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Granulocyte colony-stimulating factor (G-CSF)-producing lung tumours are rare, with their imaging features and effective treatments remaining elusive. Similarly, mesenchymal-epithelial transition (MET) exon 14 skipping mutations are also uncommon. Herein, we report a case of G-CSF-producing lung adenocarcinoma positive for a MET exon 14 skipping mutation, mimicking lung abscess. A 61-year-old man presented with cough and high fever. Contrast-enhanced chest computed tomography revealed a mass with a cavity and internal fluid accumulation. The patient initially underwent diagnostic treatment for a lung abscess but was ultimately diagnosed with lung adenocarcinoma positive for a MET exon 14 skipping mutation. Following tepotinib therapy, the primary lesion shrank, and serum G-CSF levels decreased, leading to a diagnosis of G-CSF-producing lung cancer. G-CSF-producing lung tumours can present imaging findings that mimic lung abscesses. Tepotinib therapy may be effective for patients with MET exon 14 skipping mutation, including those with G-CSF-producing lung cancer., (© 2024 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

Electroretinograms (ERGs) are often used to evaluate retinal function. However, assessing local retinal function can be challenging; therefore, photopic and scotopic ERGs are used to record whole-retinal function. This study evaluated focal retinal function in rats exposed to continuous light using a multifocal ERG (mfERG) system. The rats were exposed to 1000 lux of fluorescent light for 24 h to induce photoreceptor degeneration. After light exposure, the rats were reared under cyclic light conditions (12 h: 5 lux, 12 h: dark). Photopic and multifocal ERGs and single-flash and multifocal visual evoked potentials (mfVEPs) were recorded 7 days after light exposure. Fourteen days following light exposure, paraffin-embedded sections were prepared from the eyes for histological evaluation. The ERG and VEP responses dramatically decreased after 24 h of light exposure, and retinal area-dependent decreases were observed in mfERGs and mfVEPs. Histological assessment revealed severe damage to the superior retina and less damage to the inferior retina. Considering the recorded visual angles of mfERGs and mfVEPs, the degenerated area shown on the histological examinations correlates well with the responses from multifocal recordings.

Background: This study evaluated the efficacy and safety of baricitinib (Janus kinase-1/2 inhibitor), in adult and pediatric Japanese patients with Nakajo-Nishimura syndrome/chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (NNS/CANDLE), stimulator of interferon genes-associated vasculopathy with onset during infancy (SAVI), or Aicardi-Goutières syndrome (AGS)., Methods: A Phase 2/3, multicenter, open-label study (NCT04517253) was conducted across 52 weeks. Primary efficacy endpoint assessed the change in mean daily diary score (DDS) from baseline to the end of primary treatment period. Other efficacy endpoints included change in mean DDS to the end of maintenance period, daily corticosteroid use, Physician's Global Assessment of Disease Activity (PGA) scores, and daily symptom-specific score (DSSS) from baseline to primary and maintenance treatment periods. All treatment-emergent adverse events (TEAEs) that occurred postdosing were recorded., Results: Overall, 9 patients (5 with NNS, 3 with SAVI, and 1 with AGS) were enrolled; 55.6% were females, mean age was 26 years, and mean corticosteroid use/weight was 0.2 mg/kg. At the end of primary treatment period, mean DDS decreased from baseline in patients with NNS/CANDLE (0.22) and SAVI (0.21) and increased in the patient with AGS (0.07). At the end of maintenance treatment period, mean DDS decreased from baseline in patients with NNS/CANDLE (0.18) and SAVI (0.27) and increased in the patient with AGS (0.04). Mean percent corticosteroid use decreased by 18.4% in 3 out of 5 patients with NNS/CANDLE and 62.9% in 1 out of 3 patients with SAVI. Mean PGA score decreased from baseline in patients with NNS/CANDLE (1.60), SAVI (1.33), and AGS (1.0), and mean DSSS improved from baseline. All patients reported ≥ 1 TEAE. Frequently reported AEs included BK polyomavirus detection (3; 33.3%), increased blood creatine phosphokinase (2; 22.2%), anemia (2; 22.2%), and upper respiratory tract infection (2; 22.2%). Three (33.3%) patients reported serious adverse events, 1 of which was related to study drug. One patient with SAVI died due to intracranial hemorrhage, which was not related to study drug., Conclusion: Baricitinib may offer a potential therapeutic option for patients with NNS/CANDLE, SAVI, and AGS, with a positive benefit/risk profile in a vulnerable patient population with multiple comorbidities., Trial Registration: NLM clinicaltrials.gov, NCT04517253 . Registered 18 August 2020., (© 2023. The Author(s).)

Introduction: Baricitinib is an oral selective Janus kinase (JAK)1/JAK2 inhibitor approved in Japan and the European Union for the treatment of atopic dermatitis (AD). The aim of this study is to report pooled safety data for baricitinib in the Japanese subpopulation of the clinical development program in moderate-to-severe AD., Methods: This analysis included participant-level safety data from five double-blind, randomized clinical studies and one double-blind, randomized, long-term extension study, reported in three datasets for the Japanese subpopulation: (1) placebo-controlled, (2) baricitinib 2 mg and 4 mg extended ("2-mg-4-mg extended"), and (3) all baricitinib doses ("All-bari-AD"). The data cutoff was 13 December 2019. Safety outcomes included treatment-emergent adverse events, adverse events of special interest, and abnormal laboratory changes. Proportions of participants with events and incidence rates were calculated., Results: Data were collected for 341 participants from Japan who received baricitinib for 371.7 participant-years (median duration 371.0 days). In the placebo-controlled dataset, the frequencies of serious infections and herpes zoster were low and similar between treatment groups, and the incidence of treatment-emergent infections, in particular herpes simplex, was higher in the baricitinib groups compared with the placebo group. No gastrointestinal perforations, tuberculosis, positively adjudicated cardiovascular events, deep vein thrombosis, or pulmonary embolism were reported with exposure up to 2 years in the All-bari-AD dataset. There were no deaths in the Japanese subpopulation., Conclusions: This integrated safety analysis in the subpopulation of Japanese participants is consistent with the established safety profile of baricitinib in the global study population with moderate-to-severe AD., Gov Identifiers: NCT02576938, NCT03334396, NCT03334422, NCT03428100, NCT03733301, and NCT03334435., (© 2022. The Author(s).)

Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory compound developed for treating atopic dermatitis and known to inhibit Toll-like receptor 4, in light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once per day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 partially protected against this decrease in retinal thickness and increase in ERG amplitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregulation of C-C motif chemokine 2 by LPS stimulation was significantly inhibited by SIG-1451 treatment, and Western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 indirectly protects photoreceptor cells by attenuating light damage progression, by affecting the inflammatory responses.

Stearyl alcohol is found in various cosmetics and topical medications and is regarded as safe. Allergic contact dermatitis is reported due to this chemical on rare occasions. We report seven cases, comprising three men and four women aged between 36 and 62 between the years 2013 to 2019, of allergic contact dermatitis due to the use of topical medication, where the patient showed a positive result to a patch test using stearyl alcohol. There were 10 topical medications that we considered to be the cause of this: three were from Oronine ® H ointment, two from Eurax ® cream, one from Eurax H cream, and four from topical antifungal medications. All these medications contained stearyl alcohol. Seven cases of patch tests with stearyl alcohol all showed positive results. Moreover, having done a patch test with cetyl alcohol, two out of three tests showed positive. When researching allergic contact dermatitis due to topical medications, it is important to test for allergy to stearyl alcohol as well as their main ingredients, because it is contained in numerous products and has the ability to cause allergic contact dermatitis., (© 2022 Japanese Dermatological Association.)

