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Background and Purpose: This study aimed to translate and validate a Japanese version of the Paternal Antenatal Attachment Scale (PAAS-J). Methods: The PAAS-J was translated through a pilot study and a survey of fathers with pregnant partners. Results: The survey involved 189 fathers. A confirmatory factor analysis was performed, but the model fit was poor. Therefore, an exploratory factor analysis (EFA) was performed. Based on the results of the EFA, three items with low interitem correlations and factor loadings were deleted, and a 13-item scale consisting of 2 domains was created. Coefficient alpha was.80. The intraclass correlation coefficient of the retest method was.80, confirming its reliability. Conclusions: The PAAS-J was found to be reliable and valid. [ABSTRACT FROM AUTHOR]

Drug–drug interactions (DDIs) involving hepatic organic anion transporting polypeptides 1B1/1B3 (OATP1B) can be substantial, however, challenges remain for predicting interaction risk. Emerging evidence suggests that endogenous biomarkers, particularly coproporphyrin‐I (CP‐I), can be used to assess in vivo OATP1B activity. The present work under the International Consortium for Innovation and Quality in Pharmaceutical Development was aimed primarily at assessing CP‐I as a biomarker for informing OATP1B DDI risk. Literature and unpublished CP‐I data along with pertinent in vitro and clinical DDI information were collected to identify DDIs primarily involving OATP1B inhibition and assess the relationship between OATP1B substrate drug and CP‐I exposure changes. Static models to predict changes in exposure of CP‐I, as a selective OATP1B substrate, were also evaluated. Significant correlations were observed between CP‐I area under the curve ratio (AUCR) or maximum concentration ratio (CmaxR) and AUCR of substrate drugs. In general, the CP‐I CmaxR was equal to or greater than the CP‐I AUCR. CP‐I CmaxR < 1.25 was associated with absence of OATP1B‐mediated DDIs (AUCR < 1.25) with no false negative predictions. CP‐I CmaxR < 2 was associated with weak OATP1B‐mediated DDIs (AUCR < 2). A correlation was identified between CP‐I exposure changes and OATP1B1 static DDI predictions. Recommendations for collecting and interpreting CP‐I data are discussed, including a decision tree for guiding DDI risk assessment. In conclusion, measurement of CP‐I is recommended to inform OATP1B inhibition potential. The current analysis identified changes in CP‐I exposure that may be used to prioritize, delay, or replace clinical DDI studies. [ABSTRACT FROM AUTHOR]

Background: The number of adult patients with childhood-onset chronic diseases is increasing. However, the process of transitioning these patients from child- to adult-centered medical services faces many difficulties. Despite the key role that doctors in the pediatric field are considered to play in transition, few fact-finding surveys about transition have been conducted among these doctors. Objective: The aim of this study was to demonstrate the current status and challenges in the transition of patients with childhood-onset chronic diseases by a fact-finding survey of pediatricians and pediatric surgeons at a university hospital. Methods: A cross-sectional survey was performed using an anonymous self-administered questionnaire. Seventy-six doctors of pediatrics and pediatric surgery (excluding junior residents) in a university hospital were asked to answer an anonymous self-report questionnaire. A multidisciplinary research team selected items related to the transitional process. Results: Sixty (79%) doctors participated, of whom 52 (87%) showed awareness of transition. No doctor answered that "Transition is conducted smoothly." Doctors with shorter pediatric department experience had lower awareness and poorer experience with transition. In contrast to pediatric surgeons, pediatricians explained "job-seeking activities" and "contraceptive methods" to the patient, and reported a higher patient age at which to initiate explanation of transition to the patient and his/her family. Among factors inhibiting transition, 39 (65%) respondents selected "The patient's family members do not desire transition" and 34 (57%) selected "Although a relevant adult healthcare department is available, it will not accept the patient." The medical providers most frequently considered to have responsibility for playing a central role in the transition process were "pediatrician/pediatric surgeon," "medical social worker," and "regional medical liaison office." Discussion: To promote transition, pediatric and adult healthcare departments should share concerns about and cooperate in the establishment of more effective methods of transition, and provide multidisciplinary collaboration to support patients and their families. [ABSTRACT FROM AUTHOR]

