Pulse wave response characteristics for thickness and hardness of the cover layer in pulse sensors to measure radial artery pulse.

BACKGROUND: Piezo-resistive pressure sensors are widely used for measuring pulse waves of the radial artery. Pulse sensors are generally fabricated with a cover layer because pressure sensors without a cover layer are fragile when they come into direct contact with the skin near the radial artery. However, no study has evaluated the dynamic pulse wave response of pulse sensors depending on the thickness and hardness of the cover layer. This study analyzed the dynamic pulse wave response according to the thickness and hardness of the cover layer and suggests an appropriate thickness and hardness for the design of pulse sensors with semiconductor device-based pressure sensors. METHODS: Pulse sensors with 6 different cover layers with various thicknesses (0.8 mm, 1 mm, 2 mm) and hardnesses (Shore type A; 30, 43, 49, 71) were fabricated. Experiments for evaluating the dynamic pulse responses of the fabricated sensors were performed using a pulse simulator to transmit the same pulse wave to each of the sensors. To evaluate the dynamic responses of the fabricated pulse sensors, experiments with the pulse sensors were conducted using a simulator that artificially generated a constant pulse wave. The pulse wave simulator consisted of a motorized cam device that generated the artificial radial pulse waveform by adjusting the stroke of the cylindrical air pump and an air tube that conveyed the pulse to the artificial wrist. RESULTS: The amplitude of the measured pulse pressure decreased with increasing thickness and hardness of the cover layer. Normalized waveform analysis showed that the thickness rather than the hardness of the cover layer contributed more to waveform distortion. Analysis of the channel distribution of the pulse sensor with respect to the applied constant dynamic pressure showed that the material of the cover layer had a large effect. CONCLUSIONS: In this study, in-line array pulse sensors with various cover layers were fabricated, the dynamic pulse wave responses according to the thickness and the hardness of the cover layer were analyzed, and an appropriate thickness and hardness for the cover layer were suggested. The dynamic pulse wave responses of pulse sensors revealed in this study will contribute to the fabrication of improved pulse sensors and pulse wave analyses.

1H-NMR-based metabolomic studies of bisphenol A in zebrafish (Danio rerio).

Proton nuclear magnetic resonance (1H-NMR) spectroscopy was used to study the response of zebrafish (Danio rerio) to increasing concentrations of bisphenol A (4,4'-(propane-2,2-diyl)diphenol, BPA). Orthogonal partial least squares discriminant analysis (OPLS-DA) was applied to detect aberrant metabolomic profiles after 72 h of BPA exposure at all levels tested (0.01, 0.1, and 1.0 mg/L). The OPLS-DA score plots showed that BPA exposure caused significant alterations in the metabolome. The metabolomic changes in response to BPA exposure generally exhibited nonlinear patterns, with the exception of reduced levels of several metabolites, including glutamine, inosine, lactate, and succinate. As the level of BPA exposure increased, individual metabolite patterns indicated that the zebrafish metabolome was subjected to severe oxidative stress. Interestingly, ATP levels increased significantly at all levels of BPA exposure. In the present study, we demonstrated the applicability of 1H-NMR-based metabolomics to identify the discrete nature of metabolic changes.

Development of a Tonometric Sensor with a Decoupled Circular Array for Precisely Measuring Radial Artery Pulse.

The radial artery pulse is one of the major diagnostic indices used clinically in both Eastern and Western medicine. One of the prominent methods for measuring the radial artery pulse is the piezoresistive sensor array. Independence among channels and an appropriate sensor arrangement are important for effectively assessing the spatial-temporal information of the pulse. This study developed a circular-type seven-channel piezoresistive sensor array using face-down bonding (FDB) as one of the sensor combination methods. The three-layered housing structure that included independent pressure sensor units using the FDB method not only enabled elimination of the crosstalk among channels, but also allowed various array patterns to be created for effective pulse measurement. The sensors were arranged in a circular-type arrangement such that they could estimate the direction of the radial artery and precisely measure the pulse wave. The performance of the fabricated sensor array was validated by evaluating the sensor sensitivity per channel, and the possibility of estimating the blood vessel direction was demonstrated through a radial artery pulse simulator. We expect the proposed sensor to allow accurate extraction of the pulse indices for pulse diagnosis.

