Search

Salterns are hypersaline environments that are inhabited by diverse halophilic microorganisms, including fungi. In this study, we isolated a fungal strain SK1-1 from a saltern in the Republic of Korea, which was identified as Asperillus reticulatus. This is the first reported saline-environment-derived A. reticulatus that belongs to the Aspergillus penicillioides clade and encompasses xerophilic fungi. SK1-1 was halophilic, obligately requiring NaCl for growth, with a maximum radial growth of 6%–9% (w/v) NaCl. To facilitate the biotechnological application of halophilic fungi, we screened the SK1-1 strain for proteolytic activity. Proteases have widespread applications in food processing, detergents, textiles, and waste treatment, and halophilic proteases can enable protein degradation in high salt environments. We assessed the proteolytic activity of the extracellular crude enzyme of SK1-1 using azocasein as a substrate. The crude protease exhibited maximum activity at 40–50 °C, pH 9.5–10.5, and in the absence of NaCl. It was also able to retain up to 69% of its maximum activity until 7% NaCl. Protease inhibitor assays showed complete inhibition of the proteolytic activity of crude enzymes by Pefabloc® SC. Our data suggest that the halophilic A. reticulatus strain SK1-1 produces an extracellular alkaline serine protease.

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.

Genotyping of

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.

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.

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.

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.

Objective To evaluate the impact of surgical simulation training using a three-dimensional (3D)-printed model of tetralogy of Fallot (TOF) on surgical skill development. Materials and methods A life-size congenital heart disease model was printed using a Stratasys Object500 Connex2 printer from preoperative electrocardiography-gated CT scans of a 6-month-old patient with TOF with complex pulmonary stenosis. Eleven cardiothoracic surgeons independently evaluated the suitability of four 3D-printed models using composite Tango 27, 40, 50, and 60 in terms of palpation, resistance, extensibility, gap, cut-through ability, and reusability of. Among these, Tango 27 was selected as the final model. Six attendees (two junior cardiothoracic surgery residents, two senior residents, and two clinical fellows) independently performed simulation surgeries three times each. Surgical proficiency was evaluated by an experienced cardiothoracic surgeon on a 1-10 scale for each of the 10 surgical procedures. The times required for each surgical procedure were also measured. Results In the simulation surgeries, six surgeons required a median of 34.4 (range 32.5-43.5) and 21.4 (17.9-192.7) minutes to apply the ventricular septal defect (VSD) and right ventricular outflow tract (RVOT) patches, respectively, on their first simulation surgery. These times had significantly reduced to 17.3 (16.2-29.5) and 13.6 (10.3-30.0) minutes, respectively, in the third simulation surgery (p = 0.03 and p = 0.01, respectively). The decreases in the median patch appliance time among the six surgeons were 16.2 (range 13.6-17.7) and 8.0 (1.8-170.3) minutes for the VSD and RVOT patches, respectively. Summing the scores for the 10 procedures showed that the attendees scored an average of 28.58 ± 7.89 points on the first simulation surgery and improved their average score to 67.33 ± 15.10 on the third simulation surgery (p = 0.008). Conclusion Inexperienced cardiothoracic surgeons improved their performance in terms of surgical proficiency and operation time during the experience of three simulation surgeries using a 3D-printed TOF model using Tango 27 composite.

Background/aim Non-structural maintenance of chromosomes condensin I complex subunit H (NCAPH) is implicated in correct chromosome condensation and segregation during mitosis. However, the functional role of NCAPH in the pathogenesis of non-small-cell lung cancer (NSCLC) remains unclear. The aim of this study was to elucidate the role of NCAPH in NSCLC cells. Materials and methods A549 and H1299 NSCLC cells were transfected with small-interfering RNA (siRNA) against NCAPH. Subsequently, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony-formation assay and flow cytometry analysis were performed to reveal the role of NCAPH in NSCLC cells. In addition, migration and invasion assay were also performed. Results NCAPH knockdown inhibited cell proliferation, induced cell-cycle arrest at G2/M phase, and prevented colony formation, migration and invasion by NSCLC cells. Conclusion NCAPH is involved in NSCLC progression and development, and may be a potential therapeutic target for NSCLC treatment.