On behalf of the team I am pleased to present the second annual 'novel insights into drug transporter sciences review' focused on peer-reviewed articles that were published in the year 2021. In compiling the articles for inclusion, preprints available in 2021 but officially published in 2022 were considered to be in scope. To support this review the contributing authors independently selected one or two articles that were thought to be impactful and of interest to the broader research community. A similar approach as published last year was adopted whereby key observations, methods and analysis of each paper is concisely summarized in the synopsis followed by a commentary highlighting the impact of the paper in understanding drug transporters' role in drug disposition. As the goal of this review is not to provide a comprehensive overview of each paper but rather highlight important findings that are well supported by the data, the reader is encouraged to consult the original articles for additional information. Further, and keeping in line with the goals of this review, it should be noted that all authors actively contributed by writing synopsis and commentary for individual papers and no attempt was made to standardize language or writing styles. In this way, the review article is reflective of not only the diversity of the articles but also that of the contributors. I extend my thanks to the authors for their continued support and also welcome Diane Ramsden and Pallabi Mitra as contributing authors for this issue (Table 1). Table 1. Selected articles for this review. Title Area Authors Source 1. Atorvastatin-associated rhabdomyolysis in a patient with a novel variant of the SLCO1B1 gene: a case report Polymorphism Kiage et al. J Clin Lipidol. 2022;16(1):23–27 2. Quantitation of plasma membrane drug transporters in kidney tissue and cell lines using a novel proteomic approach enabled a prospective prediction of metformin disposition Proteomics Kikuchi et al. Drug Metab Dispos. 2021;49(10):938–946 3. Proteomics-informed prediction of rosuvastatin plasma profiles in patients with a wide range of body weight Proteomics Wegler et al. Clin Pharmacol Ther. 2021;109(3):762–771 4. Performance of plasma coproporphyrin I and III as OATP1B1 biomarkers in humans Biomarker Neuvonen et al. Clin Pharmacol Ther. 2021 Dec;110(6):1622–1632 5. Identification of appropriate endogenous biomarker for risk assessment of multidrug and toxin extrusion protein-mediated drug-drug interactions in healthy volunteers Biomarker Miyake et al. Clin Pharmacol Ther. 2021;109(2):507–516 6. Population pharmacokinetic modeling and simulation to support qualification of pyridoxic acid as endogenous biomarker of OAT1/3 renal transporters Biomarker Ahmad et al. CPT Pharmacometrics Syst Pharmacol. 2021 May;10(5):467–477 7. Acute and chronic effects of rifampin on letermovir suggest transporter inhibition and induction contribute to letermovir Pharmacokinetics Induction/Biomarkers Robbins et al. Clin Pharmacol Ther. 2022;111(3):664–675 8. Exploring the use of serum-derived small extracellular vesicles as liquid biopsy to study the induction of hepatic cytochromes P450 and organic anion transporting polypeptides Induction/Biomarkers Rodrigues et al. Clin Pharmacol Ther. 2021;110(1):248–258 9. Unraveling pleiotropic effects of rifampicin by using physiologically based pharmacokinetic modeling: assessing the induction magnitude of P-glycoprotein-cytochrome P450 3A4 dual substrates Induction Pan et al. CPT Pharmacometrics Syst Pharmacol. 2021;10:1485–1496. 10. Quantification of CYP3A and Drug transporters activity in healthy young, healthy elderly and chronic kidney disease elderly patients by a microdose cocktail approach Clinical pharmacology Rattanacheeworn et al. Front Pharmacol. 2021;12:726669. 11. Quantitative prediction of P-glycoprotein-mediated drug–drug interactions and intestinal absorption using humanized mice DDI Miyake et al. Br J Pharmacol. 2021;178(21):4335–4351. 12. Regulation of OATP1B1 function by tyrosine kinase-mediated phosphorylation Regulation Hayden et al. Clin Cancer Res. 2021;27(15):4301–4310. [ABSTRACT FROM AUTHOR]