The mixture of different parts of Nelumbo nucifera and two bioactive components inhibited tyrosinase activity and melanogenesis.

Melanin is the pigment responsible for the color of the eyes, hair, and skin in humans. Tyrosinase is well known to be the key enzyme in melanin biosynthesis. JKTM-12 is composed of the flowers, roots, seeds, and receptacles of Nelumbo nucifera (lotus). In this study, JKTM-12 was investigated for its inhibitory effects on tyrosinase activity and melanin biosynthesis in B16F10 melanoma cells. Moreover, two main bioactive compounds (hyperoside and astragalin) were found from the receptacles of N. nucifera, which are used as the main material of JKTM-12. JKTM-12 was shown to inhibit tyrosinase activity and melanin biosynthesis in alpha-melanocyte-stimulating hormone-stimulated B16F10 melanoma cells. Hyperoside and astragalin, which are the main bioactive compounds of JKTM-12, not only inhibited tyrosinase activity and melanogenesis but also tyrosinase-related protein 1 and tyrosinase-related protein 2 mRNA expression without cytotoxicity at various experiment doses (0.1, 1, and 10 µg/ml). These results suggest that JKTM-12 has the potential for skin whitening with hyperoside and astragalin as the main bioactive compounds.

Assessment of dermal safety of Scutellaria baicalensis aqueous extract topical application on skin hypersensitivity.

Scutellaria baicalensis has been used as a traditional herbal medicine for bronchitis, hepatitis, and allergic diseases. The root of Scutellaria baicalensis contains active flavonoid components, including baicalin, baicalein, wogonoside, and wogonin, which have pharmaceutical properties. In the present study, the antiallergic properties of a standardized aqueous extract of S. baicalensis were evaluated, and the skin toxicity of its dermal application was also determined. The in vivo and in vitro assays were performed by using the ß-hexosaminidase assay in rat basophilic leukemia cells (RBL-2H3) and cutaneous skin reaction in BALB/c mice, respectively. In addition, the acute dermal irritation/corrosion test was carried out in New Zealand white rabbits, and the skin sensitization test was conducted by Buhler's method in Hartley guinea pigs to estimate the safety of the standardized aqueous extract of S. baicalensis for topical application. ß-Hexosaminidase release in RBL-2H3 was markedly decreased following treatment with the standardized aqueous extract of S. baicalensis. It also ameliorated antigen-induced ear swelling compared with the control group in BALB/c mice. In the toxicological studies, it did not induce any dermal irritation/corrosion in rabbits or skin sensitization in guinea pigs. Although still limited, these results concerning the toxicological effects of S. baicalensis could be an initial step toward the topical application of S. baicalensis extracts on hypersensitive skin.

Characterization of ethanol fermentation waste and its application to lactic acid production by Lactobacillus paracasei.

In this study, an ethanol fermentation waste (EFW) was characterized for use as an alternative to yeast extract for bulk fermentation processes. EFW generated from a commercial plant in which ethanol is produced from cassava/rice/wheat/barley starch mixtures using Saccharomyces cerevisiae was used for lactic acid production by Lactobacillus paracasei. The effects of temperature, pH, and duration on the autolysis of an ethanol fermentation broth (EFB) were also investigated. The distilled EFW (DEFW) contained significant amounts of soluble proteins (2.91 g/l), nitrogen (0.47 g/l), and amino acids (24.1 mg/l). The autolysis of the EFB under optimum conditions released twice as much amino acids than in the DEFW. Batch fermentation in the DEFW increased the final lactic acid concentration, overall lactic acid productivity, and lactic acid yield on glucose by 17, 41, and 14 %, respectively, in comparison with those from comparable fermentation in a lactobacillus growth medium (LGM) that contained 2 g/l yeast extract. Furthermore, the overall lactic acid productivity in the autolyzed then distilled EFW (ADEFW) was 80 and 27 % higher than in the LGM and DEFW, respectively.

Changed Digital Technology Perceptions and Influencing Factors among Older Adults during the COVID-19 Pandemic.