Objectives: To deliver mindfulness-based cognitive therapy (MBCT) efficiently, the present study aimed (1) to identify predictors and moderators of patients who benefit from MBCT for psychological distress and (2) to explore the initial treatment reaction to identify the optimal number of sessions that produce a significant clinical effect., Methods: This is the secondary analysis of a randomized controlled trial of MBCT for breast cancer patients (N = 74). We classified the participants into remitters vs. non-remitters, and responder vs. non-responders, according to the total score of the Hospital Anxiety and Depression Scale at the end of the intervention. We conducted multivariate analyses to explore for predictors of response and remission. We adopted generalized estimating equations to explore the optimal number of sessions., Results: Sociodemographic and clinical backgrounds did not have significant influence on the treatment outcomes of the MBCT. Better program adherence, which was represented as the participants' better attendance to the MBCT program, was a significant predictor of both remission and response [odds ratio (OR) = 1.90, 95% confidence interval (CI) 1.25-2.89, p = 0.003, and OR = 1.72, 95% CI 1.12-2.65, p = 0.013, respectively]. It was not until seventh session that the remission rate exceeded 50% and the response rate showed significance., Significance of Results: Sociodemographic and clinical characteristics did not significantly influence the treatment outcomes, while homework minutes and class attendance had significant effects on treatment outcomes. This implies that MBCT is recommended to any cancer patient, if he/she is motivated to the program, regardless of their sociodemographic and clinical characteristics. Patients are encouraged to attend a standard MBCT program (eight sessions) and do the assigned homework as intensely as possible. Further studies with larger sample and objective measurements are desired.

Introduction: Pulmonary hypertension (PH) is a chronic and progressive disease. While prognoses have improved, PH patients still experience side effects and activity restrictions. Accordingly, the key questions asked by this study are 'How many PH patients have depression/anxiety symptoms?' and 'Is there a difference in the symptoms and distress factors between pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH) patients, and how are they experiencing distress?', Methods: A mixed-methods study was conducted to collect and analyse quantitative and qualitative data. We administered questionnaires (Patient Health Questionnaire (PHQ-9) and Generalised Anxiety Disorder-7) and then conducted interviews with participants who reported moderate to severe depressive symptoms (PHQ-9 ≥10)., Results: Seventy-four participants were enrolled in the study, 25 with idiopathic PAH and 49 with CTEPH. Their average age was 55.2 years (PAH 42.7 years, CTEPH 61.5 years). Overall, 44.6% of participants had mild or more severe depressive symptoms (PHQ-9 ≥5) and 17.6% had moderate or more severe depressive symptoms (PHQ-9 ≥10). PAH patients had particularly high depressive symptoms (PHQ-9 ≥5: PAH 64.0%, CTEPH 34.7%; PHQ-9 ≥10: PAH 24%, CTEPH 14.3%). We extracted four common themes from the qualitative interview data on participants' experience of psychological distress: 'Loss of myself,' 'Isolation from my surroundings,' 'Hassle associated with oxygen therapy,' and 'Fear of illness progression/deterioration.' One theme- 'Suffering from side effects'-was extracted only for PAH patients, while another-'Rumination on illness due to breathlessness'-was extracted only for CTEPH patients., Discussion and Conclusion: The study found that PH patients are prone to depression. The identification of factors and themes that influence the psychological distress of PH patients is important information that can be used to improve the support for the physical and mental health of these patients. Interventions for these distress may contribute to improving the mental status of PH patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

ATP-binding castle protein G2 (ABCG2) is thought to inhibit the activities of certain gefitinib transporters, thereby affecting drug pharmacokinetics. The C421A polymorphism affects the function and expression of ABCG2 on the cell membrane. Previous studies have shown that proton-pump inhibitors (PPIs) inhibit gefitinib absorption, as well as the function of ABCG2. We evaluated the plasma concentrations of gefitinib in patients with and without the ABCG2 C421A polymorphism, who were or were not taking PPIs. In total, 61 patients with advanced epidermal-growth-factor-positive non-small-cell lung cancer were enrolled in this study. They were treated with gefitinib at a dose of 250 mg per day. Plasma gefitinib concentration and ABCG2 C421A status were determined after 2 weeks. The patients were divided into CC- and CA/AA genotype groups. We compared the trough and peak gefitinib levels and the area under the curve (AUC) values for 24-h gefitinib concentrations. We also compared these parameters among four groups distinguished according to the presence or absence of the polymorphism and PPI use. The mean trough gefitinib level and AUC value for 24-h gefitinib concentration were significantly lower in the CA/AA group compared to the CC group (mean trough level: 333.2 vs. 454.5 ng/mL, respectively, P = 0.021; AUC: 9949.9 vs. 13,085.4 ng・h/mL, respectively, P = 0.034). Among patients taking PPIs, the mean trough gefitinib level was significantly lower in the CA/AA group than the CC group (220.1 vs. 340.5 ng/mL, respectively, P = 0.033). The CA/AA-type of ABCG2 C421A polymorphism may be associated with lower gefitinib plasma concentrations.

We isolated the Cobetia sp. strains IU 180733JP01 (5-11-6-3) and 190790JP01 (5-25-4-2) from seaweeds and showed that both strains accumulate poly(3-hydroxybutyrate) [P(3HB)] homopolymer in a nitrogen-limiting mineral salt medium containing alginate as a sole carbon source. Genome sequence analysis of the isolated strains showed that they have putative genes which encode enzymes relevant to alginate assimilation and P(3HB) synthesis, and the putative alginate-assimilating genes formed a cluster. Investigation of the optimum culture conditions for high accumulation of P(3HB) showed that when the 5-11-6-3 strain was cultured in a nitrogen-limiting mineral salt medium (pH 5.0) containing 6% NaCl and 3% (w/v) alginate as a sole carbon source for 2 days, the P(3HB) content and P(3HB) production reached 62.1 ± 3.4 wt% and 3.11 ± 0.16 g/L, respectively. When the 5-25-4-2 strain was cultured in a nitrogen-limiting mineral salt medium (pH 4.0) containing 5% NaCl and 3% (w/v) alginate for 2 days, the P(3HB) content and P(3HB) production reached 56.9 ± 2.1 wt% and 2.67 ± 0.11 g/L, respectively. Moreover, the 5-11-6-3 strain also produced P(3HB) in a nitrogen-limiting mineral salt medium (pH 5.0) containing 6% NaCl and freeze-dried and crushed waste Laminaria sp., which is classified into brown algae and contains alginate abundantly. The resulting P(3HB) content and P(3HB) productivity were 13.5 ± 0.13 wt% and 3.99 ± 0.15 mg/L/h, respectively. Thus, we demonstrated the potential application of the isolated strains to a simple P(3HB) production process from seaweeds without chemical hydrolysis and enzymatic saccharification., (Copyright © 2020 Moriya, Takita, Matsumoto, Yamahata, Nishimukai, Miyazaki, Shimoi, Kawai and Yamada.)

