Genotoxicity and safety pharmacology of the rVSVInd(GML)-mspSGtc vaccine against SARS-CoV-2 in Sprague-Dawley rats and Beagle dogs.

The emergence of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a pandemic, prompting rapid vaccine development. Although vaccines are effective, the occurrence of rare adverse events following vaccination highlights the necessity of determining whether the benefits outweigh the risks posed by the infection itself. The recombinant Vesicular Stomatitis Virus (rVSV) platform is a promising vector for vaccines against emerging viruses. However, limited studies have evaluated the genotoxicity and safety pharmacology of this viral vector vaccine, which is crucial to ensure the safety of vaccines developed using this platform. Hence, the present study aimed to assess the genotoxicity and safety pharmacology of the rVSVInd(GML)-mspSGtc COVID-19 vaccine using micronucleus and comet assays, as well as neurobehavioral, body temperature, respiratory, and cardiovascular assessments in Sprague-Dawley rats and beagle dogs. The intramuscular administration of rVSVInd(GML)-mspSGtc at doses up to 1.5 × 109 PFU/animal did not increase the number of bone marrow micronucleated polychromatic erythrocytes or cause liver DNA damage. Additionally, it had no significant impact on neurobehavioral functions in rats and showed marginal temporary changes in body temperature, respiratory rate, heart rate, and electrocardiogram parameters in rats and dogs, all of which resolved within 24 h. Overall, following genotoxicity and pharmacological safety assessments, rVSVInd(GML)-mspSGtc displayed no notable systemic adverse effects in rats and dogs, suggesting its potential as a vaccine candidate for human clinical trials.

Preclinical evaluation of general toxicity and safety pharmacology of a receptor-binding domain-based COVID-19 subunit vaccine in various animal models.

The coronavirus disease 2019 pandemic has resulted in the introduction of several naïve methods of vaccine development, which have been used to prepare novel viral vectors and mRNA-based vaccines. However, reluctance to receive vaccines owing to the uncertainty regarding their safety is prevalent. Therefore, rigorous safety evaluation of vaccines through preclinical toxicity studies is critical to determine the safety profiles of vaccine candidates. This study aimed to evaluate the toxicity profile of HuVac-19, a subunit vaccine of SARS-CoV-2 utilizing the receptor-binding domain as an antigen, in rats, rabbits, and dogs using single- and repeat-dose study designs. Repeat-dose toxicity studies in rats and rabbits showed transient changes in hematological and serum biochemical parameters in the adjuvant and/or vaccine groups; however, these changes were reversed or potentially reversible after the recovery period. Moreover, temporary reversible changes in absolute and relative organ weights were observed in the prostate of rats and the thymus of rabbits. Gross examination of the injection sites in rats and rabbits treated with the adjuvant- and HuVac-19 showed discoloration and foci, whereas histopathological examination showed granulomatous inflammation, inflammatory cell infiltration, and myofiber degeneration/necrosis. This inflammatory response was local, unassociated with other toxicological changes, and resolved. In a pharmacological safety study, no toxicological or physiological changes associated with HuVac-19 administration were observed. In conclusion, HuVac-19 was not associated with any major systemic adverse effects in the general toxicity and safety pharmacology evaluation, demonstrating that HuVac-19 is a vaccine candidate with sufficient capacity to be used in human clinical trials.

Adaptation strategies for future coastal flooding: Performance evaluation of green and grey infrastructure in South Korea.

Climate change is contributing to an increasing frequency and intensity of floods in Korea. This study predicts areas with a high probability of flooding in coastal areas of South Korea owing to future climate change, which is likely to cause extreme rainfall and sea-level rise, using a spatiotemporal downscaled future climate change scenario with random forest, artificial neural network, and k-nearest neighbor techniques. In addition, the change in coastal flooding risk probability according to the application of different adaptation strategies (green spaces and seawalls) was identified. The results showed a clear difference in the risk probability distribution in the absence and presence of either adaptation strategy. Their effectiveness in moderating future flooding risks is subject to change owing to strategy type, geographic region, and urbanization intensity and the results show that green spaces are slightly more effective than seawalls when forecasting for 2050. This demonstrates the importance of a nature-based strategy. Moreover, this study highlights the need to prepare adaptation measures according to regional characteristics to mitigate the impact of climate change. Korea is surrounded by seas on three sides that have independent geophysical and climate characteristics. The south coast has a higher risk of coastal flooding than the east and west coasts. In addition, a higher urbanization rate is associated with a higher risk probability. This implies that climate change response strategies for coastal cities are necessary as the population and socioeconomic activities of coastal urban areas are likely to increase in the future.

