Hospital water environment and antibiotic use: key factors in a nosocomial outbreak of carbapenemase-producing Serratia marcescens.

BACKGROUND: The healthcare water environment is a potential reservoir of carbapenem-resistant organisms (CROs). AIM: To report the role of the water environment as a reservoir and the infection control measures applied to suppress a prolonged outbreak of Klebsiella pneumoniae carbapenemase-producing Serratia marcescens (KPC-SM) in two intensive care units (ICUs). METHODS: The outbreak occurred in the ICUs of a tertiary hospital from October 2020 to July 2021. Comprehensive patient contact tracing and environmental assessments were conducted, and a case-control study was performed to identify factors associated with the acquisition of KPC-SM. Associations among isolates were assessed via pulsed-field gel electrophoresis (PFGE). Antibiotic usage was analysed. FINDINGS: The outbreak consisted of two waves involving a total of 30 patients with KPC-SM. Multiple environmental cultures identified KPC-SM in a sink, a dirty utility room, and a communal bathroom shared by the ICUs, together with the waste bucket of a continuous renal replacement therapy (CRRT) system. The genetic similarity of the KPC-SM isolates from patients and the environment was confirmed by PFGE. A retrospective review of 30 cases identified that the use of CRRT and antibiotics was associated with acquisition of KPC-SM (P < 0.05). There was a continuous increase in the use of carbapenems; notably, the use of colistin has increased since 2019. CONCLUSION: Our study demonstrates that CRRT systems, along with other hospital water environments, are significant potential sources of resistant micro-organisms, underscoring the necessity of enhancing infection control practices in these areas.

Three-dimensional modelling and concurrent measurements of root anatomy in mandibular first molar mesial roots using micro-computed tomography.

AIM: To obtain concurrent radicular measurements in the mesiobuccal (MB) and mesiolingual (ML) canals of mandibular first molars using scanned data of micro-computed tomography (µCT) with novel software. METHODOLOGY: The scanned data from 37 mandibular first molar mesial roots were reconstructed and analysed with custom-developed software (Kappa2). For each canal, three-dimensional (3D) surface models were re-sliced at 0.1-mm intervals perpendicular to the central axis. Dentine thicknesses, canal widths and 3D curvatures were measured automatically on each slice. Measurements were analysed statistically with anova for differences at each direction and at different levels of both canals. RESULTS: Lateral dentine thicknesses were significantly higher than mesial and distal thicknesses, at all the levels of both canals (P < 0.001). Mesial thicknesses were significantly higher than distal thicknesses in the coronal third of both canals (P < 0.001). Thinnest dentine thicknesses were mainly located on the disto-inside of both canals. Narrowest canal widths were 0.24 ± 0.10 and 0.22 ± 0.09 mm in MB and ML canals, respectively. Canal curvatures were greatest in the apical third of both canals (P < 0.001), and they were greater in the MB canals than in the ML canals (P < 0.05). CONCLUSIONS: Micro-computed tomography with novel software provided valuable anatomical information for optimizing instrumentation and minimizing mishaps in nonsurgical root canal treatment.

Inhibitory effect of chlorine and ultraviolet radiation on growth of Listeria monocytogenes in chicken breast and development of predictive growth models.

The inhibitory effect of chlorine (50, 100, and 200 mg/kg) was investigated with and without UV radiation (300 mW·s/cm(2)) for the growth of Listeria monocytogenes in chicken breast meat. Using a polynomial model, predictive growth models were also developed as a function of chlorine concentration, UV exposure, and storage temperature (4, 10, and 15°C). A maximum L. monocytogenes reduction (0.8 log cfu, cfu/g) was obtained when combining chlorine at 200 mg/kg and UV at 300 mW·s/cm(2), and a maximum synergistic effect (0.4 log cfu/g) was observed when using chlorine at 100 mg/kg and UV at 300 mW·s/cm(2). Primary models developed for specific growth rate and lag time showed a good fitness (R(2) > 0.91), as determined by the reparameterized Gompertz equation. Secondary polynomial models were obtained using nonlinear regression analysis. The developed models were validated with mean square error, bias factor, and accuracy factor, which were 0.0003, 0.96, and 1.11, respectively, for specific growth rate and 7.69, 0.99, and 1.04, respectively, for lag time. The treatment of chlorine and UV did not change the color and texture of chicken breast after 7 d of storage at 4°C. As a result, the combination of chlorine at 100 mg/kg and UV at 300 mW·s/cm(2) appears to an effective method into inhibit L. monocytogenes growth in broiler carcasses with no negative effects on color and textural quality. Based on the validation results, the predictive models can be used to accurately predict L. monocytogenes growth in chicken breast.

