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.

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.

Distribution and ecological risk assessment of priority water pollutants in surface river sediments with emphasis on industrially affected areas.

Priority water pollutants comprising six plasticizers, 18 volatile organic compounds (VOCs), total petroleum hydrocarbon (TPH), 1,4-dioxane, epichlorohydrin, formaldehyde, acrylamide, and cyanides were determined in surface river sediments to assess their distribution patterns and ecological risks. Among these, di (2-ethylhexyl) phthalate (DEHP), toluene, TPH, and acrylamide were frequently found in sediments. The industrial sites had higher concentrations of ∑plasticizers (median 628 ng/g dry weight (dw)), ∑VOCs (median 3.35 ng/g dw), acrylamide (median 0.966 ng/g dw), and TPH (median 152 µg/g dw) in sediments than the mixed and non-industrial areas. The other pollutants did not show the significant differences in levels according to site types because of their relatively low detection frequencies. Volatile and soluble substances as well as hydrophobic pollutants were predominantly detected in surface sediments from industrial areas. Sediment contamination patterns were affected by the size and composition of the industrial zones around the sampling sites. The ecological risks determined using the sediment quality guidelines (DEHP, VOCs, and TPH) and the mean probable effect level quotients (DEHP) were mostly acceptable. However, the two most representative industrial regions (the largest industrial area and the first industrial city) showed risks of concern for DEHP and TPH.

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.

Adipose tissue-derived exosomes alleviate particulate matter-induced inflammatory response and skin barrier damage in atopic dermatitis-like triple-cell model.

Recently, particulate matter (PM) has been shown to exacerbate atopic dermatitis (AD) by inducing an inflammatory response. Meanwhile, several studies revealed that exosomes derived from adipose tissue-derived mesenchymal stem cells promote wound healing and alleviate inflammation via their regenerative and immunomodulatory capacities. Our study aimed to investigate the effects of human adipose tissue-derived mesenchymal stem cell-derived (ASC)-exosomes in PM-induced AD. An AD-like triple-cell model was established by treating human keratinocytes, dermal fibroblasts, and mast cells with polyinosinic:polycytidylic acid (Poly I:C) and interleukin 1 alpha (IL-1α). The effects of PM and ASC-exosomes on the expression of pro-inflammatory cytokines and skin barrier proteins were examined using quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence. PM increased pro-inflammatory cytokines (IL-6, IL-1ß, and IL-1α) and decreased the anti-inflammatory cytokine IL-10, while the mRNA expression of skin barrier proteins (loricrin and filaggrin) decreased. However, when the cells were treated with ASC-exosomes, the PM-induced effects on pro-inflammatory cytokines and skin barrier proteins were reversed. Our results confirmed that PM-induced inflammation and skin barrier damage were alleviated by ASC-exosomes in our AD-like triple-cell model. These data suggest that ASC-exosomes can serve as a therapeutic agent for PM-exacerbated AD.

Social determinants of health of racial and ethnic minority adolescents: An integrative literature review.

Integration of adolescents with diverse cultural backgrounds into the country of residence is associated with some form of rejection and discrimination, predisposing them to undesirable health outcomes. In this regard, the aim of this study was to identify the social determinants of the health of racial and ethnic minority adolescents. In this integrative literature review, PubMed, EMBASE, Cochrane Library, and CINAHL databases were searched from 2016 to 2021 and studies were selected according to the PRISMA 2020 guidelines. Health status was limited to health outcomes according to the definition proposed by the World Health Organization and Healthy People 2020. The social determinants of health were classified according to the research framework of the National Institute on Minority Health and Health Disparities. Six types of health status were identified: self-rated health, obesity and overweight, global self-worth, emotional well-being, anthropometric measurement, and psychosocial adjustment. The social determinants of health were at the individual and interpersonal level, and the domains included the biological (gender, illness experience), psychological (acculturative stress), and sociocultural environment (e.g., socioeconomic status, parents' educational level, household death due to violence). Therefore, future research must prioritize their sociocultural environments to reduce the negative impact of discrimination and sociocultural and structural differences on racial and ethnic minority adolescents.

Comparison of new and old BacT/ALERT aerobic bottles for detection of Candida species.

