Prohibitin modulates periodontium differentiation in mice development.

Introduction: Prohibitin (PHB) is an essential scaffold protein that modulates signaling pathways controlling cell survival, metabolism, inflammation, and bone formation. However, its specific role in periodontium development remains less understood. This study aims to elucidate the expression pattern and function of PHB in periodontium development and its involvement in alveolar bone formation. Methods: Immunolocalization of PHB in the periodontium of postnatal (PN) mice were examined. Phb morpholino was micro-injected into the right-side mandible at PN5, corresponding to the position where the alveolar bone process forms in relation to the lower first molar. The micro-injection with a scramble control (PF-127) and the left-side mandibles were used as control groups. Five days post-micro-injection, immunohistochemical analysis and micro-CT evaluation were conducted to assess bone mass and morphological changes. Additionally, expression patterns of signaling molecules were examined following Phb downregulation using 24-h in vitro cultivation of developing dental mesenchyme at E14.5. Results: The immunostaining of PHB showed its localization in the periodontium at PN5, PN8, and PN10. The in vitro cultivation of dental mesenchyme resulted in alterations in Bmps, Runx2, and Wnt signalings after Phb knock-down. At 5 days post-micro-injection, Phb knocking down showed weak immunolocalizations of runt-related transcription factor (RUNX2) and osteocalcin (OCN). However, knocking down Phb led to histological alterations characterized by decreased bone mass and stronger localizations of Ki67 and PERIOSTIN in the periodontium compared 1 to control groups. The micro-CT evaluation showed decreased bone volume and increased PDL space in the Phb knock-down specimens, suggesting its regulatory role in bone formation. Discussion: The region-specific localization of PHB in the margin where alveolar bone forms suggests its involvement in alveolar bone formation and the differentiation of the periodontal ligament. Overall, our findings suggest that Phb plays a modulatory role in alveolar bone formation by harmoniously regulating bone-forming-related signaling molecules during periodontium development.

Occurrence and health risk assessment of tropane alkaloids in cereal foods consumed in Korea.

Tropane alkaloids (TA) are natural toxins found in certain plants, including cereals, of which atropine and scopolamine are the main species of concern due to their acute toxicity. This study aimed to determine the occurrence of TA in cereal foods and assess the potential health risks associated with their consumption in Korea. TA levels were analyzed in 80 raw and 71 processed cereal samples, which were distributed throughout Korea in 2021, using ultra-performance liquid chromatography-tandem mass spectrometry. At least one of the six TA species, namely atropine, scopolamine, pseudotropine, tropinone, scopine, and 6-hydroxytropinone, was detected in 10 out of the 151 samples at levels ranging from 0.12 to 88.10 µg kg-1. Dietary exposure (mean, 0.23 ng kg-1 bw day-1) to atropine and scopolamine in the Korean population was estimated to be low across all age groups. This is despite considering worst-case scenarios using the total concentrations of atropine and scopolamine in a millet sample, both of which were detected, and 95th percentile consumption for consumers of millet only. Both the hazard index and margin of exposure methods indicated that the current levels of TA exposure from millet consumption were unlikely to pose significant health risks to the Korean population.

Ginseng extracts improve circadian clock gene expression and reduce inflammation directly and indirectly through gut microbiota and PI3K signaling pathway.

Despite the potential benefits of herbal medicines for therapeutic application in preventing and treating various metabolic disorders, the mechanisms of action were understood incompletely. Ginseng (Panax ginseng), a commonly employed plant as a dietary supplement, has been reported to play its hot property in increasing body temperature and improving gut health. However, a comprehensive understanding of the mechanisms by which ginseng regulates body temperature and gut health is still incomplete. This paper illustrates that intermittent supplementation with ginseng extracts improved body temperature rhythm and suppressed inflammatory responses in peripheral metabolic organs of propylthiouracil (PTU)-induced hypothermic rats. These effects were associated with changes in gut hormone secretion and the microbiota profile. The in-vitro studies in ICE-6 cells indicate that ginseng extracts can not only act directly on the cell to regulate the genes related to circadian clock and inflammation, but also may function through the gut microbiota and their byproducts such as lipopolysaccharide. Furthermore, administration of PI3K inhibitor blocked ginseng or microbiota-induced gene expression related with circadian clock and inflammation in vitro. These findings demonstrate that the hot property of ginseng may be mediated by improving circadian clock and suppressing inflammation directly or indirectly through the gut microbiota and PI3K-AKT signaling pathways.

