) is a severe neurodegenerative disease characterized by classic motor features associated with the loss of dopaminergic neurons and appearance of Lewy bodies in the substantia nigra. Due to the complexity of PD, a definitive diagnosis in the early stages and effective management of symptoms in later stages are difficult to achieve in clinical practice. Previous research has shown that colocalization of A2A receptors (A2AR) and dopamine D2 receptors (D2R) may induce an antagonistic interaction between adenosine and dopamine. Clinical trials have found that the A2AR antagonist istradefylline decreases dyskinesia in PD and could be used as an adjuvant to levodopa treatment. Meanwhile, the incretin hormone glucagon-like peptide 1 (GLP1) mainly facilitates glucose homeostasis and insulin signaling. Preclinical experiments and clinical trials of GLP1 receptor (GLP1R) agonists show that they may be effective in alleviating neuroinflammation and sustaining cellular functions in the central nervous system of patients with PD. In this review, we summarize up-to-date findings on the usefulness of A2AR antagonists and GLP1R agonists in PD management. We explain the molecular mechanisms of these medications and their interactions with other neurotransmitter receptors. Furthermore, we discuss the efficacy and limitations of A2AR antagonists and GLP1R agonists in clinical practice.

The seasonality of African swine fever (ASF) in the summers and outbreaks in farms with high biosecurity levels suggest that the ASF virus (ASFV) may be transmitted by arthropod vectors. Arthropods were collected in this study from 14 pig farms with ASF outbreaks in Korea in 2019 to explore the role of arthropods as potential ASFV vectors. A total of 28,729 arthropods, including 28,508 (99.2%) Diptera, were collected using blacklight traps, insect nets and yellow sticky strips. All arthropod samples were negative for ASFV genomic DNA according to laboratory tests using real-time polymerase chain reaction. This result may reflect the effects of immediate control measures following the detection of farms with ASF outbreaks in the early phase of infection in Korea., (© 2021 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Diamine-appended metal-organic frameworks (MOFs) exhibit exceptional CO 2 adsorption capacities over a wide pressure range because of the strong interaction between basic amine groups and acidic CO 2 . Given that their high CO 2 working capacity is governed by solvent used during amine functionalization, a systematic investigation on solvent effect is essential but not yet demonstrated. Herein, we report a facile one-step solvent exchange route for the diamine functionalization of MOFs with open metal sites, using an efficient method to maximize diamine loading. We employed an MOF, Mg 2 (dobpdc) (dobpdc 4- = 4,4'-dioxido-3,3'-biphenyldicarboxylate), which contains high-density open metal sites. Indirect grafting with N -ethylethylenediamine (een) was performed with a minimal amount of methanol (MeOH) via multiple MeOH exchanges and diamine functionalization, resulting in a top-tier CO 2 adsorption capacity of 16.5 wt %. We established the correlation between N , N -dimethylformamide (DMF) loading and infrared peaks, which provides a simple method for determining the amount of the remaining DMF in Mg 2 (dobpdc). All interactions among Mg, DMF, diamine, and solvent were analyzed by van der Waals (vdw)-corrected density functional theory (DFT) calculations to elucidate the effect of chemical potential on diamine grafting.

The red imported fire ant (RIFA), Solenopsis invicta Buren is native to South America and is known as a global problematic invasive species. This study focused on the molecular response of RIFA by comparing gene expression profiles after exposing ants to low (10 °C) and high (40 °C) temperature stress and comparing them to untreated controls (30 °C). A total of 99,085 unigenes (the clustered non-redundant transcripts that are filtered from the longest assembled contigs) were obtained, of which 19,154 were annotated with gene descriptions, gene ontology terms, and metabolic pathways. 86 gene ontology (GO) functional sub-groups and 23 EggNOG terms resulted. Differentially expressed genes (DEGs) with log 2 FC ≥ 10 were screened and were compared at different temperatures. We found 203, 48, and 66 specific DEGs co-regulated at 10, 20, and 40 °C. Comparing transcriptome profiles for differential gene expression resulted in various DE genes, including cytochrome P450, NADH dehydrogenase subunit 1, cuticle protein and heat shock protein (HSP), which have previously been reported to be involved in cold and high temperature resistance. GO analysis revealed that antioxidant activity is up-regulated under high temperature stress. We verified the RNA-seq data by qPCR on 20 up- and down-regulated DEGs. These findings provide a basis for future understanding of the adaptation mechanisms of RIFA and the molecular mechanisms underlying the response to low and high temperatures., (© 2021. The Author(s).)

