Impact of prolonged carbapenem use-focused antimicrobial stewardship on antimicrobial consumption and factors affecting acceptance of recommendations: a quasi-experimental study.

This study aimed to assess the impact of a prolonged carbapenem use-focused antimicrobial stewardship program (ASP) on antimicrobial consumption and clinical outcomes and to analyze factors affecting adherence to interventions. Patients prescribed carbapenems for ≥ 2 weeks received intervention. Interrupted time-series analysis was performed to compare antimicrobial consumption before and after intervention. Factors associated with non-adherence to intervention were investigated. Of 273 patients who were eligible for intervention, discontinuation or de-escalation was recommended in 256 (94.1%) and intervention was accepted in 136 (53.1%) patients. Before intervention, carbapenem consumption significantly increased to 1.14 days of therapy (DOT)/1000 patient days (PD)/month (P = 0.018). However, it significantly declined by - 2.01 DOT/1000 PD/month without an increase in other antibiotic consumption (P < 0.001). Factors affecting non-adherence to intervention were younger age (odds ratio [OR] = 0.98; 95% confidence interval [CI] 0.96-1.00), solid organ malignancy (OR = 2.53, 95% CI 1.16-5.50), and pneumonia (OR = 2.59, 95% CI 1.08-6.17). However, ASP intervention was not associated with clinical outcomes such as length of hospital stay or mortality. Prolonged carbapenem prescription-focused ASP significantly reduced carbapenem consumption without adverse outcomes. Non-adherence to interventions was attributed more to prescriber-related factors, such as attitude, than patient-related factors including clinical severity.

Indolocarbazole-Based Photo-Crosslinkable Hole-Transporting Layer for Efficient Solution-Processed Organic Light-Emitting Diodes.

We designed and synthesized a new indolocarbazole-based polymer, poly(N,N-diphenyl(5,11-dihexylindolo[3,2,1-jk]carbazol-2-yl)amine) (PICA), for solution-processed organic light-emitting diodes (OLEDs). The highest occupied and lowest unoccupied molecular orbital energy levels of this polymer, -5.25 and -2.46 eV, respectively, are suitable for hole transport from the anode to the emissive layer. PICA was photo-crosslinked by UV irradiation with ethane-1,2-diyl bis(4-azido-2,3,5,6-tetrafluorobenzoate) (FPA) as the photoinitiator. Successful crosslinking was confirmed by a decreased intensity in the azide-stretching FT-IR peak and solvent test with toluene (a suitable solvent for PICA). The PICA film photo-crosslinked with 3 wt% FPA showed enhanced solvent resistance (90%) compared to the non-crosslinked neat PICA film (<20%). Moreover, OLED devices using PICA-based hole-transporting layers exhibited better device performance (EQE/LE/PE: 8.88%/12.97/8.12 in red devices, 10.84%/38.47 cd/A/25.06 lm/W in green devices) than those using poly-TPD:FPA. We demonstrated that the photo-crosslinked PICA can be applied as a hole-transporting layer in solution-processed OLEDs.

Anti-Inflammatory Response in TNFα/IFNγ-Induced HaCaT Keratinocytes and Probiotic Properties of Lacticaseibacillus rhamnosus MG4644, Lacticaseibacillus paracasei MG4693, and Lactococcus lactis MG5474.

Atopic dermatitis (AD) is a chronic inflammatory disease caused by immune dysregulation. Meanwhile, the supernatant of lactic acid bacteria (SL) was recently reported to have anti-inflammatory effects. In addition, HaCaT keratinocytes stimulated by tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) are widely used for studying AD-like responses. In this study, we evaluated the anti-inflammatory effects of SL from lactic acid bacteria (LAB) on TNF-α/IFN-γ-induced HaCaT keratinocytes, and then we investigated the strains' probiotic properties. SL was noncytotoxic and regulated chemokines (macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC)) and cytokines (interleukin (IL)-4, IL-5, IL-25, and IL-33) in TNF-α/IFN-γ-induced HaCaT keratinocytes. SL from Lacticaseibacillus rhamnosus MG4644, Lacticaseibacillus paracasei MG4693, and Lactococcus lactis MG5474 decreased the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK). Furthermore, the safety of the three strains was demonstrated via hemolysis, bile salt hydrolase (BSH) activity, and toxicity tests, and the stability was confirmed under simulated gastrointestinal conditions. Therefore, L. rhamnosus MG4644, L. paracasei MG4693, and Lc. lactis MG5474 have potential applications in functional food as they are stable and safe for intestinal epithelial cells and could improve atopic inflammation.