Efficacy of Crataegus Extract Mixture on Body Fat and Lipid Profiles in Overweight Adults: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

A Crataegus Extract Mixture (CEM) is a combination of extracts from Crataegus pinnatifida leaves and Citrus unshiu peels, well-known herbs used for treating obesity and dyslipidemia. We aimed to investigate the efficacy and safety of a CEM on the body fat and lipid profiles in overweight adults. A 12-week, randomized, double-blind, placebo-controlled, parallel-group trial was conducted on 105 subjects aged 20-60 years with body mass indexes between 25 and 30 kg/m2. Eligible subjects were randomly assigned in a 1:1:1 ratio to receive either a high dose of the CEM (400 mg tid), a low dose of the CEM (280 mg tid), or a placebo. Body fat was evaluated using dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and anthropometric measurements. The blood lipid and adipokine profiles were measured before and after the administration. After 12 weeks, the reductions in the fat percentages measured by DXA and BIA were significantly greater in the CEM groups than in the placebo group. The CEM also significantly decreased the body weights, body mass indexes, and blood leptin levels. An additional per-protocol analysis revealed that the high dose of the CEM also lowered the blood levels of triglycerides and very low-density lipoprotein cholesterol. No adverse events occurred after the CEM treatment. Our results suggest that CEMs are safe and effective for reducing the body fat and body weight and regulating the blood lipid and leptin levels in overweight or mildly obese individuals.

Yijung-tang improves thermogenesis and reduces inflammation associated with gut microbiota in hypothyroid rats.

Currently, considerable attention is focused on exploring the potential relationship between herbal medicine (HM) and the gut microbiome in terms of thermoregulation, which is an important aspect of human health, in modern system biology. However, our knowledge of the mechanisms of HM in thermoregulation is inadequate. Here, we demonstrate that the canonical herbal formula, Yijung-tang (YJT), protects against hypothermia, hyperinflammation, and intestinal microbiota dysbiosis in PTU-induced hypothyroid rats. Notably, these properties were associated with alterations in the gut microbiota and signaling crosstalk between the thermoregulatory and inflammatory mediators in the small intestine and brown adipose tissue (BAT). In contrast to the conventional drug L-thyroxine for curing hypothyroidism, YJT has an efficacy for attenuating systematic inflammatory responses, related with depression in intestinal TLR4 and Nod2/Pglyrp1 signaling pathways. Our findings suggest that YJT could promote BAT thermogenesis and prevent systemic inflammation in PTU-induced hypothyroid rats, which was associated with its prebiotic effect on modulating of the gut microbiota and gene expression with relevance in the enteroendocrine function and innate immune systems. These findings may strengthen the rationale of the microbiota-gut-BAT axis for a paradigm shift to enable holobiont-centric medicine.

Rapid in-situ growth of enzyme-mimicking Pd nanoparticles on TEMPO-oxidized nanocellulose for the efficient detection of ascorbic acid.

