GnRH peripherally modulates nociceptor functions, exacerbating mechanical pain.

The function of peripheral nociceptors, the neurons that relay pain signals to the brain, are frequently tuned by local and systemic modulator substances. In this context, neurohormonal effects are emerging as an important modulatory mechanism, but many aspects remain to be elucidated. Here we report that gonadotropin-releasing hormone (GnRH), a brain-specific neurohormone, can aggravate pain by acting on nociceptors in mice. GnRH and GnRHR, the receptor for GnRH, are expressed in a nociceptor subpopulation. Administration of GnRH and its analogue, localized for selectively affecting the peripheral neurons, deteriorated mechanical pain, which was reproducible in neuropathic conditions. Nociceptor function was promoted by GnRH treatment in vitro, which appears to involve specific sensory transient receptor potential ion channels. These data suggest that peripheral GnRH can positively modulate nociceptor activities in its receptor-specific manner, contributing to pain exacerbation. Our study indicates that GnRH plays an important role in neurohormonal pain modulation via a peripheral mechanism.

Predictors for emergency readmission in patients with ureteral calculi: a focus on pain management and stone location.

BACKGROUND: The management of patients with ureteral calculi in the emergency department (ED) remains challenging due to high revisit rates. PURPOSE: To identify predictors of revisits among patients with ureteral calculi in the ED. DESIGN, SETTING, AND PARTICIPANTS: Data from patients who presented at a tertiary academic hospital in Seoul, Republic of Korea, between February 2018 and December 2019, were analyzed retrospectively. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Variables, including the respiratory rate (RR), estimated glomerular filtration rate (eGFR), duration of pain, number of analgesic doses, location of ureteral calculi, and ED length of stay (LOS) were examined using logistic regression. We also examined some additional variables included in the STONE and CHOKAI scoring systems to examine their association with revisit. RESULTS: Significant predictors of revisits included the number of analgesic doses and the location of ureteral calculi. Patients who required multiple analgesic doses or those with proximal or mid-ureteral calculi were more likely to revisit the ED. Although the STONE and CHOKAI scores could predict uncomplicated ureteral calculi, we found that the CHOKAI score is a valuable tool for predicting the likelihood of patient revisits (p = 0.021). CONCLUSIONS: Effective pain management and consideration of calculi location are important for predicting patient revisits. More research is required to validate findings, develop precise predictive models, and empower tailored care for high-risk patients. In patients with ureteral calculi in the ED, the number of analgesics given and stone location predict return visits. Proximal ureteral calculi on CT may require early urologic intervention to prevent pain-related revisits.

Changes in agricultural nitrogen (N) balance of OECD countries and its causes and impacts.

The Organization for Economic Co-operation and Development (OECD) developed soil surface nutrient balance and made it mandatory for member countries to report annual nutrient budgets since 1990. This study aimed to evaluate the status of nitrogen (N) management in member countries and to figure out why N surplus levels differ across countries and how they relate to other agri-environmental indicators, by analyzing the N budgets from 35 OECD countries over the last 30 years. Of the three factors determining N balance (agricultural land area, N input, and N output), agricultural land area decreased in most OECD countries, negatively affecting N balance reduction. However, OECD's average N balance highly decreased from 91 to 46 kg ha-1 over the last 30 years due to the decrease in N input through inorganic fertilizers and manure, especially in EU countries with high N input levels, while N output did not meaningfully change. In comparison, in Japan and Korea, the N balance slightly increased and they became the highest N balance country recently. A higher N balance led to lower N use efficiency and higher ammonia (NH3) and nitrous oxide (N2O) emission intensities. More densely populated countries with smaller agricultural land per capita (ranging from 0.03 to 0.47 ha capita-1) showed a higher N balance (228-80 kg ha-1), presumably due to higher N input for more agricultural production on limited land. The most densely populated countries among OECD members (Belgium, the Netherlands, Korea, and Japan) had similar N input levels. However, two EU countries had much higher N output than two Asian countries due to higher pasture production, which led to a lower N balance and higher N use efficiency. Therefore, highly populated countries with small arable land areas per capita might need multilateral efforts to alleviate agricultural N balance.