Spontaneous superior ophthalmic vein thrombosis: a rare entity with potentially devastating consequences.

PURPOSE: Spontaneous superior ophthalmic vein thrombosis (SOVT) is a rare entity. We describe three patients with spontaneous ophthalmic vein thrombosis, each with various risk factors. PATIENTS AND METHODS: A retrospective review of three patients with a diagnosis of superior ophthalmic vein thrombosis. Clinical characteristics, radiographic features, management techniques and outcomes are described. RESULTS: All patients presented with unilateral painful proptosis. Two patients had intact light perception, whereas one patient presented with absent light perception. All patients had identifiable risk factors for thrombosis, which included sickle cell trait, hereditary hemorrhagic telangectasia and colon cancer with recurrent deep vein thrombosis. Anticoagulation was initiated in two patients. Resolution of proptosis was seen in all patients, with no recovery of vision in one patient. CONCLUSIONS: Risk factors for spontaneous superior ophthalmic vein thrombosis are multifactorial. MRI and MRV confirm the diagnosis of SOVT. Despite urgent intervention devastating visual loss may occur.

Autotransplantation of mesiodens for missing maxillary lateral incisor with cone-beam CT-fabricated model and orthodontics.

AIM: Autotransplantation is a viable treatment option for a missing tooth when there is a suitable donor, especially in adolescents with remaining facial growth. This report presents the aesthetic restoration of a missing maxillary lateral incisor through orthodontic treatment and autotransplantation of a mesiodens using a CBCT-fabricated rapid-prototyping model. SUMMARY: A 14-year-old male patient with a congenitally missing maxillary lateral incisor was referred from the Department of Orthodontics. The teeth were moved orthodontically to regain space for the missing lateral incisor and to close the space of the mesiodens after transplantation. A replica of the donor tooth was fabricated from a cone-beam computed tomography scan through a rapid-prototyping machine before autotransplantation surgery. The model was used to create a socket for the graft tooth, thereby shortening the extra-oral time and minimizing the damage to the root surface. After transplantation and orthodontic tooth movement, the mesiodens was finally restored with an aesthetic laminate restoration. Over 3 years, the aesthetics remained excellent, and the transplant functioned normally without any signs or symptoms of root resorption. KEY LEARNING POINT: Missing anterior teeth may be replaced through a combination of orthodontics, autotransplantation with a rapid-prototyping model and prosthodontic restoration, in growing patients.

Dietary hematein ameliorates fatty streak lesions in the rabbit by the possible mechanism of reducing VCAM-1 and MCP-1 expression.

Hematein is a compound isolated from Caesalpinia sappan that has been used in oriental medicine as both an analgesic and an anti-inflammatory agent. In this study, we examined the anti-atherogenic potential of hematein using cholesterol-fed New Zealand White (NZW) rabbits. NZW rabbits were divided into a hematein-supplemented (0.05% in diet) group (n=6), a probucol-supplemented (0.25% in diet) group (n=6), and a control group (n=6). After 8 weeks of treatments, the extent of the atherosclerotic lesions was significantly reduced in the hematein-supplemented group and the probucol-supplemented group without changing plasma lipoprotein levels. Hematein and probucol prevented the up-regulation of the vascular cell adhesion molecule-1 (VCAM-1) expression on the descending aorta induced by cholesterol diet. In culture, hematein also significantly inhibited the secretion of soluble VCAM-1 and of monocyte chemotactic protein-1 (MCP-1) respectively induced by tumor necrotic factor alpha (TNF-alpha) and mildly oxidized low density lipoprotein in human umbilical vein endothelial cell (HUVEC) culture. Also, hematein inhibited monocyte adhesion to endothelial cell and the activation of NF-kappaB in HUVECs stimulated with TNF-alpha. The results of the present study suggest that the anti-atherogenic effect of hematein is not related to control of the plasma lipid profile but probably related to the inhibition of VCAM-1 and MCP-1 expression resulting in an amelioration of lesion development in the rabbit.