Introduction: Computed tomography is useful for the diagnosis of coronavirus disease (COVID‐19) pneumonia. However, many types of interstitial lung diseases and even bacterial pneumonia can show abnormal chest shadows that are indistinguishable from those observed in COVID‐19 pneumonia. Thus, it is necessary to identify useful biomarkers that can efficiently distinguish COVID‐19 pneumonia from COVID‐19 pneumonia‐like diseases. Herein, we investigated the usefulness of serum Krebs von den Lungen 6 (KL‐6) and surfactant protein D (SP‐D) for identifying patients with COVID‐19 pneumonia among patients with abnormal chest shadows consistent with COVID‐19 pneumonia. Method: This was a retrospective cohort study of consecutive patients who underwent evaluation of serum KL‐6 and SP‐D at a single center from February 2019 to December 2020. A total of 54 patients with COVID‐19 pneumonia and 65 patients with COVID‐19 pneumonia‐like diseases were enrolled in this study from the source population. Serum KL‐6 and SP‐D levels in both groups were analyzed. Result: The serum levels of KL‐6 and SP‐D in patients with COVID‐19 pneumonia were significantly lower than those in patients with COVID‐19 pneumonia‐like disease (median [interquartile range]: 208.5 [157.5–368.5] U/ml vs. 430 [284.5–768.5] U/ml, p < 0.0001 and 24.7 [8.6–51.0] ng/ml vs. 141 [63.7–243.5] ng/ml, p < 0.0001, respectively). According to receiver operating characteristic (ROC) analysis, the areas under the ROC curves (95% confidence intervals) of serum KL‐6 and SP‐D levels for distinguishing COVID‐19 pneumonia from COVID‐19 pneumonia‐like diseases were 0.761 (0.675–0.847) and 0.874 (0.812–0.936), respectively. The area under the ROC curve of serum SP‐D was significantly larger than that of serum KL‐6 (p = 0.0213), suggesting that serum SP‐D can more efficiently distinguish COVID‐19 pneumonia from COVID‐19 pneumonia‐like diseases. Conclusion: Serum SP‐D is a promising biomarker for distinguishing COVID‐19 pneumonia from COVID‐19 pneumonia‐like diseases. Serum SP‐D can be useful for the management of patients with abnormal chest shadow mimicking COVID‐19 pneumonia. [ABSTRACT FROM AUTHOR]

Fenofibrate (FF), a peroxisome proliferator‐activated receptor‐alpha (PPAR‐α) agonist and a lipid‐lowering agent, can decrease experimental pulmonary fibrosis. However, the mechanisms underlying the antifibrotic effect of FF remain unknown. Hence, this study was conducted to evaluate the effects of FF on transforming growth factor‐beta (TGF‐β)‐induced myofibroblast differentiation and activation in lung fibroblasts. The results showed that FF inhibited alpha‐smooth muscle actin (α‐SMA) and connective tissue growth factor expression, collagen production, cell motility, SMAD3 phosphorylation and nuclear translocation, and metabolic reprogramming in TGF‐β‐exposed cells. The inhibitory effect of FF did not decrease with the addition of a PPAR‐α antagonist. Moreover, the inhibitory effect given by FF could not be reproduced with the addition of an alternative PPAR‐α agonist. FF inhibited mitochondrial respiration. However, rotenone, a complex I inhibitor, did not suppress TGF‐β‐induced myofibroblast differentiation. Furthermore, the TGF‐β‐induced nuclear reduction of protein phosphatase, Mg2+/Mn2+‐dependent 1A (PPM1A), a SMAD phosphatase, was inhibited by FF. These results showed that FF suppressed TGF‐β‐induced myofibroblast differentiation and activation independent of PPAR‐α activation and impaired mitochondrial respiration. In conclusion, this study provides information on the effects of FF on anti‐TGF‐β mechanisms. [ABSTRACT FROM AUTHOR]

