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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.

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.

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. Cellular signaling processes often involve trafficking of receptors and other proteins between subcellular compartments. Here the authors demonstrate a method based on the concept of Enhanced bystander Bioluminescence Resonance Energy Transfer (EbBRET) that allows efficient real time monitoring of endocytosis and trafficking.

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 s ). 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.

Mobile applications are increasingly used in healthcare. We have developed a smartphone healthcare application, CALO mama Plus, that can register daily diet, exercise, mood, and sleep quality, calculate dietary intake, and provide advice using artificial intelligence technology. This 3-month randomized controlled trial tested the hypothesis that CALO mama Plus could promote body weight reduction in Japanese adults with overweight or obesity. We recruited office workers as participants. The key eligibility criteria were an age of 20–65 years and a body mass index of 23–40 kg/m2. The primary outcome was body weight change over 3 months. We enrolled 141 participants and randomly assigned them to the intervention (n = 72) and control (n = 69) groups. The intervention group used CALO mama Plus, and the control group did not receive any intervention. The change in body weight was −2.4 ± 4.0 kg and −0.7 ± 3.3 kg in the intervention and control groups, respectively. An analysis of covariance adjusted for related variables showed a significant between-group difference in body weight change (−1.60 kg; 95% confidence interval −2.83 to −0.38; p = 0.011). The present study suggests that CALO mama Plus effectively promotes weight loss.

Most patients with Takotsubo Syndrome (TTS) are postmenopausal females. TTS in males is rare and gender differences have not been sufficiently investigated. Therefore, we investigated gender differences in TTS. TTS in males and females is often triggered by physical and emotional stress, respectively. Heart failure, a severe in-hospital complication, requires greater mechanical respiratory support in males. Fatal arrhythmias such as ventricular tachycardia and ventricular fibrillation and in-hospital mortality rates are higher in males. The white blood cell (WBC) count has been shown to be higher in males than in females with cardiovascular death compared with non-cardiovascular death. Therefore, the WBC count, a simple marker, may reflect severe TTS. Decreased estrogen levels, common in postmenopausal females, are a pathogenic mechanism of TTS. Females have a more significant increase in the extracellular matrix-receptor interaction than males. Moreover, the pathological findings after hematoxylin–eosin staining were different in males and females. Males had more severe complications than females in the acute phase of TTS; thus, more careful observations and interventions are likely required. From these results, it can be considered that the mechanism of the onset of TTS may be different between males and females. Therefore, it is necessary to fully understand the gender differences in order to more effectively manage TTS.

RationalePsychiatric 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 α2δ subunit of voltage-gated calcium channels and has unique binding characteristics to α2δ subunits and potent and long-lasting analgesic effects in neuropathic pain models.ObjectivesTo 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.MethodsIn 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.ResultsCCI 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.ConclusionsCCI 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.

Background Older adults requiring care often have multiple morbidities that lead to polypharmacy, including the use of potentially inappropriate medications (PIMs), leading to increased medical costs and adverse drug effects. We conducted a cross-sectional study to clarify the actual state of drug prescriptions and the background of polypharmacy and PIMs. Methods Using long-term care (LTC) and medical insurance claims data in the Ibaraki Prefecture from April 2018 to March 2019, we included individuals aged ≥ 65 who used LTC services. The number of drugs prescribed for ≥ 14 days and the number of PIMs were counted. A generalized linear model was used to analyze the association between the backgrounds of individuals and the number of drugs; logistic regression analysis was used for the presence of PIMs. PIMs were defined by STOPP-J and Beers Criteria. Results Herein, 67,531 older adults who received LTC services were included. The median number of total prescribed medications and PIMs was 7(IQR 5–9) and 1(IQR 0–1), respectively. The main PIMs were loop diuretics/aldosterone antagonists (STOPP-J), long-term use of proton pump inhibitors (Beers Criteria), benzodiazepines/similar hypnotics (STOPP-J and Beers Criteria), and nonsteroidal anti-inflammatory drugs (STOPP-J and Beers Criteria). Multivariate analysis revealed that the number of medications and presence of PIMs were significantly higher in patients with comorbidities and in those visiting multiple medical institutions. However, patients requiring care level ≥1, nursing home residents, users of short-stay service, and senior daycare were negatively associated with polypharmacy and PIMs. Conclusions Polypharmacy and PIMs are frequently observed in older adults who require LTC. This was prominent among individuals with comorbidities and at multiple consulting institutions. Utilization of nursing care facilities may contribute to reducing polypharmacy and PIMs. Graphical Abstract

Depression and anxiety are common psychiatric disorders that can occur throughout an individual's lifetime. Numerous pathways underlying the onset of these diseases have been identified in rodents using a social defeat stress protocol, whereby socially defeated individuals exhibit depression- and/or anxiety-like phenotypes that typically manifest as social avoidance behavior. However, most studies in this field have been conducted using young adult mice; therefore, information about social defeat stress-related behavioral phenotypes in older mice is limited. In this study, we exposed groups of young adult (8-16 weeks old) and aged (24 months old) C57BL/6J mice to mild social defeat stress by challenging them with aggressive CD1 mice while restricting the intensity of aggression to protect the animals from severe injuries. We then identified stress-induced behavioral changes and compared their expression between the age groups and with a non-defeated (non-stressed) control group. We found that the stressed mice in both age groups exhibited similar reduced social interactions that were indicative of increased social avoidance behavior. Moreover, unlike the young stressed and control groups, only the aged stressed group showed a reduced preference for sucrose, which was correlated with social avoidance behavior. Also, the aged stressed mice exhibited an attenuated defeat-induced increase in water intake. These findings reveal that aging alters behavioral phenotypes after social defeat and that the hedonic behavior of aged mice is more vulnerable to social defeat compared with younger mice.

Japan’s workplace reforms, including a 60-hour weekly work limit for medical residents, that has been in effect from April 2024, have raised concerns about compliance and its impact on training quality. This study analyzed data from 17,967 residents who participated in the General Medicine In-Training Examination from 2019 to 2022, focusing on weekly duty hours, clinical responsibilities, and training environments. Duty hours increased from 2019 to 2021, before declining in 2022. The proportion of residents working over 60 h per week decreased from 57 to 49%, while those working under 50 h increased from 12 to 19%. Concurrently, the percentage of residents managing zero to four inpatients rose from 18 to 39%. University hospital residents reported shorter duty hours but fewer patient encounters and diminished clinical exposure compared to community hospital residents. These findings underscore the educational consequences of duty-hour restrictions, particularly in university hospitals, where reduced clinical responsibilities may compromise competency-based training. The results highlight the need for balanced policies that ensure compliance while maintaining sufficient clinical exposure. Future reforms should prioritize equitable workload distribution, increased clinical opportunities, and targeted interventions to address disparities between hospital types, thereby ensuring the dual goals of resident well-being and high-quality medical education.