Development of a multidisciplinary medication management program in nursing homes: protocol for a randomized controlled trial : Multidisciplinary medication management in nursing homes.

BACKGROUND: Polypharmacy and the use of potentially inappropriate medications are common among nursing home residents and are associated with negative outcomes. Although deprescribing has been proposed as a way to curtail these problems, the best way to implement multidisciplinary comprehensive medication review and deprescribing and its real impact in specific high-risk populations, such as nursing home residents, is still unclear. This multicenter randomized controlled clinical trial aims to assess the effects of a multidisciplinary mediation management program on medication use and health problems. METHODS: A total of 1,672 residents aged ≥ 65 years from 22 nursing homes in South Korea who meet the targeted criteria, such as the use of ≥ 10 medications, are eligible to participate. The experimental group will receive a comprehensive medication review, deprescription, and multidisciplinary case conference with the help of platform. Outcomes will be measured at baseline, at the end of the intervention, as well as at 3, 6, 9, and 12 months after the end of the intervention. The primary endpoints will be the rate of adverse drug events, number of potentially inappropriate medications/potentially inappropriate medication users/two or more central nervous system drug/ central nervous system drug users, delirium, emergency department visits, hospitalization, and falls. The secondary endpoint will be the number of medications taken and polypharmacy users. DISCUSSION: Our trial design is unique in that it aims to introduce a structured operationalized clinical program focused on reducing polypharmacy and potentially inappropriate medications in a nursing home setting with large samples. TRIAL REGISTRATION: Ethical approval was granted by the public institutional review board of the Ministry of Health and Welfare (2022-1092-009). The study is also registered with the Clinical Research Information Service (Identifier: KCT0008157, Development and evaluation of a multidisciplinary medication management program in long-term care facility residents Status: Approved First Submitted Date: 2023/01/18 Registered Date: 2023/02/03 Last Updated Date: 2023/01/18 (nih.go.kr) https://cris.nih.go.kr/ ), which includes all items from the World Health Organization Trial Registration Dataset.

A qualitative exploration of exercise motivation among colorectal cancer survivors: an application of the theory of planned behavior.

PURPOSE: The purpose of this qualitative study was to use semi-structured interviews and thematic analysis to elicit key influencing factors (i.e., behavioral, normative, and control beliefs) related to physical activity and exercise in colorectal cancer survivors. METHODS: Colorectal cancer survivors (N = 17) were recruited from exercise programs designed for colorectal cancer survivors at the Yonsei Cancer Center, Seoul, South Korea. A purposive sampling method was used. Interview questions were informed by the theory of planned behavior (TPB). Semi-structured face-to-face interviews were conducted, and open-ended questions addressed the research question. Interviews were transcribed verbatim and analyzed using thematic analysis. RESULTS: Participants were on average 2.2 years post-treatment. The mean age of the sample was 55.9 years. Key behavioral, normative, and control beliefs emerged in the data. For behavioral beliefs, colorectal cancer survivors believed that exercise would result in physical and psychological improvements, and improve their bowel problems. For normative beliefs, most colorectal cancer survivors wanted their oncologists' approval for participation of exercise. Family members, more specifically the spouse, were also influencing factors for colorectal cancer survivors adopting physical activity. The most frequently mentioned control belief was that supervised exercise with an exercise specialist made exercise participation easier. CONCLUSIONS AND IMPLICATIONS: Beliefs identified in this study can inform TPB-based physical activity interventions tailored for colorectal cancer survivors. While information alone may not lead to behavior change, integrating these beliefs with other influential factors can potentially enhance intervention efficacy and promote physical activity in this population.

Anti­osteoclastogenic effect of fermented mealworm extract by inhibiting RANKL­induced NFATc1 action.