Marine yeasts have tremendous potential in industrial applications but have received less attention than terrestrial yeasts and marine filamentous fungi. In this study, we have screened marine yeasts for amylolytic activity and identified an amylase-producing strain PH-Gra1 isolated from sea algae. PH-Gra1 formed as a coral-red colony on yeast–peptone–dextrose (YPD) agar; the maximum radial growth was observed at 22 °C, pH 6.5 without addition of NaCl to the media. Based on the morphology and phylogenetic analyses derived from sequences of internal transcribed spacer (ITS) and a D1/D2 domain of large subunit of ribosomal DNA, PH-Gra1 was designated Sporidiobolus pararoseus. S. pararoseus is frequently isolated from marine environments and known to produce lipids, carotenoids, and several enzymes. However, its amylolytic activity, particularly the optimum conditions for enzyme activity and stability, has not been previously characterized in detail. The extracellular crude enzyme of PH-Gra1 displayed its maximum amylolytic activity at 55 °C, pH 6.5, and 0%–3.0% (w/v) NaCl under the tested conditions, and the activity increased with time over the 180-min incubation period. In addition, the crude enzyme hydrolyzed potato starch more actively than corn and wheat starch, and was stable at temperatures ranging from 15 °C to 45 °C for 2 h. This report provides a basis for additional studies of marine yeasts that will facilitate industrial applications.

Background/aim Alpha/beta-hydrolase domain containing 12 (ABHD12) is a serine hydrolase that regulates immunological and neurological mechanisms. This study aimed to elucidate the oncogenic effect of ABHD12 on human breast cancer. Materials and methods ABHD12 expression was confirmed in breast cancer tissues and breast cancer cell lines by immunohistochemistry and quantitative RT-PCR. To determine the role of ABHD12, ABHD12 siRNA-suppressed breast cancer cells (MCF7 and MDA-MB-231 cells) were investigated for cell proliferation, migration, and invasion capabilities using MTT assays, EdU assays, colony formation assays, and Boyden chamber assays. Results Immunohistochemical staining showed a higher ABHD12 expression in breast cancer tissues than in normal tissues. Additionally, ABHD12 knockdown was found to inhibit cell growth, proliferation, migration, and invasion in breast cancer cells. Conclusion ABHD12 plays a crucial role in cell proliferation, migration, and invasion of breast cancer cells.

Salterns are hypersaline environments that are inhabited by diverse halophilic microorganisms, including fungi. In this study, we isolated a fungal strain SK1-1 from a saltern in the Republic of Korea, which was identified as Asperillus reticulatus. This is the first reported saline-environment-derived A. reticulatus that belongs to the Aspergillus penicillioides clade and encompasses xerophilic fungi. SK1-1 was halophilic, obligately requiring NaCl for growth, with a maximum radial growth of 6%–9% (w/v) NaCl. To facilitate the biotechnological application of halophilic fungi, we screened the SK1-1 strain for proteolytic activity. Proteases have widespread applications in food processing, detergents, textiles, and waste treatment, and halophilic proteases can enable protein degradation in high salt environments. We assessed the proteolytic activity of the extracellular crude enzyme of SK1-1 using azocasein as a substrate. The crude protease exhibited maximum activity at 40–50 °C, pH 9.5–10.5, and in the absence of NaCl. It was also able to retain up to 69% of its maximum activity until 7% NaCl. Protease inhibitor assays showed complete inhibition of the proteolytic activity of crude enzymes by Pefabloc® SC. Our data suggest that the halophilic A. reticulatus strain SK1-1 produces an extracellular alkaline serine protease.

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.

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.