Background: Hepatitis C virus (HCV) infection is a major cause of liver diseases in Korea. Anti-HCV assays are used to screen for HCV infection. Here, we assessed the agreement and diagnostic performances of three different anti-HCV assays., Methods: We analyzed 1180 samples using three assay systems-Elecsys Anti-HCV II (Roche Diagnostics), Atellica IM aHCV (Siemens Healthineers), and Alinity s Anti-HCV (Abbott Diagnostics)-and evaluated the agreements between the results and diagnostic performances., Results: The Cohens kappa coefficients between the Roche and Siemens, Siemens and Abbott, and Roche and Abbott systems were 0.837, 0.961, and 0.849, respectively. The Fleiss kappa coefficient among the three systems was 0.883. The sensitivities and positive predictive values were 86.5 and 89.8 for Roche, 97.5 and 98.1 for Siemens, and 99.4 and 98.2 for Abbott, respectively. The area under the curves of the anti-HCV signal to cutoff (S/Co) ratios or cutoff index for predicting viremia in the Roche, Siemens, and Abbott systems were 0.432, 0.641, and 0.676, respectively; the optimal S/Co ratio was 14.715 for Siemens and 14.42 for Abbott., Conclusions: All three assays showed excellent diagnostic performance; however, anti-HCV values need to be used with caution to predict viremia; therefore, supplementary tests are necessary to confirm viremia status, especially for samples with low values., (Copyright © 2021. Published by Elsevier B.V.)

Aberrant activation of cytokine and growth factor signal transduction pathways confers enhanced survival and proliferation properties to acute myeloid leukemia (AML) cells. However, the mechanisms underlying the deregulation of signaling pathways in leukemia cells are unclear. To identify genes capable of independently supporting cytokine-independent growth, we employed a genome-wide CRISPR/Cas9-mediated loss-of-function screen in GM-CSF-dependent human AML TF-1 cells. More than 182 genes (p < 0.01) were found to suppress the cytokine-independent growth of TF-1 cells. Among the top hits, genes encoding key factors involved in sialylation biosynthesis were identified; these included CMAS, SLC35A1, NANS, and GNE. Knockout of either CMAS or SLC35A1 enabled cytokine-independent proliferation and survival of AML cells. Furthermore, NSG (NOD/SCID/IL2Rγ -/- ) mice injected with CMAS or SLC35A1-knockout TF-1 cells exhibited a shorter survival than mice injected with wild-type cells. Mechanistically, abrogation of sialylation biosynthesis in TF-1 cells induced a strong activation of ERK signaling, which sensitized cells to MEK inhibitors but conferred resistance to JAK inhibitors. Further, the surface level of α2,3-linked sialic acids was negatively correlated with the sensitivity of AML cell lines to MEK/ERK inhibitors. We also found that sialylation modulated the expression and stability of the CSF2 receptor. Together, these results demonstrate a novel role of sialylation in regulating oncogenic transformation and drug resistance development in leukemia. We propose that altered sialylation could serve as a biomarker for targeted anti-leukemic therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

ABCG subfamily proteins are highly enriched in terrestrial plants. Many of these proteins secrete secondary metabolites that repel or inhibit pathogens. To establish why the ABCG subfamily proteins proliferated extensively during evolution, we constructed phylogenetic trees from a broad range of eukaryotic organisms. ABCG proteins were massively duplicated in land plants and in oomycetes, a group of agronomically important plant pathogens, which prompted us to hypothesize that plant and pathogen ABCGs coevolved. Supporting this hypothesis, full-size ABCGs in host plants (Arabidopsis thaliana and Glycine max) and their pathogens (Hyaloperonospora arabidopsidis and Phytophthora sojae, respectively) had similar divergence times and patterns. Furthermore, generalist pathogens with broad ranges of host plants have diversified more ABCGs than their specialist counterparts. The hypothesis was further tested using an example pair of ABCGs that first diverged during multiplication in a host plant and its pathogen: AtABCG31 of A. thaliana and HpaP802307 of H. arabidopsidis. AtABCG31 expression was activated following infection with H. arabidopsidis, and disrupting AtABCG31 led to increased susceptibility to H. arabidopsidis. Together, our results suggest that ABCG genes in plants and their oomycete pathogens coevolved in an arms race, to extrude secondary metabolites involved in the plant's defense response against pathogens., (© 2019 The Authors. Physiologia Plantarum published by John Wiley & Sons Ltd on behalf of Scandinavian Plant Physiology Society.)