Context: Mindfulness-based interventions have been receiving growing attention in cancer care., Objectives: The purpose of this randomized controlled trial is to examine the effectiveness of mindfulness-based cognitive therapy (MBCT) for psychological distress (anxiety and depression), fear of cancer recurrence (FCR), fatigue, spiritual well-being, and quality of life (QOL) in Japanese ambulatory patients with Stage I-III breast cancer., Methods: A total of 74 patients were randomly assigned to either an eight-week MBCT intervention group (n = 38) or a wait-list control group (n = 36). The primary outcome was psychological distress, measured on Hospital Anxiety and Depression Scale. The secondary outcomes were FCR (Concerns About Recurrence Scale-overall anxiety subscale), fatigue (Brief Fatigue Inventory), spiritual well-being (Functional Assessment of Chronic Illness Therapy-Spiritual), QOL (Functional Assessment of Cancer Therapy-General), and mindfulness skills (Five Facet Mindfulness Questionnaire). The participants were assessed at baseline (T0), Week 8 (T1), and Week 12 (T2). The results were analyzed using a intention-to-treat linear mixed model., Results: The participants in the MBCT group experienced significantly better outcomes in their psychological distress (Cohen's d = 1.17; P < 0.001), FCR (d = 0.43; P < 0.05), fatigue (d = 0.66; P < 0.01), spiritual well-being (d = 0.98; P < 0.001), and QOL (d = 0.79; P < 0.001) compared with the control group. The difference remained significant at T2 (four weeks after completion of the intervention)., Conclusion: MBCT was demonstrated to improve well-being that encompasses psychological, physical, and spiritual domains in Japanese patients with nonmetastatic breast cancer. The favorable effect was maintained up to four weeks after the completion of the intervention., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Aim: To compare nasal glucagon (NG) with intramuscular glucagon (IMG) for the treatment of insulin-induced hypoglycaemia in Japanese patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM)., Materials and Methods: This phase 3, randomized, open-label, two-treatment, two-period crossover non-inferiority study enrolled Japanese adults with T1DM or T2DM on insulin therapy, with glycated haemoglobin levels ≤86 mmol/mol (≤10%). After ≥8 hours of fasting, hypoglycaemia was induced with human regular insulin (intravenous infusion). Patients received NG 3 mg or IMG 1 mg approximately 5 minutes after insulin termination. The primary endpoint was the proportion of patients achieving treatment success [plasma glucose (PG) increase to ≥3.9 mmol/L (≥70 mg/dL) or ≥1.1 mmol/L (≥20 mg/dL) increase from the PG nadir within 30 minutes of receiving glucagon]. Non-inferiority was declared if the upper limit of the two-sided 95% confidence interval (CI) of the mean difference in the percentage of patients achieving treatment success (IMG minus NG) was <10%., Results: Seventy-five patients with T1DM (n = 34) or T2DM (n = 41) were enrolled; 72 patients (50 men, 22 women) received ≥1 study drug dose (T1DM, n = 33; T2DM, n = 39). Sixty-eight patients completed the study and were evaluable. All NG- and IMG-treated patients achieved treatment success (treatment arm difference: 0%; upper limit of two-sided 95% CI 1.47%); NG met prespecified conditions defining non-inferiority versus IMG. Glucagon was rapidly absorbed after both nasal and intramuscular administration; PG profiles were similar between administration routes during the first 60 minutes post dose. Study drug-related treatment-emergent adverse events affecting >2 patients were rhinalgia, increased blood pressure, nausea, ear pain and vomiting in the NG group, and nausea and vomiting in the IMG group., Conclusion: Nasal glucagon was non-inferior to IMG for successful treatment of insulin-induced hypoglycaemia in Japanese patients with T1DM/T2DM, supporting use of NG as a rescue treatment for severe hypoglycaemia., (© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Introduction: Glucagon is the only approved medicine for severe hypoglycemia available for caregivers of people with diabetes. Nasal glucagon (NG) was recently approved in the USA as a needle-free, ready-to-use alternative to injectable glucagon. This simulated user experience study in Japan compared NG and intramuscular glucagon (IMG) administration by caregivers, and NG administration by untrained third parties., Methods: This was an open-label, single-center, partially randomized crossover, simulated user experience trial conducted in Japan (October 2018 to December 2018). Caregivers who live with and care for a relative with diabetes were randomized (1:1, stratified by patient diabetes type 1 or 2) to one of two simulated administration sequences (group 1: NG then IMG; group 2: IMG then NG). Caregivers received training on each device 2 weeks before simulated administration of the device. Third parties received no training and only conducted simulated NG administration. Outcome measures included the percentage of successful administrations (based on critical step completion and dose; primary outcome), time to complete administration, and user satisfaction/preferences., Results: In caregivers (N = 19), the percentage of successful administrations was greater (89.5% vs 26.3%, P < 0.001) and mean time to complete administration was shorter (23.9 vs 207.3 s, P < 0.001) with NG than with IMG. In third parties (N = 20), 95% of NG administration attempts were successful (mean time to complete administration, 55.5 s). All caregivers and 80% of third parties reported that the NG device was easy to use. All caregivers and 70% of third parties were confident and willing to use the device in a real emergency, and more than 80% of caregivers preferred the NG device to IMG., Conclusion: This simulated user experience study confirmed that glucagon administration using a nasal delivery device was quicker, easier, and had a higher success rate than intramuscular administration in Japan, where the glucagon injection kit is not available., Funding: Eli Lilly. Plain language summary available for this article.

Apple is an economically important crop, and various approaches to genetic analysis in breeding programs have been attempted, including the production of doubled haploid (DH) lines, which are genetically homozygous. In this study, we used a DH line for QTL analyses, for the first time in a fruit tree, expecting it to simplify the analysis of the inheritance of quantitative traits and thus to enhance QTL detection power. Using an F 1 population from 'Prima' × 'Apple Chukanbohon 95P6' (DH), we constructed a genetic map of 'Prima', and identified 19 QTLs for 13 traits. These QTLs had comparatively high LOD scores and explained a large part of the variation of the phenotypes. In particular, acidity, juice browning, and skin splitting clearly segregated at a 1:1 ratio, consistent with the segregation of the alleles at the detected QTLs in linkage group 16; these traits appeared to be regulated by single genes, despite general consideration that they are quantitative traits. Using this simple genetic composition of the F 1 population, we concluded that the skin splitting of apple fruit has recessive inheritance, and that the allele for splitting is tightly linked with those for high acidity and low juice browning in 'Prima'., (Copyright © 2019 by JAPANESE SOCIETY OF BREEDING.)

Background: Inhibition of cholesteryl ester transfer protein by evacetrapib when added to atorvastatin may provide an additional treatment option for patients who do not reach their low-density lipoprotein cholesterol (LDL-C) goal.Methods and Results:This multicenter, randomized, 12-week, double-blind, parallel-group, placebo-controlled, outpatient, phase 3 study evaluated the efficacy of evacetrapib with atorvastatin in reducing LDL-C in 149 Japanese patients (evacetrapib/atorvastatin, n=53; ezetimibe/atorvastatin, n=50; placebo/atorvastatin, n=46) with primary hypercholesterolemia. The primary efficacy measure was percent change from baseline to week 12 in LDL-C (β quantification). Treatment with evacetrapib 130 mg daily for 12 weeks resulted in a statistically significant treatment difference of -25.70% compared with placebo in percentage decrease in LDL-C (95% CI: -34.73 to -16.68; P<0.001). Treatment with evacetrapib 130 mg also resulted in a statistically significant difference of 126.39% in the change in high-density lipoprotein cholesterol (HDL-C) compared with placebo (95% CI: 113.54-139.24; P<0.001). No deaths or serious adverse events were reported. Four patients (3 in the evacetrapib group and 1 in the ezetimibe group) discontinued due to adverse events., Conclusions: Evacetrapib daily in combination with atorvastatin was superior to placebo in lowering LDL-C after 12 weeks, and resulted in a statistically significant increase of HDL-C compared with placebo. Also, no new safety risks were identified.