Predictive Performance Neutrophil-to-Lymphocyte Ratio of Acute Tonsillitis with Deep Neck Space Infection in Adult Patients.

The aim of this study was to examine the neutrophil-to-lymphocyte ratio (NLR) in patients diagnosed with a deep neck infection (DNI) to identify helpful indicators for the initial differential diagnosis. This study was conducted as a single-center, retrospective cohort study that utilized data from the electronic medical records of patients who visited the emergency department in a tertiary university hospital between February 2018 and April 2022. The study enrolled patients aged ≥18 years who were diagnosed with tonsillitis with or without DNI during the study period. The NLR of patients without DNI was 6.1 ± 5.03, and the NLR of patients with acute tonsillitis with DNI was 8.0 ± 5.67, showing significant differences. The rate of admission in the general wards (GWs) and ICUs was significantly higher in patients with DNI, and the length of hospital stay was also significantly longer in patients with DNI. Older age, male, lower body temperature, C-reactive protein, and NLR were significant independent risk factors for DNI in patients with tonsillitis. The cutoff value for predicting DNI in patients with body temperature <37.5 was 3.09. The NLR of patients with tonsillitis, especially those with normal body temperature, can be used to predict their prognosis.

Pamoic acid-induced peripheral GPR35 activation improves pruritus and dermatitis.

BACKGROUND AND PURPOSE: Pruritic dermatitis is a disease with a considerable unmet need for treatment and appears to present with not only epidermal but also peripheral neuronal complications. Here, we propose a novel pharmacological modulation targeting both peripheral dorsal root ganglion (DRG) sensory neurons and skin keratinocytes. GPR35 is an orphan G-protein-coupled receptor expressed in DRG neurons and has been predicted to downregulate neuronal excitability when activated. Modulator information is currently increasing for GPR35, and pamoic acid (PA), a salt-forming agent for drugs, has been shown to be an activator solely specific for GPR35. Here, we investigated its effects on dermatitic pathology. EXPERIMENTAL APPROACH: We confirmed GPR35 expression in peripheral neurons and tissues. The effect of PA treatment was pharmacologically evaluated in cultured cells in vitro and in in vivo animal models for acute and chronic pruritus. KEY RESULTS: Local PA application mitigated acute non-histaminergic itch and, consistently, obstructed DRG neuronal responses. Keratinocyte fragmentation under dermatitic simulation was also dampened following PA incubation. Chronic pruritus in 1-chloro-2,4-dinitrobenzene and psoriasis models were also moderately but significantly reversed by the repeated applications of PA. Dermatitic scores in the 1-chloro-2,4-dinitrobenzene and psoriatic models were also improved by its application, indicating that it is beneficial for mitigating disease pathology. CONCLUSION AND IMPLICATIONS: Our findings suggest that pamoic acid activation of peripheral GPR35 can contribute to the improvement of pruritus and its associated diseases.

TRPV1 inhibition overcomes cisplatin resistance by blocking autophagy-mediated hyperactivation of EGFR signaling pathway.

Cisplatin resistance along with chemotherapy-induced neuropathic pain is an important cause of treatment failure for many cancer types and represents an unmet clinical need. Therefore, future studies should provide evidence regarding the mechanisms of potential targets that can overcome the resistance as well as alleviate pain. Here, we show that the emergence of cisplatin resistance is highly associated with EGFR hyperactivation, and that EGFR hyperactivation is arisen by a transcriptional increase in the pain-generating channel, TRPV1, via NANOG. Furthermore, TRPV1 promotes autophagy-mediated EGF secretion via Ca2+ influx, which activates the EGFR-AKT signaling and, consequentially, the acquisition of cisplatin resistance. Importantly, TRPV1 inhibition renders tumors susceptible to cisplatin. Thus, our findings indicate a link among cisplatin resistance, EGFR hyperactivation, and TRPV1-mediated autophagic secretion, and implicate that TRPV1 could be a crucial drug target that could not only overcome cisplatin resistance but also alleviate pain in NANOG+ cisplatin-resistant cancer.