Rapid, efficient and green method of Pd nanoparticles (PdNPs) synthesis on TEMPO-oxidized cellulose nanofibril (TCNF) is demonstrated here. The nanohybrid (PdNPs/TCNF) exhibited peroxidase and oxidase-like activities evident by the oxidation of three chromogenic substrates. Enzyme kinetic studies using 3,3',5,5'-Tetramethylbenzidine (TMB) oxidation uncovered the excellent kinetic parameters (low Km and high Vmax) and good specific activities of 215 U/g and 107 U/g for peroxidase and oxidase-like activities, respectively. A colorimetric assay for ascorbic acid (AA) detection is proposed based on its ability to reduce oxidized TMB to its colorless form. However, presence of nanozyme caused re-oxidation of TMB to its blue colored form within few minutes resulting in time limitation and inaccurate detection. Thanks to the film forming nature of TCNF; this limitation was overcome by employing PdNPs/TCNF film strips that can be easily removed before AA addition. The assay allowed AA detection in the linear range of 0.25-10 µM with a detection limit of 0.039 µM. The results of AA detection in commercial beverages and vitamin C tablets are matching with the specified values. Further the nanozyme exhibited high tolerance to pH (2-10) and temperature (up to 80 °C) and good recyclability for five cycles.

Effect of Paeoniae Radix Rubra (Paeonia lactiflora Pall.) extract on mucin secretion, gene expression in human airway epithelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniae Radix Rubra (PRR), the root of Paeonia lactiflora Pall., is a traditional Chinese medicine which has the effects of regulating various inflammatory diseases, treating blood stasis, and enhancing blood circulation. AIM OF THE STUDY: This study examined whether Paeoniae Radix rubra extract (PRRE) and Paeoniflorin (PF) affect mucin production, gene expression including MUC5AC, and protein expression related to the ERK pathway induced by TNF-α from human airway epithelial cells. MATERIALS AND METHODS: NCI-H292 cells induced by TNF-α were treated with each agent. MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription polymerase chain reaction, staining, and enzyme-linked immunosorbent assay. Western blot was used to investigate the cell signaling pathways. RESULTS: PRRE and PF inhibited the production of MUC5AC mucin protein and gene expression in TNF-α-induced H292 cells. In Western blot, PRRE was involved in protein expression related to the ERK pathway. CONCLUSIONS: Overall, PRRE effectively inhibited the MUC5AC, and inflammatory cytokines expression caused by TNF-α, which was closely involved in the ERK pathway. PRRE may have the potential for treating mucus producing respiratory inflammation.

Bifidobacterium longum and Galactooligosaccharide Improve Skin Barrier Dysfunction and Atopic Dermatitis-like Skin.

PURPOSE: The beneficial effects of a combination therapy using Bifidobacterium longum and galactooligosaccharide (GOS) for the treatment of atopic dermatitis (AD) have not been elucidated. METHODS: Gene expressions of interleukin (IL)-4 and IL-13 from peripheral blood mononuclear cells and fecal abundance of B. longum from 12-month-old infants were evaluated. Human primary epidermal keratinocytes (HEKs) and hairless mice were treated with B. longum, GOS, B. longum-derived extracellular vesicles (BLEVs), dinitrochlorobenzene (DNCB), or a synbiotic mixture of B. longum and GOS. Expression of epidermal barrier proteins and cytokines as well as serum immunoglobulin E (IgE) levels were analyzed in HEKs and mice. Dermatitis scores, transepidermal water loss (TEWL), epidermal thickness, and fecal B. longum abundance were evaluated in mice. RESULTS: Fecal abundance of B. longum was negatively correlated with blood IL-13 expression in infants. B. longum or BLEVs increased expression of filaggrin (FLG) and loricrin (LOR) in HEKs. B. longum increased the efficacy of GOS to upregulate FLG and LOR expressions in HEKs. Oral administration of GOS increased fecal abundance of B. longum in mice. Oral administration of B. longum attenuated DNCB-induced skin inflammation, abnormal TEWL, AD-like skin, and deficiency of epidermal barrier proteins. Moreover, the combination of B. longum and GOS showed greater effects to improve DNCB-induced skin inflammation, abnormal TEWL, AD-like skin, serum IgE levels, IL-4 over-expression, and the deficiency of epidermal barrier proteins than the administration of B. longum alone. CONCLUSIONS: B. longum and GOS improve DNCB-induced skin barrier dysfunction and AD-like skin.

Inhibitory role of TRIP-Br1 oncoprotein in anticancer drug-mediated programmed cell death via mitophagy activation.