Background: Inhibition of cholesteryl ester transfer protein with evacetrapib may provide an additional treatment option for patients who do not reach their low-density lipoprotein cholesterol (LDL-C) goal with statins or patients who cannot tolerate statins.Methods and Results:This multicenter, randomized, 12-week, double-blind, parallel group, placebo-controlled, outpatient, phase 3 study evaluated the efficacy of evacetrapib in reducing LDL-C in 54 Japanese patients (27 evacetrapib, 27 placebo) with primary hypercholesterolemia. Primary efficacy measure was the percent change from baseline to week 12 in LDL-C (β quantification). Treatment with evacetrapib 130 mg once daily for 12 weeks resulted in statistically significant (P<0.001) change in LDL-C (β quantification) compared with placebo. Least-squares mean percentage changes from baseline were -34.3% in the evacetrapib group vs. 0.0% in the placebo group. Treatment with evacetrapib 130 mg also resulted in a statistically significant (P<0.001) increase in high-density lipoprotein cholesterol compared with placebo in mean percent change from baseline, with a least-squares mean difference of 124.0% (95% confidence interval: 104.6-143.5). No deaths, serious adverse events, or discontinuations because of adverse events were reported; 5 patients (18.5%) in the evacetrapib group and 7 patients (26.9%) in the placebo group experienced treatment-emergent adverse events., Conclusions: Once-daily evacetrapib 130 mg monotherapy was superior to placebo in lowering LDL-C after 12 weeks. No new safety risks were identified.

Objectives: To evaluate the safety and efficacy of tadalafil plus α 1 -blocker combination therapy in Japanese patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia., Methods: The present multicenter, randomized, double-blind, placebo-controlled, two-period cross-over study compared the effects of tadalafil and a placebo added to ongoing α 1 -blocker therapy. A total of 171 Japanese patients were randomized., Results: Tadalafil combined with an α 1 -blocker did not decrease blood pressure in the orthostatic test. The only statistically significant differences in vital signs between the combination and monotherapy groups were diastolic blood pressure and pulse (P = 0.0194 and 0.0313, respectively). However, these changes were not considered clinically meaningful. Treatment-related adverse events occurred in 28.1% (47/167) and 24.2% (39/161) of patients in the combination therapy and α 1 -blocker monotherapy groups, respectively. Additionally, 56.7% (89/157) of patients preferred combination therapy to monotherapy, though this was not statistically significant (P = 0.0937). There was a statistically significant reduction in the International Prostate Symptom Score voiding subscore in the combination therapy group (P = 0.0442)., Conclusions: Concurrent treatment with tadalafil and an α 1 -blocker seems to be safe and well tolerated in Japanese patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Adding tadalafil to baseline α 1 -blocker therapy does not translate in adverse effects on the blood pressure. Patients tend to prefer combination therapy over monotherapy, and there seems to be a clinical benefit when using combination therapy., (© 2017 The Japanese Urological Association.)

Objective: To assess efficacy and safety of tadalafil in men aged ≥75 years with lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) and additional safety in men aged ≥75 years with erectile dysfunction (ED)., Patients and Methods: We conducted an integrated analysis of 12 phase II-III randomized, double-blind and/or open-label extension studies to evaluate short-term (12-26 weeks) efficacy and short- and longer-term (42-52 weeks) safety in men aged <75 years vs men aged ≥75 years. All men received once-daily tadalafil 5 mg or placebo. The efficacy outcome was International Prostate Symptom Score (IPSS). Safety measurements included treatment-emergent adverse events (TEAEs), adverse events (AEs) leading to discontinuation, serious AEs (SAEs), and cardiovascular AEs. All analyses were intention-to-treat. Changes from baseline to efficacy endpoint and differences in changes between treatment groups were estimated as least-squares means using analysis of covariance models., Results: Change in the mean IPSS was significantly different in men aged <75 years vs those aged ≥75 years across tadalafil and placebo groups (treatment-by-age interaction P = 0.034). Tadalafil was not statistically significantly better than placebo in men aged ≥75 years, but effect size varied between studies. Maintenance of efficacy with tadalafil was observed across age groups. Short-term tadalafil safety findings for men aged <75 vs ≥75 years included: TEAEs (52 [33.8%] vs 503 [30.1%]), AEs leading to discontinuation (3 [1.9%] vs 50 [3.0%]), SAEs (4 [2.6%] vs 15 [0.9%]) and cardiovascular AEs (4 [2.6%] vs 30 [1.8%]). Long-term tadalafil safety data did not reveal clinically relevant differences between age groups. Limitations include exclusion of men with serious co-existing conditions and limited sample sizes of men aged ≥75 years., Conclusions: Efficacy with once-daily tadalafil 5 mg in the treatment of LUTS/BPH differed between men aged <75 vs ≥75 years, with significant efficacy in the <75-year age group. The older age group had more concomitant diseases and used more drugs, which may have reduced efficacy. The small sample size precluded uni-/multivariate analyses to assess plausible interference from confounding factors. Tadalafil had a reassuring safety profile and no evidence of increased cardiovascular AEs in aging men., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Objective: To assess the efficacy and safety of tabalumab, an anti-B cell activating factor (BAFF) antibody, in combination with standard of care (SoC) therapy in Japanese patients with active systemic lupus erythematosus (SLE)., Methods: A subgroup analysis was conducted in Japanese patients (n = 45) enrolled in ILLUMINATE-1, a phase III global trial in SLE patients (N = 1164). Patients received SoC plus tabalumab or placebo, starting with a loading dose (240 mg) at week 0, followed by 120 mg every 4 weeks (120 Q4W, n = 15), 120 mg every 2 weeks (120 Q2W, n = 15), or placebo Q2W (n = 15). The primary endpoint was proportion achieving SLE Responder Index-5 (SRI-5) improvement at week 52., Results: A numerically greater SRI-5 response rate was achieved with 120 Q2W (46.7%; p = 0.059 vs. placebo) compared with 120 Q4W (20.0%) and placebo Q2W (13.3%). The proportion of patients with severe SLE flare was lower for 120 Q2W (0%) and 120 Q4W (6.7%) than for placebo (26.7%). The rates of serious adverse events (AEs) and treatment-emergent AEs were similar across treatments., Conclusion: In Japanese SLE patients, tabalumab 120 Q2W improved SRI-5 response rate and reduced the frequency of severe flares compared with placebo. Safety profiles were similar with tabalumab and placebo.

Objective: The efficacy and safety of atomoxetine was assessed in adult ADHD patients from Japan, Korea, and Taiwan in this first placebo-controlled Asian clinical study in adults of an ADHD medication., Method: Atomoxetine was compared with placebo (195 atomoxetine, 196 placebo) over 10 weeks. The change from baseline to endpoint and changes over time in the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version total score (CAARS-Inv: SV total score) were assessed along with changes in quality of life (QoL) and executive function., Results: Atomoxetine treatment resulted in a mean reduction of -14.3 (placebo, -8.8) in CAARS-Inv: SV total score and a steady increase of between-group differences from Week 2. Improvements in QoL and executive functioning were also observed. Treatment-emergent adverse events leading to discontinuation were infrequent (atomoxetine: 5.2%, placebo: 1.5%)., Conclusion: Atomoxetine was tolerable and effective in improving QoL and executive function as well as ameliorating core ADHD symptoms in adult Asian patients.