Temperature sensing and control is an important factor to prevent the overheating of mechanical and electrical components in various devices. However, commercialized temperature sensors can be disadvantageous due to their limited shapes. Therefore, we propose a smart paint to solve this issue. In this study, smart paints were produced based on carbon black, and their properties were measured using thermistors. Experiments were conducted to analyze the resistance properties using carbon and four types of polymers. Through the scanning electron microscopy (SEM) images of the mixed paints, it was shown that the resistances were decreased due to the necking phenomena. Furthermore, each paint provides a different temperature coefficient depending on the polymer type.

Structural colors based on nanostructured surfaces are an environmentally friendly alternative to dyes and pigments. In this study, structural colors were produced by spherical silica nanoparticles. By controlling the size of the spherical silica nanoparticles, the changes in color were controlled. The sizes of the nanoparticles were controlled by adjusting the ammonia content in the conventional Stöber method. Spherical silica nanoparticle powders were obtained using a centrifuge and an ultrasonic grinder oven, which were subsequently dispersed in deionized water and alcohol for dip coating. The particle sizes of the samples increased with increase in the amount of ammonia used in the synthesis process and were not affected by the dip coating. Spherical silica nanoparticles were uniformly arranged on the surface of the glass slides for all the samples studied. Thus, the structural colors produced by the spherical silica nanoparticles changed according to the particle size, which can be controlled by the ammonia content during synthesis.

We previously reported that SNPs near TSPAN5 were associated with plasma serotonin (5-HT) concentrations which were themselves associated with selective serotonin reuptake inhibitor treatment outcomes in patients with major depressive disorder (MDD). TSPAN5 SNPs were also associated with alcohol consumption and alcohol use disorder (AUD) risk. The present study was designed to explore the biological function of TSPAN5 with a focus on 5-HT and kynurenine concentrations in the tryptophan pathway. Ethanol treatment resulted in decreased 5-HT concentrations in human induced pluripotent stem cell (iPSC)-derived neuron culture media, and the downregulation of gene expression of TSPAN5, DDC, MAOA, MAOB, TPH1, and TPH2 in those cells. Strikingly, similar observations were made when the cells were treated with acamprosate-an FDA approved drug for AUD therapy. These results were replicated in iPSC-derived astrocytes. Furthermore, TSPAN5 interacted physically with proteins related to clathrin and other vesicle-related proteins, raising the possibility that TSPAN5 might play a role in vesicular function in addition to regulating expression of genes associated with 5-HT biosynthesis and metabolism. Downregulation of TSPAN5 expression by ethanol or acamprosate treatment was also associated with decreased concentrations of kynurenine, a major metabolite of tryptophan that plays a role in neuroinflammation. Knockdown of TSPAN5 also influenced the expression of genes associated with interferon signaling pathways. Finally, we determined that TSPAN5 SNPs were associated with acamprosate treatment outcomes in AUD patients. In conclusion, TSPAN5 can modulate the concentrations of 5-HT and kynurenine. Our data also highlight a potentially novel pharmacogenomic mechanism related to response to acamprosate., (© 2020. The Author(s).)