Augmented osteoclast activity and differentiation can lead to destructive bone diseases, such as arthritis and osteoporosis. Therefore, modulating osteoclastogenesis and differentiation may serve to be a possible strategy for treating such diseases. Tenebrio molitor larvae, also known as mealworms, are considered a good source of protein with nutritional value, digestibility, flavor and functional properties, such as antioxidant, anti-diabetic and anti-obesity effects. However, the role of mealworms in osteoclastogenesis remains poorly understood. The present study therefore investigated the effects of fermented mealworm extract (FME) on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in bone marrow-derived macrophages (BMMs) whilst also attempting to understand the underlying mechanism, if any. The cells treated with RANKL were used as the negative control. To prepare FME, defatted mealworm powder was fermented with a Saccharomyces cerevisiae strain, and then extracted with fermented alcohol. Cell viability of BMMs isolated from 5-week-old Institute of Cancer Research mice was measured using Cell Counting Kit-8 assay. Subsequently, the effects of FME on osteoclast differentiation were measured using tartrate-resistant acid phosphatase (TRAP) staining. In addition, expression of markers associated with osteoclast differentiation was assessed by reverse transcription-quantitative PCR. Expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) was assessed by western blotting. TRAP staining revealed that FME inhibited osteoclast differentiation in a dose-dependent manner (10-100 µg/ml) without causing cytotoxicity. Specifically, the formation of osteoclasts appear to have been suppressed by FME as indicated by the reduction in the number of TRAP-positive multinucleated cells observed. Furthermore, FME treatment significantly decreased the mRNA expression of c-Fos, whilst also significantly decreasing the expression of NFATc1 on both protein and mRNA levels. c-Fos and NFATc1 are transcription factors that can regulate osteoclast differentiation. FME treatment also reduced the expression of genes associated with osteoclast differentiation and function, including dendritic cell-specific transmembrane protein, osteoclast associated Ig-like receptor, Cathepsin K and TRAP, compared with that in the control group. Subsequently, FME was found to effectively suppress RANKL-induced osteoclast differentiation compared with that by the non-fermented mealworm extract. These findings suggest that FME may confer anti-osteoclastogenic effects, providing insights into its potential application in treatment of osteoporosis.

Comparing domain- and intensity-specific physical activity in coronary heart disease and non-CHD individuals.

Although increase in physical activity is important to improve prognosis of cardiac patients in addition to hospital-based exercise cardiac rehabilitation, their physical activity levels are not properly understood. This study aimed to examine domain- and intensity-specific physical activity in individuals with coronary heart disease (CHD) and compare them with non-CHD individuals. Data from the Korean National Health and Nutrition Examination Survey (KNHANES) from 2014 to 2019 were analyzed, including 1083 CHD patients and 38,532 non-CHD individuals. The inclusion criteria were age 19 years or older and data not missing for CHD information. Before and after propensity score matching (PSM) for age, sex, body mass index, education, household income, alcohol intake, and smoking status, domain (leisure, work, transportation)-and intensity (moderate, vigorous) -specific physical activity participation levels were compared between individuals with and without CHD. Before PSM, CHD individuals were older, less educated, more sedentary, and participated less in PAs compared to non-CHD individuals. After PSM, CHD individuals had similar levels of domain-specific PAs. However, they had higher work-related PA levels (29.7 ± 209.6 vs. 42.1 ± 291.3 min/week p = 0.022) and more sedentary time (487.2 ± 224.2 vs. 514.1 ± 228.7. p = 0.003) than those without CHD. Subgroup analysis revealed lower leisure-related PA in men with CHD (63.5 ± 165.5 vs. 47.3 ± 140.2, p < 0.05) and higher work-related PA in women with CHD (18.9 ± 159.7 vs. 57.1 ± 397.5, p < 0.01). Among those < 65 years of age, individuals with CHD spent more time sedentary than individuals without CHD. CHD individuals are not physically inactive compared with non-CHD individuals who are similar in sociodemographic status and lifestyle. CHD patients' PA levels may have been underestimated.

Prevalence estimation of Tropheryma whipplei in duodenal biopsy tissues of Koreans.

