Population Pharmacokinetics of Ozoralizumab in Patients with Rheumatoid Arthritis.

Ozoralizumab is a bispecific NANOBODY compound that binds tumor necrosis factor alpha (TNFα) and human serum albumin. Ozoralizumab inhibits the TNFα physiological activity while maintaining long-term plasma retention owing to its human serum albumin-binding ability. A population pharmacokinetic (PK) model was developed using data from 494 Japanese patients with rheumatoid arthritis in Phase II/III and Phase III trials to assess the effects of potential PK covariates.

Pharmacokinetics, pharmacodynamics and safety profile of the dual orexin receptor antagonist vornorexant/TS-142 in healthy Japanese participants following single/multiple dosing: Randomized, double-blind, placebo-controlled phase-1 studies.

The pharmacokinetics, pharmacodynamics and safety profile of vornorexant were investigated in healthy Japanese participants in three double-blind studies: a single ascending dose of 1-30 mg (Study 101; n = 6) and multiple ascending doses of 10-30 mg (Study 102; n = 6). Study 202 consisted of two steps: an open-label, 20 mg repeated-dose in non-elderly individuals (Step 1; n = 12) and a double-blind, 20 mg repeated-dose in elderly individuals (Step 2; n = 8/3 for vornorexant/placebo). Vornorexant was rapidly absorbed and eliminated under fasting conditions, with a time to maximum plasma concentration of 0.

Efficacy and pharmacokinetics of ozoralizumab, an anti-TNFα NANOBODY compound, in patients with rheumatoid arthritis: 52-week results from the OHZORA and NATSUZORA trials.

Introduction: Ozoralizumab (OZR), a tumor necrosis factor alpha (TNFα) inhibitor, is a NANOBODY compound that binds to TNFα and human serum albumin. The main objective of this study was to analyze the pharmacokinetics (PK) of the drug and its correlation with clinical efficacy in patients with rheumatoid arthritis (RA).

Methods: Efficacy data were analyzed from the OHZORA trial, in which OZR 30 or 80 mg was administered to Japanese patients with RA at 4-week intervals for 52 weeks in combination with methotrexate (MTX; n = 381), and the NATSUZORA trial, in which OZR 30 or 80 mg was administered without concomitant MTX (n = 140).

The respiratory microbiome associated with chronic obstructive pulmonary disease comorbidity in non-small cell lung cancer.

Background: Research has shown that some microbiomes are linked to cancer. Hence, we hypothesize that alterations in the respiratory microbiome might be associated with lung cancer.

Methods: Through droplet digital polymerase chain reaction analysis, we investigated the abundance of Acidovorax in surgically resected primary tumors and corresponding nontumor lung tissues obtained from 50 Japanese patients with non-small cell lung cancer.

Drug-drug interaction potential and clinical pharmacokinetics of enerisant, a novel potent and selective histamine H receptor antagonist.

We evaluated the drug-drug interaction (DDI) potential of enerisant (TS-091), a histamine H receptor antagonist/inverse agonist, mediated by cytochrome P450 (CYP) and transporters, as well as the pharmacokinetics of enerisant in healthy male subjects.Enerisant did not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4 and did not induce CYP1A2, CYP2B6, or CYP3A4. Enerisant inhibited organic cation transporter 2, multidrug and toxin extrusion protein (MATE) 1, and MATE2-K, but not P-glycoprotein (P-gp), breast cancer resistance protein, organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 1, or OAT3.

Cultural influences on neural systems of intergroup emotion perception: An fMRI study.

Cultural factors, such as cultural group membership, have been shown to affect neural bases of face and emotion perception. However, little is known about how cultural factors influence neural processing of emotional faces expressed by in-group and out-group members. In this study, we examined cultural influences on neural activation during the intergroup perception of negative emotional faces.

Acinetobacter baumannii can be transferred from contaminated nitrile examination gloves to polypropylene plastic surfaces.

Background: Several observational studies suggest that gloves of health care workers are major routes of multidrug-resistant Acinetobacter baumannii transmission. However, limited experimental data are available assessing Acinetobacter transmission from gloves to environmental surfaces. This study determined whether A baumannii was easily transferred from nitrile gloves to polypropylene plastic compared with other gram-negative bacteria that cause health care-associated infections in laboratory-controlled experiments.

Thalamocortical Hyperconnectivity and Amygdala-Cortical Hypoconnectivity in Male Patients With Autism Spectrum Disorder.

