This paper discusses an indoor positioning technique aimed at human-centric services such as pedestrian navigation or service robots. The method is called “CEPHEID” and uses a light flickering ...pattern as an environmental fingerprint. The authors found that each lighting fixture has unique and distinguishable flickering characteristics. In this paper, CEPHEID is introduced as a “classifier” and its validity is shown based on experimental results. Additionally, an approach for improving the positional precision is proposed. The classifier and regressor are combined to create a zone-classified regressor model for CEPHEID. The basic performance of this concept is also tested using an experiment.
A CuIn1−xGaxSe2 (CIGS) photocathode having a specific composition exhibited remarkable promotion of hydrogen evolution from water, with a half-cell solar-to-hydrogen conversion efficiency of 12.5%. ...CIGS thin films with various compositions (defined by x = Ga/(In + Ga)) were prepared via a three-stage method employing a vacuum evaporation system. The photocurrent from CIGS photocathode surfaces modified with CdS and Pt (Pt/CdS/CIGS) significantly increased along with x as a result of a reduction in the conduction band offset at the CIGS/CdS interface. Using an optimized aqueous electrolyte resulted in enhanced photocurrents of 28 and 18 mA cm−2 at 0 and 0.6 VRHE, respectively, under simulated AM1.5G sunlight. A tandem-type PEC cell containing the newly developed CIGS photocathode and a BiVO4 semi-transparent photoanode demonstrated stoichiometric hydrogen and oxygen evolution with a solar-to-hydrogen conversion efficiency of 3.7% without the application of an external bias voltage.
Purulent pericarditis is an infection of the pericardial cavity that produces purulent fluid and is commonly caused by Streptococcus pneumoniae. We herein report an autopsy case that is unique in two ...respects: the patient had pneumococcal bacteremia from a skin and soft tissue infection associated with acupuncture as well as purulent pericarditis from pneumococcal bacteremia. This case suggests that bloodstream infection should be included in the differential diagnosis on observing pneumococcal pericarditis. Furthermore, it is necessary to recognize that S. pneumoniae may be the organism responsible for skin and soft tissue infections caused by trauma in immunosuppressed patients.
TAFRO syndrome is a systemic inflammatory disorder resembling multicentric Castleman disease; it is characterized by thrombocytopenia, anasarca, a fever, reticulin fibrosis, and organomegaly. ...Involvement of the adrenal glands, including adrenal infarction, hemorrhaging, and adrenomegaly, has recently been reported in several cases and been considered a characteristic early-stage symptom. We herein report a case of TAFRO syndrome initially presenting with bilateral adrenal infarctions and review the literature on TAFRO syndrome related to adrenal involvement. This case suggests that adrenal abnormalities as an early clinical feature of TAFRO syndrome may be useful for the early diagnosis.
Endocytosis and intracellular trafficking of receptors are pivotal to maintain physiological functions and drug action; however, robust quantitative approaches are lacking to study such processes in ...live cells. Here we present new bioluminescence resonance energy transfer (BRET) sensors to quantitatively monitor G protein-coupled receptors (GPCRs) and β-arrestin trafficking. These sensors are based on bystander BRET and use the naturally interacting chromophores luciferase (RLuc) and green fluorescent protein (rGFP) from Renilla. The versatility and robustness of this approach are exemplified by anchoring rGFP at the plasma membrane or in endosomes to generate high dynamic spectrometric BRET signals on ligand-promoted recruitment or sequestration of RLuc-tagged proteins to, or from, specific cell compartments, as well as sensitive subcellular BRET imaging for protein translocation visualization. These sensors are scalable to high-throughput formats and allow quantitative pharmacological studies of GPCR trafficking in real time, in live cells, revealing ligand-dependent biased trafficking of receptor/β-arrestin complexes.
Rationale
Psychiatric disorders such as anxiety and depression are frequently observed in neuropathic pain patients, and negatively impact their quality of life. Mirogabalin is a novel ligand for the ...α
2
δ subunit of voltage-gated calcium channels and has unique binding characteristics to α
2
δ subunits and potent and long-lasting analgesic effects in neuropathic pain models.
Objectives
To provide further information on the pharmacological profile of mirogabalin and its utility for chronic pain therapy, we investigated its anxiolytic effects in an experimental animal model for neuropathic pain.
Methods
In chronic constriction injury (CCI) model rats, mechanical hypersensitivity was determined by the von Frey test. Anxiety- and depression-related behaviours were evaluated using the elevated plus maze test and forced swimming test, respectively.