Whipple's disease caused by Tropheryma whipplei is difficult to diagnose because of a broad spectrum of manifestations and non-specific clinical signs. In the current global era, the incidence of duodenal infection/inflammation caused by T. whipplei in Korea may has been underestimated. Here we estimated the prevalence of T. whipplei in duodenal biopsy tissues of Koreans using real-time PCRs (RT-PCRs). A total of 252 duodenal biopsy tissues were collected from Korean patients who underwent esophagogastroduodenoscopy and duodenal biopsy. DNA extracted from the duodenal biopsy tissues was analyzed using three RT-PCRs targeting T. whipplei-specific regions of the 16S-23S rRNA intergenic spacer, hsp65, and Dig15 in parallel. In the samples positive in RT-PCRs, direct sequencing was performed for each RT-PCR target. The prevalence of T. whipplei was estimated based on the RT-PCR and sequencing results. Among the analyzed samples, T. whipplei was not detected. The prevalence of T. whipplei in duodenal biopsy tissues of Koreans was estimated to be less than 0.4%. This is the first study to attempt to detect T. whipplei in duodenal biopsy tissues of Koreans and estimate its prevalence. Our findings infer that while T. whipplei carriers exist in Korea, the incidence of duodenal infection/inflammation caused by T. whipplei is extremely rare.

"Nulichal" Barley Extract Suppresses Nitric Oxide and Pro-Inflammatory Cytokine Production by Lipopolysaccharides in RAW264.7 Macrophage Cell Line.

The cultivar "Nulichal," a type of naked waxy barley (Hordeum vulgare L.), was developed by the National Institute of Crop Science, Rural Development Administration, Korea, in 2010. In this study, we investigated the anti-inflammatory and antioxidant properties of the "Nulichal" ethanol extract (NRE) using various assays. The NRE exhibited a total phenolic content of 7.55±0.30 mg gallic acid equivalent/g and a flavonoid content of 1.74±0.08 mg rutin equivalent/g. Cell viability assays showed no toxicity of NRE on RAW264.7 macrophage cells up to concentrations of 500 µg/mL. The NRE (300 and 500 µg/mL) significantly reduced nitric oxide (NO) production induced by lipopolysaccharides (LPS). It also down-regulated the mRNA expression and protein levels of inducible NO synthase and cyclooxygenase-2 in a dose-dependent manner. Moreover, the NRE treatment significantly decreased the levels of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, and their mRNA expression compared to LPS treatment alone. The NRE demonstrated strong free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals in a dose-dependent manner. The ferric reducing antioxidant power assay also showed increased antioxidant activity with increasing NRE concentrations. These findings suggest that the NRE can be used as a functional food with anti-inflammatory and antioxidant properties.

Functional characterization of genes encoding cadmium pumping P1B-type ATPases in Aspergillus fumigatus and Aspergillus nidulans.

Several P1B-type ATPases are important Cd2+/Cu2+ pumps in Aspergillus species, and they are tightly associated with the heavy metal stress tolerance of these ascomycetous fungi. To better understand the roles of the two P1B-type ATPases, Aspergillus nidulans CrpA Cd2+/Cu2+ pump (orthologue of the Candida albicans Crp1 Cd2+/Cu2+ pump) and Aspergillus fumigatus PcaA Cd2+ pump (orthologue of the Saccharomyces cerevisiae Pca1 Cd2+ pump), we have generated individual mutants and characterized their heavy metal susceptibilities. The deletion of CrpA in A. nidulans has led to the increased sensitivity of the fungus to stresses induced by Zn2+, Fe2+, or the combination of oxidative-stress-inducing menadione sodium bisulfite and Fe3+. Heterologous expression of A. fumigatus PcaA in the S. cerevisiae pca1 deletion mutant has resulted in enhanced tolerance of the yeast to stresses elicited by Cd2+or Zn2+ but not by Fe2+/Fe3+ or Cu2+. Mammalian host immune defense can attack microbes by secreting Zn2+ or Cu2+, and the oxidative stress induced by host immune systems can also disturb metal (Cu2+, Fe2+, and Zn2+) homeostasis in microbes. In summary, PcaA and CrpA can protect fungal cells from these complex stresses that contribute to the virulence of the pathogenic Aspergillus species. Moreover, due to their presence on the fungal cell surface, these P1B-type ATPases may serve as a novel drug target in the future. IMPORTANCE Mammalian host immune defense disrupts heavy metal homeostasis of fungal pathogens. P1B-type ATPase of Aspergillus fumigatus and Aspergillus nidulans may help to cope with this stress and serve as virulence traits. In our experiments, both A. nidulans Cd2+/Cu2+ pump CrpA and A. fumigatus Cd2+ pump PcaA protected fungal cells from toxic Zn2+, and CrpA also decreased Fe2+ susceptibility most likely indirectly. In addition, CrpA protected cells against the combined stress induced by the oxidative stressor menadione and Fe3+. Since P1B-type ATPases are present on the fungal cell surface, these proteins may serve as a novel drug target in the future.