Preclinical assessment of thrombin-preconditioned human Wharton's jelly-derived mesenchymal stem cells for neonatal hypoxic-ischaemic brain injury.

Hypoxic-ischaemic encephalopathy (HIE) is a type of brain injury affecting approximately 1 million newborn babies per year worldwide, the only treatment for which is therapeutic hypothermia. Thrombin-preconditioned mesenchymal stem cells (MSCs) exert neuroprotective effects by enriching cargo contents and boosting exosome biogenesis, thus showing promise as a new therapeutic strategy for HIE. This study was conducted to evaluate the tissue distribution and potential toxicity of thrombin-preconditioned human Wharton's jelly-derived mesenchymal stem cells (th-hWJMSCs) in animal models before the initiation of clinical trials. We investigated the biodistribution, tumorigenicity and general toxicity of th-hWJMSCs. MSCs were administered the maximum feasible dose (1 × 105 cells/10 µL/head) once, or at lower doses into the cerebral ventricle. To support the clinical use of th-hWJMSCs for treating brain injury, preclinical safety studies were conducted in newborn Sprague-Dawley rats and BALB/c nude mice. In addition, growth parameters were evaluated to assess the impact of th-hWJMSCs on the growth of newborn babies. Our results suggest that th-hWJMSCs are non-toxic and non-tumorigenic in rodent models, survive for up to 7 days in the brain and hold potential for HIE therapy.

Selective Generation of Lamb Wave Modes in a Finite-Width Plate by Angle-Beam Excitation Method.

A Lamb wave in a plate with a finite width has both thickness and width modes, whereas only thickness modes exist in an infinitely wide plate. The thickness and width modes are numerously formed in a finite-width plate, and they all have different cut-off frequencies, wave velocities, and wave structures. These different characteristics can be utilized in various applications, but a selective generation method for a particular Lamb wave mode in a finite-width plate has not been sufficiently studied, and only a method using multiple elements has been reported. This paper presents the selective generation of a certain Lamb wave mode in a finite-width plate by an angle-beam excitation method using single or dual wedges. In the proposed generation method, a specially designed wedge with grooves or a patch having insulation layers is employed for partial acoustic insulation of the ultrasonic energy incident into the plate. The feasibility of the proposed method was investigated through finite element method (FEM) simulations for Lamb wave excitation and propagation, and then experimentally demonstrated by the measurement of Lamb wave propagation using a laser scanning vibrometer.

Differential Expression of miRNAs and Behavioral Change in the Cuprizone-Induced Demyelination Mouse Model.

The demyelinating diseases of the central nervous system involve myelin abnormalities, oligodendrocyte damage, and consequent glia activation. Neurotoxicant cuprizone (CPZ) was used to establish a mouse model of demyelination. However, the effects of CPZ on microRNA (miRNA) expression and behavior have not been clearly reported. We analyzed the behavior of mice administered a diet containing 0.2% CPZ for 6 weeks, followed by 6 weeks of recovery. Rotarod analysis demonstrated that the treated group had poorer motor coordination than control animals. This effect was reversed after 6 weeks of CPZ withdrawal. Open-field tests showed that CPZ-treated mice exhibited significantly increased anxiety and decreased exploratory behavior. CPZ-induced demyelination was observed to be alleviated after 4 weeks of CPZ treatment, according to luxol fast blue (LFB) staining and myelin basic protein (MBP) expression. miRNA expression profiling showed that the expression of 240 miRNAs was significantly changed in CPZ-fed mice compared with controls. Furthermore, miR-155-5p and miR-20a-5p upregulations enhanced NgR induction through Smad 2 and Smad 4 suppression in demyelination. Taken together, our results demonstrate that CPZ-mediated demyelination induces behavioral deficits with apparent alterations in miRNA expression, suggesting that differences in miRNA expression in vivo may be new potential therapeutic targets for remyelination.

Subchronic oral toxicity study of Korean red ginseng extract in Sprague-Dawley rats with a 4-week recovery period.