Background: Predicting the incidence of chemotherapy‐triggered acute exacerbation of interstitial lung disease (AE‐ILD) in patients with lung cancer is important because AE‐ILD confers a poor prognosis. The Glasgow prognostic score (GPS), which is an inflammation‐based index composed of serum levels of C‐reactive protein and albumin, predicts prognosis in patients with small cell lung cancer (SCLC) without ILD. In this study, we investigated AE‐ILD and survival outcome based on the GPS in patients with ILD associated with SCLC who were receiving chemotherapy. Methods: Medical records of patients who received platinum‐based first‐line chemotherapy between June 2010 and May 2019 were retrospectively reviewed to compare the incidence of AE‐ILD and overall survival (OS) between GPS 0, 1, and 2. Results: Among our cohort of 31 patients, six (19.3%) experienced chemotherapy‐triggered AE‐ILD. The AE‐ILD incidence increased from 9.5% to 25.0% and 50.0% with increase in GPS of 0, 1, and 2, respectively. Univariate and multivariate analyses revealed remarkable associations between GPS 2 and both AE‐ILD (odds ratio for GPS 2, 18.69; p = 0.046) and prognosis (hazard ratio of GPS 2, 13.52; p = 0.002). Furthermore, median OS in the GPS 0, 1, and 2 groups was 16.2, 9.8, and 7.1 months, respectively (p < 0.001). Conclusions: Our results suggest that GPS 2 is both a predictor of risk of chemotherapy‐triggered AE‐ILD and a prognostic indicator in patients with ILD associated with SCLC. We propose that GPS may be used as a guide to distinguish chemotherapy‐tolerant patients from those at high risk of AE‐ILD. [ABSTRACT FROM AUTHOR]

Aim: To verify the reliability and validity of a Japanese translation of the Satter eating competence Inventory‐2.0™ (ecSI‐2.0™) for parents of fifth and sixth grade elementary school students. Methods: Participants were parents who prepared meals for their children aged 10–12 years. A preliminary study was conducted with 11 parents using semi‐structured interviews and questionnaires, followed by a main study of 2,825 parents. Internal consistency and test–retest methods were used to verify reliability. Face and content validity were confirmed in the preliminary study, and feasibility was examined by the valid response rate and response time. Construct validity was verified using factor validity and known population validity. Results: Of the 2,825 persons surveyed, 626 returned valid responses, and among the 60 persons who received the re‐survey, 48 returned valid responses. The average score of the Japanese translation of the ecSI‐2.0™ was 33.1 (SD ± 7.8) points. Cronbach's alpha coefficient for the whole scale was.87 and ranged from.67–.79 for the four subscales. The test–retest method confirmed the scale's stability. Factor analysis confirmed that reproducibility of the four factors was similar to the original version. In the examination of known population validity, the same correlation as the original edition was confirmed. Conclusions: The Japanese translation of the ecSI‐2.0™ may be reliable and valid for understanding eating competence related to behavior of parents of school‐age children. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung disease (ILD) in patients with non‐small cell lung cancer (NSCLC) worsens the prognosis for overall survival (OS) due to chemotherapy‐triggered acute exacerbation (AE)‐ILD. The Glasgow Prognostic Score (GPS), which is based on serum C‐reactive protein and albumin levels, has been suggested as a reliable prognostic tool for mortality in cancer patients, including NSCLC. In this study, we investigated whether GPS is a predictor for chemotherapy‐triggered AE‐ILD and the prognosis in patients with NSCLC and pre‐existing ILD. Methods: We conducted a retrospective review on 56 NSCLC and ILD patients at our hospital who received platinum agent‐based treatment as first‐line chemotherapy between June 2010 and May 2019. We categorized these patients according to their GPS (0–2) and compared the incidence of chemotherapy‐triggered AE‐ILD and OS. Results: The GPS 0, 1, and 2 groups included 31, 16, and nine patients, respectively, out of 56. A total of 12 (21.4%) patients showed chemotherapy‐triggered AE‐ILD. The median OS was at 11.5 months (95% confidence interval: 8.0–15.1). The incidence of chemotherapy‐triggered AE‐ILD within the first year of chemotherapy in the GPS 0, 1, and 2 groups was three (9.6%), four (25.0%), and five (55.5%), and the median OS time was 16.9, 9.8 and 7.6 months, respectively. Univariate and multivariate analyses indicated that only GPS 2 could predict both chemotherapy‐triggered AE‐ILD and OS (P < 0.05). Conclusions: GPS assessment of patients with NSCLC and pre‐existing ILD is a valuable prognostic tool for predicting chemotherapy‐triggered AE‐ILD and OS. Key points: Significant findings of the study: We found that GPS 2 was an independent risk factor for chemotherapy‐triggered AE‐ILD and prognosis in patients with ILD associated with NSCLC. What this study adds: GPS may potentially enable the discrimination of patients tolerant of chemotherapy from those at an increased risk of AE‐ILD and predict the prognosis in patients with NSCLC and ILD receiving chemotherapy. [ABSTRACT FROM AUTHOR]

Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are involved in the disposition of a variety of commonly prescribed drugs. The evaluation of OATP1B1/1B3 inhibition potential by investigational drugs is of interest during clinical drug development due to various adverse events associated with increased exposures of their substrates. Regulatory guidance documents on the in vitro assessment of OATP1B1/1B3 inhibition potential are conservative with up to a third of predictions resulting in false positives. This work investigated the utility of OATP1B1/1B3 endogenous biomarkers, coproporphyrin (CP)‐I and CP‐III, to assess clinical inhibition of OATP1B1/1B3 and potentially eliminate the need for prospective clinical drug‐drug interaction (DDI) studies. Correlations between CP‐I exposures and various OATP1B1 static DDI predictions were also evaluated. Glecaprevir/pibrentasvir (GLE/PIB) 300/120 mg fixed‐dose combination is known to cause clinical inhibition of OATP1B1/1B3. In a clinical study evaluating the relative bioavailability of various formulations of GLE/PIB regimen, CP‐I peak plasma concentration (Cmax) ratio and 0–16‐hour area under the concentration‐time curve (AUC0–16) ratio relative to baseline increased with increasing GLE exposures, whereas there was a modest correlation between GLE exposure and CP‐III Cmax ratio but no correlation with CP‐III AUC0–16 ratio. This suggests that CP‐I is superior to CP‐III as an endogenous biomarker for evaluation of OATP1B1 inhibition. There was a significant correlation between CP‐I and GLE Cmax (R2 = 0.65; P < 0.001) across individual subjects. Correlation analysis between GLE OATP1B1 R values and CP‐I exposures (Cmax ratio and AUC0–16 ratio) suggests that an R value of > 3 can predict a biologically meaningful inhibition of OATP1B1 when the inhibitor clinical pharmacokinetic parameters are available. [ABSTRACT FROM AUTHOR]

As part of control techniques, gust-alleviation systems using airborne Doppler lidar technology are expected to enhance aviation safety by significantly reducing the risk of turbulence-related accidents. Accurate measurement and estimation of the vertical wind velocity are very important in the successful implementation of such systems. An estimation algorithm for the airflow vector based on data from airborne lidars is proposed and investigated for preview control to prevent turbulence-induced aircraft accidents in flight. An existing technique – simple vector conversion – assumes that the wind field between the lidars is homogeneous, but this assumption fails when turbulence occurs due to a large wind-velocity fluctuation. The proposed algorithm stores the line-of-sight (LOS) wind data at every moment and uses recent and past LOS wind data to estimate the airflow vector and to extrapolate the wind field between the airborne twin lidars without the assumption of homogeneity. Two numerical experiments – using the ideal vortex model and numerical weather prediction, respectively – were conducted to evaluate the estimation performance of the proposed method. The proposed method has much better performance than simple vector conversion in both experiments, and it can estimate accurate two-dimensional wind-field distributions, unlike simple vector conversion. The estimation performance and the computational cost of the proposed method can satisfy the performance demand for preview control. [ABSTRACT FROM AUTHOR]