Emticicia fluvialis sp. nov., a potential hormone-degrading bacterium isolated from Nakdong River, Republic of Korea.

A novel species of the genus Emticicia, designated BHSR1T, was isolated from a water sample that was collected from the Nakdong River, Republic of Korea, and its taxonomic affiliation was studied using a polyphasic approach. This bacterium was Gram-stain-negative, non-motile, aerobic, curved, rod-shaped, and oxidase- and catalase-negative. The bacterium grew optimally at 37 °C, pH 7.5 and 0% (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain BHSR1T should be affiliated with the genus Emticicia, with a high similarity to Emticicia fontis KCTC 52248T (98.10%). Phylogenomic analysis also suggested that the strain represents a novel species in the genus Emticicia. The genomic G + C content was 41.9%. The average nucleotide identity, average amino acid identity and digital DNA-DNA hybridization between strain BHSR1T and its closely related relatives in the genus Emticicia were in ranges of 71.1-75.8%, 69.4-77.5% and 18.6-19.9%, respectively. The gene cluster within BHSR1T contained genes encoding enzymes that could be involved in hormone degradation. The major cellular fatty acids (> 10%) were summed feature 3 (comprising C16:1ω6c and/or C16:1ω7c) and iso-C15:0. With regards to the polar lipid profile, phosphatidylethanolamine (PE), two unidentified aminolipids and three unidentified lipids were identified as the major compounds. The major respiratory quinone was menaquinone (MK)-7. Based on its phylogenetic, phenotypic, chemotaxonomic, and genomic features, strain BHSR1T should be considered a novel species in the genus Emticicia of the family Spirosomaceae, for which the name Emticicia fluvialis sp. nov. is proposed. The type strain was considered BHSR1T (= KCTC 92622T = GDMCC 1.3740T).

Serial Comparison of Patient-Reported Outcomes of Immediate Breast Reconstruction: Direct-to-Implant Versus Deep Inferior Epigastric Perforator Flap.

BACKGROUND: Direct-to-implant (DTI) and deep inferior epigastric artery perforator (DIEP) flaps are the two most common methods of immediate breast reconstruction. This study aimed to compare patient-reported outcomes between the two methods and to evaluate whether outcomes change over time. METHODS: The data of patients who underwent immediate breast reconstruction using DTI or DIEP flaps between July 2017 and October 2021 were retrospectively reviewed. Patients who completed the BREAST-Q Reconstruction Module at 6 months and > 12 months after reconstruction were analyzed. Mann-Whitney and Wilcoxon signed-rank test were used to compare outcome between DTI and DIEP groups, and serial comparisons were performed. RESULTS: Of 375 patients included in the analysis, 146 patients completed questionnaires > 1 year of follow-up (20.79 ± 8.55 months). The DTI and DIEP groups had 102 (69.9%) and 44 (30.1%) patients, respectively. There were no intergroup differences in the mean scores representing any of the domains at 6 postoperative months. After > 1 year of follow-up, patients who underwent DIEP-flap reconstruction had greater satisfaction with their breast reconstructions (p < 0.001) and greater satisfaction with their overall outcomes (p < 0.001). In the DTI group, satisfaction scores did not change over time in any of the domains. In the DIEP group, however, the mean scores reflecting satisfaction with the breast (p = 0.001), overall outcome (p = 0.045), psychosocial well-being (p = 0.015), and sexual well-being (p = 0.042) significantly increased over long-term follow-up relative to the scores at 6 postoperative months. CONCLUSIONS: Patient-reported outcomes improved over time in association with DIEP reconstructions, reflecting higher satisfaction levels than those associated with DTI reconstruction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Leisingera thetidis sp. nov., isolated from coastal water.