Gpr83 Tunes Nociceptor Function, Controlling Pain.

The function of peripheral nociceptors is frequently tuned by the action of G protein-coupled receptors (GPRs) that are expressed in them, which contribute to pain alteration. Expanding new information on such GPRs and predicting their potential outcomes can help to construct new analgesic strategies based on their modulations. In this context, we attempted to present a new GPR not yet acknowledged for its pain association. Gpr83 exhibits relatively high expressions in the peripheral nervous system compared to other tissues when we mined and reconstructed Gene Expression Omnibus (GEO) metadata, which we confirmed using immunohistochemistry on murine dorsal root ganglia (DRG). When Gpr83 expression was silenced in DRG, neuronal and behavioral nociception were all downregulated. Pathologic pain in hind paw inflammation and chemotherapy-induced peripheral neuropathy were also alleviated by this Gpr83 knockdown. Dependent on exposure time, the application of a known endogenous Gpr83 ligand PEN showed differential effects on nociceptor responses in vitro. Localized PEN administration mitigated pain in vivo, probably following Gq/11-involved GPR downregulation caused by the relatively constant exposure. Collectively, this study suggests that Gpr83 action contributes to the tuning of peripheral pain sensitivity and thus indicates that Gpr83 can be among the potential GPR targets for pain modulation.

Drosophila ppk19 encodes a proton-gated and mechanosensitive ion channel.

In Drosophila larvae, nociceptive mdIV sensory neurons detect diverse noxious stimuli and prompt a nociceptive rolling response. Intriguingly, the same neurons also regulate stereotyped larval movement. The channels responsible for transducing these stimuli into electric signals are not yet fully identified. Here we undertook genetic and electrophysiological analysis of Ppk19, a member of the Deg/ENaC family of cationic channels. ppk19 mutants exhibited an impaired nociceptive rolling response upon mechanical force and acid, but no impairment in response to noxious temperature and gentle touch. Mutants also exhibited defective larval movement. RNAi against ppk19 in mdIV neurons likewise produced larvae with defects in mechanical and acid nociception and larval movement, but no impairment in detection of heat and gentle touch. Cultured cells transfected with ppk19 produced currents in acid and hypotonic solution, suggesting that ppk19 encodes an ion channel that responds to acid and cell swelling. Taken together, these findings suggest that Ppk19 acts in mdIV neurons as a proton- and mechano-gated ion channel to mediate acid- and mechano-responsive nociception and larval movement.

Genotyping of Coxiella burnetii from Cattle by Multispacer Sequence Typing and Multiple Locus Variable Number of Tandem Repeat Analysis in the Republic of Korea.

Genotyping of Coxiella burnetii using multispacer sequence typing (MST) and multiple locus variable number tandem repeat analysis (MLVA) was conducted from infected animals for the first time in the Republic of Korea. C. burnetii was detected by real-time PCR, and followed by MST and MLVA genotyping. The result showed that detected C. burnetii all had the same MLVA genotype, 6-13-2-7-9-10 for markers MS23-MS24-MS27-MS28-MS33-MS34, respectively, and genotype group 61 for MST. The same genotypes were previously identified in Poland. Importantly, this MLVA type was detected in humans in France, suggesting that the Korean strain can also potentially cause Q fever in humans. MST and MLVA were very useful tools for analyzing the molecular epidemiology of C. burnetii and helpful for interpreting the epidemiological relationship between isolates from domestic and international resources.

Characterization of Chitinolytic and Antifungal Activities in Marine-Derived Trichoderma bissettii Strains.