Background: High-dose use of benzodiazepines (BZPs) reportedly causes adverse effects on cognitive function and quality of life in patients with schizophrenia. However, effects of BZPs on the clinical course of schizophrenia have not been clarified. This study was set out to investigate the association between BZPs and rehospitalization of patients with schizophrenia., Methods: In this retrospective study, patients with schizophrenia who were discharged from Tokyo Medical University Hospital between January 2009 and February 2012 were eligible as subjects. One hundred and eight patients who continued treatment for >2 years after hospital discharge were included in this study. Clinical characteristics, doses of prescribed medication such as BZPs and antipsychotics, and Global Assessment of Functioning scores at discharge were investigated. The primary outcome was rehospitalization of patients for any reason., Results: In a total of 108 subjects with schizophrenia, 44 subjects (40.7%) experienced rehospitalization during the 2-year study period. A multivariate analysis by the Cox proportional hazards model revealed that low educational history (hazard ratio =2.43, P =0.032), younger onset age of schizophrenia (hazard ratio =2.10, P =0.021), and higher diazepam-equivalent dose (hazard ratio =6.53, P =0.011) were significantly associated with the time to rehospitalization after hospital discharge., Conclusion: The results of this study suggest that high-dose use of BZPs at discharge in patients with schizophrenia might be associated with a shorter time to rehospitalization., Competing Interests: Yoshikazu Takaesu has received lecture fees from Otsuka Pharmaceutical, Meiji Seika Pharma, Eli Lilly, Eisai, Mitsubishi Tanabe Pharma, and Yoshitomi Pharmaceutical and has received research funding from Otsuka Pharmaceutical, Meiji Seika Pharma, and Eisai. Yuichi Inoue has received clinically pertinent fees, lecture fees, and research funding from Nippon Boehringer Ingelheim, Takeda Pharmaceutical, Astellas Pharma, Philips Respironics, Alfresa Pharma, MSD, Pacific Medico, Otsuka Pharmaceutical, Eisai, Yoshitomiyakuhin, and Hisamitsu Pharmaceutical. Takeshi Inoue has received honoraria from GlaxoSmithKline, Pfizer, Eli Lilly, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Otsuka Pharmaceutical, Meiji Seika Pharma, Asahi Kasei Pharma, Shionogi, Dainippon Sumitomo Pharma, Takeda Pharmaceutical, MSD, Eisai, AbbVie GK, and Yoshitomiyakuhin; he has received research/grant support from Otsuka Pharmaceutical, Eli Lilly, Eisai, Mitsubishi Tanabe Pharma, Yoshitomiyakuhin, AbbVie GK, Pfizer, Astellas, MSD, and Meiji Seika Pharma; he is a member of the advisory boards of GlaxoSmithKline, Pfizer, Eli Lilly, Mochida Pharmaceutical, and Mitsubishi Tanabe Pharma. The authors report no other conflicts of interest in this work.

Aims: To examine the efficacy and safety of once-weekly dulaglutide 0.75 mg monotherapy compared with once-daily liraglutide 0.9 mg in Japanese patients with type 2 diabetes (T2D) for 52 weeks., Methods: We conducted a phase III, randomized, 52-week (26-week primary endpoint), active- and placebo-controlled trial comparing 492 Japanese patients (dulaglutide, n = 281; liraglutide, n = 141; and placebo, n = 70). Participants and investigators were blinded to treatment assignment for dulaglutide and placebo but not for liraglutide (open-label comparator); after 26 weeks, patients randomized to placebo were switched to once-weekly dulaglutide 0.75 mg (open-label). The present paper reports results for patients treated with dulaglutide and patients treated with liraglutide for 52 weeks., Results: At week 52, dulaglutide decreased HbA1c significantly from baseline compared with liraglutide [least squares mean difference: -0.20; 95% confidence interval (CI) -0.39, -0.01; p = 0.04]. At week 52 (last observation carried forward), dulaglutide significantly decreased pre- and post-dinner blood glucose (BG) levels, the mean of seven-point self-monitored BG profiles, the mean of all postprandial BG levels and circadian variation compared with liraglutide. Body weight was generally stable in both groups through 52 weeks. The most frequently reported adverse events were nasopharyngitis, constipation, nausea and diarrhoea. Eight dulaglutide-treated (2.9%) and four liraglutide-treated (2.9%) patients reported hypoglycaemia, with no event being severe., Conclusions: Monotherapy with once-weekly dulaglutide 0.75 mg was effective and safe in Japanese patients with T2D, with better glycaemic control compared with once-daily liraglutide 0.9 mg., (© 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To examine the efficacy and safety of once-weekly dulaglutide monotherapy (0.75 mg) compared with placebo and once-daily liraglutide (0.9 mg) in Japanese patients with type 2 diabetes., Methods: This was a phase III, 52-week (26-week primary endpoint), randomized, double-blind, placebo-controlled, open-label comparator (liraglutide) trial comparing 492 Japanese patients with type 2 diabetes (dulaglutide, n = 281; liraglutide, n = 141; and placebo, n = 70) who were aged ≥20 years. Patients and investigators were blinded to treatment assignment for dulaglutide and placebo but not for liraglutide. The primary objective evaluated the superiority of dulaglutide versus placebo on change from baseline in glycated haemoglobin (HbA1c) at 26 weeks. Analyses were performed on the full analysis set., Results: At 26 weeks, once-weekly dulaglutide was superior to placebo and non-inferior to once-daily liraglutide for HbA1c change from baseline [least squares mean difference: dulaglutide vs placebo -1.57% (95% confidence interval -1.79 to -1.35); dulaglutide vs liraglutide -0.10% (95% confidence interval -0.27 to 0.07)]. The most frequently reported adverse events were nasopharyngitis, constipation, diarrhoea, nausea, abdominal distension and decreased appetite; only decreased appetite was different between the dulaglutide and liraglutide groups [dulaglutide, n = 2 (0.7%); liraglutide, n = 8 (5.8%); p = 0.003]. Nine (1.8%) patients experienced hypoglycaemia [dulaglutide, n = 6 (2.1%); liraglutide, n = 2 (1.5%); placebo, n = 1 (1.4%)], with no event being severe., Conclusions: In Japanese patients with type 2 diabetes, once-weekly dulaglutide (0.75 mg) was superior to placebo and non-inferior to once-daily liraglutide (0.9 mg) for reduction in HbA1c at 26 weeks. Dulaglutide was safe and well tolerated., (© 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: The purpose of this study was to evaluate the performance characteristics and safety of florbetapir ((I8)F) positron emission tomography (PET) in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and cognitively normal (CN) control patients from Japan., Methods: Florbetapir ((I8)F) PET was obtained in 48 subjects (15 AD patients, 15 MCI patients, and 18 CNs) within a multicenter phase 2/3 study. Amyloid burden was assessed visually and classified as positive or negative for pathologic levels of amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVRs) were determined from the florbetapir ((I8)F) PET images. Safety was assessed by monitoring adverse events, vital signs, clinical laboratory assessments, and electrocardiograms. Demographic variables and cognitive scales were summarized by using descriptive statistics for each group. Fisher's exact test and one-way analysis of variance were used to compare amyloid positivity and mean SUVRs, respectively, between diagnostic groups., Results: Florbetapir ((I8)F) PET was rated visually amyloid positive in 80.0% of AD patients, 33.3% of MCI patients, and 16.7% of CNs. Mean SUVRs were highest in the AD group and lowest in the CN group for each brain region (P < 0.01) and globally (P < 0.05). Kappa statistics showed strong inter-reader agreement (Fleiss' kappa = 0.82) and individual reader's agreement with the majority of readers (kappa ranged from 0.79 to 1.0). Seventeen of the 48 subjects (35.4%) were Apolipoprotein E genotype ε4 positive, which included 10 subjects in the AD group and 7 subjects in the MCI group. A total of 6 subjects (5 of whom were in the CN group) had at least 1 treatment-emergent adverse event (TEAE)., Conclusions: These data indicate that amyloid positivity increased with diagnostic category (CN < MCI < AD) and are consistent with expected rates of amyloid positivity among individuals with clinical diagnoses of AD and MCI. In addition, these results were similar to those obtained in United States studies. Florbetapir ((18)F) was safe and well tolerated. The reliability of both qualitative and quantitative assessments of florbetapir ((18)F) in this study population provides support for potential use in clinical settings in Japan.