A Gram-strain-negative, strictly aerobic, rod-shaped, catalase-positive, oxidase-positive and pinkish beige colony-forming bacterial strain designated as BMJM1T was isolated from a marine sample collected from coastal water near Tongyeong, Republic of Korea. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that BMJM1T represents a member of the genus Leisingera as it is closely related to Leisingera daeponensis KCTC 12794T (98.27%), Leisingera caerulea DSM 24564T (97.98%), Leisingera aquaemixtae KCTC 32538T (97.91%), Leisingera methylohalidivorans DSM 14336T (97.26%) and Leisingera aquimarina DSM 24565T (97.25%). Optimal growth occurred at 25-30°C, pH 7.0 and with 2% NaCl. Digital DNA-DNA hybridisation (dDDH) and average nucleotide identity (ANI) values between strain BMJM1T and the closely related species of the genus Leisingera were below 40 and 90%, respectively, which are far below the thresholds to delineate a novel species. The predominant fatty acids (>10%) are summed feature 8 (C18:1ω7c and/or C18:1ω6c) (68.4%) and C14:1iso E (11.6%). The major polar lipids were phosphatidylethanolamine and phospholipid. The major isoprenoid quinone was ubiquinone-10. The DNA G+C content was 64.0%. On the basis of the results of the polyphasic taxonomic characterisation, BMJM1T represents a novel species of the genus Leisingera, for which the name is Leisingera thetidis sp. nov. is proposed, with that type strain BMJM1T (= KCTC 92110T = GDMCC 1.2992T).

Delayed Reconstruction of Nasal Tip Amputation After a Dog Bite Using a Cartilage Graft and Paramedian Forehead Flap.

The timing and method of reconstruction of an amputated nose due to a dog bite are still controversial. Here, we describe a delayed reconstruction using the paramedian forehead flap with a simultaneous cartilage graft to address a contracted nose from a dog bite. A healthy, 52-year-old patient was attacked by his acquaintance's dog, resulting nasal tip amputation that included cartilage. The composite graft was performed, and secondary healing resulted in a short nose deformity. Five months after the injury, a conchal cartilage graft and paramedian forehead flap were performed simultaneously to correct the shape of the deformity. At 1 year postoperatively, the flap survived without complications, and the short nose deformity was successfully corrected. In summary, immediate composite graft after a dog bite could result in a contracted nose, but the deformity can be corrected by a simultaneous paramedian forehead flap and cartilage graft.

Isolation, Characterization and Whole-Genome Analysis of Paenibacillus andongensis sp.nov. from Korean Soil.

The genus Paenibacillus contains a variety of biologically active compounds that have potential applications in a range of fields, including medicine, agriculture, and livestock, playing an important role in the health and economy of society. Our study focused on the bacterium SS4T (KCTC 43402T = GDMCC 1.3498T), which was characterized using a polyphasic taxonomic approach. This strain was analyzed using antiSMASH, BAGEL4, and PRISM to predict the secondary metabolites. Lassopeptide clusters were found using all three analysis methods, with the possibility of secretion. Additionally, PRISM found three biosynthetic gene clusters (BGC) and predicted the structure of the product. Genome analysis indicated that glucoamylase is present in SS4T. 16S rRNA sequence analysis showed that strain SS4T most closely resembled Paenibacillus marchantiophytorum DSM 29850T (98.22%), Paenibacillus nebraskensis JJ-59T (98.19%), and Paenibacillus aceris KCTC 13870T (98.08%). Analysis of the 16S rRNA gene sequences and Type Strain Genome Server (TYGS) analysis revealed that SS4T belongs to the genus Paenibacillus based on the results of the phylogenetic analysis. As a result of the matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF/MS) results, SS4T was determined to belong to the genus Paenibacillus. Comparing P. marchantiophytorum DSM 29850T with average nucleotide identity (ANI 78.97%) and digital DNA-DNA hybridization (dDDH 23%) revealed values that were all less than the threshold for bacterial species differentiation. The results of this study suggest that strain SS4T can be classified as a Paenibacillus andongensis species and is a novel member of the genus Paenibacillus.