Chemotherapy has been widely used as a clinical treatment for cancer over the years. However, its effectiveness is limited because of resistance of cancer cells to programmed cell death (PCD) after treatment with anticancer drugs. To elucidate the resistance mechanism, we initially focused on cancer cell-specific mitophagy, an autophagic degradation of damaged mitochondria. This is because mitophagy has been reported to provide cancer cells with high resistance to anticancer drugs. Our data showed that TRIP-Br1 oncoprotein level was greatly increased in the mitochondria of breast cancer cells after treatment with various anticancer drugs including staurosporine (STS), the main focus of this study. STS treatment increased cellular ROS generation in cancer cells, which triggered mitochondrial translocation of TRIP-Br1 from the cytosol via dephosphorylation of TRIP-Br1 by protein phosphatase 2A (PP2A). Up-regulated mitochondrial TRIP-Br1 suppressed cellular ROS levels. In addition, TRIP-Br1 rapidly removed STS-mediated damaged mitochondria by activating mitophagy. It eventually suppressed STS-mediated PCD via degradation of VDACI, TOMM20, and TIMM23 mitochondrial membrane proteins. TRIP-Br1 enhanced mitophagy by increasing expression levels of two crucial lysosomal proteases, cathepsins B and D. In conclusion, TRIP-Br1 can suppress the sensitivity of breast cancer cells to anticancer drugs by activating autophagy/mitophagy, eventually promoting cancer cell survival.

Effective fabrication of cellulose nanofibrils supported Pd nanoparticles as a novel nanozyme with peroxidase and oxidase-like activities for efficient dye degradation.

Nanozyme-based dye degradation methods are promising for the remediation of water pollution. Though Pd nanoparticles (PdNPs) are known to act as nanozymes, their dye degradation capability has not been investigated. Low nanozyme activities, easy aggregation, difficulties in recovery and reuse are the major challenges in achieving this. For the first time, cellulose nanofibrils-supported PdNPs (PdNPs/PCNF) as a novel nanozyme with good peroxidase and oxidase-mimicking activities and easy recyclability is explored for dye degradation. An efficient and rapid method of PdNPs/PCNF preparation was demonstrated by adjusting the pH and microwave irradiation. Enzyme kinetic studies revealed good kinetic parameters and specific activities of 415 and 277 U/g for peroxidase and oxidase, respectively. PdNPs/PCNF offered 99.64% degradation of methylene blue within 12 min (0.468 min-1) with 0.4 M H2O2 at pH 5.0. Mechanistic studies revealed the involvement of hydroxyl and superoxide radicals. Owing to the network-like structure of PCNF, films and foams were prepared, their dye degradation potentials were compared, and recyclability was tested. Successful degradation of mixed dye solutions and spiked real water samples was achieved and a continuous flow method was demonstrated using a foam-packed column.

Factors Associated With Depressive Symptoms in Individuals Who Have Experienced COVID-19 Self-Quarantine.

The purpose of this study was to identify the factors associated with depressive symptoms in individuals who have experienced self-quarantine because of coronavirus disease exposure or infection using Lazarus and Folkman's stress, coping, and adaptation theory, and George's Social Antecedent Model of Depression. This was a cross-sectional study that used data from the 2020 Korean Community Health Survey. A complex sample design was used to analyze the data. Descriptive statistics, the Rao-Scott X2 test, and logistic regression analysis were conducted to identify factors associated with depressive symptoms. Approximately 5.3% of the subjects had depressive symptoms. The factors associated with depressive symptoms were age, level of education, household income, changes in daily life due to coronavirus disease, whether someone provided assistance during the self-quarantine, perceived health status, and hospital consultation due to depressive symptoms. The findings of this study will be utilized as basic data for the development of programs to alleviate and prevent depressive symptoms in self-quarantine individuals.

Enhancing ionic conductivity in solid electrolyte by relocating diffusion ions to under-coordination sites.