Trichoderma fungi have been intensively studied for mycoparasitism, and the latter is closely related to their cell-wall degrading enzymes including chitinase. Here, we studied marine-derived Trichoderma spp., isolated from distinct sources and locations, for chitinolytic and antifungal activity. Based on morphological and phylogenetic analyses, two strains designated GJ-Sp1 and TOP-Co8 (isolated from a marine sponge and a marine alga, respectively) were identified as Trichoderma bissettii. This species has recently been identified as a closely related species to Trichoderma longibrachiatum. The extracellular crude enzymes of GJ-Sp1 and TOP-Co8 showed activities of chitobiosidase and ß-N-acetylglucosaminidase (exochitinase) and chitotriosidase (endochitinase). The optimum chitinolytic activity of the crude enzymes was observed at 50 °C, pH 5.0, 0-0.5% NaCl concentrations, and the activities were stable at temperatures ranging from 10 to 40 °C for 2 h. Moreover, the crude enzymes showed inhibitory activity against hyphal growth of two filamentous fungi Aspergillus flavus and Aspergillus niger. To the best of our knowledge, this is the first report of the chitinolytic and antifungal activity of T. bissettii.

SIAH2 regulates DNA end resection and replication fork recovery by promoting CtIP ubiquitination.

Human CtIP maintains genomic integrity primarily by promoting 5' DNA end resection, an initial step of the homologous recombination (HR). A few mechanisms have been suggested as to how CtIP recruitment to damage sites is controlled, but it is likely that we do not yet have full understanding of the process. Here, we provide evidence that CtIP recruitment and functioning are controlled by the SIAH2 E3 ubiquitin ligase. We found that SIAH2 interacts and ubiquitinates CtIP at its N-terminal lysine residues. Mutating the key CtIP lysine residues impaired CtIP recruitment to DSBs and stalled replication forks, DSB end resection, overall HR repair capacity of cells, and recovery of stalled replication forks, suggesting that the SIAH2-induced ubiquitination is important for relocating CtIP to sites of damage. Depleting SIAH2 consistently phenocopied these results. Overall, our work suggests that SIAH2 is a new regulator of CtIP and HR repair, and emphasizes that SIAH2-mediated recruitment of the CtIP is an important step for CtIP's function during HR repair.

Epidemiology and Clinical Characteristics of Older Patients Transferred from Long-Term-Care Hospitals (LTCHs) to Emergency Departments by a Comparison with Non-LTCHs in South Korea: A Cross-Sectional Observational Study.

The South Korean population is rapidly aging, and the number of older patients in long-term-care hospitals (LTCHs) continues to increase. This study aims to investigate the epidemiologic data, characteristics, and clinical outcomes of patients aged 65 years and older transferred from LTCHs to emergency departments (EDs). This is a retrospective study based on National Emergency Department Information System data from 2014 to 2019. Of the 6,209,695 older patients visiting EDs for disease treatment, 211,141 (3.4%) were transferred from LTCHs. Among patients from LTCHs (211,141), 24.2% were discharged from EDs, 43.0% were admitted to general wards, 20.7% were hospitalized in intensive care units, 3.1% were transferred to another hospital, 6.1% returned to LTCHs, and 2.1% died in EDs. ED stays were the longest for those returning to LTCHs (710.49 ± 1127.43 min). Foley catheterization (40.3%) was most frequently performed in preventable ED visits. In South Korea, older patients being discharged from the ED or returning to LTCHs, after being transferred from LTCHs to EDs, increased. ED stays among older LTCH patients were longer than among non-LTCH older patients, contributing to congestion. To reduce avoidable transfer to EDs from LTCHs, it is necessary to discuss policies, such as expanding appropriate medical personnel and transitional treatment.

Toxoplasma gondii and Rickettsia spp. in ticks collected from migratory birds in the Republic of Korea.