This correlational study aimed to identify factors that contribute to changes in perceptions of digital technology among older adults during the COVID-19 pandemic. This study utilized raw data from "The 2021 Report on the Digital Divide," a nationwide survey conducted in South Korea. Data were collected from 1171 older adults (aged ≥ 65 years) from September to December 2021. Multiple regression analyses were performed to examine the factors influencing changes in the perception of digital technology. Over one-third of the participants reported positive changes in their perceptions of digital technology during the pandemic. Key factors included self-efficacy for digital devices (ß = 0.35, p < 0.001), digital networking (ß = 0.11, p < 0.001), accessibility to digital devices (ß = 0.10, p = 0.002), and perceived health (ß = 0.08, p = 0.003). The expansion of digital technology owing to the pandemic has served as a catalyst for changes in older adults' perceptions. Healthcare providers and caregivers should consider digital technology perceptions and influencing factors when providing digital healthcare services. The results can be utilized to identify vulnerable older adults with negative perceptions of digital technology, thus minimizing disparities in access to digital healthcare services.

"Untold and unexpected clinical practice stress," nursing students' experience of disgust: A phenomenological approach.

BACKGROUND: In the clinical learning environment, nursing students often face situations that cause physical disgust. Previous studies have shown that more than half of the students experienced disgust, and that high disgust sensitivity in students was related to negative results in terms of academic and caring behavior. OBJECTIVES: This study aims to understand the experience of disgust felt by nursing students in a clinical learning environment. DESIGN: A qualitative study using phenomenological method. METHODS: In-depth, one-on-one interviews were conducted with 18 nursing students at a university in South Korea. The data obtained through the interviews were used to explore the essential structure and meaning of disgust using phenomenological analysis. RESULTS: This study derived four categories, nine theme clusters, and twenty-one themes. The four categories were "fear that stimulates the senses," "untold and unexpected clinical practice stress," "ambivalence towards myself and patients," and "struggling to become a nursing professional." CONCLUSIONS: Nurse educators must be aware that nursing students may feel disgust in clinical settings and are therefore under stress. They must also assist students so that their concerns caused by emotions that they cannot easily reveal do not affect their nursing careers.

Effects of self-management education on COVID-19 prevention in patients undergoing hemodialysis.

Aim: To develop self-management education for preventing coronavirus disease 2019 (COVID-19) in patients on hemodialysis and to verify its effects. Background: During the current pandemic, studies on various areas, such as infection control in dialysis units, infection rates, clinical characteristics, treatment progress, and the emotional and psychological states of dialysis patients, have been actively reported. However, experimental research verifying the effects of interventions on infection prevention in hemodialysis patients is very rare. Methods: This study included 34 patients on hemodialysis in a South Korean general hospital (18 in the experimental group and 16 in the control group). Data were collected from September to October 2021. The experimental group was provided with self-care behavior for infection prevention education for 8 weeks, and the control group was provided with usual nursing care. Results: The patients on hemodialysis showed moderate fear of COVID-19, good compliance with patient role behavior and self-management efficacy, and poor handwashing practice. After the intervention, there were no significant differences concerning fear of COVID-19, compliance with patient role behavior, and self-management efficacy between the experimental and control groups. However, confidence in handwashing (subjective norm) and proper handwashing practice improved significantly in the experimental group compared with the control group. Conclusion: The infection prevention education developed in this study positively affected confidence in handwashing and proper handwashing practice in patients undergoing hemodialysis. This intervention can be used in various clinical settings where care is provided for patients with chronic illness, including those on hemodialysis.

Myrrh inhibits LPS-induced inflammatory response and protects from cecal ligation and puncture-induced sepsis.

Myrrh has been used as an antibacterial and anti-inflammatory agent. However, effect of myrrh on peritoneal macrophages and clinically relevant models of septic shock, such as cecal ligation and puncture (CLP), is not well understood. Here, we investigated the inhibitory effect and mechanism(s) of myrrh on inflammatory responses. Myrrh inhibited LPS-induced productions of inflammatory mediators such as nitric oxide, prostaglandin E(2), and tumor necrosis factor-α but not of interleukin (IL)-1ß and IL-6 in peritoneal macrophages. In addition, Myrrh inhibited LPS-induced activation of c-jun NH(2)-terminal kinase (JNK) but not of extracellular signal-regulated kinase (ERK), p38, and nuclear factor-κB. Administration of Myrrh reduced the CLP-induced mortality and bacterial counts and inhibited inflammatory mediators. Furthermore, administration of Myrrh attenuated CLP-induced liver damages, which were mainly evidenced by decreased infiltration of leukocytes and aspartate aminotransferase/alanine aminotransferase level. Taken together, these results provide the evidence for the anti-inflammatory and antibacterial potential of Myrrh in sepsis.