Solid electrolytes are highly important materials for improving safety, energy density, and reversibility of electrochemical energy storage batteries. However, it is a challenge to modulate the coordination structure of conducting ions, which limits the improvement of ionic conductivity and hampers further development of practical solid electrolytes. Here, we present a skeleton-retained cationic exchange approach to produce a high-performance solid electrolyte of Li3Zr2Si2PO12 stemming from the NASICON-type superionic conductor of Na3Zr2Si2PO12. The introduced lithium ions stabilized in under-coordination structures are facilitated to pass through relatively large conduction bottlenecks inherited from the Na3Zr2Si2PO12 precursor. The synthesized Li3Zr2Si2PO12 achieves a low activation energy of 0.21 eV and a high ionic conductivity of 3.59 mS cm-1 at room temperature. Li3Zr2Si2PO12 not only inherits the satisfactory air survivability from Na3Zr2Si2PO12 but also exhibits excellent cyclic stability and rate capability when applied to solid-state batteries. The present study opens an innovative avenue to regulate cationic occupancy and make new materials.

Preparation and Characterization of Polybutylene Succinate Reinforced with Pure Cellulose Nanofibril and Lignocellulose Nanofibril Using Two-Step Process.

This study reports the preparation of a polybutylene succinate (PBS) film reinforced with pure cellulose nanofibril (PCNF) and lignocellulose nanofibril (LCNF) by a two-step process that consists of solvent dispersion and twin-screw extrusion. Compared to the conventional one-step process, this method offered improved mechanical properties. The addition of 5% CNF increased the tensile properties up to 18.8%. Further, the effect of the lignin content was also studied by using LCNF as a reinforcement. The LCNF was prepared with and without a deep eutectic solvent (DES) pretreatment to gain LCNF with a lignin content that varied between 5, 19, and 30%. The mechanical properties results show that a 5% addition of LCNF to the PBS matrix increased its tensile strength and elastic modulus. Further, the morphological and thermal properties of the composites were also studied in detail.

Wet-Spun Composite Filaments from Lignocellulose Nanofibrils/Alginate and Their Physico-Mechanical Properties.

Lignocellulose nanofibrils (LCNFs) with different lignin contents were prepared using choline chloride (ChCl)/lactic acid (LA), deep eutectic solvent (DES) pretreatment, and subsequent mechanical defibrillation. The LCNFs had a diameter of 15.3-18.2 nm, which was similar to the diameter of commercial pure cellulose nanofibrils (PCNFs). The LCNFs and PCNFs were wet-spun in CaCl2 solution for filament fabrication. The addition of sodium alginate (AL) significantly improved the wet-spinnability of the LCNFs. As the AL content increased, the average diameter of the composite filaments increased, and the orientation index decreased. The increase in AL content improved the wet-spinnability of CNFs but deteriorated the tensile properties. The increase in the spinning rate resulted in an increase in the orientation index, which improved the tensile strength and elastic modulus.

Preparation and Characterization of Cellulose Acetate Film Reinforced with Cellulose Nanofibril.

In this study, cellulose acetate (CA)/cellulose nanofibril (CNF) film was prepared via solvent casting. CNF was used as reinforcement to increase tensile properties of CA film. CNF ratio was varied into 3, 5, and 10 phr (parts per hundred rubbers). Triacetin (TA) and triethyl citrate (TC) were used as two different eco-friendly plasticizers. Two different types of solvent, which are acetone and N-methyl-2-pyrrolidone (NMP), were also used. CA/CNF film was prepared by mixing CA and CNF in acetone or NMP with 10% concentration and stirred for 24 h. Then, the solution was cast in a polytetrafluoroethylene (PTFE) dish followed by solvent evaporation for 12 h at room temperature for acetone and 24 h at 80 °C in an oven dryer for NMP. The effect of solvent type, plasticizers type, and CNF amount on film properties was studied. Good dispersion in NMP was evident from the morphological study of fractured surface and visible light transmittance. The results showed that CNF has a better dispersion in NMP which leads to a significant increase in tensile strength and elastic modulus up to 38% and 65%, respectively, compared with those of neat CA. CNF addition up to 5 phr loading increased the mechanical properties of the film composites.

