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Treatment of Candidemia has become increasingly complicated as more and more non-albicans Candida species are being isolated in recent years.We launched an investigation of the species, the MIC value, and the state of administration of antifungal drugs for all the cases with Candida spp. confirmed by blood cultures for the 7-year period from 2012 to 2018 at our hospital. In total, 192 cases were found and 206 strains of Candida species were isolated. Overall, 49.5% of the 206 isolated strains were Candida albicans (102 strains), followed by Candida glabrata (40 strains, 19.4%), and Candida parapsilosis (38 strains, 18.4%). The most frequently used antifungal drug for the initial dose was MCFG (120 cases, 59.2%), while the most frequently switched antifungal agent was L-AMB. Cases with an inappropriate end-of-treatment time represented 58.7% of all the cases.We investigated the Candidemia situation at our hospital for a period of seven years. We believe that it is important for medical institutions to gather detailed data on candidemia at their own hospitals. Likewise, the hospital's Infection Control Team/Antimicrobial Stewardship Team should inform the physicians-in-charge about the appropriate diagnosis and treatment based on the data obtained.

Objective To elucidate the role of the fractalkine (FKN)/CX3 CR1 pathway in joint destruction in rheumatoid arthritis. Methods We examined the effect of treatment with anti-mouse FKN (anti-mFKN) monoclonal antibody (mAb) on joint destruction and the migration of osteoclast precursors (OCPs) into the joint, using the collagen-induced arthritis (CIA) model. DBA/1 mice were immunized with bovine type II collagen to induce arthritis, and then treated with anti-mFKN mAb. Disease severity was monitored by arthritis score, and joint destruction was evaluated by soft x-ray and histologic analyses. Plasma levels of joint destruction markers were assessed by enzyme-linked immunosorbent assay. FKN expression on endothelial cells was detected by immunohistochemistry. Bone marrow-derived OCPs were labeled with fluorescein and transferred to mice with CIA, and the migration of the OCPs to the joints was then analyzed. Results Both prophylactic and therapeutic treatment with anti-mFKN mAb significantly decreased the arthritis and soft x-ray scores. Plasma levels of cartilage oligomeric matrix protein and matrix metalloproteinase 3 decreased after treatment with anti-mFKN mAb. Histologic analysis revealed that anti-mFKN mAb inhibited synovitis, pannus formation, and cartilage destruction, as well as suppressed bone damage, with a marked reduction in the number of tartrate-resistant acid phosphatase-positive osteoclasts. Anti-mFKN mAb strongly inhibited the migration of bone marrow-derived OCPs into the affected synovium. Conclusion Anti-mFKN mAb notably ameliorates arthritis and joint destruction in the CIA model, as well as inhibits migration of OCPs into the synovium. These results suggest that inhibition of the FKN/CX3 CR1 pathway could be a novel strategy for treatment of both synovitis and joint destruction in rheumatoid arthritis.

Crystals belonging to P1 and P21 space groups are fascinating research targets because of their potential applications in various fields by taking advantage of their chirality and polarity. However, molecules intrinsically prefer symmetric, achiral nonpolar space groups due to canceling out of dipole moments and close packing in crystalline states. Therefore, it remains difficult to selectively obtain the P1 and P21 crystals, especially from achiral molecules. Here we achieve construction of the chiral P1 and P21 crystals from achiral molecules based on stacking control of chiral two-dimensional hydrogen-bonded layers by halogen bonds (XBs). Precise investigations and theoretical calculations of their crystal structures revealed that space group selectivity among the chiral P1, P21, and achiral space groups is the result of a subtle balance between the stronger interaction: charge-assisted hydrogen bonds and the weaker interactions: van der Waals interaction of alkyl chains and the bonding involving halog...

Metal-free supramolecular clusters, comprising organic salts of triphenylacetic acid and primary amines, were characterized for the first time as the analogues of octacoordinated polyhedrons with a novel supramolecular chirality in the crystalline state. A ternary system yields triangular dodecahedrons with chiral belts composed of four triphenylmethyl (trityl) groups involving right- or left-handed twist combinations (Δ:Λ = 4:0 or 0:4). The 12 benzene rings are divided into three layers along a 2-fold axis of symmetry, affording a structure that is similar to a censer (a traditional vessel for fragrance) comprising three parts: a head, body, and foot. A binary system with t-butylammonium or t-amylammonium provides different chiral triangular dodecahedrons, while the system with isobutylammonium provides a trans-bicapped octahedron with a 3-fold rotational axis of symmetry to yield a chiral belt of four trityl groups (Δ:Λ = 3:1 or 1:3).

We investigated antimicrobial susceptibility and the molecular mechanism involved in conferring high-level macrolide resistance in 47 clinical isolates of Moraxella nonliquefaciens from Japan. Antimicrobial susceptibility was determined using Etest and agar dilution methods. Thirty-two erythromycin-non-susceptible strains were evaluated for the possibility of clonal spreading, using PFGE. To analyse the mechanism related to macrolide resistance, mutations in the 23S rRNA gene and the ribosomal proteins, and the presence of methylase genes were investigated by PCR and sequencing. The efflux system was examined using appropriate inhibitors. Penicillin, ampicillin, amoxicillin, cefixime, levofloxacin and antimicrobials containing β-lactamase inhibitors showed strong activity against 47 M. nonliquefaciens isolates. Thirty-two (68.1 %) of the 47 isolates showed high-level MICs to macrolides (MIC ≥128 mg l−1) and shared the A2058T mutation in the 23S rRNA gene. The geometric mean MIC to macrolides of A2058T-mutated strains was significantly higher than that of WT strains (PM. nonliquefaciens strains, 43 (91.5 %) were bro-1 and 4 (8.5 %) were bro-2 positive. Our results suggest that most M. nonliquefaciens clinical isolates show high-level macrolide resistance conferred by the A2058T mutation in the 23S rRNA gene. This study represents the first characterization of M. nonliquefaciens.

