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Microphysiological system (MPS), a new technology for in vitro testing platforms, have been acknowledged as a strong tool for drug development. In the central nervous system (CNS), the blood‒brain barrier (BBB) limits the permeation of circulating substances from the blood vessels to the brain, thereby protecting the CNS from circulating xenobiotic compounds. At the same time, the BBB hinders drug development by introducing challenges at various stages, such as pharmacokinetics/pharmacodynamics (PK/PD), safety assessment, and efficacy assessment. To solve these problems, efforts are being made to develop a BBB MPS, particularly of a humanized type. In this study, we suggested minimal essential benchmark items to establish the BBB-likeness of a BBB MPS; these criteria support end users in determining the appropriate range of applications for a candidate BBB MPS. Furthermore, we examined these benchmark items in a two-dimensional (2D) humanized tricellular static transwell BBB MPS, the most conventional design of BBB MPS with human cell lines. Among the benchmark items, the efflux ratios of P-gp and BCRP showed high reproducibility in two independent facilities, while the directional transports meditated through Glut1 or TfR were not confirmed. We have organized the protocols of the experiments described above as standard operating procedures (SOPs). We here provide the SOPs with the flow chart including entire procedure and how to apply each SOP. Our study is important developmental step of BBB MPS towards the social acceptance, which enable end users to check and compare the performance the BBB MPSs.

Objectives: This study assessed the concentration of SARS-CoV-2 in the air of hospital rooms occupied by patients with COVID-19 who had viable SARS-CoV-2 in nasopharyngeal (NP) samples in early infection. Methods: Between July and October 2021, NP swabs were collected from 20 patients with early SARS-CoV-2 infection admitted to a tertiary hospital in Japan. Air samples were collected from their rooms, tested for SARS-CoV-2 RNA, and cultured to determine potential infectivity. Results: The NP swab samples of 18 patients were positive for viable SARS-CoV-2 (median concentration: 4.0 × 105 tissue culture infectious dose 50/ml). In the air samples, viral RNA (median concentration: 1.1 × 105 copies/m3) was detected in 12/18 (67%) patients, and viable virus (median concentration: 8.9 × 102 tissue culture infectious dose 50/m3) was detected in 5/18 (28%) patients. The median time between illness onset and sampling was 3 days. The RNA concentration was significantly higher in samples wherein viable SARS-CoV-2 was detected than in samples in which viable virus was not detected (P-value = 0.027). Conclusion: Viable SARS-CoV-2 can be detected in the air surrounding patients with early SARS-CoV-2 infection. Health care workers should pay attention to infection control when caring for patients with early SARS-CoV-2 infection.

This review aims to synthesize the evaluation evidence for parent-engagement programs that focus on reducing juvenile truancy as the primary outcome. Delinquent behavior will be assessed as a secondary outcome when included. This objective is guided by the following research questions: (1) what is the effectiveness of parent-engagement programs for children in preschool (ages 4-5) through secondary education (ages 13-19) on primarily (a) reducing student truancy (i.e., unexcused or unauthorized absence) and secondarily (and when included) (b) reducing delinquent behaviors? (2) Is there variability in the effectiveness of parent-engagement programs across moderators such as gender, age, grade levels, settings, and contexts? (3) What factors (e.g., groups, settings, and contexts) explain the variability in the effectiveness of engagement programs in a multivariate framework?

Abstract Objective Psychosis is an important comorbidity in epilepsy, but its pathophysiology is still unknown. The imaging modality 18F‐fluorodeoxyglucose‐positron emission tomography (18F‐FDG PET) is widely used to measure brain glucose metabolism, and we speculated that 18F‐FDG PET may detect characteristic alteration patterns in individuals with temporal lobe epilepsy (TLE) and psychosis. Methods We enrolled 13 patients with TLE and interictal psychosis (TLE‐P) and 21 patients with TLE without psychosis (TLE‐N). All underwent interictal 18F‐FDG‐PET scanning. Statistical Parametric Mapping (SPM)12 software was used for the normalization process, and we performed a voxel‐wise comparison of the TLE‐P and TLE‐N groups. Results Cerebral hypometabolic areas were observed in the ipsilateral temporal pole to hippocampus in both patient groups. In the TLE‐P group, the voxel‐wise comparison revealed significantly increased 18F‐FDG signals in the upper cerebellum, superior cerebellar peduncle, and midbrain. There were no significant between‐group metabolic differences around the focus or other cerebral areas. Significance Our results demonstrated significant hypermetabolism around the upper cerebellum in patients with TLE and interictal psychosis compared to patients with TLE without psychosis. These findings may reflect the involvement of the cerebellum in the underlying neurobiology of interictal psychosis and could contribute to a better understanding of this disorder.