Ticks are important vectors of various pathogens that result in clinical illnesses in humans and domestic and wild animals. Information regarding tick infestations and pathogens transmitted by ticks is important for the identification and prevention of disease. This study was a large-scale investigation of ticks collected from dogs and their associated environments in the Republic of Korea (ROK). It included detecting six prevalent tick-borne pathogens (Anaplasma spp., A. platys, Borrelia spp., Babesia gibsoni, Ehrlichia canis, and E. chaffeensis). A total of 2293 ticks (1110 pools) were collected. Haemaphysalis longicornis (98.60%) was the most frequently collected tick species, followed by Ixodes nipponensis (0.96%) and H. flava (0.44%). Anaplasma spp. (24/1110 tick pools, 2.16%) and Borrelia spp. (4/1110 tick pools, 0.36%) were detected. The phylogenetic analyses using 16S rRNA genes revealed that the Anaplasma spp. detected in this study were closely associated with A. phagocytophilum reported in humans and rodents in the ROK. Borrelia spp. showed phylogenetic relationships with B. theileri and B. miyamotoi in ticks and humans in Mali and Russia. These results demonstrate the importance of tick-borne disease surveillance and control in dogs in the ROK.

Modulation of the function of somatosensory neurons is an important analgesic strategy, requiring the proposal of novel molecular targets. Many G-protein-coupled receptors (GPRs) have been deorphanized, but the receptor locations, outcomes due to their activations, and their signal transductions remain to be elucidated, regarding the somatosensory nociceptor function. Here we report that GPR171, expressed in a nociceptor subpopulation, attenuated pain signals via Gi/o-coupled modulation of the activities of nociceptive ion channels when activated by its newly found ligands. Administration of its natural peptide ligand and a synthetic chemical ligand alleviated nociceptor-mediated acute pain aggravations and also relieved pathologic pain at nanomolar and micromolar ranges. This study suggests that functional alteration of the nociceptor neurons by GPR171 signaling results in pain alleviation and indicates that GPR171 is a promising molecular target for peripheral pain modulation.

Excessive nutrient balance is a very crucial issue for environmental hazards. The constant addition of high-amounts of nutrient sources in agricultural production generates negative environmental conditions in Korea and Japan yet to be resolved. Therefore, it is obligatory to comprehend the nutrient (nitrogen (N) and phosphorus (P)) balance that is assessed by the difference between nutrient input and output in the soil surface in Korea and Japan. Among 34 Economic Co-operation and Development (OECD) countries, Korea and Japan had the highest N and P balances and thus both countries are primarily responsible for severe environmental pollution via nutrient release. The cultivable land area in both countries has constantly decreased during 1990–2017 at approximately 20 and 15% in Korea and Japan, respectively. Even N and P use efficiency sharply decreased with increasing N and P balance in both targeted countries. Japanese P balance, Korean N and P balances were decreased after the mid-1990s whereas, Japanese N balance almost unchanged for the last 28 years. Unlike chemical fertilizer input, Korean manure input level significantly increased from 78 kg N ha−1 in 1990 to 157 kg N ha−1 in 2017. Japanese manure input level was higher than that of chemical fertilizer without any big change for the last 28 years. The lion share of high N and P balance in both countries could generate from manure inputs, therefore, the number of livestock and their produced debris need to be used with more cautious for the reduction of national N and P surpluses at a benchmark level. These findings ensure to make a more environment friendly policy that can further reduce nutrient balance as well as improve soil health.