In polymer electrolyte fuel cell (PEFC) systems, small amounts of ammonia (NH3 ) present in the reformate gas deactivate the supported ruthenium catalysts used for preferential oxidation (PROX) of carbon monoxide (CO). In this study, we investigated how the addition of a small amount of platinum to a Ru/α-Al2 O3 catalyst (Pt/Ru=1:9 w/w) affected the catalyst's PROX activity in both the absence and the presence of NH3 (130 ppm) under conditions mimicking the reformate conditions during steam reforming of natural gas. The activity of undoped Ru/α-Al2 O3 decreased sharply upon addition of NH3 , whereas Pt/Ru/α-Al2 O3 exhibited excellent PROX activity even in the presence of NH3 . Ruthenium K-edge X-ray absorption near-edge structure (XANES) spectra indicated that in the presence of NH3 , some of the ruthenium in the undoped catalyst was oxidized in the presence of NH3 , whereas ruthenium oxidation was not observed with Pt/Ru/α-Al2 O3 . These results suggest that ruthenium oxidation is retarded by the platinum, so that the catalyst shows high activity even in the presence of NH3 ., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: This article aims to assess the efficacy and safety of atomoxetine in Korean adults with attention-deficit hyperactivity disorder (ADHD)., Methods: This post hoc double-blind, placebo-controlled study of atomoxetine (40-120 mg/day) over 10 weeks in adults with ADHD at 45 Japanese, Korean, and Taiwanese study sites focused on patient data from Korea (atomoxetine, n = 37; placebo, n = 37). Primary efficacy outcome was change in baseline-to-endpoint Conners' Adult ADHD Rating Scale-Investigator-rated: Screening Version (CAARS-Inv:SV) Total ADHD Symptoms score. Secondary efficacy outcomes included changes in Adult ADHD Quality of Life (AAQoL) total, Behavior Rating Inventory of Executive Function-Adult Version Self-Report (BRIEF-A:Self-Report), and Clinical Global Impression-ADHD-Severity (CGI-ADHD-S) scale scores., Results: Atomoxetine-treated patients demonstrated a mean 18.9-point reduction in CAARS-Inv:SV total ADHD Symptoms score, compared with the 7.45-point reduction in placebo-treated patients (P ≤ 0.01). Significantly greater improvement was found for atomoxetine versus placebo in CGI-ADHD-S (P ≤ 0.01), BRIEF-A:Self-Report global executive composite (P ≤ 0.05), and metacognition index (P ≤ 0.01) executive function scores. Nausea, decreased appetite, and dry mouth were reported with significantly greater frequency by atomoxetine-treated patients, and only one placebo-treated patient discontinued because of adverse event. A 2.1-kg reduction in weight and a 7.5-beat/minute increase in pulse rate were observed in atomoxetine-treated patients., Discussion: These data support a significant benefit of 80- to 120-mg once daily atomoxetine versus placebo for treatment of ADHD in adult Korean patients. A high placebo response rate was observed in this adult Korean sample; a higher discontinuation rate was also observed in atomoxetine-treated patients. These observations warrant further investigation., (© 2014 Wiley Publishing Asia Pty Ltd.)

Introduction: The primary aim of this study was to evaluate the long-term safety/tolerability of atomoxetine in Japanese adults with attention deficit hyperactivity disorder (ADHD)., Methods: This 48-week, open-label extension study involved participants with ADHD who completed a 10-week randomized controlled trial of atomoxetine. Participants received atomoxetine 40 mg/day, followed by step-wise titration to a maximum of 120 mg/day. The primary outcome was safety/tolerability. Secondary outcomes were symptoms of ADHD (Conners' Adult ADHD Rating Scales-Investigator Rated: Screening Version 18-item total score), quality of life (Adult Attention-Deficit/Hyperactivity Disorder Quality of Life scale), and executive function (Behavior Rating Inventory of Executive Function-Adult Version: Self-report)., Results: Of the 39.5% of participants overall who discontinued the study, 15.9% (37/233) of participants discontinued because of adverse events (AEs), primarily nausea (4.3%; 10/233). Overall, 93.6% (218/233) of participants experienced treatment-emergent AEs (TEAEs), most commonly nausea (56.2%; 131/233), nasopharyngitis (25.3%; 59/233), thirst (19.3%; 45/233), headache (17.2%; 40/233), and decreased appetite (16.3%; 38/233). Most TEAEs (70.8%; 165/233) were mild in intensity. Overall, 79.8% (186/233) of participants experienced ≥1 adverse drug reaction, primarily nausea (55.4%; 129/233). Five participants experienced serious AEs during the open-label extension; none was related/possibly related to treatment. There were statistically significant increases in vital signs and decreases in body weight that were not considered clinically significant. Symptoms of ADHD, quality of life, and executive function were significantly improved from baseline to endpoint (P < 0.05)., Discussion: Despite discontinuations due to the long-term, open-label design, AE related discontinuations were modest, suggesting that atomoxetine has acceptable long-term safety and tolerability in Japanese adults with ADHD. Symptoms of ADHD improved and remained improved throughout the study., (© 2013 Wiley Publishing Asia Pty Ltd.)

Introduction: The primary objective of this study was to assess the overall safety and tolerability of atomoxetine in Korean, Chinese, and Taiwanese adults with attention-deficit/hyperactivity disorder (ADHD)., Methods: A total of 44 patients aged ≥18 years who met the Conners' Adult ADHD Diagnostic Interview for DSM-IV diagnostic criteria for ADHD were enrolled from China, Korea, and Taiwan. In this open-label, dose-escalation study, patients received atomoxetine orally once daily over a period of eight weeks, starting at 40 mg/day (one week) up to a maximum dosage of 120 mg/day. Tolerability was evaluated by rate of discontinuation due to adverse events. Safety was assessed by recording all adverse events, laboratory tests, vital signs, and electrocardiograms. ADHD symptoms were evaluated by the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) for efficacy assessment., Results: Thirty-four patients (77.3%) completed the study. Atomoxetine was well tolerated with a discontinuation rate of 2.3% (1/44) due to adverse events. The most commonly reported adverse events were nausea, dizziness, and somnolence. The mean change from baseline to endpoint in CAARS-Inv:SV total ADHD symptom score was -12.5 (P < 0.001). A significant reduction in the CAARS-Inv:SV subscales (inattentive, hyperactive/impulsive, and ADHD index score, P < 0.001) was observed., Discussion: This is the first atomoxetine clinical trial in adult patients with ADHD in China, Korea, and Taiwan. Atomoxetine was well tolerated in doses of up to 120 mg/day with no unknown safety concerns., (Copyright © 2012 Blackwell Publishing Asia Pty Ltd.)