Esterification of Lignin Isolated by Deep Eutectic Solvent Using Fatty Acid Chloride, and Its Composite Film with Poly(lactic acid).

In this study, the effect of lignin esterification with fatty acid chloride on the properties of lignin and lignin/poly(lactic acid) (PLA) composites was investigated. Lignocellulose (Pinus densiflora S. et Z.) was treated using a deep eutectic solvent (DES) with choline chloride (ChCl)/lactic acid (LA). From the DES-soluble fraction, DES-lignin (DL) was isolated by a regeneration process. Lignin esterification was conducted with palmitoyl chloride (PC). As the PC loading increased for DL esterification, the Mw of esterified DL (EDL) was increased, and the glass transition temperature (Tg) was decreased. In DL or EDL/PLA composite films, it was observed that EDL/PLA had cleaner and smoother morphological characteristics than DL/PLA. The addition of DL or EDL in a PLA matrix resulted in a deterioration of tensile properties as compared with neat PLA. The EDL/PLA composite film had a higher tensile strength and elastic modulus than the DL/PLA composite film. DL esterification decreased water absorption with lower water diffusion coefficients. The effect of lignin esterification on improving the compatibility of lignin and PLA was demonstrated. These results are expected to contribute to the development of high-strength lignin composites.

Positive influence of gut microbiota on the effects of Korean red ginseng in metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Ginseng, a traditional herbal medicine, has been used for thousands of years to treat various diseases including metabolic syndrome (MS). However, the underlying mechanism(s) of such beneficial actions of ginseng against MS is poorly understood. Emerging evidence indicates a close association of the host gut microbiota with MS. The present study was conducted to examine, whether the beneficial effects of Korean red ginseng (KRG) against MS could be influenced by gut microbial population and whether gut microbial profile could be considered a valuable biomarker for targeted treatment strategy for MS in compliance with the predictive, preventive, and personalized medicine (PPPM / 3PM). METHODS: This clinical study was a randomized, double-blind, placebo-controlled trial evaluating the effects of KRG treatment for 8 weeks on patients with MS. The anthropometric parameters, vital signs, metabolic biomarkers, and gut microbial composition through 16S rRNA gene sequencing were assessed at the baseline and endpoint. The impact of KRG was also evaluated after categorizing the subjects into responders and non-responders, as well as enterotypes 1 and 2 based on their gut microbial profile at the baseline. RESULTS: Fifty out of 60 subjects who meet the MS criteria completed the trial without showing adverse reactions. The KRG treatment caused a significant decrease in systolic blood pressure (SBP). Microbial analysis revealed a decrease in Firmicutes, Proteobacteria, and an increase in Bacteroidetes in response to KRG. In patient stratification analysis, the responders showing marked improvement in the serum levels of lipid metabolic biomarkers TC and LDL due to the KRG treatment exhibited higher population of both the family Lachnospiraceae and order Clostridiales compared to the non-responders. The homeostasis model assessment-insulin resistance (HOMA-IR) and insulin level were decreased in enterotype 1 (Bacteroides-abundant group) and increased in enterotype 2 (prevotella-abundant group) following the KRG treatment. CONCLUSION: In this study, the effects of KRG on the glucose metabolism in MS patients were influenced by the relative abundances of gut microbial population and differed according to the individual enterotype. Therefore, the analysis of enterotype categories is considered to be helpful in predicting the effectiveness of KRG on glucose homeostasis of MS patients individually. This will further help to decide on the appropriate treatment strategy for MS, in compliance with the perspective of PPPM.

Preparation and Properties of Wet-Spun Microcomposite Filaments from Various CNFs and Alginate.