Inhibitory activity of lignan components from the flower buds of Magnoliae fargesii on the expression of cell adhesion molecules.

Inhibitory activity of lignans isolated from Magnoliae fargesii Cheng on cell adhesion molecules on the surface of THP-1 human monocytic cell lines were investigated. Among 16 lignan components tested, six displayed relatively potent inhibitory activity on the expression of both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1).

Semialactone, isofouquierone peroxide and fouquierone, three new dammarane triterpenes from Rhus javanica.

Three new dammarane triterpenes and semialactic acid were isolated from the stem bark of Rhus javanica. The structures of these triterpenes, named semialactone, isofouquierone peroxide and fouquierone, were elucidated by 2D-NMR analysis (HMQC, 1H-1H COSY and HMBC), and the 13C-NMR data of semialatic acid is revised.

Effect of genistein analogs on oxygen radical production in leukocytes stimulated by unopsonized zymosan.

Effects of genistein analogs on oxygen radical production have been analyzed in human neutrophils, human monocytes or murine macrophages Raw264.7 stimulated with unopsonized zymosan by lucigenin- and luminol-enhanced chemiluminescence assays. Genistein exhibited IC50 values of 10.7-11.5 microM on the oxygen radical production in human neutrophils, 10.9-11.0 microM in human monocytes, and 14.8-27.3 microM in Raw264.7 cells. Orobol, a genistein analog with an additional hydroxy group at the 3' position, exhibited IC50 values of 3.0-3.3 microM on the oxygen radical production in human neutrophils, 2.8-3.1 microM in human monocytes, and 1.5-3.9 microM in Raw264.7 cells. Genistin and sophoricoside are genistein glycosides with a glucose moiety at 7 or 4' position, respectively. The genistein glycosides exhibited 23-37% inhibitory effects at 100 microM on the oxygen radical production.

Inhibition of cytokine-induced vascular cell adhesion molecule-1 expression; possible mechanism for anti-atherogenic effect of Agastache rugosa.

Adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) play an important role during the early stages of atherogenesis. Agastache rugosa has an anti-atherogenic effect in low density lipoprotein receptor -/- mice. Moreover, A. rugosa reduced macrophage infiltration and VCAM-1 expression has been localized in aortic endothelium that overlies early foam cell lesions. This study ascertained that tilianin (100 microM), a major component of A. rugosa, inhibits the tumor necrotic factor-alpha (TNF-alpha)-induced expression of VCAM-1 by 74% in cultured human umbilical vein endothelial cells (HUVECs). Also, tilianin (100 microM) reduced TNF-alpha-induced activation of nuclear factor-kappaB in HUVECs.

Hematein inhibits tumor necrotic factor-alpha-induced vascular cell adhesion molecule-1 and NF-kappaB-dependent gene expression in human vascular endothelial cells.

Monocyte adhesion to the endothelium via adhesion molecules is one of the earliest events in atherogenesis. It has been suggested that vascular cell adhesion molecule-1 (VCAM-1) plays a very important role in the recruitment of monocytes in atherosclerosis. The aim of our study was to evaluate whether hematein can influence the expression of VCAM-1 and the transcription of nuclear factor-kappaB (NF-kappaB)-dependent genes. Immunohistochemistry revealed that mouse aortic artery endothelial cells express VCAM-1 after feeding a high cholesterol diet for 8 weeks. Hematein dose dependently suppressed TNF-alpha-induced VCAM-1 in both surface (30.8%) and soluble protein (65%) production in HUVECs. The transcription level of VCAM-1 was measured by Northern blot analysis, and decreased VCAM-1 protein expression was associated with a reduction of VCAM-1 mRNA expression. Transient transfection study of NF-kappaB promoter construct and electrophoretic mobility shift assay suggested that hematein inhibited both NF-kappaB-dependent gene expression and NF-kappaB activation induced by TNF-alpha. Our results suggest that the down-regulation of VCAM-1 expression by hematein may in part be due to the inhibition of NF-kappaB-dependent gene expression.

Inhibitory activity of stilbenes from medicinal plants on the expression of cell adhesion molecules on THP1 cells.