Single-molecule fingerprinting of protein-drug interaction using a funneled biological nanopore.

In drug discovery, efficient screening of protein-drug interactions (PDIs) is hampered by the limitations of current biophysical approaches. Here, we develop a biological nanopore sensor for single-molecule detection of proteins and PDIs using the pore-forming toxin YaxAB. Using this YaxAB nanopore, we demonstrate label-free, single-molecule detection of interactions between the anticancer Bcl-xL protein and small-molecule drugs as well as the Bak-BH3 peptide. The long funnel-shaped structure and nanofluidic characteristics of the YaxAB nanopore enable the electro-osmotic trapping of diverse folded proteins and high-resolution monitoring of PDIs. Distinctive nanopore event distributions observed in the two-dimensional (ΔI/Io-versus-IN) plot illustrate the ability of the YaxAB nanopore to discriminate individual small-molecule drugs bound to Bcl-xL from non-binders. Taken together, our results present the YaxAB nanopore as a robust platform for label-free, ultrasensitive, single-molecule detection of PDIs, opening up a possibility for low-cost, highly efficient drug discovery against diverse drug targets.

Collinsella urealyticum sp. nov., a urease-positive bacterial strain isolated from swine faeces.

A novel actinobacterial strain, designated AGMB00827T, was isolated from swine faeces. Strain AGMB00827T was obligately anaerobic, Gram-stain-positive, non-motile, non-spore-forming and rod-shaped bacterium. Comparative analyses based on the 16S rRNA gene and whole genome sequence revealed that strain AGMB00827T was affiliated to the genus Collinsella, and was most closely related to Collinsella vaginalis Marseille-P2666T (= KCTC 25056T). Biochemical analysis showed strain AGMB00827T was negative for catalase and oxidase. Interestingly, strain AGMB00827T possessed urease activity, which was determined by traditional methods (API test and Christensen's urea medium), unlike related strains. Furthermore, the major cellular fatty acids (> 10%) of the isolate were C18:1 ω9c, C16:0, C16:0 DMA and C18:2 ω9,12c DMA. Based on the whole genome sequence analysis, the DNA G + C content of strain AGMB00827T was 52.3%, and the genome size and numbers of rRNA and tRNA genes were 1,945,251 bp, 3 and 46, respectively. The average nucleotide identity and digital DNA-DNA hybridization values between strain AGMB00827T and C. vaginalis KCTC 25056 T were 71.0 and 23.2%, respectively. Additionally, the genome analysis revealed that strain AGMB00827T possesses urease gene cluster including ureABC and ureDEFG while the related strains do not have those genes, which is consistent with the urease activity. On the basis of polyphasic taxonomic approach, strain AGMB00827T represents a novel species within the genus Collinsella, for which the name Collinsella urealyticum sp. nov. is proposed. The type strain is AGMB00827T (= KCTC 25287T = GDMCC 1.2724T).

Estimating the measurement uncertainties of the international sensitivity index of 12 thromboplastins through Monte Carlo simulation.