We aimed to improve the mechanical properties of alginate fibers by reinforcing with various cellulose nanofibrils (CNFs). Pure cellulose nanofibril (PCNF), lignocellulose nanofibril (LCNF) obtained via deep eutectic solvent (DES) pretreatment, and TEMPO-oxidized lignocellulose nanofibril (TOLCNF) were employed. Sodium alginate (AL) was mixed with PCNF, LCNF, and TOLCNF with a CNF content of 5-30%. To fabricate microcomposite filaments, the suspensions were wet-spun in calcium chloride (CaCl2) solution through a microfluidic channel. Average diameters of the microcomposite filaments were in the range of 40.2-73.7 µm, which increased with increasing CNF content and spinning rate. The tensile strength and elastic modulus improved as the CNF content increased to 10%, but the addition of 30% CNF deteriorated the tensile properties. The tensile strength and elastic modulus were in the order of LCNF/AL > PCNF/AL > TOLCNF/AL > AL. An increase in the spinning rate improved the tensile properties.

A quasi-experimental study on stethoscopes contamination with multidrug-resistant bacteria: Its role as a vehicle of transmission.

Stethoscopes have been suggested to be a possible vector of contact transmission. However, only a few studies have focused on the prevalence of contamination by multidrug-resistant (MDR) bacteria and effectiveness of disinfection training to reduce. This study is to investigate the burden of stethoscope contamination with nosocomial pathogens and multidrug-resistant (MDR) bacteria and to analyze habit changes in disinfection of stethoscopes among healthcare workers (HCWs) before and after education and training. We performed a prospective pre and post quasi-experimental study. A total of 100 HCWs (55 doctors and 45 nurses) were recruited. HCWs were surveyed on their disinfection behavior and stethoscopes were cultured by pressing the diaphragm directly onto a blood agar plate before and after education on disinfection. Pulsed-field gel electrophoresis was performed to determine the relatedness of carbapenem-resistant Enterobacteriaceae. Most of the stethoscopes were contaminated with microorganisms before and after the intervention (97.9% and 91.5%, respectively). The contamination rate of stethoscopes with nosocomial pathogens before and after education was 20.8% and 19.2%, respectively. Stethoscope disinfection habits improved (55.1% vs 31.0%; p<0.001), and the overall bacterial loads of contamination were reduced (median colony-forming units, 15 vs 10; p = 0.019) after the intervention. However, the contamination rate by nosocomial pathogens and MDR bacteria did not decrease significantly. A carbapenemase-producing Klebsiella pneumoniae isolates from a stethoscope was closely related to isolates from the patients admitted at the same ward where the stethoscope was used. Stethoscopes were contaminated with various nosocomial pathogens including MDR bacteria and might act as a vehicle of MDR bacteria. Continuous, consistent education and training should be provided to HCWs using multifaceted approach to reduce the nosocomial transmission via stethoscopes.

Particulate matter causes skin barrier dysfunction.

The molecular mechanisms that underlie the detrimental effects of particulate matter (PM) on skin barrier function are poorly understood. In this study, the effects of PM2.5 on filaggrin (FLG) and skin barrier function were investigated in vitro and in vivo. The levels of FLG degradation products, including pyrrolidone carboxylic acid, urocanic acid (UCA), and cis/trans-UCA, were significantly decreased in skin tape stripping samples of study subjects when they moved from Denver, an area with low PM2.5, to Seoul, an area with high PM2.5 count. Experimentally, PM2.5 collected in Seoul inhibited FLG, loricrin, keratin-1, desmocollin-1, and corneodesmosin but did not modulate involucrin or claudin-1 in keratinocyte cultures. Moreover, FLG protein expression was inhibited in human skin equivalents and murine skin treated with PM2.5. We demonstrate that this process was mediated by PM2.5-induced TNF-α and was aryl hydrocarbon receptor dependent. PM2.5 exposure compromised skin barrier function, resulting in increased transepidermal water loss, and enhanced the penetration of FITC-dextran in organotypic and mouse skin. PM2.5-induced TNF-α caused FLG deficiency in the skin and subsequently induced skin barrier dysfunction. Compromised skin barrier due to PM2.5 exposure may contribute to the development and the exacerbation of allergic diseases such as atopic dermatitis.