PURPOSE: A new version of aerobic blood culture media has been developed for the BacT/ALERT (bioMérieux) blood culture system. We evaluated the time to detection and yeast cell counts in positive blood cultures for each Candida spp. according to changes in media. METHODS: Isolates from defibrinated horse blood were inoculated into three types of bottles: the old version of aerobic bottle, new version of aerobic bottle, and anaerobic bottle. All bottles were incubated in the BacT/ALERT Virtuo blood culture system. The time to detection was monitored for each bottle, and yeast cell counts were performed immediately after testing positive, determined via the plate count method. Clinical retrospective data of the candidemia samples before and after aerobic bottle change also were analyzed. RESULTS: The median time to detection was 52.47 hours in the old aerobic bottles versus 19.92 hours in the new aerobic bottles (P < 0.001) for Candida glabrata, and standard and clinical strains showed similar results. C. albicans (27.6 to 24.95 hours) and C. guilliermondii (28.92 to 26.9 hours) had shorter time to detection. However, C. auris (25.43 to 28.25 hours) had a longer time to detection in the new aerobic bottle. The retrospective clinical analysis showed a significant decrease in time to detection (45.0 to 19.4 hours) for C. glabrata, which is consistent with our simulated study result for C. glabrata. As a result of analysis including all blood specimens, C. tropicalis showed a significant delay in time to detection in new aerobic bottles. In an analysis limited to peripheral blood specimens, the time to detection of C. parapsilosis was longer in new aerobic bottles than in old aerobic bottles. CONCLUSION: Most Candida species did not show remarkable TTD differences, but TTD of C. glabrata was markedly reduced in the New FA Plus bottle. The reduction of time to detection enables faster detection and therapeutic approach for C. glabrata infections.

Case report: A novel occurrence of persistent left cranial vena cava coexisting with polycystic kidney disease in a cat.

A 7-year-old castrated male Munchkin cat was presented with anorexia. This cat had been diagnosed with chronic kidney disease due to polycystic kidney disease. Tachycardia with a systolic murmur (grade III/VI) was auscultated and for further diagnosis, echocardiography was performed. Based on echocardiography, persistent left cranial vena cava (PLCVC) was suspected due to enlargement of the coronary sinus and confirmed by saline contrast echocardiography. The dilated coronary sinus compressed the left atrium, and left ventricular hypertrophy with the systolic anterior motion of the mitral valve, aortic regurgitation, and mitral regurgitation were identified. After medical management using atenolol, left atrial function and other hemodynamics of the heart were improved, including the disappearance of regurgitation and normalization of left ventricular wall thickness. This case report describes the echocardiographic characteristics, diagnostic procedures, and disease progression in a cat with PLCVC after medical management using atenolol. Additionally, this is the first report of a cat with PLCVC, coexisting with polycystic kidney disease.

Effects of Mealworm Fermentation Extract and Soy Protein Mix Ratio on Hepatic Glucose and Lipid Metabolism in Obese-Induced Mice.

Previous studies found that mealworm fermentation extract (TMP) reduced alcoholic hepatic steatogenesis. This study examined how the ratio of TMP and soy protein (SP) mix affected glucose and lipid metabolism in obese mice given a high-fat diet (HFD). Mice were given HFD supplemented with 100% SP or the following three ratios of TMP and SP mix for 12 weeks: 20% (S4T1), 40% (S3T2), and 60% (S2T3) TMP. When compared to the SP group, the S2T3 group had considerably lower body weight gain and food consumption. When compared to the SP group, the S2T3 group had slightly lower blood insulin and leptin levels, as well as a lower homeostasis model assessment of insulin resistance score. The use of TMP instead of SP reduced the size of epididymal adipose tissue cells. An increase in the extent of substitution of SP with TMP inhibited the gene expression of hepatic fructolysis/gluconeogenesis (KHK, ALDOB, DLD, and FBP1), lipogenesis (FAS, SCD1, CD36, and DGAT2), and its transcriptional factors (PPARγ and ChREBP). Furthermore, the S2T3 group dramatically reduced the expression of hepatic genes implicated in endoplasmic reticulum stress (PDI) and antioxidant defense (SOD1). The 60% TMP mix, in particular, reduced the expression of hepatic glucose and lipid metabolismrelated genes in HFD-fed mice. The manufacturing of functional processed goods may be accomplished by combining SP and TMP in a 2:3 ratio.

"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.

Clinical performance of SARS-CoV-2 antigen-detection rapid diagnostic test using SERS-based lateral flow immunoassay.