BACKGROUND: Measurement uncertainty (MU) estimation has become an important process in clinical laboratories; however, calculating the MUs of the international sensitivity index (ISI) of thromboplastins is difficult because of the complex mathematical calculations required in calibration. Therefore, this study quantifies the MUs of ISIs through the Monte Carlo simulation (MCS), which involves random sampling of numerical values to solve a complex mathematical calculation. METHODS: Eighty blood plasmas and commercially available certified plasmas (ISI Calibrate) were used to assign the ISIs of each thromboplastin. Prothrombin times were measured using reference thromboplastin and 12 commercially available thromboplastins (Coagpia PT-N, PT Rec, ReadiPlasTin, RecombiPlasTin 2G, PT-Fibrinogen, PT-Fibrinogen HS PLUS, Prothrombin Time Assay, Thromboplastin D, Thromborel S, STA-Neoplastine CI Plus, STA-Neoplastine R 15, and STA-NeoPTimal) with two automated coagulation instruments: ACL TOP 750 CTS (ACL TOP; Instrumentation Laboratory, Bedford, MA, USA) and STA Compact (Diagnostica Stago, Asnières-sur-Seine, France). Then, the MUs of each ISI were simulated through MCS. RESULTS: The MUs of ISIs ranged from 9.7 % to 12.1 % and 11.6 % to 12.0 % when blood plasma and ISI Calibrate were used, respectively. For some thromboplastins, the ISI claimed by manufacturers significantly differed from the estimated results. CONCLUSIONS: MCS is adequate to estimate the MUs of ISI. These results would be clinically useful for estimating the MUs of the international normalized ratio in clinical laboratories. However, the claimed ISI significantly differed from the estimated ISI of some thromboplastins. Therefore, manufacturers should provide more accurate information about the ISI value of thromboplastins.

Establishment of Reference Intervals of Cytokeratin 19 Fragment Antigen 21-1 in Korean Adults.

Cytokeratin 19 fragment antigen 21-1 (CYFRA 21-1) is useful for predicting and monitoring non-small cell lung cancer prognosis. We established reference intervals (RIs) of CYFRA 21-1 in Korean adults, including those older than 60 years. Data of 4,098 apparently healthy subjects (age range, 20-87 years) were analyzed after excluding those with a history of malignancy, high tumor marker concentrations (except CYFRA 21-1), and/or abnormal findings on a chest computed tomography scan through medical chart review. After removing two outliers, RIs of CYFRA 21-1 were determined using data of 4,096 subjects based on the non-parametric method (2.5th and 97.5th percentiles) according to CLSI guidelines EP28-A3c. The subjects were divided into two and four groups according to sex and age (20-40, 41-50, 51-60, and >60 years), respectively, and the median CYFRA 21-1 concentration was compared between the groups. The RI of CYFRA 21-1 was 0.66-3.84 ng/mL, applicable to both men and women. Regardless of sex, the CYFRA 21-1 concentration increased with age, suggesting that age-dependent RIs of CYFRA 21-1 should be applied. Rather than using a single RI provided by the manufacturer, the RI of CYFRA 21-1 should be continually verified and established in each clinical laboratory.

Three-dimensional Volume Changes of the Reconstructed Breast Following DIEP Flap Breast Reconstruction.

BACKGROUND: This study aimed to assess whether the reconstructed breast volume changed postoperatively following a deep inferior epigastric artery perforator (DIEP) flap. METHODS: Patients were included if they had undergone unilateral breast reconstruction with a DIEP flap at the two selected centers between April 2017 and September 2019. Serial 3-D surface imaging of both breasts was taken at 1, 3, 6, and 12 months postoperatively. The primary outcome was a volume ratio of the reconstructed to the contralateral breast. A linear mixed-effect model was used to evaluate whether the DIEP flap volume changed according to the postoperative time. RESULTS: A total of 74 patients were included in the analysis. The mean volume ratio of the reconstructed side compared with the contralateral breast at 1, 3, 6, and 12 months postoperatively were 106.9%, 105.9%, 108.7%, and 107.6%, respectively. In the linear mixed effect model, the volume ratio of the reconstructed breast did not change over time for immediate reconstructions (p = 0.376). However, there was an increase over time in delayed reconstructions (p = 0.043). Adjuvant radiation, chemotherapy, and hormone therapy did not influence the volume ratio of the reconstruced breast. Correlation analysis using repeatedly measured values showed that both reconstruced and healthy breast volumes had positive correlation with the patient's body weight (p < 0.001). On the other hand, volume ratio of the breasts was not influenced by the patient's body weight (p = 0.493). The volume ratio of the reconstructed breast significantly decreased in the upper inner (p = 0.003) and the upper outer (p = 0.006) quadrants, while increasing in the lower outer (p = 0.002) quadrant throughout the first-year postoperative period. CONCLUSION: The volume ratio of the reconstructed to the contralateral breast does not decrease postoperatively following DIEP flap breast reconstruction.

