This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control.Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 1011 colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5–6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.

Acetylsalicylic acid (ASA) is one of the most commonly used medications in global market, with a risk of intoxication in certain patients. However, monitoring blood drug concentration often requires frequent hospital visits; hence there is an unmet need to increase patientcentricity by conducting blood sampling at home. Volumetric absorptive microsampling (VAMS) is a device that allows collection of homogenous and accurate volume of blood without venipuncture, and can be utilized by patients who are not in hospital settings; but because ASA is prone to hydrolysis and stabilizing reagents cannot be added to VAMS samples, a way to improve sample stability must be developed. The objective of this study was to identify the cause of instability with ASA samples collected by VAMS, and to evaluate ways to improve sample stability. A liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used for analysis of ASA concentration in whole blood. Samples collected with VAMS were kept under different drying conditions (desiccator, pressurized, nitrogen gas and household vacuum sealer) and were compared to the control samples collected by conventional venous sampling. The recovery of ASA was about 31% of the control when VAMS sample was dried at room temperature, whereas VAMS samples under humidity controlled conditions showed more than 85% of recovery. Our results suggest that adequate level of humidity control was critical to ensure sample stability of ASA, and this humidity control could also be achieved at home using household vacuum sealer, thus enabling patient-centric clinical trials to be conducted.

Purpose: This study was conducted in order to examine the usefulness of osteoconductive bone substitutes with zeta potential control (geneX® ds; Biocomposites, England) by comparing the complications and radiographic evaluation with or without geneX® ds augmentation for internal fixation with proximal femur nail antirotation (PFNA) for treatment of osteoporotic unstable intertrochanteric fractures. Materials and Methods: A retrospective study of 101 patients who underwent fixation with PFNA in osteoporotic unstable intertrochanteric fractures was conducted from December 2015 to August 2020. The radiographic evaluation and complication rates were compared between patients with geneX® ds (Group A: 41 cases) and those without geneX® ds (Group B: 60 cases). Results: In radiological valuation, the degree of blade sliding from the time immediately after surgery to one year after surgery was 1.4±1.2 mm and 5.8±2.7 mm in Group A and Group B, respectively (P<0.001). During the same time frame, a significant difference of 2.3±2.2° and 7.4±3.1° , respectively (P<0.001), in varus collapse, was observed for Group A and Group B. Conclusion Among patients fixed with PFNA for treatment of unstable intertrochanteric fractures, less blade sliding and varus collapse was observed for those with geneX® ds augmentation compared to those without it. In addition, there was no increase in the incidence of complications. The authors believe it can be regarded as a safe and effective additive for intramedullary fixation for treatment of unstable intertrochanteric fractures.

Gefitinib is an anti-cancer drug used to treat non-small cell lung cancer. The objective of this study was to compare the pharmacokinetics and evaluate the bioequivalence of 2 orally administered gefitinib 250 mg tablets in healthy Korean subjects. A randomized, openlabel, single-dose, crossover bioequivalence study was conducted. A total of 50 healthy male volunteers were randomized into 2 sequence groups. During each treatment, the subjects received the test or reference formulation of 250 mg gefitinib with a washout period of 21 days. The plasma samples were collected at pre-dose and up to 144 hours post-dose, and plasma drug concentrations were measured using validated liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated, and the formulations were considered as bioequivalent if the 90% confidence intervals (CIs) of the geometric mean ratios were within the bioequivalence limits of 0.8 to 1.25. Forty-one subjects completed the study and were included in the pharmacokinetic analysis. The 90% CIs of the geometric mean ratios of the test formulation to the reference formulation were 0.8115 to 0.9993 for maximum plasma concentration and 0.9119 to 1.0411 for area under the plasma concentration versus time curve from dosing to the last measurable concentration. There were no serious or unexpected adverse events during the study. In healthy Korean adult subjects, the test and reference formulations of gefitinib 250 mg had similar pharmacokinetic parameters and similar plasma concentration-time profiles. The test formulation of gefitinib met the regulatory criteria for assuming bioequivalence. Both formulations were safe and well-tolerated.