Limosilactobacillus fermentum MG4294 and Lactiplantibacillus plantarum MG5289 Ameliorates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced Mice.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and the leading cause of liver-related deaths worldwide. It has been established that microorganisms are involved in the interaction between the intestinal lumen and the liver; therefore, studies on probiotics as potential candidates are increasing. This study evaluated the effects of Limosilactobacillus fermentum MG4294 and Lactiplantibacillus plantarum MG5289 on NAFLD. The MG4294 and MG5289 reduced lipid accumulation in FFA-induced HepG2 by suppressing the adipogenic proteins through the regulation of AMP-activated protein kinase (AMPK). The administration of these strains in the HFD-induced mice model lowered body weight, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and cholesterol levels. In particular, MG4294 and MG5289 restored liver TG and TC to normal levels by lowering lipid and cholesterol-related proteins via the modulation of AMPK in the liver tissue. In addition, the administration of MG4294 and MG5289 reduced pro-inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1ß-, and IL6) in the intestinal tissues of the HFD-induced mouse model. In conclusion, MG4294 and MG5289 can be presented as probiotics with the potential to prevent NAFLD.

Latilactobacillus sakei Wikim0066 Protects Skin through MMP Regulation on UVB-Irradiated In Vitro and In Vivo Model.

Ultraviolet (UV) B exposure induces wrinkle formation, collagen fiber breakdown, and transepidermal water loss (TEWL). UVB irradiation induces the expression of mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1), and nuclear factor kappa B (NF-κB), which affect the expression of matrix metalloproteinases (MMP). We confirmed the effects of Latilactobacillus sakei wikim0066 (wikim0066) on UVB-irradiated Hs68 cells and HR-1 hairless mice cells. wikim0066 restored the production of type I procollagen by regulating the expression of MMP-1 and -3, MAPK, AP-1, and NF-κB in UVB-irradiated Hs68 cells and HR-1 mice. Oral administration of wikim0066 alleviates wrinkle formation, epidermal thickness, and TEWL in UVB-irradiated HR-1 hairless mice. These results indicated that wikim0066 has the potential to prevent UVB-induced wrinkle formation.

Lactic Acid Bacteria Improve the Photoprotective Effect via MAPK/AP-1/MMP Signaling Pathway on Skin Fibroblasts.

Ultraviolet B (UVB) exposure causes a breakdown of collagen, oxidative stress, and inflammation. UVB activates mitogen-activated protein kinase (MAPK), activator protein-1 (AP-1), and matrix metalloproteinases (MMPs). In this study, we evaluated 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) radical scavenging activity and the photoprotective effect of lactic acid bacteria LAB strains, including Lactobacillus, Bifidobacterium, and Streptococcus genera in UVB-exposed skin fibroblasts. Nine LAB strains displayed antioxidant activity by regulating superoxide dismutase in UVB-exposed skin fibroblasts. Four LAB strains (MG4684, MG5368, MG4511, and MG5140) recovered type I procollagen level by inhibiting MMPs, MAPK, and AP-1 protein expression. Additionally, these four strains reduced the expression of proinflammatory cytokines by inhibiting oxidative stress. Therefore, L. fermentum MG4684, MG5368, L. rhamnosus MG4511, and S. thermophilus MG5140 are potentially photoprotective.

Protective Effect of Bifidobacterium animalis subs. lactis MG741 as Probiotics against UVB-Exposed Fibroblasts and Hairless Mice.

Skin photoaging, which causes wrinkles, increased epidermal thickness, and rough skin texture, is induced by ultraviolet B (UVB) exposure. These symptoms by skin photoaging have been reported to be involved in the reduction of collagen by the expression of matrix metalloproteinases (MMPs) and activator protein-1 (AP-1). This study investigated the protective effects of Bifidobacterium animalis subsp. lactis MG741 (Bi. lactis MG741) in Hs-68 fibroblasts and hairless mice (HR-1) following UVB exposure. We demonstrated that the Bi. lactis MG741 reduces wrinkles and skin thickness by downregulating MMP-1 and MMP-3, phosphorylation of extracellular signal-regulated kinase (ERK), and c-FOS in fibroblasts and HR-1. Additionally, in UVB-irradiated dorsal skin of HR-1, Bi. lactis MG741 inhibits the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), an inflammation-related factor. Thus, Bi. lactis MG741 has the potential to prevent wrinkles and skin inflammation by modulating skin photoaging markers.

Lacticaseibacillus rhamnosus MG4706 Suppresses Periodontitis in Osteoclasts, Inflammation-Inducing Cells, and Ligature-Induced Rats.