Background: Measuring the quality of cardiopulmonary resuscitation (CPR) is important for improving outcomes in cardiac arrest. Cerebral perfusion pressure (CePP) could represent cerebral circulation during CPR, but it is difficult to measure non-invasively. In this study, we developed the electroencephalogram (EEG) based brain index (EBRI) derived from EEG signals by machine learning techniques, which could estimate CePP accurately in a porcine cardiac arrest model., Methods: We conducted a randomised crossover study using nine female pigs. After 1 min of untreated ventricular fibrillation, we performed CPR with 12 different 2-min tilting angle sessions, including two different head-up tilt (HUT) angles (30°, 15°) twice, horizontal angle (0°) four times and two different head-down tilt (HDT) angles (-15°, -30°) twice with the random order. We collected EEG signals using a single channel EEG electrode in real-time during CPR. We derived the EBRI models to predict the CePP classified by the 5 or 10 groups using three different machine learning algorithms, including the support vector machine (SVM), k-nearest neighbour (KNN) and random forest classification (RFC) method. We assessed the accuracy, sensitivity and specificity of each model., Results: The accuracy of the EBRI model using an SVM algorithm in the 5-group CePP classification was 0.935 with a standard deviation (SD) from 0.923 to 0.946. The accuracy in the 10-group classification was 0.904 (SD: 0.896, 0.913). The accuracy of the EBRI using the KNN method in the 5-group classification was 0.927 (SD: 0.920, 0933) and in the 10-group was 0.894 (SD: 0.880, 0.907). The accuracy of the RFC algorithm was 0.947 (SD: 0.931, 0.963) in the 5-group classification and 0.920 (SD: 0.911, 0.929) in the 10-group classification., Conclusion: We developed the EBRI model using non-invasive acquisition of EEG signals to predict CePP during CPR. The accuracy the EBRI model was 0.935, 0.927 and 0.947 for each machine learning algorithm, and the EBRI could be used as a surrogate indicator for measuring cerebral perfusion during CPR., Competing Interests: Declaration of Competing Interest There are no conflicts of interest with the manufacturers of EEG related devices., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: Determining which patients with pericardial effusion require urgent intervention can be challenging. We sought to develop a novel, simple risk prediction score for patients with pericardial effusion., Methods and Results: Adult patients admitted through the emergency department (ED) with pericardial effusion were retrospectively evaluated. The overall cohort was divided into a derivation and validation cohort for the generation and validation of a novel risk score using logistic regression. The primary outcome was a pericardial drainage procedure or death attributed to cardiac tamponade within 24 h of ED arrival. Among 195 eligible patients, 102 (52%) experienced the primary outcome. Four variables were selected for the novel score: systolic blood pressure < 100 mmHg (1.5 points), effusion diameter [1-2 cm (0 points), 2-3 cm (1.5 points), >3 cm (2 points)], right ventricular diastolic collapse (2 points), and mitral inflow velocity variation > 25% (1 point). The need for pericardial drainage within 24 h was stratified as low (<2 points), intermediate (2-4 points), or high (≥4 points), which corresponded to risks of 8.1% [95% confidence interval (CI) 3.0-16.8%], 63.8% [95% CI 50.1-76.0%], and 93.7% [95% CI 84.5-98.2%]. The area under the curve of the simplified score was 0.94 for the derivation and 0.91 for the validation cohort., Conclusion: Among ED patients with pericardial effusion, a four-variable prediction score consisting of systolic blood pressure, effusion diameter, right ventricular collapse, and mitral inflow velocity variation can accurately predict the need for urgent pericardial drainage. Prospective validation of this novel score is warranted., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Microwave absorbers using conductive ink are generally fabricated by printing an array pattern on a substrate to generate electromagnetic fields. However, screen printing processes are difficult to vary the sheet resistance values for different regions of the pattern on the same layer, because the printing process deposits materials at the same height over the entire surface of substrate. In this study, a promising manufacturing process was suggested for engraved resistive double square loop arrays with ultra-wide bandwidth microwave. The developed manufacturing process consists of a micro-end-milling, inking, and planing processes. A 144-number of double square loop array was precisely machined on a polymethyl methacrylate workpiece with the micro-end-milling process. After engraving array structures, the machined surface was completely covered with the developed conductive carbon ink with a sheet resistance of 15 Ω/sq. It was cured at room temperature. Excluding the ink that filled the machined double square loop array, overflowed ink was removed with the planing process to achieve full filled and isolated resistive array patterns. The fabricated microwave absorber showed a small radar cross-section with reflectance less than - 10 dB in the frequency band range of 8.0-14.6 GHz.

Abstract: To evaluate the effectiveness of percutaneous removal of common bile duct (CBD) stones using a modified balloon technique (balloon catheter sphincteroplasty and expulsion of the stones using half-captured balloons within the sheath) in patients difficult to treat with endoscopy.Fifty patients underwent a modified balloon technique (balloon group), and 53 patients underwent CBD stone removal by the basket method (stone basket group) between 2016 and 2019. We compared the balloon and stone basket groups to evaluate the effectiveness of the modified balloon technique. Outcome variables such as demographics, technical success rates, procedural details, and complications were analyzed. Statistical analysis was performed using Student t test, Fisher exact test, or the χ2 test.The technical success rate in the balloon group was 66% (33/50) in 1 session, 32% (16/50) in 2 sessions, and 2% (1/50) in 3 sessions. That of the stone basket group was 45% (24/53) in 1 session, 38% (20/53) in 2 sessions, and 17% (9/53) in 3 sessions.The total procedure time was significantly shorter in the balloon group (29.5 ± 15.1 minutes) than in the stone basket group (41.7 ± 20.2 minutes) (P < .01), whereas the number of stones was higher in the balloon group than in the stone basket group (P = .03). Maximal stone size, balloon size, pancreatitis, and hospitalization stay did not show statistical differences between the 2 groups. Most complications (9 patients, balloon group; 8 patients, stone basket group) were mild and transient. Major complications occurred in one patient in the stone basket group, who experienced hemobilia due to arterial injury caused by percutaneous transhepatic biliary drainage, which was treated by endovascular embolization without mortality.The modified balloon technique is an effective and safe treatment method for CBD stone removal in patients presenting difficulties in the endoscopic approach., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