Piperine inhibits lipopolysaccharide-induced maturation of bone-marrow-derived dendritic cells through inhibition of ERK and JNK activation.

Piperine, one of the main components of Piper longum Linn. and P. nigrum Linn., is a plant alkaloid with a long history of medicinal use. Piperine has been shown to modulate the immune response, but the mechanism underlying this modulation remains unknown. Here, we examined the effects of piperine on lipopolysaccharide (LPS)-induced inflammatory responses in bone-marrow-derived dendritic cells (BMDCs). Piperine significantly inhibited the expression of major histocompatibility complex class II, CD40 and CD86 in BMDCs in a dose-dependent manner. Furthermore, piperine treatment led to an increase in fluorescein-isothiocyanate-dextran uptake in LPS-treated dendritic cells and inhibited the production of tumour necrosis factor alpha and interleukin (IL)-12, but not IL-6. The inhibitory effects of piperine were mediated via suppression of extracellular signal-regulated kinases and c-Jun N-terminal kinases activation, but not p38 or nuclear factor-κB activation. These findings provide insight into the immunopharmacological role of piperine.

Fermentation and evaluation of Klebsiella pneumoniae and K. oxytoca on the production of 2,3-butanediol.

Klebsiella is one of the genera that has shown unbeatable production performance of 2,3-butanediol (2,3-BD), when compared to other microorganisms. In this study, two Klebsiella strains, K. pneumoniae (DSM 2026) and K. oxytoca (ATCC 43863), were selected and evaluated for 2,3-BD production by batch and fed-batch fermentations using glucose as a carbon source. Those strains' morphologies, particularly their capsular structures, were analyzed by scanning electron microscopy (SEM). The maximum titers of 2,3-BD by K. pneumoniae and K. oxytoca during 10 h batch fermentation were 17.6 and 10.9 g L(-1), respectively; in fed-batch cultivation, the strains showed the maximum titers of 50.9 and 34.1 g L(-1), respectively. Although K. pneumoniae showed higher productivity, SEM showed that it secreted large amounts of capsular polysaccharide, increasing pathogenicity and hindering the separation of cells from the fermentation broth during downstream processing.

Association between Seafood Intake and Cardiovascular Disease in South Korean Adults: A Community-Based Prospective Cohort Study.

Cardiovascular disease (CVD) is the most common non-communicable diseases causing 18.6 million deaths worldwide. Several studies have revealed that seafood consumption has a protective effect against CVD. This study investigated the correlation between CVD and seafood intake based on a 10-year follow-up of the Korean Genome and Epidemiology Study (KoGES). The study population, which included 6565 adults age, 55.65 (±8.68), was divided into seafood intake-based tertiles. CVD included myocardial infarction, coronary artery disease, congestive heart failure, cerebrovascular disease, and peripheral vascular disease. At baseline, participants with low seafood intake also had low eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes. Prospectively, hazard ratios (HRs) with 95% confidence intervals (CIs) for CVD were analyzed using Cox proportional hazards regression models. Seafood intake exhibited a significantly inverse relationship with the cumulative CVD incidence over 10 years regardless of sex (women: log-rank test p < 0.001 and men: log-rank test p < 0.0401). The longitudinal association of low seafood intake with the CVD risk was significantly stronger in female participants after adjusting for confounding variables (HR (95% confidence interval (CI)) = 0.718 (0.519−0.993) p-trend = 0.043). These results suggested that seafood consumption potentially ameliorates CVD risk in middle-aged adults.

Association between Dietary Diversity Score and Metabolic Syndrome in Korean Adults: A Community-Based Prospective Cohort Study.