Collective Thomson scattering (CTS) diagnostic requires a strong probing beam to diagnose a bulk and fast ion distribution function in fusion plasmas. A mega-watt gyrotron for electron cyclotron resonance heating is used as a probing beam in the large helical device. Spurious mode oscillations are often observed during the turning on/off phase of the modulation. The frequency spectra of the 77-GHz gyrotron output power have been measured, and then one of the spurious modes, which interferes with the CTS receiver system, is identified as the TE(17,6) mode at the frequency of 74.7 GHz. The mode competition calculation indicates that the increase of the magnetic field strength at the gyrotron resonator can avoid such a spurious mode and excite only the main TE(18,6) mode. The spurious radiation at the 74.7 GHz is experimentally demonstrated to be suppressed in the stronger magnetic field than that optimized for the high-power operation.

Objective: To assess the safety and efficacy of 18-week olanzapine monotherapy in Japanese patients with bipolar mania, following a 6-week, placebo- and haloperidol-controlled double-blind study (acute study). For those who discontinued the acute study due to lack of efficacy, safety and efficacy was assessed with a combination therapy of olanzapine and a mood stabilizer., Research Design and Methods: In this open-label, multicenter extension study, patients who completed the acute study received olanzapine (5-20 mg/day) as monotherapy, and patients who discontinued the acute study due to lack of efficacy with greater Young Mania Rating Scale (YMRS) total score than the acute study baseline, received olanzapine in combination with one of three mood stabilizers: lithium, carbamazepine, or valproate. Safety was assessed by treatment-emergent adverse events (TEAEs), vital signs, weight, and extrapyramidal symptoms (EPSs). Efficacy measures included YMRS total score, and response and remission rates of manic symptoms., Main Outcome and Measures: There were no deaths or serious adverse events considered potentially related to olanzapine in the monotherapy group (N = 100) or the combination-therapy group (N = 39). TEAEs occurred in 59.0% and 79.5% of patients in the monotherapy and combination-therapy groups, respectively, and their severities were mostly mild or moderate. Regarding the efficacy measures, in the monotherapy group, mean YMRS change from extension study baseline to endpoint was -3.0, and the response and remission rates at endpoint were 97.0% and 93.0%, respectively. In the combination-therapy group, mean YMRS change from extension-study baseline was -19.8; response and remission rates increased from the extension-study baseline (both 0.0%) to 64.1% and 61.5% respectively by endpoint., Conclusion: Olanzapine was generally well tolerated during the 18-week extension period in Japanese patients with bipolar mania. Results of both groups were also generally consistent with US and European studies. Monitoring of metabolic parameters is recommended.

Background: No current data were available regarding the efficacy and safety of olanzapine in Japanese patients with bipolar I disorder with a current manic/mixed episode., Methods: Patients received blindly olanzapine (5-20 mg/day; N=105), haloperidol (2.5-10 mg/day; N=20), or placebo (N=99) for 3 weeks. For the following 3 weeks, the olanzapine and haloperidol groups continued their treatment, while the placebo group switched blindly to olanzapine. The primary efficacy measure was the mean change in Young Mania Rating Scale (YMRS) total score; secondary efficacy measures included bipolar disorder remission rate and switch-to depression. Safety measures included treatment-emergent adverse events (TEAEs), weight and extrapyramidal symptoms (EPSs)., Results: YMRS total score significantly decreased in the olanzapine group compared with the placebo group (-5.62 [95% CI: -8.87, -2.37], p<0.001) after 3 weeks. Compared with haloperidol, olanzapine was not markedly different in improving overall bipolar symptomatology, and fewer olanzapine-treated patients switched to symptomatic depression (2.4% vs 16.7%, p=0.014). Overall incidences of TEAEs were not significantly different among the groups, and EPSs in olanzapine group were less severe than in the haloperidol group., Limitations: The small haloperidol sample size limited the conclusions that can be drawn from the statistical comparisons between the active treatments., Conclusions: This was the first study to evaluate an atypical antipsychotic in Japanese patients with manic bipolar I disorder. Consistent with previous non-Japanese studies, olanzapine was generally well-tolerated and superior to placebo in improving the severity of manic symptoms. Compared to haloperidol, fewer olanzapine-treated patients switched to symptomatic depression, and EPSs were less severe., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Aims: The main purpose of this first atomoxetine study in Japanese adults with attention-deficit/hyperactivity disorder (ADHD) was to investigate the tolerability of an 8-week treatment regimen., Methods: This was an open-label, dose escalation study conducted in 45 Japanese patients aged at least 18 years with DSM-IV-defined ADHD. Patients received atomoxetine orally for 8 weeks. Atomoxetine administration was started at 40 mg/day (7 days), and subsequently increased to a maximum dose of 120 mg/day. Tolerability was assessed by discontinuation rate due to adverse events. Adverse events, laboratory tests, vital signs and electrocardiograms were collected. In addition, ADHD symptoms were assessed by using the Japanese version of the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) scores., Results: Thirty-nine patients completed the study period. Atomoxetine was well tolerated with a 6.7% (3/45) discontinuation rate due to nausea, malaise and anorexia. The most commonly reported adverse events were nausea, nasopharyngitis and headache; there were no unexpected safety concerns. No deaths or serious adverse events were reported. Mean CAARS-Inv:SV-J total ADHD symptom scores decreased in a time-dependent manner; the mean change from baseline to endpoint was -15.0 (P<0.001)., Conclusions: This study showed that atomoxetine was well tolerated in these patients and suggested that atomoxetine at a maximum dose of 120 mg/day would be safe in Japanese ADHD patients., (© 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.)

Hepatocellular carcinoma with metastases to lymph nodes and adrenal glands was found in a 26-year-old male Hokkaido brown bear (Ursus arctos yesoensis). Left hepatic lobe was largely replaced by well-differentiated neoplastic cells, whereas poorly differentiated tumor cells had proliferated in part of the left hepatic lobe, in scattered nodules in the remaining liver tissue, and at the metastatic sites. Immunoreactivity for hepatocyte antigen (hepatocyte paraffin 1 antibody) and alpha-fetoprotein was observed in both well- and poorly differentiated neoplastic cells in the liver and metastatic foci. To our knowledge, this case is the first report of hepatocellular carcinoma in brown bears.

Objectives: Until the recent approval of methylphenidate (MPH), Japan had no approved treatment for attention-deficit/hyperactivity disorder (ADHD). The need still exists for an effective, safe, nonstimulant treatment. This first placebo-controlled Japan study of an ADHD nonstimulant therapy assessed atomoxetine efficacy and safety to determine the optimal dose for controlling ADHD symptoms in children and adolescents., Methods: A total of 245 Japanese children and adolescents, aged 6-17 years and diagnosed with ADHD, were randomly assigned to receive placebo or one of three atomoxetine doses (0.5, 1.2, and 1.8 mg/kg per day) over 8 weeks. Symptoms were assessed with the Japanese Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator scored and integrated with teacher reports (ADHD RS-IV-J:I/Sch). Adverse events, vital signs, laboratory tests, and electrocardiograms (ECGs) were obtained for safety analysis., Results: In all, 234 patients completed the study. Atomoxetine at 1.8 mg/kg per day was significantly superior to placebo in reducing ADHD symptoms (p = 0.01; one-sided). Decreased appetite and vomiting were significantly greater in the atomoxetine treatment groups; however, no clinically significant differences were observed. Two patients discontinued due to affect lability and headache. A linear dose-response and vital signs similar to those from other atomoxetine studies were observed., Conclusion: Atomoxetine provides an effective and safe nonstimulant option for the treatment of Japanese pediatric patients with ADHD.