Migratory birds disperse ticks and associated tick-borne pathogens along their migratory routes. Four selected pathogens of medical importance (Coxiella burnetii, Rickettsia spp., Francisella tularensis, and Toxoplasma gondii) were targeted for detection in 804 ticks (365 pools) collected from migratory birds at Hong and Heuksan Islands in the Republic of Korea (ROK) from 2010 to 2011 and 2016. Toxoplasma gondii and Rickettsia spp., were detected in 1/365 (0.27%) and 34/365 (9.32%) pools of ticks, respectively. T. gondii and five rickettsial species were recorded in ticks collected from migratory birds for the first time in ROK. The five rickettsial species (R. monacensis, Candidatus Rickettsia longicornii, R. japonica, R. raoultii, and R. tamurae) were identified using sequence and phylogenetic analysis using ompA and gltA gene fragments. Rickettsia spp. are important pathogens that cause rickettsiosis in humans, with cases recorded in the ROK. These results provide important evidence for the potential role of migratory birds in the introduction and dispersal of T. gondii and Rickettsia spp. along their migratory routes and raise awareness of potential transmission of zoonotic tick-borne pathogens associated with migratory birds in the ROK.

Improving methane mitigating functionality of blast furnace slag by adding electron acceptor.

Blast furnace slag (BFS), a byproduct of iron-producing process, has been applied as silicate fertilizer in rice paddy. Silicate fertilizer contains lime and silicate as main components and iron and manganese as electron acceptors. This amendment improves soil productivity and mitigates methane (CH4) emissions. However, its suppression effect was limited to <20 % at a field level, and its functionality needs improvement to encourage recycling. We hypothesized that the effect of silicate fertilizer on suppressing CH4 emission might improve by increasing electron acceptor concentration. To investigate the feasibility of electron acceptor added silicate fertilizer on increasing CH4 flux suppression, four byproducts of the iron-production process (basic oxygen slag-BOF, ferromanganese slag-FerroMn, iron rust, and Kambara reactor slag-KR) were selected and compared through soil incubation test. Iron rust effectively suppressed CH4 production by 67 %, which is comparable with a 15-30 % reduction of others. To find the optimum mixing ratio of iron rust, it was mixed to BFS with the rate of 0-5 % (wt wt-1), and their effect on CH4 flux was compared. The 3 % mixing ratio highly increased the BFS functionality on suppressing CH4 production. To confirm the field adaptability of the improved BFS, three types of silicate fertilizer (mixing iron rust with the ratios of 0, 2.5, and 5 %) were applied with the recommendation level (1.5 Mg ha-1) before rice transplanting. Seasonal CH4 flux was significantly decreased by the original silicate fertilizer (BFS0) application to 20 % over control. This effectiveness was enhanced by adding 2.5 % iron rust but thereafter, not more increased. Silicate fertilization (BFS0) significantly increased rice grain productivity by 9 % over control, and the improved silicate fertilizer (BFS2.5 & 5.0) more highly increased by 13 %. In conclusion, the BFS's functionality to increase rice productivity and suppress CH4 emission could be improved by adding an effective electron acceptor such as Fe2O3.

Anti-Cancer Effects of YAP Inhibitor (CA3) in Combination with Sorafenib against Hepatocellular Carcinoma (HCC) in Patient-Derived Multicellular Tumor Spheroid Models (MCTS).

PURPOSE: To assess the expression levels of YAP and TAZ in patient-derived HCC tissue and identify the effects of YAP/TAZ inhibition depending on the baseline YAP/TAZ expression when combined with sorafenib using a patient-derived multicellular tumor spheroid (MCTS) model. METHODS: Primary HCC cell lines were established from patient-derived tissue. Six patient-derived HCC cell lines were selected according to YAP/TAZ expression on Western blot: high, medium, low. Then, MCTS was generated by mixing patient-derived HCC cells and stroma cells (LX2, WI38, and HUVECs) and YAP/TAZ expression was assessed using Western blot. Cell viability of MCTS upon 48 h of drug treatment (sorafenib, sorafenib with CA3 0.1 µM, and CA3 (novel YAP1 inhibitor)) was analyzed. RESULTS: Out of six patient-derived HCC cell lines, cell lines with high YAP/TAZ expression at the MCTS level responded more sensitively to the combination therapy (Sorafenib + CA3 0.1 µM) despite the potent cytotoxic effect of CA3 exhibited in all of the patient-derived HCCs. CONCLUSION: Targeting YAP/TAZ inhibition using the novel YAP1 inhibitor CA3 could be a promising therapeutic strategy to enhance sensitivity to sorafenib especially in HCCs with high YAP/TAZ expression in MCTS.