Dietary diversity is recognized as a key indicator of dietary quality and is known to affect the burden of non-communicable diseases. This study examined the gender-stratified association between dietary diversity score (DDS) and risk of metabolic syndrome (MetS) in 5468 adults aged 40−69 years during a 12-year follow-up of the Korean Genome and Epidemiology Study (KoGES). DDS was calculated according to the consumption of the five food groups based on the Dietary Reference Intakes (DRIs) for Koreans. The Cox proportional hazard model was used to evaluate MetS risk according to DDS. A higher DDS was negatively associated with the consumption of grains but positively associated with the consumption of fruits and non-salted vegetables. Furthermore, participants with a higher DDS showed higher consumption of fish and milk. Prospectively, a higher DDS was significantly associated with a lower risk of MetS in men (HR: 0.76, 95% CI: 0.63−0.92, p < 0.01). In all participants, a higher DDS was inversely associated with the incidence of abdominal obesity (men, HR: 0.76, 95% CI: 0.62−0.93, p < 0.01; women, HR: 0.79, 95% CI: 0.67−0.94, p < 0.01). Furthermore, men with a higher DDS had a lower risk of hypertriglyceridemia (HR: 0.83, 95% CI: 0.71−0.97, p < 0.05). These findings suggested that eating a more varied diet might have favorable effects on preventing MetS in Korean adults.

[Interorganizational Networks for Smoking Prevention and Cessation: A Blockmodeling Approach].

PURPOSE: This study examined characteristics and patterns of interorganizational networks for smoking prevention and cessation in Korea. METHODS: We surveyed two community health centers, ninety-five hospitals or clinics, ninety-two pharmacies, and sixty-five health welfare organizations in two districts of Seoul in 2020. Data on the organizations' characteristics of smoking cessation and interorganizational activities for information sharing, client referral, and program collaboration were collected and analyzed using network statistics and blockmodeling. RESULTS: Network size was in the order of information sharing, client referral, and program collaboration networks. Network patterns for interorganizational activities on information sharing, client referral, and program collaboration among four organizations were similar between the two districts. Community health centers provided information and received clients from a majority of the organizations. Their interactions were not unidirectional but mutual with other organizations. Pharmacies were involved in information sharing with health welfare organizations and client referrals to hospitals or clinics. Health welfare organizations were primarily connected with the community health centers for client referrals and program collaboration. CONCLUSION: A community health center is the lead agency in interorganizational activities for smoking prevention and cessation. However, hospitals or clinics, pharmacies, and health welfare organizations also participate in interorganizational networks for smoking prevention and cessation with diverse roles. This study would be evidence for developing future interorganizational networks for smoking prevention and cessation.

Can Different Forest Structures Lead to Different Levels of Therapeutic Effects? A Systematic Review and Meta-Analysis.

In recent decades, forests have expanded from natural resources for conservation and production to health-promoting resources. With the growing body of evidence supporting the therapeutic effects of forests, the number of investigations on the relationship between forest characteristics and therapeutic effects have increased. However, quantitative synthesis of primary studies has rarely been conducted due to a limited number of health studies including forest description and high heterogeneity of forest variables. In this study, we conducted a systematic review and meta-analysis to evaluate the relationship between the forest structure and the therapeutic effect. We systematically searched the studies examining the therapeutic effects of forests with different stand density and canopy density and synthesized the results. As a result of subgroup analysis, we found that stand density modifies the therapeutic effects. Emotional and cognitive restoration showed greatest improvement in low-density forests with a stand density of less than 500/ha and the therapeutic effects diminish as the stand density increases. The impact of canopy density was not found due to a lack of studies reporting canopy density. Although some limitations remain, the findings in this study have great significance in providing the basis for establishing management strategies of forests for therapeutic use.

Variability of electrochemical skin conductance for screening diabetes mellitus.

Electrochemical skin conductance (ESC) has been suggested as a noninvasive diabetic screening tool. We examined the relevance of ESC method for screening type 2 diabetes. A meal tolerance test (MTT) was conducted for 40 diabetic and 42 control subjects stratified by age, sex and body mass index (BMI). The glucose levels and ESC were measured before the MTT and every 30 min after meal intake up to 120 min. There was no correlation between the blood glucose level and ESC (r = 0.249) or ESC variability (ESCV) (r = - 0.173). ESC (ESCV) was higher (lower) in diabetic patients than in normal control (p = 0.02 for ESC and p = 0.06 for ESCV). Receiver operating characteristic analysis showed that the area under the curve (AUC) values of the ESC and ESCV were 0.654 and 0.691, respectively. The novel variable, ESCV, showed 5.7% higher AUC than ESC. Contrary to some previous reports, ESC values in diabetic patients was higher than in age, sex and BMI matched control group. In our study, ESC or ESCV showed a marginal accuracy to be used as a screening tool for diabetes mellitus.