To seek the cause of Burkholderia cepacia complex (Bcc) infection outbreak and evaluate the efficacy of new methods for nebulizer maintenance.We investigated the annual number of Bcc isolates recovered from clinical samples in our hospital between 1999 and 2013. Swab samples were randomly collected for bacterial culture before patient use from 10 each of the two machine types in August 2001; these included 20 samples from each of the following: Drain tubes, operating water chambers, oscillators, and nebulizing chambers. In addition, 10 samples each of nebulizer solutions before and after use were cultured. For environmental investigation, 10 samples were collected from sinks in the nurse stations of the wards where patients positive for Bcc were hospitalized. Numbers of Bcc isolates were compared before and after introduction of new methods for nebulizer maintenance in October 2001. In addition, randomly amplified polymorphic DNA (RAPD) assay was applied to find the genetic divergence of the Bcc isolates obtained from clinical samples and nebulizers.From January 1999 to December 2013, a total of 487 Bcc isolates were obtained from clinical specimens from 181 patients. Notably, 322 (66.1%) Bcc isolates were obtained from clinical specimens from 1999 to 2001, including 244 (115 patients) from sputum and 34 (11 patients) from blood. During this period, 14 isolates were obtained from nebulizer components. Among these, six were derived from nebulizer drain tubes, five from operating water chambers, and one from the oscillator before patient use, and two from nebulizer solutions after patient use. When Bcc was isolated from the nebulizer solution after patient use, Bcc was simultaneously detected in other parts of the nebulizer. Bcc was not isolated from any nebulizer solution before use. RAPD assays revealed similar DNA profiles in isolates obtained from patients and nebulizers. Investigation revealed damaged diaphragms in many nebulizers. The new maintenance methods for nebulizers, including restriction of the usage period, thorough disinfection, and routine check for diaphragm breakage, remarkably reduced Bcc isolation (165 isolates from patients in 12 years and 0 isolate from nebulizers in periodical sampling). In particular, Bcc has been isolated from blood from only one patient since the new methods were introduced.Appropriate maintenance of ultrasonic nebulizers is crucial for preventing Bcc contamination of nebulizers and subsequent respiratory tract and blood infections.

Functions of clusters in nano or sub-nano scale significantly depend on not only kinds of their components but also arrangements, or symmetry, of their components. Therefore, the arrangements in the clusters have been precisely characterized, especially for metal complexes. Contrary to this, characterizations of molecular arrangements in supramolecular clusters composed of organic molecules are limited to a few cases. This is because construction of the supramolecular clusters, especially obtaining a series of the supramolecular clusters, is difficult due to low stability of non-covalent bonds compare to covalent bonds. From this viewpoint, utilization of organic salts is one of the most useful strategies. A series of the supramolecules could be constructed by combinations of a specific organic molecule with various counter ions. Especially, primary ammonium carboxylates are suitable as typical examples of supramolecules because various kinds of carboxylic acids and primary amines are commercially available, and it is easy to change their combinations. Previously, it was demonstrated that primary ammonium triphenylacetates using various kinds of primary amines specifically construct supramolecular clusters, which are composed of four ammoniums and four triphenylacetates assembled by charge-assisted hydrogen bonds, in crystals obtained from non-polar solvents. This study demonstrates an application of the specific construction of the supramolecular clusters as a strategy to conduct systematical symmetric study for clarification of correlations between molecular arrangements in supramolecules and kinds and numbers of their components. In the same way with binary salts composed of triphenylacetates and one kind of primary ammoniums, ternary organic salts composed of triphenylacetates and two kinds of ammoniums construct the supramolecular clusters, affording a series of the supramolecular clusters with various kinds and numbers of the components.

Supramolecular hidden chirality of hydrogen-bonded (HB) networks of primary ammonium carboxylates was exposed by advanced graph set analysis from a symmetric viewpoint in topology. The ring-type HB (R-HB) networks are topologically regarded as faces, and therefore exhibit prochirality and positional isomerism due to substituents attached on the faces. To describe the symmetric properties of the faces, additional symbols, Re (right-handed or clockwise), Si (left-handed or anticlockwise), and m (mirror), were proposed. According to the symbols, various kinds of faces were classified based on the symmetry. This symmetry consideration of the faces enables us to precisely evaluate supramolecular chirality, especially its handedness, of 0D-cubic, 1D-ladder and 2D-sheet HB networks that are composed of the faces. The 1D-ladder and 2D-sheet HB networks generate chirality by accumulating the chiral faces in 1D and 2D manners, respectively, whereas 0D-cubic HB networks generate chirality based on combinations of eight kinds of faces, similar to the chirality of dice.