Aim: Nurses are expected to have a role in the transition of care from pediatric to adult medical practices for adolescents and young adults with childhood‐onset chronic diseases. This study compares the experience, knowledge, and perceptions regarding the ideal care among adult unit and pediatric nurses regarding the transition to adult care for those with childhood‐onset chronic diseases. Methods: A cross‐sectional study using self‐report questionnaires was conducted with nurses in a tertiary hospital in Tokyo. Questions were generated based on a literature review and expert discussion. Data from 1,064 participants were analyzed (adult unit nurses: n = 959, 90.1%; pediatric nurses: n = 105, 9.9%). Results: Among 623 adult unit nurses who had care experience for adult patients with a childhood‐onset chronic disease, 458 nurses (73.6%) were unaware of the concept of transitional care. As the obstructive factors for transition, pediatric nurses recognized problems in healthcare providers' attitudes and lack of transitional care coordinators, while the adult unit nurses emphasized the patients' wishes to continue to receive pediatric healthcare. Most adult unit nurses expected pediatric nurses to function as transitional care coordinators. Conclusion: Adult unit and pediatric nurses had different perceptions of the barriers in transitioning children with chronic diseases to adult care. It is important to have educational programs focusing on transitional care for all nurses, both to enable pediatric nurses to improve transition readiness of children with chronic diseases and to offer adult patients with a childhood‐onset chronic disease continuing support through adult unit nurses. [ABSTRACT FROM AUTHOR]

The tumor microenvironment has previously been reported to be hypercapnic (as high as ~84 mmHg), although its effect on tumor cell behaviors is unknown. In this study, high CO 2 levels, ranging from 5% to 15%, protected lung cancer cells from anticancer agents, such as cisplatin, carboplatin and etoposide, by suppressing apoptosis. The cytoprotective effect of a high CO 2 level was independent of acidosis and was due to mitochondrial metabolic reprogramming that reduced mitochondrial respiration, as assessed by oxygen consumption, oxidative phosphorylation, mitochondrial membrane and oxidative potentials, eventually leading to reduced reactive oxidant species production. In contrast, high CO 2 levels did not affect cisplatin-mediated DNA damage responses or the expression of Bcl-2 family proteins. Although high CO 2 levels inhibited glycolysis, this inhibition was not mechanistically involved in high CO 2 -mediated reductions in mitochondrial respiration, because a high CO 2 concentration inhibited isolated mitochondria. A cytoprotective effect of high CO 2 levels on mitochondria DNA-depleted cells was not noted, lending support to our conclusion that high CO 2 levels act on mitochondria to reduce the cytotoxicity of anticancer agents. High CO 2 -mediated cytoprotection was also noted in a 3D culture system. In conclusion, the hypercapnic tumor microenvironment reprograms mitochondrial respiratory metabolism causing chemoresistance in lung cancer cells. Thus, tumor hypercapnia may represent a novel target to improve chemosensitivity. fx1 • Tumor microenvironment is hypercapnic. • Hypercapnia reprograms mitochondrial metabolism, reducing ROS and chemosensitivity. • Reduced chemosensitivity induced by hypercapnia is independent of acidosis. • Tumor hypercapnia represents a novel target to improve cancer chemosensitivity. [ABSTRACT FROM AUTHOR]