In light of the shift toward patient-centric clinical trials, a measure of simplifying blood collection process and minimizing the volume of blood samples is on the rise. Volumetric absorptive microsampling (VAMS) is a microsampling device developed for blood sampling in non-hospital settings, which enables accurate hematocrit-independent collection of 10 or 20 µL of whole blood with a simple finger prick. In this study, liquid chromatography (LC)-tandem mass spectrometry workflow for quantification of rosuvastatin after VAMS sampling was developed and validated. The VAMS sample was stabilized by matrix drying and the optimum LC conditions and extraction methods were used to reach adequate sensitivity with lower limit of quantification verified at 1 ng/mL in 10 µL of blood. The bioanalytical method to quantify rosuvastatin from 1 to 100 ng/mL in VAMS sample was qualified by specificity, carryover, linearity, within-run and between-run reproducibility and stability. Inaccuracy was less than ± 6% and imprecision was less than 10% after analyzing the samples on 5 different days at all concentration levels. In addition, the feasibility of delivery to the analytical laboratory after home sampling during the guaranteed stability period of 10 days at room temperature was confirmed by evaluating concentration changes after VAMS sampling without adding pH buffer. Our results suggest that VAMS sampling did not have an effect on the stability of rosuvastatin, and it is a viable option for simple and accurate blood collection at home.

Background: The aim of this study is to compare the postoperative analgesic effect of infiltration between the popliteal artery and the capsule of the knee (IPACK) and the effect of periarticular multimodal drug injection (PMDI) in addition to adductor canal block (ACB) after total knee arthroplasty. Methods: Among patients who received total knee arthroplasty from June 2017 to December 2017, 50 who underwent ACB with additional IPACK and 50 who received ACB with additional PMDI were selected for this study.We compared the postoperative pain numerical rating scale (NRS), the number of times patient-controlled analgesia was administered and the amount administered, the total amount of opioids given, and complications associated with the procedure between the two groups. Results: NRS measured at rest and 45° knee flexion at days 1 and 2 after surgery was significantly lower in the IPACK group than in the PMDI group. The resting NRS measured at day 3 after surgery was also significantly lower in the IPACK group than in the PMDI group, and the NRS at 45° knee flexion measured from day 3 to day 5 showed a significant reduction in the IPACK group. No complications relating to the procedure occurred. Conclusions IPACK may be a better option than PMDI for controlling acute phase pain in patients undergoing total knee arthroplasty.

BACKGROUND: To investigate whether human adipose-derived stem cells (hADSCs) seeded on multilayered poly (L-lactide-co-ε-caprolactone) (PLCL) sheets improve bladder function in a rat model of detrusor smooth muscle-removed bladder. METHODS: Male rats were randomly divided into 4 groups: Normal, injury (detrusor smooth muscle-removed bladder), PLCL (detrusor smooth muscle-removed bladder implanted with PLCL sheets), and PLCL + ADSC (detrusor smooth muscle-removed bladder implanted with PLCL sheets seeded with hADSCs). Four weeks after the treatment, physiological, histological, immunohistochemical, and immunoblot analyses were performed. RESULTS: hADSCs were compatible with PLCL sheets. Further, the physiological study of PLCL + ADSC group showed significant improvement in compliance and contractility suggesting the functional improvement of the bladder. Histological, immunohistochemical and immunoblot analyses revealed the uniform distribution of hADSCs in between PLCL sheets as well as differentiation of hADSCs into smooth muscle cells (SMC) which is illustrated by the expression of SMC markers. CONCLUSION: hADSCs seeded on the multilayered PLCL sheets has the potential to differentiate into SMC, thus facilitating the recovery of compliance and contractility of the injured bladder.
Animals ; Clothing ; Compliance ; Humans ; Male ; Models, Animal ; Muscle, Smooth ; Myocytes, Smooth Muscle ; Rats ; Stem Cells ; Tissue Engineering ; Urinary Bladder