SF(6) was selectively hydrolyzed to SO(3) over rare earth (RE) phosphates above 800 K. CePO(4) was the most active catalyst, followed by GdPO(4), YbPO(4), DyPO(4), ErPO(4), SmPO(4), PrPO(4), TbPO(4), NdPO(4), and LaPO(4). The middle RE phosphates were found to be more active than the light RE phosphates, but the reason for the high activity of CePO(4), which belongs to the light RE group, is not clear. The catalytic activity was independent of the specific surface area (SSA), acid amount, and acid concentration of the catalysts. RE phosphates were single-phase, and a broad inversely proportional relation was observed between the crystallite size and SSA, except in the case of CePO(4). The combination of highly active AlPO(4) and CePO(4) creates synergetic effects in the catalytic activity and SO(3) selectivity over all ranges of composition. Binary catalysts were a mixture of small crystalline AlPO(4) and CePO(4). The addition of Ce promoted the crystallization of AlPO(4), which was controlled to about 10 nm at 10-50% Ce content. The turnover frequency for SF(6) decomposition was proportional to the surface concentration of hydroxyls of binary catalysts. Therefore, synergy effects may come from the number of hydroxyl (OH) pair sites on which a bidentate intermediate of hydrolysis of SF(6) may be formed by the moderate crystallization of AlPO(4). The addition of Ce, Pr, or Y to AlPO(4) brings about a small promotion effect for SF(6) decomposition, but the addition of La, Nd > Gd > Yb diminishes the activity. The addition of Gd, Pr, or Nd greatly improved the SO(3) selectivity. A linear relationship between catalytic activity and the concentration of surface hydroxyls of the catalysts supports a reaction mechanism in which two F atoms of an SF(6) molecule interact with two surface hydroxyls to form a bidentate intermediate.

Addition of medical ingredients to cosmetics is prohibited. However, last year some cases of illegal cosmetics containing steroids were successfully identified. We have already reported an analytical method to detect steroids in cosmetics [Bull. Natl. Inst. Health Sci, 126, 51-56 (2008)]. In this study, we initially examined whether this method could be applied for the detection of some new steroids as target chemicals. We then used this developed method to detect steroids in cosmetics obtained from manufacturers by spot checks. These manufacturers have been advertising the effectiveness of a steroid-free cream against atopic dermatitis. The results revealed that clobetasol propionate (CP) was present in this facial moisturizing cream, which was available in the market. The steroid was extracted with methanol. After ultrasonication and centrifugation, the resulting supernatant was injected into the high-performance liquid chromatography system equipped with an ODS column. The separation was achieved using a mixture of acetonitrile and water as the mobile phase. The retention times of the observed peaks were in accordance with those of some preservatives and CP. The presence of CP was also confirmed by thin-layer chromatography. The concentration of CP in the cream was approximately 0.039%. CP is a steroid that has the strongest effect as compared to those of other steroids. The cream was therefore recalled for safety reasons.

Millimeter-wave components were re-examined for high power (Mega-Watt) and steady-state (greater than one hour) operation. Some millimeter-wave components, including waveguide joints, vacuum pumping sections, power monitors, sliding waveguides, and injection windows, have been improved for high power CW (Continuous Waves) transmission. To improve transmission efficiency, information about the wave phase and mode content of high power millimeter-waves propagating in corrugated waveguides, which are difficult to measure directly, were obtained by a newly developed method based on retrieved phase information. To optimize the plasma heating efficiency, a proof-of-principle study of the injection polarization feedback control was performed in the low power test stand.

ORP150 is a hypoxic stress-induced protein located in the endoplasmic reticulum. Transgenic mice overexpressing ORP150 (ORP-Tg) exhibit vacuolar degeneration in the heart. To determine whether vacuolization is present in skeletal muscle, we pathologically examined ORP-Tg mice. After 60 days of age, severe vacuolization was found in the soleus muscles of the hind legs of the ORP-Tg mice. Immunohistochemical staining of ORP150 revealed co-localization of ORP150 and vacuolization in the affected cells. Electron microscopy revealed a marked increase in the number of rough-surfaced endoplasmic reticula (rER) and distention of the cisterna. These findings suggest that overexpression of ORP150 causes accumulation of ORP150 in the rER, resulting in vacuolar degeneration in the skeletal muscle of ORP-Tg mice.

We describe a case of purpura fulminans due to septicemia after artificial abortion. Our patient suffered purpuric progressive skin necrosis on the back, extremities and buttock. Rhabdomyolysis involvement was confirmed by high level of creatinine phosphokinase and appearance of much brownish discharge from necrotic gluteal muscle and latissimus dorsi muscle. Amputation of both feet and second, third, fourth and fifth fingers of the right hand was performed. The buttock lesion was reconstructed with the posterolateral thigh V-Y flap after debridement. Other lesions were covered with split-thickness skin grafts.

Hypertrophic pyloric stenosis (HPS) is the principal disease to consider in neonates presenting with frequent projectile vomiting and poor weight gain. Ramstedt pyloromyotomy is commonly used for the surgical treatment of HPS. The present study investigated the efficacy of nonsurgical medical treatment using intravenous administration of atropine and the examined the clinical course and results of ultrasonography and a contrast upper gastrointestinal series. A 34-day-old girl was admitted with chief complaints of projectile vomiting and poor weight gain. HPS was diagnosed on the basis of the clinical course and results of imaging studies. After intravenous administration of atropine, projectile vomiting resolved and weight increased without complications. On imaging studies, barium introduced into the stomach by tube rapidly entered the duodenum after atropine administration. Ultrasonography initially showed no reductions in hypertrophic muscle in the pyloric region, but gradual reductions were identified in subsequent months.

A 6-year-old boy was hospitalized because of dark feces and facial pallor of 1 weeks duration. Other gastrointestinal symptoms, including vomiting and abdominal pain, were absent, but he felt dizziness when standing and fatigue on effort. Hematologic studies revealed iron-deficiency anemia, and endoscopy showed gastric erosions and a duodenal ulcer. All test results for Helicobacter pylori infection, including H. pylori antigen in stool, anti-H. pylori IgG immunoassay in serum, and the (13)C-urea breath test, were positive. Because an H. pylori-associated gastric ulcer had been diagnosed with endoscopy in the patients father 3 years earlier, father-son transmission was suspected. The patient was treated with triple-agent eradication therapy (proton pump inhibitor [lansoprazol], amoxicillin, and clarithromycin) for 2 weeks. One month after therapy was completed, eradication of H. pylori was confirmed by negative results on the stool antigen test. Peptic ulcer disease can occur in young children, as in this case. The stool antigen test kit is a useful and reliable method that can be used even in preschool children to diagnose H. pylori infection.

Carotenemia is characterized by an abnormal yellowish orange pigmentation of the skin, most prominently seen on the palms and soles. Although it is associated with several disease such as diabetes, hypothyroidism and anorexia nervosa, it is caused by excessive intake of carotene-rich food such as oranges and carrots in most cases. Herein, we describe an interesting case of carotenemia in a 66-year-old female secondary to increased ingestion of oral supplements of carotene in order to improve hemorrhage in the eyeground. There could be an increasing trend of intake of commercial nutrient supplements in which case it is necessary to remind ourselves that commercial nutrient supplements could cause various skin disorders as side-effects.