Ginseng is a major herbal remedy used in Asian countries for thousands of years and known to restore and enhance vital energy. Korean red ginseng, which is processed by steaming and drying fresh Panax ginseng, is most popular and contains unique ginsenosides, which have anticancer and anti-inflammatory properties. The present study was carried out to evaluate the repeated oral dose toxicity of Korean red ginseng extract. The test article was administered orally once a day to male and female Sprague-Dawley rats at dose levels of 0, 500, 1000, or 2000 mg/kg/day for 13 consecutive weeks (15 animals/sex/group in the vehicle control and 2000 mg/kg/day groups, and 10 animals/sex/group in the 500 and 1000 mg/kg/day groups). Ten animals per group were sacrificed at the end of the 13-week treatment period, and the remaining rats were sacrificed after a 4-week recovery period. Administration of Korean red ginseng extract did not result in any toxicologically significant changes in mortality, body weight, food consumption, ophthalmoscopy, hematology, serum biochemistry, gross pathological findings, absolute/relative organ weights, or histopathology. It was established that the no observed adverse effect level (NOAEL) of the test article was 2000 mg/kg/day for both sexes in this study.

Effects of remifentanil maintenance during recovery on emergence delirium in children with sevoflurane anesthesia.

BACKGROUND: Emergence delirium is a common complication of sevoflurane anesthesia in children. AIMS: We examined the effects of maintaining remifentanil infusion during the recovery period on the incidence of emergence delirium in preschool-age children undergoing strabismus surgery under sevoflurane anesthesia. METHODS: Eighty children (aged 3-7 years) were randomly assigned to either the control group (group C; intraoperative remifentanil infusion) or the intervention group (group R; intraoperative remifentanil infusion followed by remifentanil maintenance during the recovery phase). Intraoperative remifentanil infusion (0.2 µg/kg/min) was discontinued upon surgery completion in the group C, and was maintained until the discharge criteria were met at a dose of 0.05 µg/kg/min in the group R. The incidence of emergence delirium was assessed using a five-point agitation scale and the Pediatric Anesthesia Emergence Delirium scale after arrival in the postanesthesia care unit. Postoperative pain was assessed using the Children's Hospital of Eastern Ontario Pain Scale. RESULTS: The incidence of emergence delirium according to the five-point agitation scale (scores ≥ 4) was lower in the group R (33.3%) compared to the group C (68.3%) (odds ratio 0.206; 95% CI 0.080 to 0.531; P = 0.002). Similar results were obtained using the Pediatric Anesthesia Emergence Delirium scale (scores > 12), with an incidence of 5.1% in the group R and 34.0% in the control group (odds ratio 0.104; 95% CI 0.022 to 0.497; P = 0.001). The Children's Hospital of Eastern Ontario Pain Scale scores and occurrence of postoperative adverse events including laryngospasm, desaturation, nausea, and vomiting were similar between the two groups. CONCLUSION: Maintaining a low dose of remifentanil (0.05 µg/kg/min) throughout the recovery phase attenuated the incidence of emergence delirium in children undergoing strabismus surgery under sevoflurane anesthesia.

Construction of Bacillus thuringiensis Simulant Strains Suitable for Environmental Release.

For a surrogate bacterium to be used in outdoor studies, it is important to consider environmental and human safety and ease of detection. Recently, Bacillus thuringiensis, a popular bioinsecticide bacterium, has been gaining attention as a surrogate bacterium for use in biodefense. In this study, we constructed simulant strains of B. thuringiensis with enhanced characteristics for environmental studies. Through transposon mutagenesis, pigment genes were inserted into the chromosome, producing yellow-colored colonies for easy detection. To prevent persistence of spores in the environment, a genetic circuit was designed to produce a spore without sporulation capability. Two loxP sites were inserted, one on each side of the spo0A gene, which encodes a sporulation master regulator, and a sporulation-dependent Cre expression cassette was inserted into the chromosome. This genetic circuit successfully deleted spo0A during sporulation, producing spores that lacked the spo0A gene. In addition, two major α/ß-type small acid-soluble spore protein (SASP) genes, predicted by synteny analysis, were deleted. The spores of the mutant strain showed increased UV-C sensitivity and quickly lost viability when tested in a solar simulator. When the spores of the mutant strain were administered to the lungs of BALB/c mice, cells were quickly removed from the body, suggesting enhanced in vivo safety. All strains constructed in this study contain no antibiotic resistance markers and all heterologous genes were inserted into the chromosome, which are useful features for simulants to be released into the environment.IMPORTANCEB. thuringiensis has recently been receiving increasing attention as a good spore simulant in biodefense research. However, few studies were done to properly address many important features of B. thuringiensis as a simulant in environmental studies. Since spores can persist in the environment for years after release, environmental contamination is a big problem, especially when genetically engineered strains are used. To solve these problems, we report here the development of B. thuringiensis simulant strains that are capable of forming yellow colonies for easy detection, incapable of forming spores more than once due to a genetic circuit, and lacking in two major SASP genes. The genetic circuit to produce a spore without sporulation capability, together with the deletion of SASP genes, ensures the environmental and human safety of the simulant strains developed in this study. All of these features will allow wider use of B. thuringiensis as a simulant for Bacillus anthracis in environmental release studies.