Study on the Relevance of Metabolic Syndrome and Incidence of Gastric Cancer in Korea.

(1) Background: This study aimed to determine the relevance between stages of metabolic syndrome (MS) progression and the incidence of gastric cancer utilizing a big data cohort for the national health checkup. (2) Methods: There were 7,785,098 study subjects, and three stages of metabolic syndrome were categorized using the health checkup results from 2009. Incidence of gastric cancer was traced and observed from the date of the health insurance benefit claim in 2009 until 31 December, 2016, and Cox hazard-proportional regression was performed to determine the risk of gastric cancer incidence based on the stage of progression for metabolic syndrome. (3) Results: Hazard ratio (HR) incidence rate for the MS group was 2.31 times higher than the normal group (95% CI 2.22⁻2.40) after adjustment (Model 4). The HR incidence rate of gastric cancer for the pre-MS group was 1.08 times higher (95% CI 1.04⁻1.12) than the normal group, while the HR incidence rate of gastric cancer for the MS group was 1.26 times higher (95% CI 1.2⁻1.32). (4) Conclusions: Causal relevance observed in this study between metabolic syndrome and incidence of gastric cancer was high. Promotion and education for active responses in the general population and establishment of appropriate metabolic syndrome management systems to prevent gastric cancer are needed.

Glucose-independent segmental phase angles from multi-frequency bioimpedance analysis to discriminate diabetes mellitus.

We investigated segmental phase angles (PAs) in the four limbs using a multi-frequency bioimpedance analysis (MF-BIA) technique for noninvasively diagnosing diabetes mellitus. We conducted a meal tolerance test (MTT) for 45 diabetic and 45 control subjects stratified by age, sex and body mass index (BMI). HbA1c and the waist-to-hip-circumference ratio (WHR) were measured before meal intake, and we measured the glucose levels and MF-BIA PAs 5 times for 2 hours after meal intake. We employed a t-test to examine the statistical significance and the area under the curve (AUC) of the receiver operating characteristics (ROC) to test the classification accuracy using segmental PAs at 5, 50, and 250 kHz. Segmental PAs were independent of the HbA1c or glucose levels, or their changes caused by the MTT. However, the segmental PAs were good indicators for noninvasively screening diabetes In particular, leg PAs in females and arm PAs in males showed best classification accuracy (AUC = 0.827 for males, AUC = 0.845 for females). Lastly, we introduced the PA at maximum reactance (PAmax), which is independent of measurement frequencies and can be obtained from any MF-BIA device using a Cole-Cole model, thus showing potential as a useful biomarker for diabetes.

Simultaneous determination of imperatorin and its metabolite xanthotoxol in rat plasma and urine by LC-MS/MS and its application to pharmacokinetic studies.

An accurate, precise, selective, and sensitive liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of imperatorin (IMP) and its metabolite, xanthotoxol (XAN), in rat plasma and urine samples. The analytes, along with psoralen as an internal standard, were determined by multiple reaction monitoring (MRM) operated in the positive electrospray ionization (ESI) mode. Chromatographic separation was performed on an Acquity UPLC BEH C18 column (50mm×2.1mm, 1.7µm) with a mobile phase consisting of 0.1% formic acid solution and 0.1% formic acid in methanol at a flow rate of 0.3mL/min. The run time was 6min per sample and the injection volume was 5µL. The method had a lower limit of quantification (LLOQ) of 0.25ng/mL for IMP in plasma and urine, and 1ng/mL for XAN in urine. The linear calibration curves were fitted over the range of 0.25-1000ng/mL for IMP in plasma, 0.25-1000ng/mL for IMP in urine, and 1-1000ng/mL for XAN in urine, with correlation coefficients greater than 0.995. The inter- and intra-day accuracies (relative error, RE%) were between -8.5% and 3.5%, and the precisions (relative standard deviation, RSD%) were less than 10.0% for all quality control samples (QCs). The analytes were extracted from rat plasma and urine samples using a liquid-liquid extraction method with the extraction recovery in the range of 60.3-79.1%. A good stability of the analytes was observed in all the analysis procedures. The method was successfully validated and applied to determine the pharmacokinetics of IMP in rat plasma and, for the first time, the metabolite kinetics of IMP to XAN in rat urine after IMP administration.