The inhibitory activity of stilbenes isolated from medicinal plants on cell adhesion molecules on the surface of THP-1 human monocytic cell lines was investigated. Among ten stilbenes tested, four stilbenes displayed a significant inhibitory activity on the expression of both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). A cell-to-cell adhesion assay showed that 3,5-dihydroxy-4'-methoxystilbene and 2,3,4',5-tetrahydroxystilbene-2-O-beta-D-glucopyranoside as well as resveratrol blocked significantly TNF-alpha-inducing cell-cell adhesion between human umbilical vein endothelial cells (HUVEC) and THP-1 cells.

Effects of triterpenoids from Pueraria lobata on immunohemolysis: beta-D-glucuronic acid plays an active role in anticomplementary activity in vitro.

The anticomplementary properties of kaikasaponin III (4) and soyasaponin I (8) from Pueraria lobata and their hydrolytic analogs were investigated in vitro. Diglycosidic saponins [kaikasaponin I (3), soyasaponin III (7)] showed most potent anticomplementary activities, followed by monoglycosidic saponins [soyasapogenol B monoglucuronide (6), sophoradiol monoglucuronide (2)] and triglycosidic saponins [soyasaponin I (8), kaikasaponin III (4)], whereas sophoradiol (1) and soyasapogenol B (5) showed enhancement of hemolysis under the presence of serum on the classical pathway of complement system. But all of them showed very weak or no anticomplementary activities on the alternative pathway of complement system. The anticomplementary activity of the saponins was influenced by the nature of glucuronic acid, where the free acid forms (-COOH) showed much more potent activity than the sodium salt forms (-COO-Na+) or methyl ester forms (-COOCH3), and the reduced forms (-CH2OH) decreased the activity significantly.

Nuclear Notch1 signaling and the regulation of dendritic development.

To understand the function of Notch in the mammalian brain, we examined Notch1 signaling and its cellular consequences in developing cortical neurons. We found that the cytoplasmic domain of endogenous Notch1 translocated to the nucleus during neuronal differentiation. Notch1 cytoplasmic-domain constructs transfected into cortical neurons were present in multiple phosphorylated forms, localized to the nucleus and could induce CBF1-mediated transactivation. Molecular perturbation experiments suggested that Notch1 signaling in cortical neurons promoted dendritic branching and inhibited dendritic growth. These observations show that Notch1 signaling to the nucleus exerts an important regulatory influence on the specification of dendritic morphology in neurons.

Acylated flavonol glycosides with anti-complement activity from Persicaria lapathifolia.

During a search for biologically active compounds from traditional medicines, a crude extract of Persicaria lapathifolia was found to have anti-complement activity. Bioassay-guided chromatographic separation of the active constituents led to the isolation of a new acylated kaempferol glycoside (1) and three known acylated quercetin glycosides (2-4). The structures of compounds 1-4 were characterized as kaempferol 3-O-beta-D-(6"-p-hydroxybenzoyl)-galactopyranoside, quercetin 3-O-beta-D-(6"-feruloyl)-galactopyranoside, quercetin 3-O-beta-D-(2"-galloyl)-rhamnopyranoside and quercetin 3-O-beta-D-(2"-galloyl)-glucopyranoside, respectively. Compounds 1-4 showed strong anti-complement activity (IC50 values of 4.3, 9.7, 3.9 and 7.6 x 10(-5) M, respectively) on the classical pathway of the complement. On the other hand, six isolated flavonol glycosides (5-10) did not show any activity on this system.

Anticomplement activities of oleanolic acid monodesmosides and bisdesmosides isolated from Tiarella polyphylla.

Seven known oleanolic acid glycosides (1-7) were isolated from the MeOH extract of Tiarella polyphylla. The structures were identified to be 3-O-(beta-D-glucopyranosyl) oleanolic acid (1), 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] oleanolic acid (2), 3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl] oleanolic acid (3), 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] oleanolic acid 28-O-beta-D-glucopyranosyl ester (4), 3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl] oleanolic acid 28-O-beta-D-glucopyranosyl ester (5), 3-O-[a-L-rhamnopyranosyl-(1-->3)-beta-D-glucuronopyranosyl] oleanolic acid (6), and 3-O-[alpha-L-rhamnopyranosyl-(1-->3)-beta-D-glucuronopyranosyl] oleanolic acid 28-O-beta-D-glucopyranosyl ester (7) on the basis of physicochemical and spectral data. These triterpene glycosides were tested for the anticomplement activity and hemolytic activity. Bisdesmosidic saponins, 4, 5, and 7, showed anticomplement activity; in contrast, monodesmosidic saponins, 1-3, and 6, showed direct hemolytic activity. Methyl esterified monodesmosidic saponins showed anticomplement activity at a low concentration and hemolytic activity at a high concentration.