Potential urinary biomarkers of nephrotoxicity in cyclophosphamide-treated rats investigated by NMR-based metabolic profiling.

The anticancer-drug cyclophosphamide (CP) is known to have nephrotoxicity. The aim of this study was to identify urinary biomarkers indicating CP-induced nephrotoxicity. We investigated the urine metabolic profiles using nuclear magnetic resonance spectrometry of rats administered with single high-doses of CP (0, 30, and 100 mg/kg body weight) and daily low-doses over a 4-week period (0, 1, 3, and 10 mg/kg body weight). Among 18 identified urinary metabolites, 2-oxoglutarate, citrate, hippurate, formate, valine, and alanine for short-term and 2-oxoglutarate, citrate, hippurate, isoleucine, leucine, allantoin, valine, and lysine for long-term were selected as potential biomarkers. Pathway-enrichment analysis suggested that the urinary metabolism of CP is related to valine, leucine, and isoleucine biosynthesis; taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; citrate cycle; and alanine, aspartate, and glutamate metabolism, with high pathway impact. The potential biomarkers obtained in this study could be used to monitor CP-induced nephrotoxicity relative to dose and treatment time.

Twenty-six-week oral carcinogenicity study of 3-monochloropropane-1,2-diol in CB6F1-rasH2 transgenic mice.

The carcinogenic potential of 3-monochloro-1,2-propanediol (3-MCPD) was evaluated in a short-term carcinogenicity testing study using CB6F1 rasH2-Tg (rasH2-Tg) mice. 3-MCPD is found in many foods and food ingredients as a result of storage or processing and is regarded as a carcinogen since it is known to induce Leydig cell and kidney tumors in rats. Male and female rasH2-Tg mice were administered 3-MCPD once daily by oral gavage at doses of 0, 10, 20, and 40 mg/kg body weight (bw) per day for 26 weeks. As a positive control, N-methyl-N-nitrosourea (MNU) was administered as a single intraperitoneal injection (75 mg/kg). In 3-MCPD-treated mice, there was no increase in the incidence of neoplastic lesions compared to the incidence in vehicle control mice. However, 3-MCPD treatment resulted in an increased incidence of tubular basophilia in the kidneys and germ cell degeneration in the testes, with degenerative germ cell debris in the epididymides of males at 20 and 40 mg/kg bw per day. In 3-MCPD-treated females, vacuolation of the brain and spinal cord was observed at 40 mg/kg bw per day; however, only one incidence of vacuolation was observed in males. Forestomach and cutaneous papilloma and/or carcinoma and lymphoma were observed in most rasH2 mice receiving MNU treatment. We concluded that 3-MCPD did not show carcinogenic potential in the present study using rasH2-Tg mice. The findings of this study suggest that the carcinogenic potential of 3-MCPD is species specific.

Clinical Evaluation of Rapid Diagnostic Test Kit for Scrub Typhus with Improved Performance.