Background: 'ACROSIS COVID-19 Ag (NPS)' kit (SG Medical, Seoul, Korea) is a newly developed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen-detection rapid diagnostic test (Ag-RDT) using surface-enhanced Raman scattering (SERS)-based lateral flow immunoassay (LFIA). We evaluated its clinical performance compared with STANDARD Q COVID-19 Ag (SD Biosensor, Suwon, Korea), a previously approved Ag-RDT. Methods: A total of 286 nasopharyngeal swab specimens were collected: 104 positive and 182 negative specimens in SARS-CoV-2 real-time reverse-transcription polymerase-chain-reaction (rRT-PCR). SARS-CoV-2-positive specimens were divided according to the cycle threshold (Ct) value in rRT-PCR. The clinical performance of ACROSIS was compared with that of STANDARD Q. Results: ACROSIS showed significantly higher sensitivity than STANDARD Q (92.3% vs. 85.6%, P = 0.02), especially in specimens with 25 ≤ Ct < 30 (78.6% vs. 42.9%). The Ct values of RdRp/S genes for 95% detection rates by ACROSIS and STANDARD Q were 25.8 and 23.0, respectively. Conclusions: This is the first study that evaluated the performance of ACROSIS compared with STANDARD Q. The overall clinical performance of ACROSIS was superior to that of STANDARD Q, especially in specimens with 25 ≤ Ct < 30. ACROSIS could be useful for SARS-CoV-2 Ag detection even in relatively low viral load specimens.

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).

Polychlorinated biphenyls and organochlorine pesticides in surface sediments from river networks, South Korea: Spatial distribution, source identification, and ecological risks.

In this study, the nationwide monitoring of 65 polychlorinated biphenyls (PCBs) and 23 organochlorine pesticides (OCPs) in surface sediments was conducted at 77 sites in river networks in South Korea. The concentrations of ∑PCBs were relatively high in industrial sites (0.0297-138 ng/g dry weight (dw); mean 15.1 ng/g dw; median 5.44 ng/g dw), followed by industrial and agricultural (not detected (ND)-15.2 ng/g dw; mean 1.23 ng/g dw; median 0.513 ng/g dw), other sites (0.0369-0.209 ng/g dw; mean 0.116 ng/g dw; median 0.101 ng/g dw), and agricultural (0.0119-0.359 ng/g dw; mean 0.117 ng/g dw; median 0.0476 ng/g dw). The distribution and composition of PCBs in sediments are affected by past use of commercial products, atmospheric deposition, wastewater effluents, and manufacturing processes. The concentrations of ∑OCPs in industrial sites ranged from 0.0587 to 8.70 ng/g dw (mean 1.85 ng/g dw; median 0.989 ng/g dw), followed by industrial and agricultural (ND-8.54 ng/g dw; mean 0.739 ng/g dw; median 0.343 ng/g dw), other sites (0.0247-0.143 ng/g dw; mean 0.0939 ng/g dw; median 0.114 ng/g dw), and agricultural (0.00838-0.931 ng/g dw; mean 0.232 ng/g dw; median 0.0752 ng/g dw). Hexachlorobenzene and pentachlorobenzene are unintentionally generated in industries and combustion processes. Dichlorodiphenyltrichloroethanes and chlordane were dominantly distributed by historical use, whereas recent inputs (i.e., long-range transport and atmospheric deposition) were related to aldrin, heptachlor, and hexachlorocyclohexanes. The ecological risks determined by the sediment quality guidelines and mean probable effect level quotients were acceptable, except at two sites.

Inclusion, Diversity, Access, and Equity in Infectious Diseases Fellowship Training: Tools for Program Directors.

The Infectious Diseases Society of America (IDSA) has set clear priorities in recent years to promote inclusion, diversity, access, and equity (IDA&E) in infectious disease (ID) clinical practice, medical education, and research. The IDSA IDA&E Task Force was launched in 2018 to ensure implementation of these principles. The IDSA Training Program Directors Committee met in 2021 and discussed IDA&E best practices as they pertain to the education of ID fellows. Committee members sought to develop specific goals and strategies related to recruitment, clinical training, didactics, and faculty development. This article represents a presentation of ideas brought forth at the meeting in those spheres and is meant to serve as a reference document for ID training program directors seeking guidance in this area.

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).

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.