Results
CCI model rats showed sustained tactile allodynia followed by anxiety-related behaviours, not depression-related behaviours. The tactile allodynia (significant decreases in paw withdrawal threshold) developed within 2 weeks after model preparation, whereas the anxiety-related behaviours (significant decreases in the number of entries and time spent in open arms and significant increases in time spent in closed arms) were observed at 5 weeks but not 4 weeks after model preparation. Single oral administration of mirogabalin (3 or 10 mg/kg) dose-dependently alleviated the above-mentioned anxiety-related behaviours and tactile allodynia.
Conclusions
CCI model rats showed anxiety-related behaviours in a time-dependent manner in the elevated plus maze test. Mirogabalin alleviated both the anxiety-related behaviours and tactile allodynia in CCI model rats. Mirogabalin may provide effective anxiety relief as well as pain relief in patients with neuropathic pain.
Some studies have reported a high incidence of small bowel injuries in 60%-80% of subjects who take nonselective nonsteroidal anti-inflammatory drugs and PPIs simultaneously. We performed a ...randomized, double-blind, controlled study to determine whether proton pump inhibitors (PPIs) exacerbate nonsteroidal anti-inflammatory drug-induced small bowel injury.
Fifty-seven healthy subjects were randomly assigned groups given the cyclooxygenase (COX) 2 inhibitor celecoxib (200 mg, twice daily) plus placebo for 2 weeks (COX-2 + placebo group, n = 30), or celecoxib plus the PPI rabeprazole (20 mg, once daily) for 2 weeks (COX-2 + PPI group, n = 27). The study was performed from October 2012 through September 2013 at a tertiary medical center in Japan. All subjects were evaluated by capsule endoscopy at the start of the study and then after 2 weeks administration of celecoxib with rabeprazole or placebo. The incidence rates and the numbers of small bowel injuries (ulcers and erosions) that were observed under capsule endoscopy were compared between groups. The primary endpoint was the incidence of mucosal injuries at the second capsule endoscopy examination.
A significantly higher proportion of subjects in the COX-2 + PPI group developed small bowel injury (12 of 27 subjects; 44.4%) than in the COX-2 + placebo group (5 of 30 subjects; 16.7%; P = .04). Subjects in the COX-2 + PPI group had a significant increase in risk of small bowel injury compared with the COX-2 + placebo group (relative risk, 2.67; 95% confidence interval, 1.08-6.58). The number of erosions in each member of the COX-2 + PPI group was greater than in each member of the COX-2 + placebo group (P = .02). The number of ulcers did not differ between groups. Twenty-six percent of subjects in the COX-2 + PPI group developed mucosal injury in the jejunum, compared with none of the subjects in the COX-2 + placebo group (P = .003); no such trend was found in the ileum.
In a randomized, controlled trial, PPIs increased the risk of short-term nonsteroidal anti-inflammatory drug-induced small bowel injury. UMIN clinical trial registry number: UMIN000008883.
This article examines the impact of working‐hour restrictions on the well‐being, performance, and education of medical residents in Japan. Despite Japan's plan to introduce new regulations for ...resident working hours by 2024, there is still an ongoing debate regarding their appropriateness. This review provides a comprehensive overview of the current regulations of resident working hours worldwide, with a specific focus on weekly hours. The varying regulations are highlighted, including the 80‐hour‐per‐week regulation in the United States and the 48‐h‐per‐week regulation in the European Union influencing other regions. The article also discusses the effectiveness of working‐hour restrictions on residents' mental health, with shorter working hours having potentially greater benefits. However, the impacts on medical safety and resident education are mixed, and further reduction in working hours must be carefully considered to avoid adverse effects. The planned changes to working‐hour limits for residents in Japan offer a unique opportunity to gain new evidence on the impact of such regulations, which will be of interest to policymakers and researchers worldwide.
The recognition that individual GPCRs can activate multiple signaling pathways has raised the possibility of developing drugs selectively targeting therapeutically relevant ones. This requires tools ...to determine which G proteins and βarrestins are activated by a given receptor. Here, we present a set of BRET sensors monitoring the activation of the 12 G protein subtypes based on the translocation of their effectors to the plasma membrane (EMTA). Unlike most of the existing detection systems, EMTA does not require modification of receptors or G proteins (except for G
). EMTA was found to be suitable for the detection of constitutive activity, inverse agonism, biased signaling and polypharmacology. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity. Overall, this work describes unique resources for studying the complexities underlying GPCR signaling and pharmacology.