Publications by authors named "Ippei Yoshida"

Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent threat to public health requiring the development of novel therapies. TP0586532 is a novel non-hydroxamate LpxC inhibitor that inhibits the synthesis of lipopolysaccharides, which are components of the outer membranes of Gram-negative bacteria. Based on the mechanism of action of TP0586532, we hypothesized that it might enhance the antibacterial activity of other antibiotics by increasing the permeability of the outer bacterial membrane.

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Introduction: TP0586532 is a novel non-hydroxamate UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) inhibitor. Pharmacokinetic/pharmacodynamic (PK/PD) indices and magnitude of index that correlated with the efficacy of TP0586532 were determined and used to estimate the clinically effective doses of TP0586532.

Methods: Dose-fractionation studies were conducted using a murine neutropenic lung infection model caused by carbapenem-resistant Enterobacteriaceae.

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UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) is an essential enzyme in the biosynthesis of Lipid A, an active component of lipopolysaccharide (LPS), from UDP-3-O-acyl-N-acetylglicosamine. LPS is a major component of the cell surface of Gram-negative bacteria. LPS is known to be one of causative factors of sepsis and has been associated with high mortality in septic shock.

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The emergence of multi-drug resistant pathogenic bacteria, especially Gram-negative bacteria, is a worldwide health problem. New antibiotics directed at previously unexplored targets are urgently needed to overcome resistance to existing antibiotic classes. UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) is an attractive target for a new antibacterial agent.

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Background: Medial meniscus posterior root tears (MMPRTs) can result in the development of osteoarthritis or osteonecrosis. Clinical experience suggests that symptoms such as dull pain or discomfort in the popliteal area or the calf area, which are sometimes misdiagnosed as sciatic nerve pain, may precede impending rupture. We found that bone marrow edema emanating from the meniscal root on magnetic resonance imaging (MRI) scans-spreading roots sign-may indicate the preliminary stage of an MMPRT.

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The development of effective respiratory syncytial virus (RSV) fusion glycoprotein (F protein) inhibitors against both wild-type and the D486N-mutant F protein is urgently required. We recently reported a 15-membered macrocyclic pyrazolo[1,5-a]pyrimidine derivative 4 that exhibited potent anti-RSV activities against not only wild-type, but also D486N-mutant F protein. However, NMR studies revealed that the 15-membered derivative 4 existed as a mixture of atropisomers.

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Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in early childhood. However, no vaccines have yet been approved for prevention of RSV infection, and the treatment options are limited. Therefore, development of effective and safe anti-RSV drugs is needed.

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A novel series of macrocyclic pyrazolo[1,5-]pyrimidine derivatives as respiratory syncytial virus (RSV) fusion glycoprotein (F protein) inhibitors were designed and synthesized based on docking studies of acyclic inhibitors. This effort resulted in the discovery of several macrocyclic compounds, such as , , and , with low nanomolar to subnanomolar activities against the wild-type RSV F protein A2. In addition, showed a single-digit nanomolar potency against the previously reported drug-resistant mutant D486N.

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Objective: To verify the effect of adjusting the challenge-skill balance with respect to rehabilitation process.

Design: A single-blind, two-arm, parallel-group, randomized controlled trial.

Setting: Recovery rehabilitation unit of Harue Hospital, Japan.

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Introduction: Occupational therapy (OT) is defined as the promotion of client health and well-being through a client-centred practice. However, there is a tendency to rely on the therapist's experiences and values, and there is a difference between the client's and therapist's perceptions regarding the current activity that the client is engaged in. In previous studies that have applied 'flow', activities supported by OT in elderly people were analysed, indicating a difference in recognition.

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Objective: We sought to investigate whether occupational therapy that includes adjusting the challenge-skill balance improves health-related quality of life (HRQOL) for older adults in comparison with standard occupational therapy.

Method: In this single-blind, randomized controlled trial, 56 older adults were assigned to two groups that received 10 sessions of occupational therapy with and without adjustment of challenge-skill balance. The primary outcome was change in HRQOL after 10 sessions of occupational therapy.

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We characterized in vitro activities of α-methoxyimino acylides against macrolide-resistant clinical isolates of Streptococcus pneumoniae, Streptococcus pyogenes and Mycoplasma pneumoniae with ribosome modification or substitution and selected acylide-resistant mutants to clarify the binding point of the acylides. The acylides had low MICs against erm(B) gene-containing S. pneumoniae and S.

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