Periodontitis is a chronic inflammatory disease characterized by tooth loss due to inflammation and the loss of alveolar bone. Periodontitis is closely related to various systemic diseases and is emerging as a global health problem. In this study, we investigated the anti-inflammatory effect of lactic acid bacteria (LAB) in vitro on Porphyromonas gingivalis (P. gingivalis) LPS-activated RAW264.7 and human gingival fibroblasts-1 (HGF-1) cells and the anti-osteoclastogenic effect of LAB on RANKL-induced RAW264.7 cells. All LAB strains (Lacticaseibacillus rhamnosus MG4706, MG4709, and MG4711) inhibited nitric oxide (NO)/inducible nitric oxide synthase (iNOS) in P. gingivalis LPS-activated RAW264.7 cells and pro-inflammatory cytokines (IL-1ß and IL-6) and matrix metalloproteinase (MMP-8 and MMP-9) in HGF-1 cells. In addition, LAB treatment inhibited osteoclastogenesis by reducing tartrate-resistant acid phosphatase (TRAP) activity and cathepsin K (CtsK) through the downregulation of nuclear factor of activated T cells cytoplasmic 1 (NFATc1) and c-fos gene expression in RANKL-induced RAW264.7 cells. Administration of MG4706 alleviated alveolar bone loss indices and reduced the gene expression of IL-1ß, IL-6, MMP-8, MMP-9, and RANKL/OPG ratio in gingival tissue. In conclusion, L. rhamnosus MG4706 has the potential to alleviate periodontitis.

Neuroprotective Effects of Coreopsis lanceolata Flower Extract against Oxidative Stress-Induced Apoptosis in Neuronal Cells and Mice.

Coreopsis lanceolata L. is a perennial plant of the family Asteraceae, and its flower is known to contain flavonoids with various bioactivities. We evaluated the effect of Coreopsis lanceolata L. flower (CLF) extracts on H2O2-induced oxidative stress (OS) in neuronal cells and mouse neurons. The flowering part of CL was used as CLF1 (70% ethanol extract) and CLF2 (water extract), and 10 types of phenolic compounds were quantified using high-performance liquid chromatography. To evaluate the neuroprotective effects of CLF, the antioxidant activities of the extracts were measured, and the expression levels of antioxidant enzymes and proteins related to OS-induced apoptosis in neuronal cells and mouse neurons treated with the extracts were investigated. In the in vitro study, CLF ameliorated H2O2-induced oxidative stress and induced the expression of antioxidant enzymes in PC12 cells. Furthermore, CLF1 enhanced the expression of the Bcl-xL protein but reduced the expression of Bax and the cleavage of caspase-3. In the same manner, CLF1 showed neuroprotective effects against OS in vivo. Pretreatment with CLF1 (200 mg/kg) increased the Bcl-2 protein and decreased Bax compared with the 1-methyl-4-phenylpyridinium ion (MPP+)-treated C57BL/6 mice model group. Our results suggest that the protective effects of CLF1 on MPP+-induced apoptosis may be due to its anti-apoptotic activity, through regulating the expression of the Bcl-2 family. CLF1 exerts neuroprotective effects against OS-induced apoptosis in PC12 cells in a Parkinson's disease model mouse. This effect may be attributable to the upregulation of Bcl-2 protein expression, downregulation of Bax expression, and inhibition of caspase-3 activation. These data indicate that CLF may provide therapeutic value for the treatment of progressive neurodegenerative diseases.

Sasa quelpaertensis Leaf Extract Ameliorates Dyslipidemia, Insulin Resistance, and Hepatic Lipid Accumulation in High-Fructose-Diet-Fed Rats.

BACKGROUND: Increased dietary fructose consumption is closely associated with lipid and glucose metabolic disorders. Sasa quelpaertensis Nakai possesses various health-promoting properties, but there has been no research on its protective effect against fructose-induced metabolic dysfunction. In this study, we investigated the effects of S. quelpaertensis leaf extract (SQE) on metabolic dysfunction in high-fructose-diet-fed rats. METHODS: Animals were fed a 46% carbohydrate diet, a 60% high-fructose diet, or a 60% high-fructose diet with SQE (500 mg/kg of body weight (BW)/day) in drinking water for 16 weeks. Serum biochemical parameters were measured and the effects of SQE on hepatic histology, protein expression, and transcriptome profiles were investigated. RESULTS: SQE improved dyslipidemia and insulin resistance induced in high-fructose-diet-fed rats. SQE ameliorated the lipid accumulation and inflammatory response in liver tissues by modulating the expressions of key proteins related to lipid metabolism and antioxidant response. SQE significantly enriched the genes related to the metabolic pathway, namely, the tumor necrosis factor (TNF) signaling pathway and the PI3K-Akt signaling pathway. CONCLUSIONS: SQE could effectively prevent dyslipidemia, insulin resistance, and hepatic lipid accumulation by regulation of metabolism-related gene expressions, suggesting its role as a functional ingredient to prevent lifestyle-related metabolic disorders.