OBJECTIVE: Restless legs syndrome (RLS) is a highly heritable and common neurological sensorimotor disease disturbing sleep. The objective of study was to investigate significant gene for RLS by performing GWA and replication study in a Korean population. METHODS: We performed a GWA study for RLS symptom group (n=325) and non-RLS group (n=2,603) from the Korea Genome Epidemiology Study. We subsequently performed a replication study in RLS and normal controls (227 RLS and 229 controls) to confirm the present GWA study findings as well as previous GWA study results. RESULTS: In the initial GWA study of RLS, we observed an association of rs11645604 (OR=1.531, p=1.18×10−6) in MPHOSPH6 on chromosome 16q23.3, rs1918752 (OR=0.6582, p=1.93×10−6) and rs9390170 (OR=0.6778, p=7.67×10−6) in UTRN on chromosome 6q24. From the replication samples, we found rs9390170 in UTRN (p=0.036) and rs3923809 and rs9296249 in BTBD9 (p=0.045, p=0.046, respectively) were significantly associated with RLS. Moreover, we found the haplotype polymorphisms of rs9357271, rs3923809, and rs9296249 (overall p=5.69×10−18) in BTBD9 was associated with RLS. CONCLUSION: From our sequential GWA and replication study, we could hypothesize rs9390170 polymorphism in UTRN is a novel genetic marker for susceptibility to RLS. Regarding with utrophin, which is encoded by UTRN, is preferentially expressed in the neuromuscular synapse and myotendinous junctions, we speculate that utrophin is involved in RLS, particularly related to the neuromuscular aspects.
Epidemiology ; Genetic Markers ; Genome ; Genome-Wide Association Study* ; Haplotypes ; Korea ; Restless Legs Syndrome* ; Synapses ; Utrophin

PURPOSE: This study was conducted to compare the characteristics of first suicide attempt patients with self-poisoning with those of self-injured patients. METHODS: In this retrospective data analysis, data were collected from emergency department patients who made a first suicide attempt between October 2013 and January 2017. Data included demographic, socioeconomic, physical and mental health status, method of suicide attempt, and authenticity of suicide intent. Patients were classified into a self-poisoning and self-injury group. RESULTS: Among 2,252 patients, 788 patients were making their first suicide attempt. Of these patients, 443 were self-poisoning patients. Males were less common among the self-poisoning group. Cohabitants (303 [89.4%] vs. 193 [81.4%]; p=0.010), married state (214 [57.4%] vs. 108 [41.2%]; p<0.001), and asking for help after suicide attempt (136 [86.1%] vs. 103 [73.6%]; p=0.009) was more common in the self-poisoning group than the self-injury group. However, planned suicide attempt was more frequent in the self-injury group (26 [16.0%] vs. 9 [4.7%]; p=0.001). Moreover, authenticity of suicide intent was higher in the self-injury group (12 [11.3%] vs. 42 [40.4%]; p<0.001). CONCLUSION: In the self-poisoning group, there was a higher rate of females, married people, existing cohabitants, and tendency to ask for help after suicide attempt. There were also more impulsive suicide attempts in this group. The results presented herein will help prevent self-poisoning suicide attempts among high risk patients.
Emergency Service, Hospital ; Female ; Humans ; Male ; Mental Health ; Methods ; Poisoning ; Retrospective Studies ; Statistics as Topic ; Suicide*

OBJECTIVES: To examine direct causes of attempted suicides, methods adopted to commit suicide, and psychiatric diagnoses among suicide attempters in South Korea. METHODS: A total of 1359 suicide attempters who had visited emergency department of 17 medical centers due to suicide attempt from May 2013 to Nov 2013 were interviewed using semi-structured questionnaires. RESULTS: Psychiatric symptoms were the most common cause of suicide attempts (62.2%), followed by interpersonal relationships (24.4%). Women attempted suicide more often for interpersonal reasons, whereas men were more likely to do so for financial and jobrelated reasons. Half of participants (55.8%) attempted suicide by drug intoxication, which was more prevalent among females and those who had previous history of psychiatric disease or previous suicide attempt. Men were more likely to use more lethal methods such as pesticide poisoning and gas inhalation than women. Pesticide poisoning was also prevalent among the elderly group and the rural population. Near ninety-five percent (94.5%) of participants received a psychiatric diagnosis : the most frequent diagnosis was depressive disorder. CONCLUSIONS: This is the first nationwide study of cases of attempted suicide. When stratified by age groups, gender, urbanicity, living alone or not, presence of physical illness, previous psychiatric history, and previous suicide attempt, there were significant differences with respect to causes, methods of attempted suicides and psychiatric diagnoses of suicide attempters.
Aged ; Depressive Disorder ; Diagnosis* ; Emergency Service, Hospital ; Female ; Humans ; Inhalation ; Korea* ; Male ; Mental Disorders ; Methods* ; Poisoning ; Rural Population ; Suicide* ; Suicide, Attempted