GLP-1 agonists have become increasingly interesting as a new Parkinson's disease (PD) clinical treatment strategy. Additional preclinical studies are important to validate this approach and define the disease stage when they are most effective. We hence characterized the efficacy of PT320, a sustained release formulation of the long acting GLP-1 agonist, exenatide, in a progressive PD (MitoPark) mouse model. A clinically translatable biweekly PT320 dose was administered starting at 5 weeks of age and longitudinally evaluated to 24 weeks, and multiple behavioral/cellular parameters were measured. PT320 significantly improved spontaneous locomotor activity and rearing in MitoPark PD mice. "Motivated" behavior also improved, evaluated by accelerating rotarod performance. Behavioral improvement was correlated with enhanced cellular and molecular indices of dopamine (DA) midbrain function. Fast scan cyclic voltammetry demonstrated protection of striatal and nucleus accumbens DA release and reuptake in PT320 treated MitoPark mice. Positron emission tomography showed protection of striatal DA fibers and tyrosine hydroxylase protein expression was augmented by PT320 administration. Early PT320 treatment may hence provide an important neuroprotective therapeutic strategy in PD., Competing Interests: The authors declare the following competing financial interest(s): J.J. and H.C. are employees of Peptron Inc. D.S.C. is a scientific advisor to Peptron, Inc. The Intramural Research Program of the National Institute on Aging, NIH, and Peptron, Inc., have a Cooperative Research and Development Agreement to develop Ex-4 as a treatment strategy for neurodegenerative disorders for which NIA and Peptron, Inc., hold patent rights via the work of H.C. and N.G. L.O. is a former co-owner of a company owning commercial rights to the MitoPark mouse., (© 2021 The Authors. Published byAmerican Chemical Society.)

Existing soft actuators for adaptive microlenses suffer from high required input voltage, optical loss, liquid loss, and the need for assistant systems. In this study, we fabricate a polyvinyl chloride-based gel using a new synergistic plasticization method to achieve simultaneously a high optical transparency and an ultrasoft rubber-like elastic behavior with a large voltage-induced deformation under a weak electric field. By compressing the smooth gel between two sets of annular electrodes, a self-contained biconvex microlens is realized that is capable of considerable shape changes in the optical path. Each surface of the dual-curvature microlens can be independently adjusted to focus or scatter light to capture real or virtual images, yield variable focal lengths (+31.8 to -11.3 mm), and deform to various shapes to improve aberrations. In addition to simple fabrication, our microlens operates silently and consumes low power (0.52 mW), making it superior to existing microlenses.

Treatment of skeletal Class III malocclusion in young patients is very challenging. Facemask therapy has been proven to be effective in early correction of Class III malocclusion. With the aid of skeletal anchorage, the orthopaedic effects are expected to be greater than the effects with conventional facemask with tooth-borne anchorage. However, only a few studies have reported on the long-term stability of facemask therapy combined with skeletal anchorage. This report examines two patients with skeletal Class III malocclusion who were treated with facemask and skeletal anchorage followed by orthodontic treatment using fixed orthodontic appliances. The long-term effects of facemask therapy with skeletal anchorage are discussed and compared with the conventional facemask therapy., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Psychiatric illness is a prevalent and highly debilitating disorder, and more than 50% of the general population in both middle- and high-income countries experience at least one psychiatric disorder at some point in their lives. As we continue to learn how pervasive psychiatric episodes are in society, we must acknowledge that psychiatric disorders are not solely relegated to a small group of predisposed individuals but rather occur in significant portions of all societal groups. Several distinct brain regions have been implicated in neuropsychiatric disease. These brain regions include corticolimbic structures, which regulate executive function and decision making (e.g., the prefrontal cortex), as well as striatal subregions known to control motivated behavior under normal and stressful conditions. Importantly, the corticolimbic neural circuitry includes the hippocampus, a critical brain structure that sends projections to both the cortex and striatum to coordinate learning, memory, and mood. In this review, we will discuss past and recent discoveries of how neurobiological processes in the hippocampus and corticolimbic structures work in concert to control executive function, memory, and mood in the context of mental disorders.