Aims To evaluate whether low-intensity pulsed ultrasound (LIPUS) accelerates bone healing at osteotomy sites and promotes functional recovery after open-wedge high tibial osteotomy (OWHTO). Methods Overall, 90 patients who underwent OWHTO without bone grafting were enrolled in this nonrandomized retrospective study, and 45 patients treated with LIPUS were compared with 45 patients without LIPUS treatment in terms of bone healing and functional recovery postoperatively. Clinical evaluations, including the pain visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) score, were performed preoperatively as well as six weeks and three, six, and 12 months postoperatively. The progression rate of gap filling was evaluated using anteroposterior radiographs at six weeks and three, six, and 12 months postoperatively. Results The pain VAS and JOA scores significantly improved after OWHTO in both groups. Although the LIPUS group had better pain scores at six weeks and three months postoperatively, there were no significant differences in JOA score between the groups. The lateral hinge united at six weeks postoperatively in 34 (75.6%) knees in the control group and in 33 (73.3%) knees in the LIPUS group. The progression rates of gap filling in the LIPUS group were 8.0%, 15.0%, 27.2%, and 46.0% at six weeks and three, six, and 12 months postoperatively, respectively, whereas in the control group at the same time points they were 7.7%, 15.2%, 26.3%, and 44.0%, respectively. There were no significant differences in the progression rate of gap filling between the groups. Conclusion The present study demonstrated that LIPUS did not promote bone healing and functional recovery after OWHTO with a locking plate. The routine use of LIPUS after OWHTO was not recommended from the results of our study. Cite this article: Bone Jt Open 2022;3(11):885–893.

Metallo-β-lactamases cleave β-lactam moiety of many broadly used antibiotics. Here the authors captured mechanistic details of the enzyme catalyzed reaction using time-resolved xray synchrotron serial crystallography.

Abstract Alzheimer’s disease (AD) is characterized by a reorganization of brain activity determining network hyperexcitability and loss of synaptic plasticity. Precisely, a dysfunction in metabotropic GABAB receptor signalling through G protein-gated inwardly rectifying K+ (GIRK or Kir3) channels on the hippocampus has been postulated. Thus, we determined the impact of amyloid-β (Aβ) pathology in GIRK channel density, subcellular distribution, and its association with GABAB receptors in hippocampal CA1 pyramidal neurons from the APP/PS1 mouse model using quantitative SDS-digested freeze-fracture replica labelling (SDS-FRL) and proximity ligation in situ assay (P-LISA). In wild type mice, single SDS-FRL detection revealed a similar dendritic gradient for GIRK1 and GIRK2 in CA1 pyramidal cells, with higher densities in spines, and GIRK3 showed a lower and uniform distribution. Double SDS-FRL showed a co-clustering of GIRK2 and GIRK1 in post- and presynaptic compartments, but not for GIRK2 and GIRK3. Likewise, double GABAB1 and GIRK2 SDS-FRL detection displayed a high degree of co-clustering in nanodomains (40–50 nm) mostly in spines and axon terminals. In APP/PS1 mice, the density of GIRK2 and GIRK1, but not for GIRK3, was significantly reduced along the neuronal surface of CA1 pyramidal cells and in axon terminals contacting them. Importantly, GABAB1 and GIRK2 co-clustering was not present in APP/PS1 mice. Similarly, P-LISA experiments revealed a significant reduction in GABAB1 and GIRK2 interaction on the hippocampus of this animal model. Overall, our results provide compelling evidence showing a significant reduction on the cell surface density of pre- and postsynaptic GIRK1 and GIRK2, but not GIRK3, and a decline in GABAB receptors and GIRK2 channels co-clustering in hippocampal pyramidal neurons from APP/PS1 mice, thus suggesting that a disruption in the GABAB receptor–GIRK channel membrane assembly causes dysregulation in the GABAB signalling via GIRK channels in this AD animal model.