Background Q fever, a zoonosis caused by Coxiella burnetii, has adverse effects on public health. Ticks are vectors of C. burnetii and they contribute to the transmission of the pathogen. A tool for rapid, sensitive, and accurate detection of C. burnetii from ticks is important for the prevention of Q fever. Methods Ultra-rapid real-time PCR (UR-qPCR) as a chip-based real-time PCR system was developed for the detection of C. burnetii from ticks. The UR-qPCR system was established and evaluated for the rapidity, sensitivity, and specificity of C. burnetii detection. Results C. burnetii was detected using UR-qPCR from 5644 larval, nymphal, and adult ticks from 408 pools collected from livestock and epidemiologically linked environments in two provinces, Gangwon and Jeju, in Korea. Ticks from three species were identified; Haemaphysalis longicornis accounted for the highest number, present in 333 of 408 pools (81.62%), followed by Haemaphysalis flava in 62 pools (15.19%) and Ixodes nipponensis in 13 pools (3.19%). The rapidity and sensitivity of PCR detection was demonstrated with the sufficient amplification and detection of approximately 56 copies of C. burnetii DNA with only 20 min of PCR amplification. The kappa value for the diagnostic agreement between UR-qPCR and stationary qPCR was in perfect agreement (κ = 1). PCR detection and sequencing indicated that C. burnetii was present in 5 of the 408 pools (1.23%), in which four pools contained H. longicornis and one pool contained H. flava. The infection rates of C. burnetii in the tick pools collected from Gangwon and Jeju Provinces were 1.70% and 0.58%, respectively. Phylogenetic analysis indicated a close relationship between the detected C. burnetii and those originating from goats, humans, and ticks in different countries, such as the USA, France, Germany, and Serbia. Conclusions The methods described in this study could be important for the prevention and control of Q fever in the two provinces. The UR-qPCR, with its features of mobility, sensitivity, and rapidity, is helpful for constructing early alert systems in the field for C. burnetii in ticks and could help alleviate the transmission of and economic damage due to Q fever. Graphical Abstract

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.

Hypovolemia is a major risk factor for morbidity and mortality among elderly older patients. The inferior vena cava (IVC) diameter is known to predict the fluid volume status in ill patients. This study aimed to evaluate the predictive performance of the IVC diameter ratio, as determined by computed tomography (CT), for poor outcomes among low risk patients 65 years of age and older. This single-center retrospective study was conducted on patients who taken CT during the clinical process between January 2019 and December 2020. IVC diameter ratio measurement was estimated by dividing the maximum value of the anteroposterior diameter from the maximum value of transverse diameter at the level right above the renal vein. The IVC diameter ratio’s prognostic performance was evaluated by using the area under the receiver operating characteristic (AUROC) curve. The mean IVC diameter ratio was 1.78. Multivariable logistic regression analysis revealed age, pulse rate, aspartate aminotransferase level, and IVC diameter ratio as significant risk factors for in-hospital death. The area under the receiver operating curve for predicting death using the IVC diameter ratio of patients with pulse rates under 95 was 0.701 and the cut-off value was 1.638, with an 88.9% sensitivity and 45.2% specificity. The odds ratio for higher IVC diameter ratio values was statistically significant (p = 0.031) for predicting in-hospital death. IVC measurement using abdomen& pelvic computed tomography (APCT ) demonstrated capability for predicting poor outcomes, including all-cause mortality among older patients with low risk in the emergency department.

Background/aim Caspase recruitment domain family, member 14 (CARD14) is a member of the CARD family of proteins, which play an important role in immune and inflammatory response, and cell survival and proliferation. Here, we identified the role of CARD14 in human breast cancer. Materials and methods Immunohistochemistry was performed to evaluate CARD14 expression in breast cancer. Using CARD14 knockdown cells by small interfering RNA, colony formation and MTT assays, flow cytometry analyses, and migration assays were performed to evaluate the proliferation, cell cycle distribution, apoptosis, and migration ability of MCF7 and SK-BR-3 cells. Results CARD14 expression was significantly higher in breast cancer samples than in normal breast samples. CARD14 knockdown inhibited cell proliferation and migration, caused cell cycle arrest at the G1/S boundary, and promoted apoptosis. Conclusion CARD14 regulates the proliferation and migration of MCF7 and SK-BR-3 cells; it is thus, a novel potential therapeutic target in breast cancer.