Olsenella intestinalis sp. nov., isolated from cow feces.

A Gram-stain-negative, anaerobic, non-motile, rod-shaped bacterium, designated as BGYT1T, was isolated from the feces of a cow in Andong, Republic of Korea. It was studied using a polyphasic method to determine its taxonomic position. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain BGYT1T formed a lineage within the genus Olsenella and was most closely related to O. umbonate KCTC 15140T (98.2%). The complete genome sequence of strain BGYT1T was 2,476,083 bp long with a G + C content of 66.9 mol% and contained 1835 genes and 8 contigs. The N50 value was 604,117 bp. There were 50 tRNAs, 6 rRNAs (5S, 16S, 23S), 1778 CDSs and 2 BGCs and 1 tmRNA. The values for ANI (76.8%), AAI (67.3%), and dDDH (22.2%) compared to the closest related species were all below the threshold for bacterial species delineation. In addition, genes encoding the cell wall degrading enzymes such as chitinases, ß-1,3 glucanases, and proteases were also detected. The strain was able to grow at pH 6.0-8.0 (optimum, pH 7.0), in the presence of 0.5-1.5% NaCl (optimum, 0.5%, w/v) and at the temperature range of 35-40 °C (optimum, 35 °C). The predominant fatty acids were C16:0 DMA (20.2%), C16:0 (20.2%), C18:0 (10.5%) and C18:1 cis 9 (17.0%). The polar lipids consisted of an unidentified phospholipid, four unidentified glycolipids and three unidentified lipids. Based on its phenotypic analyses, phylogenetic and physiological characteristics, strain BGYT1T represented a novel species within the genus Olsenella, for which the name Olsenella intestinalis sp. nov. is proposed. The type strain is BGYT1T (= KCTC 25379T = GDMCC 1.3011T).

Single-Molecule Sensing of an Anticancer Therapeutic Protein-Protein Interaction Using the Chemically Modified OmpG Nanopore.

Nanopore sensors are a highly attractive platform for single-molecule sensing for sequencing, disease diagnostics, and drug screening. Outer membrane protein G (OmpG) nanopores have advantages for single-molecule sensing owing to their rigid monomeric structure, which comprises seven flexible loops, providing distinct gating patterns upon analyte binding. Blocking of the protein-protein interaction between B-cell lymphoma-extra-large (Bcl-xL) and the BH3 domain of Bcl-2 homologous antagonist/killer (Bak-BH3) has been reported as a promising strategy for anticancer therapy. Here, we characterized the interaction between Bcl-xL and Bak-BH3 as well as its inhibition by a small-molecule inhibitor using click chemistry-based Bak-BH3 peptide-conjugated OmpG nanopores. The binding of Bcl-xL to Bak-BH3 generated characteristic gating signals involving significant changes in the amplitudes of noise and gating parameters such as gating frequency, open probability, and durations of open and closed states. Notably, specific inhibition of Bcl-xL by the small-molecule antagonist, ABT-737, led to the recovery of the noise and gating parameters. Collectively, these results revealed that the chemically modified OmpG nanopore can serve as a valuable sensor platform for ultrasensitive, rapid, and single-molecule-based drug screening against protein-protein interactions, which are therapeutic targets for various diseases.