Diagnosis of scrub typhus is challenging due to its more than twenty serotypes and the similar clinical symptoms with other acute febrile illnesses including leptospirosis, murine typhus and hemorrhagic fever with renal syndrome. Accuracy and rapidity of a diagnostic test to Orientia tsutsugamushi is an important step to diagnose this disease. To discriminate scrub typhus from other diseases, the improved ImmuneMed Scrub Typhus Rapid Diagnostic Test (RDT) was evaluated in Korea and Sri Lanka. The sensitivity at the base of each IgM and IgG indirect immunofluorescent assay (IFA) in Korean patients was 98.6% and 97.1%, and the specificity was 98.2% and 97.7% respectively. The sensitivity and specificity for retrospective diagnosis at the base of IFA in Sri Lanka was 92.1% and 96.1%. ImmuneMed RDT was not reactive to any serum from seventeen diseases including hemorrhagic fever with renal syndrome (n = 48), leptospirosis (n = 23), and murine typhus (n = 48). ImmuneMed RDT shows superior sensitivity (98.6% and 97.1%) compared with SD Bioline RDT (84.4% at IgM and 83.3% at IgG) in Korea. The retrospective diagnosis of ImmuneMed RDT exhibits 94.0% identity with enzyme-linked Immunosorbent assay (ELISA) using South India patient serum samples. These results suggest that this RDT can replace other diagnostic tests and is applicable for global diagnosis of scrub typhus. This rapid and accurate diagnosis will be beneficial for diagnosing and managing scrub typhus.

Remifentanil postconditioning has cross talk with adenosine receptors in the ischemic-reperfused rat heart.

BACKGROUND: Although there is a possibility of cross talk between opioid and adenosine signaling pathways in the ischemic-reperfused myocardium, it is not clear that an ultra-short-acting opioid receptor agonist remifentanil-induced postconditioning (RPostC) has cross talk with adenosine receptor (ADR). The purpose of this study was to determine whether there is cross talk with ADR in RPostC. MATERIALS AND METHODS: Isolated rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. RPostC was induced by 100 ng/mL of remifentanil perfusion, 5 min before reperfusion, followed by 5 min of reperfusion. The nonspecific opioid receptor antagonist naloxone (NAL) and the nonspecific ADR antagonist 8-(p-sulfophenyl) theophylline hydrate (8-SPT) were perfused for a 20-min period, 10 min before RPostC to the end of RPostC. Western blot analysis was performed to detect phospho-ERK1/2 in cultured cardiomyocytes. RESULTS: In cultured cardiomyocytes, remifentanil incubation significantly increased the phosphorylation of ERK1/2 and this effect was blocked by both NAL and 8-SPT (P < 0.01 and P < 0.05, respectively). RPostC significantly reduced infarct size over ischemic area at risk from 34.1 ± 10.5% to 16.6 ± 7.5% (P < 0.05 versus control). The infarct-limitation effect of RPostC was reversed by both NAL (33.8 ± 13.0%, P < 0.05) and 8-SPT (35.7 ± 14.5%, P < 0.01). CONCLUSIONS: This study strongly implies that the intracellular signaling pathways of cardioprotection by RPostC has cross talk with ADR in the ischemic-reperfused myocardium.

Video Distraction and Parental Presence for the Management of Preoperative Anxiety and Postoperative Behavioral Disturbance in Children: A Randomized Controlled Trial.

BACKGROUND: The anxiolytic efficacy of video watching, in the absence of parents, during the mask induction of anesthesia in young children with high separation anxiety has not been clearly established. We performed this study to determine whether the effect of video distraction on alleviating preoperative anxiety is independent of parental presence and whether a combination of both interventions is more effective than either single intervention in alleviating preoperative anxiety and postoperative behavioral disturbance in preschool children. METHODS: In this prospective trial, 117 children aged 2 to 7 years scheduled for elective minor surgery were randomly allocated to 1 of 3 groups, a video distraction group (group V), a parental presence group (group P), or a combination of video distraction plus parental presence group (group VP) during induction of sevoflurane anesthesia. The Modified Yale Preoperative Anxiety Scale (mYPAS) was used to assess anxiety in the preoperative holding area (baseline), immediately after entry to the operating room, and during mask induction. Compliance during induction, emergence delirium during recovery, and negative behavioral changes at 1 day and 2 weeks postoperatively were also assessed. RESULTS: The mYPAS scores were comparable (P = 0.558), and the number of children exhibiting baseline anxiety (an mYPAS score > 30) were not different among the 3 groups in the preoperative holding area (P = 0.824). After intervention, the changes in mYPAS scores from baseline to induction were not different among the 3 groups (P = 0.049). The proportion of children with increased mYPAS scores was higher in group P compared with group V from baseline to operating room entry (Bonferroni-adjusted 95% confidence interval for difference, 2 to 49) but similar from baseline to induction in all 3 groups. Although children in group V were more cooperative during mask induction than those in the other 2 groups (P < 0.001 versus group P and P = 0.001 versus group VP), no significant intergroup differences were observed in the incidence of emergence delirium or new-onset negative behavioral change after surgery. CONCLUSIONS: Video distraction, parental presence, or their combination showed similar effects on preoperative anxiety during inhaled induction of anesthesia and postoperative behavioral outcomes in preschool children having surgery.