Background and Objectives: Patients who overdose on doxylamine, hypnotic agent, usually exhibit good outcomes, but some experience serious complications. Some patients who present with normal creatinine phosphokinase levels in the emergency department later develop rhabdomyolysis during observation. We investigated factors associated with delayed-onset rhabdomyolysis in patients with doxylamine overdoses. Methods: Our investigation period was between 1 January 2011 and 29 February 2016. The initial blood samples were obtained for arterial blood gas analysis and measurements of the levels of electrolytes, creatinine phosphokinase, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase. Urine analyses including pH and occult blood analyses were performed. Follow-up samples were obtained at 6 and 12 h after admission. Delayed-onset rhabdomyolysis was defined by a follow-up serum creatinine phosphokinase level greater than fivefold the upper limit of normal (>1000 IU/L). Comparisons of categorical variables between groups were performed using either the χ2 or Fisher exact tests. Continuous variables were compared between groups using the Mann–Whitney U test. Results: A total of 337 patients were enrolled. The large amount of ingested doxylamine (odds ratio = 7.002), tachycardia (odds ratio = 2.809), low arterial blood gas analysis pH (odds ratio = 2.267), and presence of occult blood in the urine (odds ratio = 2.048) were significant associated with delayed-onset rhabdomyolysis. Conclusion: Laboratory follow-up examinations were required for patients, ingested more than 18 mg/kg doxylamine poisoning, who had pulses exceeding 120 beats/min, had arterial blood gas analysis pH values below 7.3 on blood and urine testing, and/or exhibited the presence of occult blood in the urine, even if the initial creatinine phosphokinase level was normal.

Animals must detect aversive compounds to survive. Bitter taste neurons express heterogeneous combinations of bitter receptors that diversify their response profiles, but this remains poorly understood. Here we describe groups of taste neurons in Drosophila that detect the same bitter compounds using unique combinations of gustatory receptors (GRs). These distinct complexes also confer responsiveness to non-overlapping sets of additional compounds. While either GR32a/GR59c/GR66a or GR22e/GR32a/GR66a heteromultimers are sufficient for lobeline, berberine, and denatonium detection, only GR22e/GR32a/GR66a responds to strychnine. Thus, despite minimal sequence-similarity, Gr22e and Gr59c show considerable but incomplete functional overlap. Since the gain- or loss-of-function of Gr22e or Gr59c alters bitter taste response profiles, we conclude a taste neuron’s specific combination of Grs determines its response profile. We suspect the heterogeneity of Gr expression in Drosophila taste neurons diversifies bitter compound detection, improving animal fitness under changing environmental conditions that present a variety of aversive compounds., Taste sensilla are Drosophila sensory organs containing taste neurons, which have differential tuning for bitter compounds. Here, the authors systematically examine what combinations of gustatory receptor genes confer a specific taste response profile in different bitter taste neurons.

Neurofibromatosis 1 is an autosomal dominant disorder characterized by cafe-au-lait spots, cutaneous neurofibroma, and bony deformities. Vascular abnormality such as stenosis, aneurysm, or rupture associated with neurofibromatosis 1 is rare. Rupture of vertebral artery aneurysm into the thoracic cavity is extremely rare. The outcomes of patients with aneurysmal ruptures are very poor when spontaneous hemothorax occur. A 31-year-old woman presented to the emergency department with left shoulder pain and with both lower chest wall pain and left supraclavicular area swelling. The chest computed tomography scan revealed about 4-cm pseudo-aneurysm probable arising from the left vertebral artery with large hematoma at left supraclavicular area. Neurofibromatosis 1 is generally being regarded as a benign disease but has the potential for serious vascular complications. When aneurysms were ruptured, cervical hematoma, hemothorax, or hypotension was developed. It is potentially a life-threatening condition, so it must require emergent management. Emergency physicians must remember the relation of neurofibromatosis 1 and serious vascular complications and ensure rapid access to rule out vascular lesions, so as to prevent the life-threatening condition.