The supercooling degree (SD), which refers to the difference between the ice nucleation temperature and freezing point of kimchi, varies depending on the type of kimchi, manufacturer, recipe, and manufacturing season. The aim of this study is to investigate the major influencing factors for the supercooled storage of kimchi and to analyze the possibility of supercooled storage for commercial kimchi. Pearson correlation analysis determined that, in commercial kimchi manufactured between March and July 2018, the SD of kimchi correlated to the number of aerobic bacteria (P < 0.01), however, was not associated with lactic acid bacteria. Moreover, the ice nucleation temperature of saline solution inoculated with aerobic bacteria was reduced from -3.03 ± 0.04 to -6.18 ± 0.11 °C by 10 kGy gamma ray sterilization. Meanwhile, the ice nucleation temperatures of 1.8 kg of commercial red cabbage kimchi and 500 g of white cabbage kimchi manufactured in February 2020 were -3.93 ± 0.06 °C and -3.57 ± 0.06 °C, respectively, and they could be stored at -2.5 °C for 12 weeks without freezing. Additionally, supercooled storage of kimchi at -2.5 °C caused a fermentation delay effect compared to control storage at 1 °C, considering the acidity and amount of lactic acid bacteria. Therefore, if the number of aerobic bacteria is controlled during the manufacturing process of kimchi, supercooled storage at temperatures below -2.5 °C may extend the shelf life of kimchi. PRACTICAL APPLICATION: We have shown that aerobic bacteria are the key influencing factor for ice nucleation of kimchi during supercooled storage. Aside from the initial sterilization process, fermentation of kimchi can also be delayed by lowering the storage temperature below -2.5 °C. Moreover, the method of direct cool refrigeration may have an industrial-level application., (© 2021 Institute of Food Technologists®.)

Mutations in any of the genes encoding the four subunits of succinate dehydrogenase (SDH), a mitochondrial membrane-bound enzyme complex that is involved in both the tricarboxylic acid cycle and the electron transport chain, can lead to a variety of disorders. Recognized conditions with such mutations include Leigh syndrome and hereditary tumors such as pheochromocytoma and paraganglioma (PPGL), renal cell carcinoma, and gastrointestinal stromal tumor. Tumors appear in SDH mutation carriers with dominant inheritance due to loss of heterozygosity in susceptible cells. Here, we describe a mouse model intended to reproduce hereditary PPGL through Cre-mediated loss of SDHC in cells that express tyrosine hydroxylase (TH), a compartment where PPGL is known to originate. We report that while there is modest expansion of TH + glomus cells in the carotid body upon SDHC loss, PPGL is not observed in such mice, even in the presence of a conditional dominant negative p53 protein and chronic hypoxia. Instead, we report an unexpected phenotype of nondiabetic obesity beginning at about 20 weeks of age. We hypothesize that this obesity is caused by TH + cell loss or altered phenotype in key compartments of the central nervous system responsible for regulating feeding behavior, coupled with metabolic changes due to loss of peripheral catecholamine production., (© 2020 Federation of American Societies for Experimental Biology.)

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r g ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r g = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r g = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r g = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r gs = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors., (© 2020 Society for the Study of Addiction.)

The corticostriatal circuitry and its glutamate-γ-aminobuturic acid (GABA) interactions play an essential role in regulating neuronal excitability during reward-seeking behavior. However, the contribution of GABAergic interneurons in the corticostriatal circuitry remains unclear. To investigate the role of GABAergic interneurons, we focused on parvalbumin-expressing fast-spiking interneurons (Pv-FSI) in the corticostriatal circuitry using the designer receptors exclusively activated by designer drugs approach in a Pv-Cre mouse model. We hypothesize that Pv-FSI activation elicits changes in cortical glutamate levels and reward-seeking behaviors. To determine molecular and behavioral effects of Pv-FSI, we performed microdialysis and operant conditioning tasks for sucrose and alcohol rewards. In addition, we also examined how alcohol reward itself affects Pv-FSI functioning. Interestingly, our microdialysis results demonstrate that alcohol exposure inhibits Pv-FSI functioning in the medial prefrontal cortex (mPFC) and this consequently can regulate glutamate levels downstream in the nucleus accumbens. For sucrose reward-seeking behaviors, Pv-FSI activation in the mPFC increases sucrose self-administration whereas it does not promote alcohol seeking. For alcohol rewards, however, Pv-FSI activation in the mPFC results in increased compulsive head entry in operant chambers during devaluation procedures. Overall, our results suggest that not only do Pv-FSI contribute to changes in the cortical microcircuit and reward-seeking behaviors but also that alcohol affects Pv-FSI neurotransmission. Therefore, Pv-FSI has prompted interest in their role in maintaining a balance in neuronal excitation/inhibition and in regulating reward-seeking processes such as compulsivity, all of which are important factors for excessive alcohol seeking., (© 2020 International Society for Neurochemistry.)