The effective bolus dose of remifentanil to facilitate laryngeal mask airway insertion during inhalation induction of sevoflurane in children.

PURPOSE: The additional administration of remifentanil during inhalation induction with sevoflurane could provide better conditions for laryngeal mask airway (LMA) insertion than sevoflurane alone. This study was designed to evaluate the 50 % effective bolus dose (ED50) and 95 % effective bolus dose (ED95) of remifentanil required for LMA insertion in children during inhalation induction with sevoflurane. METHODS: Pediatric patients aged 3-12 years requiring general anesthesia were recruited. A predetermined dose of remifentanil was injected over 30 s after the induction of general anesthesia with sevoflurane. LMA insertion was attempted 60 s after remifentanil injection. The dose of remifentanil was determined using the Dixon's up-and-down method, starting from 0.5 µg/kg (step size of 0.05 µg/kg). RESULTS: The study was conducted until seven cross-over points and 29 children were collected. The ED50 of remifentanil for successful LMA insertion during sevoflurane inhalation induction in children was 0.168 ± 0.035 µg/kg using Dixon's method. In addition, the ED50 and ED95 of remifentanil from the probit analysis were 0.176 µg/kg (95 % confidence limits, 0.102-0.216 µg/kg) and 0.268 µg/kg (95 % confidence limits, 0.223-0.659 µg/kg), respectively. CONCLUSION: The ED50 and ED95 of remifentanil for successful LMA insertion in children were estimated to be 0.176 (0.168) and 0.268 µg/kg during inhalation induction with 2.1 % sevoflurane.

Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations.

Sotos syndrome is an overgrowth syndrome with characteristic facial dysmorphism, variable severity of learning disabilities and macrocephaly with overgrowth. Haploinsufficiency of the nuclear receptor SET domain-containing protein 1 (NSD1) gene located on 5q35 has been implicated as the cause of Sotos syndrome. This study was performed to investigate the mutation spectrum of NSD1 abnormalities and meaningful genotype-phenotype correlations in Korean patients with Sotos syndrome. Eighteen unrelated Korean patients with Sotos syndrome were enrolled for clinical and molecular analyses. Cytogenetic studies were performed to confirm 5q35 microdeletion, and NSD1 sequencing analysis was performed to identify intragenic mutations. NSD1 abnormalities were identified in 15 (83%) patients. Among them, eight patients (53%) had 5q35 microdeletions and the other seven patients (47%) had seven different NSD1 intragenic mutations including four novel mutations. The mutation spectrum of Korean patients with Sotos syndrome was similar to that of previous studies for Japanese patients. Height was significantly shorter and age of walking alone was significantly older in the microdeletion group compared with those in the intragenic mutation group. No significant differences were observed for other clinical characteristics between the microdeletion and intragenic mutation groups. Further studies with a larger number of patients will be necessary to draw conclusive genotype-phenotype correlations.

Improvement of the diagnostic sensitivity of scrub typhus using a mixture of recombinant antigens derived from Orientia tsutsugamushi serotypes.

Diagnosis of scrub typhus is difficult because its symptoms are very similar to other acute febrile illnesses, such as leptospirosis, murine typhus, and other viral hemorrhagic fevers. To differentiate scrub typhus from other acute febrile diseases, a rapid and reliable serological diagnosis is important. We have developed a chimeric recombinant antigen cr56 and two other recombinant antigens, r21 and kr56, from various serotypes of Orientia tsutsugamushi. They were tested for the detection of antibodies against O. tsutsugamushi in the patient's serum samples using enzyme-linked immunosorbent assay (ELISA) and dot-blot analyses. As of conventional immunofluorescence assay (IFA), when the mixture of these three recombinant antigens was used, both sensitivity and specificity of the recombinant antigens were increased up to 98% in IgM and IgG at ELISA and dot blotting. Additionally, both sensitivity and specificity by detection of IgM and IgG antibodies at rapid diagnostic test (RDT), using the mixture of three antigens and gold conjugated antibodies, were 99%. Our results suggest the use of mixture of these recombinant antigen proteins in ELISA or RDT is suitable as a diagnostic test for scrub typhus.