A 69‐year‐old man with a history of type 2 diabetes and high blood pressure was diagnosed with coronavirus disease 2019 (COVID‐19). He had hyperferritinaemia and respiratory failure. Despite the initiation of favipiravir and high‐dose corticosteroid and ceftriaxone, his respiratory failure progressed and serum ferritin levels increased. After polymyxin B‐immobilized fibre column direct haemoperfusion (PMX‐DHP) therapy, there was improvement of the respiratory failure and hyperferritinaemia. We report the first case of COVID‐19‐induced hyperferritinaemia and severe respiratory failure successfully treated by PMX‐DHP. [ABSTRACT FROM AUTHOR]

ABSTRACT: This study proposes an algorithm that combines ensemble numerical weather‐prediction model data and aircraft flight data in a wind nowcasting system for safe and efficient aircraft operation. It uses an ensemble‐weighted average method based on sequential importance sampling (SIS), which is a particle filter method for forecasting the wind field in real time. SIS is applied to the ensemble forecast data and control run data of the European Centre for Medium‐Range Weather Forecasts (ECMWF), Japan Meteorological Agency (JMA), Korea Meteorological Administration (KMA), National Centers for Environmental Prediction (NCEP) and United Kingdom Met Office (UKMO) for the two case studies that use flight data from 72 commercial aircraft flights. The results show that SIS can forecast better than the other four methods: direct ensemble average (DEA), elite strategy (ES), and selective ensemble average (SEAV) and weighted average (SEWE), with average improvements in forecast performance of about 10–15%, even at 300 min ahead. In addition, the overall forecast performance between the forecast wind and observation of the radiosonde of SIS was slightly better than DEA. In both cases, the forecast performance was significantly improved on points along the flight path of the aircraft used for this study. Case analyses and the impact of differences in the hyper‐parameters of SIS on forecast performance are also presented in this study. [ABSTRACT FROM AUTHOR]

Key message: If a double‐ring sign is found in contrast‐enhanced computed tomography, this should raise concern not only for Takayasu arteritis, but also for granulocyte colony‐stimulating factor‐induced vasculitis. [ABSTRACT FROM AUTHOR]

Key message: In lung cancer patients, brain metastasis is often suspected when neurological symptoms appear; however, if ptosis, ocular motility disorder or optic nerve disorder is observed, it is important to identify and treat the orbital apex syndrome. [ABSTRACT FROM AUTHOR]

1. Accurate predictions of clinical transporter-mediated drug–drug interactions (DDI) fromin vitrodata can be challenging when compounds have poor solubility and/or high nonspecific binding. Additionally, current DDI predictions for compounds with high plasma–protein binding assume that the unbound fraction in plasma is 0.01, if the experimental value is less than 0.01 or cannot be determined. This approach may result in an overestimation of DDI risk. To overcome these challenges, it may be beneficial to conduct inhibition studies under physiologically relevant conditions. 2. Here, IC50values, determined in the presence of 4% bovine serum albumin approximating human plasma albumin concentrations, were successfully used to predict DDI for uptake transporters, OATP1B1/1B3, OCT1/2, OAT1/3 and MATE1/2K. 3. The IC50values of reference inhibitors with 4% bovine serum albumin, considered total IC50, were comparable to the predicted values based on nominal IC50values determined under protein-free conditions and unbound fraction in plasma. Calculation of R-total andCmax/IC50,totalvalues using total plasma exposure and total IC50values explained the clinical DDI or absence of it for these inhibitors. 4. These results suggest that IC50determinations in the presence of 4% albumin can be used, in the context of clinical total exposure, to predict DDI involving uptake transporters. [ABSTRACT FROM PUBLISHER]

The aim of this article is to understand the bereavement of a family as a unit from multiple perspectives. Using qualitative metasynthesis, we described family members’ bereavement experiences from multiple perspectives. The most common perspectives reported were those of parents who had lost their children. No studies reported the perspectives of husbands. Every article explicitly or implicitly referred to a continued connection with the deceased and the effect of this connection on family relationships. This article addresses the importance of focusing on more than one relationship within a family, which should be investigated further in future research. [ABSTRACT FROM PUBLISHER]