Solution-Processed Organic Light-Emitting Diodes Using a Photo-Crosslinkable Hole-Transporting Layer.

Photo-crosslinkable hole transporting layer (HTL) consisting of a blend of poly(bis-4-butylphenyl-N,N-bisphenyl)benzidine (poly-TPD) and bis(4-azido-2,3,5,6-tetrafluorobenzoate) (FPA) was applied to red and green organic light-emitting diodes (OLEDs) by solution processing. This photocrosslinking reaction rendered the HTL insoluble in organic solvents and enabled subsequent solution deposition of an upper emissive layer. The solvent resistance of the photo-crosslinked poly-TPD:FPA (1 wt%) film was enhanced compared to that of the non-crosslinked neat poly-TPD film. Solution-processed red and green OLEDs with the poly-TPD:FPA (1 wt%) photo-crosslinked HTL exhibited higher device performances than those with the non-crosslinked poly-TPD HTL.

Erigeron annuus Protects PC12 Neuronal Cells from Oxidative Stress Induced by ROS-Mediated Apoptosis.

Reactive oxygen species (ROS), associated with oxidative stress, are involved in many biological processes such as apoptosis, necrosis, and autophagy. Oxidative stress might induce neuronal damage via ROS generation, causing neurodegenerative diseases. Erigeron annuus (EA) has antioxidant properties and could protect neurons from oxidative stress. In this study, we investigated the protective effect of the aerial parts (EAA) and flowers (EAF) from EA on ROS-mediated apoptosis in pheochromocytoma 12 cells. We quantified 18 types of phenolic compounds using high-performance liquid chromatography. Pretreatment of the cells with EAA and EAF attenuated ROS generation and induced the expression of antioxidant enzymes such as superoxide dismutase 2, catalase, and glutathione peroxidase. In addition, EAF reduced the expression of apoptotic proteins such as Bax/Bcl-xL, caspase-3, and caspase-8 to a greater extent than that with EAA. These results suggested that the protective effect of EAF against oxidative stress-induced apoptosis might be due to the prevention of ROS generation mediated by oxidative enzymes.

Differences in anti-inflammatory effect of immature and mature of Rubus coreanus fruits on LPS-induced RAW 264.7 macrophages via NF-κB signal pathways.

BACKGROUND: Rubus coreanus fruit (RF) has been used as a traditional medicine formulation to treat various diseases including diarrhea, asthma, and cancer in East Asia (Korea, China, and Japan). RF, which is native to Korea, has a larger fruit size than that of exotic species. In this study, we aimed to compare the anti-inflammatory activities of immature and mature RF extracted with different solvents. METHODS: Mature and immature RF (MRF and IRF) were extracted with 30% ethanol, 70% ethanol and water at room temperature. The antioxidant activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assays. Anti-inflammatory activity was determined by measuring nitric oxide (NO) production, expression of inflammatory proteins (inducible NO synthase [iNOS], cyclooxygenase [COX]-2, nuclear factor [NF]-κB, and inhibitor of NF-κB [IκB]), and inflammatory cytokines using polymerase chain reaction in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. RESULTS: The IRF 30% ethanol extract showed higher radical scavenging activity in DPPH and ABTS assays (half-maximal inhibitory concentration [IC50] 16.0 ± 0.5 and 15.9 ± 0.4) than MRF did. In addition, the IRF 30% ethanol extract (200 µg/mL) significantly reduced the production of the inflammatory mediator NO by approximately 80% and inhibited iNOS, COX-2, phosphorylated (p)-IκB, and p-NF-κB activation compared with MRF. Moreover, IRF extract decreased the inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 compared with the MRF extract. CONCLUSIONS: This study revealed that IRF showed more beneficial effects than MRF did in LPS-stimulated RAW 264.7 macrophages, suggesting that IRF may be a useful anti-inflammatory agent.

Thermally Cross-Linkable Styrene-Based Host Materials for Solution-Processed Organic Light-Emitting Diodes.

Thermally cross-linkable host materials, DV-TPACZ, DV-TPADBCZ, and TV-TPBI, were designed and synthesized for solution-processed organic light-emitting diodes (OLEDs). The synthesized styrene-functionalized host materials were thermally cross-linked by curing at 150-200 °C without using a polymerization initiator. Excellent solvent resistance was observed for all cured host films. They exhibited low highest occupied molecular orbital energy levels of 5.4-5.7 eV, which indicated a low hole injection barrier from the hole transport layer to the emissive layer. A solution-processed red phosphorescent OLED with 5 wt% (MPHMQ)2Ir (tmd) dopant in the thermally cross-linkable DV-TPACZ host exhibited a current efficiency of 5.3 cd/A, power efficiency of 3.2 lm/W, and external quantum efficiency of 3.6%.