Glutamatergic dysregulation is known to contribute to obsessive-compulsive disorder (OCD). Astrocytic glutamate transporter 1 (GLT1) is responsible for the majority of glutamate clearance. However, the role of GLT1 in OCD-like behavior remains unclear. Here, we found that astrocytic GLT1 deficient mice showed increased wheel running activity but reduced home cage activity. Notably, they exhibited elevated grooming/rearing time and increased repetitive behavior counts in contextual and cued fear conditioning. In addition, they showed increased rearing counts in the metabolic chamber, and also augmented rearing time and jumping counts in the open field test. Taken together, our findings suggest that astrocytic GLT1 deficiency promotes OCD-like repetitive behaviors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Immune activation contributes to the pathophysiology of psychiatric disorders. Administration of a single dose of lipopolysaccharides (LPS) has been shown to induce depressive- and anxiety-like behaviors in rodents through activation of the kynurenine pathway, increasing levels of the N-methyl-d-aspartate (NMDA) receptor agonist quinolinic acid. Conversely, repeated administration of LPS produces increased levels of the NMDA receptor antagonist kynurenic acid. Here we show that repeated LPS administration increases sensitivity to D-amphetamine and produces cognitive deficits and anxiety-like behavior. Together, our behavioral data suggests that repeated LPS administration may be useful to study the contribution of inflammation to psychiatric disorders such as schizophrenia., (Copyright © 2020. Published by Elsevier B.V.)

Although numerous porous adsorbents have been investigated for NH 3 capture applications, these materials often exhibit insufficient NH 3 uptake, low NH 3 affinity at the ppm level, and poor chemical stability against wet NH 3 conditions. The NH 3 capture properties of M 2 (dobpdc) complexes (M=Mg 2+ , Mn 2+ , Co 2+ , Ni 2+ , and Zn 2+ ; dobpdc 4- =4,4-dioxidobiphenyl-3,3-dicarboxylate) that contain open metal sites is presented. The NH 3 uptake of Mg 2 (dobpdc) at 298 K was 23.9 mmol g -1 at 1 bar and 8.25 mmol g -1 at 570 ppm, which are record high capacities at both pressures among existing porous adsorbents. The structural stability of Mg 2 (dobpdc) upon exposure to wet NH 3 was superior to that of the other M 2 (dobpdc) and the frameworks tested. Overall, these results demonstrate that Mg 2 (dobpdc) is a recyclable compound that exhibits significant NH 3 affinity and capacity, making it a promising candidate for real-world NH 3 -capture applications., (© 2020 Wiley-VCH GmbH.)

Background: Habitual reward-seeking behavior is a hallmark of addictive behavior. The role of the dorsomedial striatum (DMS) in regulating goal-directed reward-seeking behavior has been long appreciated. However, it remains unclear how the astrocytic activities in the DMS differentially affect the behavioral shift., Methods: To investigate the astrocytic activity-driven neuronal synaptic events and behavioral consequences, we chemogenetically activated astrocytes in the DMS using GFAP promoter-driven expression of hM3Dq, the excitatory DREADDs (designer receptors exclusively activated by designer drugs). First, we confirmed the chemogenetically induced cellular activity in the DMS astrocytes using calcium imaging. Then, we recorded electrophysiological changes in the synaptic activity of the two types of medium spiny neurons (MSNs): direct and indirect pathway MSNs. To evaluate the behavioral consequences, we trained mice in nose-poking operant chambers that developed either habitual or goal-directed reward-seeking behaviors., Results: The activation of DMS astrocytes reduced the frequency of spontaneous excitatory postsynaptic currents in the direct pathway MSNs, whereas it increased the amplitude of the spontaneous excitatory postsynaptic currents and decreased the frequency of spontaneous inhibitory postsynaptic currents in the indirect pathway MSNs. Interestingly, astrocyte-induced DMS neuronal activities are regulated by adenosine metabolism, receptor signaling, and transport. Importantly, mice lacking an astrocytic adenosine transporter, ENT1 (equilibrative nucleoside transporter 1; Slc29a1), show no transition from habitual to goal-directed reward-seeking behaviors upon astrocyte activation, while restoring ENT1 expression in the DMS facilitated this transition., Conclusions: Our findings reveal that DMS astrocyte activation differentially regulates MSNs' activity and facilitates shifting from habitual to goal-directed reward-seeking behavior., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