Introduction: In the background of the increased suicide rate in the second decade of life, analysis of the characteristics of poisoning-related attempted suicide in adolescents and evaluation of the differences from adults may form an important basis for establishing measures to prevent deaths from poisoning. Objective: We aimed to investigate the types of toxic substances ingested for attempted suicide by poisoning in adolescents admitted to the emergency department (ED). Method: This cross-sectional study retrospectively analyzed and investigated the medical records of patients aged 13 or older, admitted to the ED of a tertiary medical institute over a period of 3 years, for attempted suicide by poisoning. Results: The psychiatric diagnoses among patients in the adolescent group included depression (75.8%), bipolar disorder (12.5%), and panic disorder (12.5%). In terms of the type of drug used for poisoning, antidepressants or anti-psychotics and sleeping pills were the most commonly used in the adolescent (43 subjects, 45.2%) and adult (286 subjects, 37.6%) groups, respectively. Conclusion: As there is a higher chance of poisoning by easily accessible drugs, the emergency physician needs to investigate any preceding diagnoses of psychiatric or medical illnesses in the adolescent patients attempting suicide with unknown drugs.

Peripheral nociceptors and their synaptic partners utilize neuropeptides for signal transmission. Such communication tunes the excitatory and inhibitory function of nociceptor-based circuits, eventually contributing to pain modulation. Corticotropin-releasing hormone (CRH) is the initiator hormone for the conventional hypothalamic-pituitary-adrenal axis, preparing our body for stress insults. Although knowledge of the expression and functional profiles of CRH and its receptors and the outcomes of their interactions has been actively accumulating for many brain regions, those for nociceptors are still under gradual investigation. Currently, based on the evidence of their expressions in nociceptors and their neighboring components, several hypotheses for possible pain modulations are emerging. Here we overview the historical attention to CRH and its receptors on the peripheral nociception and the recent increases in information regarding their roles in tuning pain signals. We also briefly contemplate the possibility that the stress-response paradigm can be locally intrapolated into intercellular communication that is driven by nociceptor neurons. Such endeavors may contribute to a more precise view of local peptidergic mechanisms of peripheral pain modulation.

Highlights • Fisetin inhibits PI3K activity at the enzymatic and cellular levels. • Fisetin induces the apoptosis of Raji cells by downregulating cIAP-2 protein expression. • The pro-apoptotic activity of fisetin may be linked to a potential to inhibit mTOR signaling and to induce DNA damage., Aberrant regulation of phosphatidylinositol-3-kinases (PI3Ks) is known to be involved in the progression of cancers. PI3K-binding flavonoids such as quercetin and myricetin have been shown to inhibit PI3K activity, but the direct targeting of fisetin to PI3K has not been established. Here, we carried out an in silico investigation of fisetin binding to PI3K and determined fisetin’s inhibitory activity in enzymatic and cell-based assays. In addition, fisetin induced apoptosis in human Burkitt’s lymphoma Raji cells by inhibiting both PI3Ks and mammalian target of rapamycin (mTOR). Our results indicate that fisetin may serve as a natural backbone for the development of novel dual inhibitors of PI3Ks and mTOR for the treatment of cancer.

Endogenous pain-inhibitory substances have rarely been found. A group of powerful pain suppressor molecules that are endogenously generated are now emerging: resolvins and related compounds including neuroprotectins and maresins. These molecules began to be unveiled in a series of inflammation studies more than a decade ago, rapidly shifting the paradigm that explains the mechanism for the inflammatory phase switch. The resolution phase was considered a passive process as proinflammatory mediators disappeared; it is now understood to be actively drawn by the actions of resolvins. Surprisingly, these substances potently affect the pain state. Although this research area is not fully matured, consistently beneficial outcomes have been observed in a variousin vivoandin vitropain models. Furthermore, multiple hypotheses on the neuronal and molecular mechanisms for alleviating pain are being tested, deriving inspiration from existing inflammation and pain studies. This paper serves as a brief summary of the proresolving roles of resolvins and related lipid mediators in inflammation and also as a review for accumulated information of their painkilling actions. This also includes potential receptor-mediated mechanisms and discusses future scientific perspectives. Further diverse approaches will help to construct a hidden axis of natural protection principles and establish proofs of concept for pain relief.