Creating new value of blast furnace slag as soil amendment to mitigate methane emission and improve rice cropping environments.

Blast furnace slag (BFS), a by-product of iron making, has been utilized as silicate fertilizer in Korean and Japanese rice paddy. Silicate fertilizer, which has high contents of active iron and manganese as electron acceptor, was newly known to suppress methane (CH4) emission in flooded rice paddies, but the effect of its long-term application on rice cropping environment is still debatable. To evaluate the effect of silicate fertilization on suppressing CH4 emissions, the changes of CH4 index, indicating the ratio (%) of seasonal CH4 flux at the silicate fertilization treatment to that at the control, were generalized using the global investigation data (42 observations from 8 fields in Bangladesh, China, and Korea). Seasonal CH4 fluxes significantly decreased with increasing silicate fertilization levels. In CH4 index changes, 1.5 Mg ha-1 of silicate fertilizer application (the recommended level of rice cultivation in Korea) decreased by 15% of seasonal CH4 fluxes. Rice grain yield highly increased with increasing silicate fertilization rates and maximized at approximately 4 Mg ha-1 with 18% higher than no-silicate fertilization due to overall improvement of soil properties. To evaluate the long-term silicate fertilization effect on rice cropping environments, silicate (1.5 Mg ha-1 year-1) and non-silicate fertilization treatments were installed in a typical temperate-monsoon climate paddy field in South Korea in 1990. Periodic silicate fertilization significantly increased rice grain productivity by an average of 14% over the control for the last 28 years. This fertilization evidently improved rice quality without changes in chemical quality. Consecutive silicate fertilization effectively improved soil physical and chemical properties but did not increase any acid extractable heavy metal concentration in soil. In conclusion, BFS as silicate fertilizer could be a beneficial amendment to mitigate CH4 emission in the rice paddy and improve soil properties and rice productivity and quality without hazardous material accumulation.

A new approach to suppress methane emissions from rice cropping systems using ethephon.

Rice is the main staple food for more than half of the world's population. Yet, rice cultivation is subjected to criticism because of its important role in methane (CH4) emissions. Although several agronomic practices such as controlled irrigation and conservation tillage have been widely adopted to mitigate CH4 emissions from rice cultivation, the benefits gained by these practices are highly dependent on site-specific soil and climate conditions, and often offset by yield reduction. The use of plant growth regulating compounds having the potential to increase the crop yield and mitigate CH4 emissions may be an innovative approach to sustainable agriculture. Ethylene (C2H4), a plant growth regulator is known to have a strong inhibitory effect on methanogenesis. However, due to gaseous form and low water solubility, C2H4 has not been used to suppress methanogenesis in paddy fields. To develop C2H4 as a prospective soil amendment for reducing methane (CH4) emissions, ethephon (2-Chloroethylphosphonic acid), a precursor of C2H4 was tested. We found that ethephon reduced CH4 formation by 43%, similar to other well known methanogenic inhibitors (2-Bromoethanesulfonate, 2-Chlomoethanesulfonate, 2-Mercaptoethanesulfonate). However, ethephon rapidly hydrolyzed to C2H4 and methanogenic activity recuperated completely after C2H4 removal. To slow down the release of C2H4, ethephon was mixed with bio-degradable polymers such as cellulose acetate and applied to paddy soils. We found that compared with the control, the C2H4 release of ethephon slowed down to 90 days, and the CH4 emissions were reduced by 90%. The application of ethephon at lower concentrations did not significantly alter bacterial communities, their relative abundance, and the abundance of methanotrophs, but it significantly reduced archaeal communities and the relative abundance and expression level of methanogens in paddy soils. Results suggest that cellulose acetate-mixed ethephon has great promise to suppress CH4 emissions in rice paddies while ensuring sustainable yields.