Background Health-related quality of life ( HRQOL) is an important outcome in pediatric solid organ transplantation. Considering the emerging problems after transplantation, an evaluation of transplant-specific aspects of HRQOL is essential, but no validated HRQOL measure is available in Japan. The aim of this study was therefore to develop the Japanese version of the Pediatric Quality of Life Inventory™ (Peds QL) Transplant Module Child Self-Report and to investigate its feasibility, reliability, and validity. Methods Based on the Peds QL linguistic validation process, the Japanese version of the Peds QL Transplant Module was developed through translation and cognitive interviews (patient testing). The scale's reliability and validity were investigated, using statistical analyses of field tests of the target population. Results Eighty-seven pairs of pediatric liver-transplant recipients and their parents participated in the field test. The pediatric patients completed the measure in 3-7 min, and the rate of missing items was low (0.27%). Excellent internal consistency and test-retest reliability were confirmed. Known-groups validity, concurrent validity, and convergent and discriminant validity also were confirmed. Conclusions Excellent feasibility, reliability, and validity of this Japanese self-report version of the Peds QL Transplant Module Child Self-Report were verified. As a measure of transplant-specific aspects of HRQOL in Japanese pediatric patients who have undergone organ transplants, the Japanese version of the Peds QL Transplant Module is appropriate for use in clinical and research settings. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of airway obstructive diseases, such as chronic obstructive pulmonary disease, asthma and bronchiolitis obliterans syndrome after lung transplantation. However, whether EMT occurs in an experimental model of airway fibrosis is not well known. We explored evidence of EMT in a murine model of airway fibrosis induced by repeated exposure to naphthalene. Mice were administered intraperitoneal injections of naphthalene or corn oil vehicle once weekly for 14 consecutive weeks. The animals were sacrificed 5 days after the final injection of naphthalene or corn oil vehicle. EMT was evaluated in lung tissue sections using immunohistochemistry and immunofluorescence. Repeated naphthalene exposure induced loss of club cells, hyperplasia of epithelial cells and peribronchial fibrosis. However, we did not find any loss of E-cadherin expression or any acquisition of vimentin, S100A4 or αSMA in epithelial cells in control or naphthalene-exposed mice. These results suggest that EMT does not contribute significantly to naphthalene-induced airway fibrosis in mice. [ABSTRACT FROM AUTHOR]

An integrated method consisting of a proper orthogonal decomposition (POD)-based reduced-order model (ROM) and a particle filter (PF) is proposed for real-time prediction of an unsteady flow field. The proposed method is validated using identical twin experiments of an unsteady flow field around a circular cylinder for Reynolds numbers of 100 and 1000. In this study, a PF is employed (ROM-PF) to modify the temporal coefficient of the ROM based on observation data because the prediction capability of the ROM alone is limited due to the stability issue. The proposed method reproduces the unsteady flow field several orders faster than a reference numerical simulation based on Navier–Stokes equations. Furthermore, the effects of parameters, related to observation and simulation, on the prediction accuracy are studied. Most of the energy modes of the unsteady flow field are captured, and it is possible to stably predict the long-term evolution with ROM-PF. [ABSTRACT FROM AUTHOR]

The phased-array weather radar (PAWR) is a new-generation weather radar that can make a 100-m-resolution three-dimensional (3D) volume scan every 30 s for 100 vertical levels, producing ~100 times more data than the conventional parabolic-antenna radar with a volume scan typically made every 5 min for 15 scan levels. This study takes advantage of orders of magnitude more rapid and dense observations by PAWR and explores high-precision nowcasting of 3D evolution at 1-10-km scales up to several minutes, which are compared with conventional horizontal two-dimensional (2D) nowcasting typically at O(100) km scales up to 1-6 h. A new 3D precipitation extrapolation system was designed to enhance a conventional algorithm for dense and rapid PAWR volume scans. Experiments show that the 3D extrapolation successfully captured vertical motions of convective precipitation cores and outperformed 2D nowcasting with both simulated and real PAWR data. [ABSTRACT FROM AUTHOR]