Abstract Background and purpose Quantitative measures have been proposed to aid the visual interpretation of amyloid PET. Our objective was to develop and validate quantitative software that enables calculation of the Centiloid (CL) scale and Z‐score for amyloid PET with 18F‐florbetapir. Methods This software was developed as a toolbox in statistical parametric mapping 12 running on MATLAB Runtime. For each participant's amyloid PET, this software calculates the CL scale using the standard MRI‐guided pipeline proposed by the Global Alzheimer's Association Interactive Network (GAAIN) and generates a Z‐score map for comparison with a new amyloid‐negative database constructed from 20 healthy controls. In 23 cognitively impaired patients with suspected Alzheimer's disease, Z‐score values for a target cortical area from the new database were compared with those from the GAAIN database constructed from 13 healthy controls. The CL values obtained using low‐dose CT of PET/CT equipment were then compared with those obtained using MRI. Results The CL calculation was validated with the 18F‐florbetapir dataset in the GAAIN repository. Z‐score values obtained from the new database were significantly higher (mean ± standard deviation, 1.05 ± 0.77; p

AbstractIt is well known that the volatility spillover increases when a large economic shock occurs, and then the volatility spillover pattern in the market changes. Accordingly, many papers note that clarifying the time-varying pattern of volatility transmission in domestic and international markets is useful for investors and policymakers. This paper focuses on information contagion across various industrial sectors, investigates portfolio strategies based on the volatility spillovers, and aims to clarify whether an investment strategy based on volatility spillovers benefits investors. Regarding portfolio reallocation, as soon as we observe an increase or a decrease in the effect/timing of a volatility spillover, we obtain a smaller number of reallocations and a more informative portfolio. Our results compare our proposed method with periodic portfolios, for example, daily or annually, showing that our proposed method has larger returns and a greater Sharpe ratio than the others.

It is widely hypothesized that there is a seizure-free state, termed the “latent period,” between brain injury and the onset of symptomatic epilepsy. During the latent period, structural and functional alterations gradually mediate epileptogenesis. Kainate (KA) induces epilepsy in rats in a manner similar to that induced by human epilepsy. During the model's latent period, rats administered KA-exhibited innate behaviour such as self-grooming. We previously reported that self-grooming bouts are facilitated during the latent period in this model. Here, we investigated self-grooming changes during the latent period of the KA rat model. We analysed various parameters of self-grooming – including duration, number, and percentage of correct transitions (CT%). Self-grooming bouts included a syntactic chain consisting of CT. CT% was defined as the ratio of the number of CT scans to the total number of transitions. The results showed that CT%, number, and duration were significantly increased during the latent period in KA rats. We attempted to mine the features that detect the latent period using a neural network. Our results suggest that the CT% of self-grooming will detect changes in the latent period in the KA rat epilepsy model.

This article presents a review of catalytic processes used at low temperatures to reduce emissions of nitrogen oxides (NOx) and nitrous oxide (N2O), which are exceedingly important in terms of their environmental impacts on the Earth. With conventional purification technologies, it has been difficult to remove these compounds under low-temperature conditions. By applying a catalytic process in an electric field for the three reactions of three-way catalysts (TWC), NOx storage reduction catalysts (NSR), and direct decomposition of N2O, we have achieved high catalytic activity even at low temperatures. By promoting ion migration on the catalyst surface, we have filled in the gaps in conventional catalytic technology and have opened the way to more efficient conversion of NOx and N2O. [ABSTRACT FROM AUTHOR]

AbstractLimited studies have examined the factor loadings of a commonly used parentification scale, the Parentification Questionnaire (Session & Jurvokic, 1986), among college students. The purpose of the current research was to identify the best-fitting factor structure of the Parentification Questionnaire among 269 predominately African American college students (M age = 20.62, SD age = 1.83). Exploratory factor analysis using weighted least square mean and variance adjusted estimator with geomin factor rotation was conducted to examine a 1- to 5-factor mode. Based on the results, we concluded that the 3-factor model was the best-fitting model. [ABSTRACT FROM AUTHOR]