Analyses of resting-state functional magnetic resonance imaging (rs-fMRI) have been performed to investigate pathophysiological changes in the brains of patients with autism spectrum disorder (ASD) relative to typically developing controls (CTLs). However, the results of these previous studies, which have reported mixed patterns of hypo- and hyperconnectivity, are controversial, likely due to the small sample sizes and limited age range of included participants. To overcome this issue, we analyzed multisite neuroimaging data from a large sample (n = 626) of male participants aged between 5 and 29 years (mean age = 13 years).

Discovery of Terbinafine Low Susceptibility Trichophyton rubrum strain in Japan.

This is the first confirmed report of terbinafine low susceptibility Trichophyton rubrum, BGUTR13, in Japan collected from the whole sole of the elderly over 65s with cotton swab sampling method at the special nursing care-home in 2016. We revealed BGUTR13 showed low susceptibility (MIC, >128 μg/mL) against terbinafine. But, BGUTR13 exhibited normal susceptibility to itraconazole, did not showed cross-resistance.

Molecular Epidemiological Analysis of the Spreading Conditions of Trichophyton in Long-Term Care Facilities in Japan.

Tinea pedis and tinea unguium are common infectious diseases, and many elderly people are reported to contract these infections. In this study, to investigate whether strains of the same origin are spreading inside a long-term care facility, we analyzed Trichophyton rubrum and Trichophyton mentagrophytes, isolated from the residents and staff at the facilities located in the Kanto area, using a genomic analytical method targeting tandem repeat regions in the nontranscribed spacer (NTS) region of ribosomal DNA. Five NTS types were confirmed in T.

[Epidemiological Study on Trichophyton Disseminating from the Feet of the Elderly].

Objectives: To grasp the colonization status of Trichophyton in terms of spreading rate, we investigated the intergenerational epidemiological difference in the spreading rate of Trichophyton from teenagers to the elderly aged over 65. In addition, the elderly people were divided into two groups: those living at nursing homes and those living at their homes. We compared the two groups in terms of the difference in the spreading rate of Trichophyton.

In vitro evaluation of potential drug interactions mediated by cytochrome P450 and transporters for luseogliflozin, an SGLT2 inhibitor.

1. We evaluated potential in vitro drug interactions of luseogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, mediated by CYP inhibition, CYP induction and drug transporters using human liver microsomes, primary hepatocytes and recombinant cells-expressing efflux or uptake transporters, respectively. 2.

Cultural influences on neural basis of inhibitory control.

Research on neural basis of inhibitory control has been extensively conducted in various parts of the world. It is often implicitly assumed that neural basis of inhibitory control is universally similar across cultures. Here, we investigated the extent to which culture modulated inhibitory-control brain activity at both cultural-group and cultural-value levels of analysis.

Use of a Physiologically Based Pharmacokinetic Model for Quantitative Prediction of Drug-Drug Interactions via CYP3A4 and Estimation of the Intestinal Availability of CYP3A4 Substrates.

The purpose of this study was to predict the drug-drug interactions (DDIs) via CYP3A4 by estimating the extent of hepatic CYP3A4 inhibition based on a physiologically based pharmacokinetic (PBPK) model of both substrate and inhibitor and the increase in the intestinal availability (Fg ) due to the enzyme inhibition. For the DDIs resulting from reversible inhibition of CYP3A4, the prediction using in vivo Ki values estimated from other clinical DDI studies and predicted in vivo Ki values calculated using the correlation between the log P and the in vivo Ki /in vitro Ki ratio was more accurate than that using in vitro Ki values. Incorporating inhibition of both intestinal and hepatic metabolism resulted in better prediction than that obtained considering inhibition in the liver alone, and all the DDIs (AUC increase by the inhibitor) were predicted within 2-fold accuracy when in vivo Ki values were used.

Molecular analysis of the integrons of metallo-β-lactamase-producing Pseudomonas aeruginosa isolates collected by nationwide surveillance programs across Japan.

Background: We investigate the evolving molecular epidemiology of metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa isolates collected in a 100 institution, nationwide surveillance study in Japan from 2004 to 2006.

Results: MBL-producers were detected in 23/996 isolates (2.3%) in 2004 and 21/992 (2.

Autistic empathy toward autistic others.

Individuals with autism spectrum disorder (ASD) are thought to lack self-awareness and to experience difficulty empathizing with others. Although these deficits have been demonstrated in previous studies, most of the target stimuli were constructed for typically developing (TD) individuals. We employed judgment tasks capable of indexing self-relevant processing in individuals with and without ASD.

From social-signal detection to higher social cognition: an fMRI approach.