Sophoricoside analogs as the IL-5 inhibitors from Sophora japonica.

Fruits of Sophora japonica L. (Leguminosae) exhibited an inhibitory effect in the IL-5 bioassay of mIL-5-dependent Y16 proliferation. The isoflavonoids of sophoricoside, genistein, orobol, and genistin were isolated as the IL-5 inhibitors from fresh fruits of the plant by activity-guided fractionation. Among the IL-5 inhibitors, sophoricoside exhibited the highest inhibitory effect with 89% inhibition at 12.5 microM, 82% at 6.3 microM, 72% at 3.1 microM, 59% at 1.6 microM, and 24% at 0.8 microM where the 50% inhibition (IC50) was shown at the concentration of 1.5 microM. Oxyphenylbutazone as the positive control exhibited the IC50 value at the concentration of 31.7 microM. In the order of IC50 values the inhibitory potency in the IL-5 bioassay was sophoricoside > orobol (9.8 microM) approximately equal to genistin (10.6 microM) > genistein (51.9 microM). The position of O-glycosylation and number of hydroxy groups in the isoflavonoids seem to play an important role in the inhibitory effect in the IL-5 bioassay.

In vitro anticomplementary activity of hederagenin saponins isolated from roots of Dipsacus asper.

Anticomplementary activity of hederagenin and related saponins isolated from Dipsacus asper was investigated in vitro. HN saponin F (3) was most potent with IC50 value of 3.7x10(-5) M followed by 3-O-beta-D-glucopyranosyl-(1->3)-alpha-L-rhamnopyranosyl-(1->2)-beta-L-+ ++arabi nopyranosyl hederagenin 28-O-beta-D-glucopyranosyl-(1->6)-beta-D-glucopyrano side (8), 3-O-beta-L-arabinopyranosyl hederagenin 28-O-beta-D-glucopyranosyl-(1->6)-beta-D-glucopyranoside (5), dipsacus saponin A (4), and hederagenin (1) on the classical pathway (CP) of complement system, while the saponins 3-5 did not show the inhibition of hemolysis and rather increase the hemolysis on the alternative pathway (AP). However, all of C-3 monodesmosides [prosapogenin CP (2), dipsacus saponin B (6), and dipsacus saponin C (7)] evoked hemolysis directly on the erythrocytes.

Structure-activity relationships of lignans from Schisandra chinensis as platelet activating factor antagonists.

We studied the structure-activity relationships of lignans from Schisandra chinensis and their derivatives as platelet activating factor (PAF) antagonists. Strong activity was shown in lignans without an ester group at C-6, a hydroxyl group at C-7 or a methylene dioxy moiety and with an R-biphenyl configuration. 6(7)-Dehydroschisandrol A, a derivative of schisandrol A, showed the highest activity (IC50, 2.1x10(-6) M) in this study.

Anticomplementary activity of stilbenes from medicinal plants.

The anticomplementary activity of stilbenes from medicinal plants in Korea was investigated in vitro. 3,5-Dihydroxy-4'-methoxystilbene (3) was most potent with IC50 value of 1.5 x 10(-4) M followed by rhapontigenin (4), oxyresverastrol (2), 2,3,4',5-tetrahydroxystilbene-2-O-beta-glucoside (9), rhaponticin (8), resverastrol (1), and piceid (7). The activity was found to be increased by a methylation on a hydroxy group of C-4' of 1, but decreased by further methylation on hydroxy groups of C-3 and C-5 and glucosylation on any hydroxy group of 1. Addition of hydroxy group on C-2' of 1 or C-3' of 3 was little affected on the anticomplementary activity but the activity was increased by O-glucosylation on C-2 of 1.