Multi-hazard exposure mapping under climate crisis using random forest algorithm for the Kalimantan Islands, Indonesia.

Numerous natural disasters that threaten people's lives and property occur in Indonesia. Climate change-induced temperature increases are expected to affect the frequency of natural hazards in the future and pose more risks. This study examines the consequences of droughts and forest fires on the Indonesian island of Kalimantan. We first create maps showing the eleven contributing factors that have the greatest impact on forest fires and droughts related to the climate, topography, anthropogenic, and vegetation. Next, we used RF to create single and multi-risk maps for forest fires and droughts in Kalimantan Island. Finally, using the Coupled Model Intercomparison Project (CMIP6) integrated evaluation model, a future climate scenario was applied to predict multiple risk maps for RCP-SSP2-4.5 and RCP-SSP5-8.5 in 2040-2059 and 2080-2099. The probability of a 22.6% drought and a 21.7% forest fire were anticipated to have an influence on the study's findings, and 2.6% of the sites looked at were predicted to be affected by both hazards. Both RCP-SSP2-4.5 and RCP-SSP5-8.5 have an increase in these hazards projected for them. Researchers and stakeholders may use these findings to assess risks under various mitigation strategies and estimate the spatial behavior of such forest fire and drought occurrences.

Comparison of health inequalities according to socioeconomic status: findings from the fourth Korean working condition survey (a cross-sectional study).

Introduction: this study aims to examine health inequalities among Korean workers by sex, age, education, monthly income, occupation, and employment type and identify groups of workers who may be neglected in the process of resolving health inequalities. Methods: we used data from the Fourth Korean Working Condition Survey conducted by the Korea Occupational Safety and Health Research Institute and compared the number of health symptoms among various groups using the t-test and one-way analysis of variance to determine their health status. We also calculated the Gini index of the number of health symptoms of each group and plotted the Lorenz curve to illustrate health inequalities. Results: we found that the number of health symptoms was higher in groups with lower socioeconomic status (e.g., female, blue-collar workers, older, low education, low monthly income, and self-employed workers). However, the Gini index and Lorenz curve with respect to socioeconomic status indicated that health inequalities were higher among white-collar and permanent workers vis-à-vis blue-collar and self-employed workers, respectively. Further, it was found that health inequalities were higher among males than females with respect to the same occupational groups and employment types. Conclusion: general health policies are often targeted at the socially and economically vulnerable group, but according to the results of this study, it can be considered that there may be subjects who are vulnerable to health problems even in groups that are not socioeconomically vulnerable.

Comparison of remimazolam and propofol induction on hemodynamic response in hypertensive patients.

BACKGROUND: Hemodynamic variations during the induction of general anesthesia are more profound in hypertensive patients, and the risk of hypoperfusion-induced organ damage followed by hypotensive episodes is higher in hypertensive patients than in normotensive patients. Thus, we compared the effects of remimazolam and propofol on hemodynamics during general anesthesia induction in hypertensive patients. METHODS: Patients were randomly divided into the remimazolam (Group R, n = 48) and propofol (Group P, n = 48) groups: remimazolam was continued at 6 mg/kg/hour until the patient lost consciousness, followed by 1 mg/kg/hour until 5 minutes after tracheal intubation. Propofol was administered as a slow bolus of 1.5 to 2 mg/kg, followed by 3 to 6 mg/kg/hour 5 minutes after tracheal intubation. Hemodynamic parameters including mean blood pressure (MBP), systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, and incidence of hypotension were analyzed during the induction period, pre-induction (T1), immediately after loss of consciousness (T2), at 1 and 3 minutes after neuromuscular blockade (T3, T4), immediately after tracheal intubation (T5), and at 1, 3, and 5 minutes after tracheal intubation (T6, T7, T8). RESULTS: The MBP, SBP, and DBP were significantly lower in the propofol group than in the remimazolam group (MBP: at T2, T3, T4, and T5; SBP: at T2, T3, and T4; DBP: at T5). HR was significantly lower in the propofol group at T3, T4, and T8. The incidence of hypotension was significantly higher in the propofol group than that in the remimazolam group. The incidence of bradycardia was comparable between the groups. CONCLUSIONS: Remimazolam induction was more stable than propofol induction in preserving normal hemodynamics and was associated with a relatively lower incidence of hypotension. Remimazolam may be preferable to propofol for induction of anesthesia in patients with hypertension.