Synthesis and Characterization of Novel Triarylmethane-Based Dyes for Thermally Stable Blue Color Filters.

Two new triarylmethane-based dye molecules with a dimeric structure, TAM-1 and TAM-2, were designed and synthesized as potential blue color filter materials for liquid-crystal displays. The dimeric structure of TAM-1 was designed to improve the thermal stability of a well-known blue dye, Victoria Blue BO. TAM-2 was designed to further improve the solubility of TAM-1 by introducing long alkyl ester groups. The synthesized dyes TAM-1 and TAM-2 were transmissive in the wavelength range of 410-460 nm and showed good thermal stability with 5% weight degradation temperatures (T5d) of 259 °C and 289 °C, respectively, and less than 1% of weight loss at 230 °C. Moreover, TAM-2 showed excellent solubility (20.1 wt%) as opposed to Victoria Blue BO (0.03 wt%) and TAM-1 (3.5 wt%) in PGMEA.

Blue Phosphorescent Bipyridine-Based Iridium(III) Complex for Vacuum-Deposited Organic Light-Emitting Diodes.

We have synthesized and characterized a blue phosphorescent iridium(III) complex (dfpypy)2Ir(tftamp), which contains 2',6'-difluoro-2,3'-bipyridine (dfpypy) as the main ligand and 4-methyl-2-(3'-trifluoromethyl-1'H-1',2',4'-triazol-5'-yl)pyridine (tftamp) as the ancillary ligand. The photophysical, electrochemical, and electroluminescent (EL) properties of (dfpypy)2Ir(tftamp) were investigated. Vacuum-deposited blue and white organic light-emitting diodes (OLEDs) were fabricated using (dfpypy)2Ir(tftamp) in 1,3-bis(carbazol-9-yl)benzene (mCP) as the emitting layer. The EL spectrum of (dfpypy)2Ir(tftamp) exhibited emission maximum at 472 nm with a full-width at half-maximum (FWHM) of 81 nm and Commission Internationale de L'Eclairage (CIE) coordinates of (0.17, 0.27) at 100 cd · m-2. In addition, white-light-emitting devices were fabricated, which exhibited CIE coordinates of (0.42, 0.40) and a correlated color temperature (CCT) of 3,237 K at 1000 cd · m-2, close to the standard warm-white light CIE coordinates of (0.44, 0.40) and CCT of 3,000 K.

Isolation and characterization of avian metapneumovirus from chickens in Korea.

Avian metapneumovirus (aMPV) causes upper respiratory tract infections in chickens and turkeys. Although the swollen head syndrome (SHS) associated with aMPV in chickens has been reported in Korea since 1992, this is the study isolating aMPV from chickens in this country. We examined 780 oropharyngeal swab or nasal turbinate samples collected from 130 chicken flocks to investigate the prevalence of aMPV and to isolate aMPV from chickens from 2004-2008. Twelve aMPV subtype A and 13 subtype B strains were detected from clinical samples by the aMPV subtype A and B multiplex real-time reverse transcription polymerase chain reaction (RRT-PCR). Partial sequence analysis of the G glycoprotein gene confirmed that the detected aMPVs belonged to subtypes A and B. Two aMPVs subtype A out of the 25 detected aMPVs were isolated by Vero cell passage. In animal experiments with an aMPV isolate, viral RNA was detected in nasal discharge, although no clinical signs of SHS were observed in chickens. In contrast to chickens, turkeys showed severe nasal discharge and a relatively higher titer of viral excretion than chickens. Here, we reveal the co-circulation of aMPV subtypes A and B, and isolate aMPVs from chicken flocks in Korea.

Anisotropic rupture of polymer strips driven by Rayleigh instability.

We demonstrate that the separated polymer strips of micro- and sub-micro-length-scales rupture anisotropically along the strip direction, resulting in the formation of distinctly observable, regularly spaced polymer drops. The wavelength of the polymer drops and the surface tension dependence of the rupture behavior are found to be well represented by a relationship derived on the basis of Rayleigh instability. The period is proportional to the square root of the cross-sectional area of the strip and the proportionality constant depends on the contact angle. The rupture of polymer strips into polymer blocks instead of drops, which result when annealed with physically confining walls in place, is found to be well described by the same relationship.