Uncertainty of methane emissions coming from the physical volume of plant biomass inside the closed chamber was negligible during cropping period.

In rice paddy, the closed chamber method is broadly used to estimate methane (CH4) emission rate. Since rice plants can significantly affect CH4 production, oxidation and emission, rice plantation inside the chamber is standardized in IPCC guidelines. Methane emission rate is calculated using the increased concentration inside the headspace. Biomass growth might decrease the headspace volume, and thus CH4 emission rates might be overestimated. To evaluate the influence of chamber headspace decreased by rice plant development on CH4 emission rates, five Korean rice cultivars were cultivated in a typical rice paddy, and physical volume changes in rice biomass were assayed using water displacement method. The recommended acrylic closed chambers (H. 1.2 m x W. 0.6 m x L. 0.6 m) were installed, and eight rice plants were transplanted inside the chamber with the same space interval with the outside. Biomass growth significantly decreased the headspace volume of the chamber. However, this volume covered only 0.48-0.55% of the closed chamber volume at the maximum growth stage. During the whole cropping period, mean 0.24-0.28% of chamber headspace was allocated by plant biomass, and thus this level of total CH4 emissions was overestimated. However, this overestimation was much smaller than the errors coming from other investigation processes (i.e., chamber closing hour, temperature recording, inconstant flooding level, different soil environments, etc.) and rice physiological changes. In conclusion, the influence of physical biomass volume inside the closed chamber was negligible to make the error in total CH4 emission assessment in rice paddies.

Molecular Detection and Phylogenetic Analysis of Tick-Borne Pathogens in Ticks Collected from Horses in the Republic of Korea.

The horse industry has grown rapidly as a leisure industry in the Republic of Korea (ROK) in parallel with an increased demand for equestrian activities. As a result, there has been an increase in horse breeding and equestrian population and potential exposure to ticks and their associated pathogens. To provide a better understanding of the potential disease risks of veterinary and medical importance, a study was conducted to determine the geographical distribution and diversity of ticks collected from horses and vegetation associated with horse racetracks/ranches throughout the ROK. This included a survey of five associated common pathogens, Anaplasma phagocytophilum, Ehrlichia chaffeensis, Borrelia spp., Babesia caballi, and Theileria equi. A total 9220 ticks were collected from horses and associated pastures. Ticks were identified to species, stage of development, and sex. Two species of ticks, Haemaphysalis longicornis (99.9%) and Ixodes nipponensis (0.1%) were identified. Two of the target pathogens, A. phagocytophilum and Borrelia spp., were detected in 5/1409 tick pools (0.35%) and 4/1409 pools (0.28%) of H. longicornis, respectively, both of which are zoonotic pathogens of medical importance. The results of 16S rRNA phylogenetic analysis of A. phagocytophilum showed a close relationship to strains distributed in China, USA, Germany, Italy, Turkey, and Poland. Borrelia spp. showed a close relationship, based on 16S rRNA gene, to the strains reported from the USA (B. burgdorferi and B. americana) and Japan (B. tanukii and B. garinii). These results provide information about the potential risks of veterinary and medical importance and the development of mitigation strategies for disease prevention.

The role of oxytocin, vasopressin, and their receptors at nociceptors in peripheral pain modulation.

Oxytocin and vasopressin are neurohypophyseal hormones with sequence similarity and play a central role in bodily homeostatic regulation. Pain is currently understood to be an important phenotype that those two neurohormones strongly downregulate. Nociceptors, the first component of the ascending neural circuit for pain signals, have constantly been shown to be modulated by those peptides. The nociceptor modulation appears to be critical in pain attenuation, which has led to a gradual increase in scientific interest about their physiological processes and also drawn attention to their translational potentials. This review focused on what are recently understood and stay under investigation in the functional modulation of nociceptors by oxytocin and vasopressin. Effort to produce a nociceptor-specific view could help to construct a more systematic picture of the peripheral pain modulation by oxytocin and vasopressin.