In this study, we propose a personalized glucose prediction model using deep learning for hospitalized patients who experience Type-2 diabetes. We aim for our model to assist the medical personnel who check the blood glucose and control the amount of insulin doses. Herein, we employed a deep learning algorithm, especially a recurrent neural network (RNN), that consists of a sequence processing layer and a classification layer for the glucose prediction. We tested a simple RNN, gated recurrent unit (GRU), and long-short term memory (LSTM) and varied the architectures to determine the one with the best performance. For that, we collected data for a week using a continuous glucose monitoring device. Type-2 inpatients are usually experiencing bad health conditions and have a high variability of glucose level. However, there are few studies on the Type-2 glucose prediction model while many studies performed on Type-1 glucose prediction. This work has a contribution in that the proposed model exhibits a comparative performance to previous works on Type-1 patients. For 20 in-hospital patients, we achieved an average root mean squared error (RMSE) of 21.5 and an Mean absolute percentage error (MAPE) of 11.1%. The GRU with a single RNN layer and two dense layers was found to be sufficient to predict the glucose level. Moreover, to build a personalized model, at most, 50% of data are required for training.

Crotamiton is an anti-scabies drug, but it was recently found that crotamiton also suppresses non-scabietic itching in mice. However, the underlying mechanism is largely unclear. Therefore, aim of the study is to investigate mechanisms of the anti-pruritic effect of crotamiton for non-scabietic itching. Histamine and chloroquine are used as non-scabietic pruritogens. The effect of crotamiton was identified using fluorometric intracellular calcium assays in HEK293T cells and primary cultured dorsal root ganglion (DRG) neurons. Further in vivo effect was evaluated by scratching behavior tests. Crotamiton strongly inhibited histamine-induced calcium influx in HEK293T cells, expressing both histamine receptor 1 (H1R) and transient receptor potential vanilloid 1 (TRPV1), as a model of histamine-induced itching. Similarly, it also blocked chloroquine-induced calcium influx in HEK293T cells, expressing both Mas-related G-protein-coupled receptor A3 (MRGPRA3) and transient receptor potential A1 (TRPA1), as a model of histamine-independent itching. Furthermore, crotamiton also suppressed both histamine- and chloroquine-induced calcium influx in primary cultures of mouse DRG. Additionally, crotamiton strongly suppressed histamine- and chloroquine-induced scratching in mice. Overall, it was found that crotamiton has an anti-pruritic effect against non-scabietic itching by histamine and chloroquine. Therefore, crotamiton may be used as a general anti-pruritic agent, irrespective of the presence of scabies.

Alcohol use disorder (AUD) is characterized as a chronic, relapsing disease with a pattern of excessive drinking despite negative consequences to an individual's life. Severe chronic alcohol use impairs the function of the medial prefrontal cortex (mPFC), which contributes to alcohol-induced cognitive and executive dysfunction. The mPFC contains more mitochondria compared to other cortical areas, which suggests mitochondrial damage may occur in AUD and trigger subsequent behavior change. Here, we identified morphological and functional changes in mitochondria in the mPFC in C57BL6/J mice after 8 h of withdrawal from chronic intermittent alcohol (CIA) exposure. Three-dimensional serial block-face scanning electron microscopy (SBFSEM) reconstruction revealed that CIA exposure elongated mPFC mitochondria and formed mitochondria-on-a-string (MOAS). Furthermore, alcohol significantly affected mitochondrial bioenergetics, including oxidative phosphorylation and electron transport, with inhibited aerobic respiration in mPFC mitochondria after CIA exposure. We also found decreased expression of fusion (mitofusin 2, Mfn2) and increased fission (mitochondrial fission 1 protein, Fis1) proteins in the mPFC of alcohol-treated mice. In sum, our study suggests that CIA exposure impairs mitochondrial dynamics and function in the mPFC., (Copyright © 2020 Shang, Lindberg, Starski, Peyton, Hong, Choi and Choi.)