Implicit or automatic detection of social signals, which discriminate animate, intentional objects in the environment, is essential for higher social cognition and its development. Using functional magnetic resonance imaging, we identified the neural substrate of detecting simple visual social signals and examined its functional link with the mechanism of inferring another's mental state. Healthy participants were presented with the eye-gaze shift (EG) and self-propelling motion (SP) under both implicit and explicit task conditions.

Comparison of four reading methods of broth microdilution based on the clinical and laboratory standards institute M27-A3 method for Candida spp.

This study aimed to compare the susceptibilities of 5 reference strains and 28 isolates of Candida spp., to micafungin, amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, and miconazole, obtained by visually determined minimum inhibitory concentration (MIC) using the agitation method (V-A), as described in the Clinical and Laboratory Standards Institute M27-A3 document; visual determinations without agitation (V-NA); and spectrophotometric determinations for the presence or absence of agitation (SP-A and SP-NA, respectively). Our results indicate that when the V-NA, SP-A, and SP-NA-the 3 alternative microdilution procedures for MIC endpoint determinations-were compared with the V-A, excellent agreements were observed between the V-NA and V-A rather than with the spectrophotometric methods (between the SP-A or SP-NA, and V-A).

Usefulness of rat skin as a substitute for human skin in the in vitro skin permeation study.

Sprague-Dawley (SD) rats are broadly used in preclinical studies for drug development, so a lot of information for the rats can be obtained especially from pharmacokinetic, pharmacological and toxicological studies. The purpose of this study was to clarify whether SD rat skin can be used to predict human skin permeability. In vitro permeation studies of the three model drugs, nicorandil, isosorbide dinitrate, and flurbiprofen, through human skin and SD rat skin were performed using Franz-type diffusion cells.

The representation of social interaction in episodic memory: a functional MRI study.

The representation of social interaction in episodic memory is a critical factor for the successful navigation of social relationships. In general, it is important to separate episodic memory during social interaction from episodic memory during the self-generation of action events. Different cortical representations have been associated with social interaction vs.

Decoding what one likes or dislikes from single-trial fNIRS measurements.

Recent functional neuroimaging studies have shown the possibility of decoding human mental states from their brain activity using noninvasive neuroimaging techniques. In this study, we applied multivariate pattern classification, in conjunction with a short interval of functional near-infrared spectroscopy measurements of the anterior frontal cortex, to decode whether a human likes or dislikes a presented visual object; an ability that is quite beneficial for a number of clinical and technological applications. A variety of objects comprising sceneries, cars, foods, and animals were used as the stimuli.

In vitro potentiation of carbapenems with ME1071, a novel metallo-beta-lactamase inhibitor, against metallo-beta-lactamase- producing Pseudomonas aeruginosa clinical isolates.

ME1071, a maleic acid derivative, is a novel specific inhibitor for metallo-beta-lactamases (MBL). In this study, the potentiation of ME1071 in combination with several beta-lactams was evaluated using MBL-producing Pseudomonas aeruginosa isolates. The rates of susceptibility of MBL producers to carbapenems (imipenem, biapenem, and doripenem) and ceftazidime were increased by 8 to 27% in the presence of 32 microg/ml of ME1071.

Theory and methods in cultural neuroscience.

Cultural neuroscience is an emerging research discipline that investigates cultural variation in psychological, neural and genomic processes as a means of articulating the bidirectional relationship of these processes and their emergent properties. Research in cultural neuroscience integrates theory and methods from anthropology, cultural psychology, neuroscience and neurogenetics. Here, we review a set of core theoretical and methodological challenges facing researchers when planning and conducting cultural neuroscience studies, and provide suggestions for overcoming these challenges.

Beyond the memory mechanism: person-selective and nonselective processes in recognition of personally familiar faces.

Special processes recruited during the recognition of personally familiar people have been assumed to reflect the rich episodic and semantic information that selectively represents each person. However, the processes may also include person nonselective ones, which may require interpretation in terms beyond the memory mechanism. To examine this possibility, we assessed decrease in differential activation during the second presentation of an identical face (repetition suppression) as an index of person selectivity.

Dissociable roles of the anterior temporal regions in successful encoding of memory for person identity information.

Memory for person identity information consists of three main components: face-related information, name-related information, and person-related semantic information, such as the person's job title. Although previous studies have demonstrated the importance of the anterior temporal lobe (ATL) in the retrieval of associations between these kinds of information, there is no evidence concerning whether the ATL region contributes to the encoding of this memory, and whether ATL roles are dissociable between different levels of association in this memory. Using fMRI, we investigated dissociable roles within the ATL during successful encoding of this memory.