Background: Droplet digital PCR (ddPCR) is a highly sensitive tool for detecting bacterial DNA in bacterial bloodstream infections (BSI). This study aimed to examine the sensitivity and specificity of ddPCR and the association between bacterial DNA load in whole blood and the time-to-positivity (TTP) of blood culture (BC) in patients with Escherichia coli BSI. Methods: This prospective study enrolled patients with E. coli BSI confirmed via BC at the Hiroshima University Hospital from June 2023 to August 2024. The E. coli DNA load in whole blood, which was simultaneously obtained from two BC sets, was measured using ddPCR with E. coli specific primer and probe. Whole blood samples from 50 patients with BC positive for pathogens other than E. coli (n = 25) and BC negative (n = 25) were also evaluated using ddPCR. Results: A total of 131 patient samples were analyzed in this study. Of the 81 patients with E. coli BSI, ddPCR detected E. coli DNA in 67 (82.7%). The results of ddPCR for E. coli had a sensitivity of 82.7% (95% CI: 73.1–89.4%), specificity 100% (95% CI: 93.0–100%). Patients with positive ddPCR results had significantly shorter TTP than those with negative results (median, 8.8 h vs. 10.7 h, p < 0.001). The positivity rate for both BC sets was significantly higher in patients with positive ddPCR results than in those with negative results (89.6% vs. 35.1%, p < 0.001). Among ddPCR-positive patients, septic shock was significantly associated with intestinal perforation, higher E. coli DNA load, higher 28-d mortality, shorter TTP, and higher positivity rate for four bottles of BC than those without septic shock. The E. coli DNA load in whole blood negatively correlated with TTP (p < 0.001, R2 = 0.38). Conclusion: The E. coli DNA load in whole blood is inversely correlated with TTP. Notably, a higher E. coli DNA load is associated with septic shock. [ABSTRACT FROM AUTHOR]

Objectives: The current study examined the association between the possession of personal growth initiative (PGI) skills and symptoms of mental illness (i.e., depression, anxiety, and stress) and the potential mediating role of daily engagement of PGI skills during the COVID‐19 pandemic. Methods: The participants consisted of 73 individuals (Mage = 41.62, SDage = 12.44) who were recruited from Amazon's Mechanical Turk (MTurk). Data for possessed PGI was collected in April 2020, and the daily survey started approximately 1 month later at the beginning of May 2020 for 29 days. Results: Controlling for demographic variables, multilevel mediation models revealed significant association between PGI skills and PGI engagement. However, our hypothesized indirect effects were not found. When inspecting the direct effects controlling for the effect of PGI engagement and demographic variables, the paths between PGI skills and both depression and anxiety were negatively associated. When examining the effect of time, there were no significant changes during the period of 29 days in the levels of PGI skills among individuals. However, a significant fluctuation within individuals in how much participants have utilized PGI skills during the study period was found. Conclusion: The current study highlights the influence of PGI skills at both the between‐individual as well as within‐individual levels in predicting symptoms of mental illness, and it also uncovers the role of PGI skills by separating into general PGI skills and individual's daily engagement in utilizing the PGI skills in predicting symptoms of mental illness. [ABSTRACT FROM AUTHOR]

Abstract Background Centiloid (CL) scaling has become a standardized quantitative measure in amyloid PET because it facilitates the direct comparison of results across institutions, even when different analytical methods or tracers are used. Standard volumes of interest must be used to calculate the CL scale after the anatomic standardization of amyloid PET images using coregistered MRI; if the MRI is unavailable, the CL scale cannot be accurately calculated. This study sought to determine the substitutability of low-dose CT, which is used to correct PET attenuation in PET/CT equipment, by evaluating the measurement accuracy when low-dose CT is used as an alternative to MRI in the calculation of the CL scale. Amyloid PET images obtained using 18F-flutemetamol from 24 patients with possible or probable Alzheimer’s disease were processed to calculate the CL scale using 3D T1-weighted MRI and low-dose CT of PET/CT. CLMRI and CLCT were, respectively, defined as the use of MRI and CT for anatomic standardization and compared. Regional differences in the CT-based and MRI-based standardized anatomic images were also investigated. Trial registration: Japan Registry of Clinical Trials, jRCTs031180321 (registered 18 March 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031180321 ). Results A Bland–Altman plot showed that CLCT was slightly but significantly underestimated (mean ± standard deviation, − 1.7 ± 2.4; p