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Introduction: Data are lacking on the extent to which patients with non-valvular atrial fibrillation (AF) who are aged ≥80 years benefit from ablation treatment. The question pertains especially to patients' postablation quality of life (QoL) and long-term clinical outcomes., Methods and Analysis: We are initiating a prospective, registry-based, multicentre observational study that will include patients aged ≥80 years with non-valvular AF who choose to undergo treatment by catheter ablation and, for comparison, such patients who do not choose to undergo ablation (either according to their physician's advice or their own preference). Study subjects are to be enrolled from 52 participant hospitals and three clinics located throughout Japan from 1 June 2022 to 31 December 2023, and each will be followed up for 1 year. The planned sample size is 660, comprising 220 ablation group patients and 440 non-ablation group patients. The primary endpoint will be the composite incidence of stroke/transient ischaemic attack (TIA) or systemic embolism (SE), another cardiovascular event, major bleeding and/or death from any cause. Other clinical events such as postablation AF recurrence, a fall or bone fracture will be recorded. We will collect standard clinical background information plus each patient's Clinical Frailty Scale score, AF-related symptoms, QoL (Five-Level Version of EQ-5D) scores, Mini-Mental State Examination (optional) score and laboratory test results, including measures of nutritional status, on entry into the study and 1 year later, and serial changes in symptoms and QoL will also be secondary endpoints. Propensity score matching will be performed to account for covariates that could affect study results., Ethics and Dissemination: The study conforms to the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies issued by the Ministry of Health, Labour and Welfare, Japan. Results of the study will be published in one or more peer-reviewed journals., Trial Registration Number: UMIN000047023., Competing Interests: Competing interests: The following authors have potential conflicts of interest: YO received research funding from Bayer Healthcare, Daiichi-Sankyo, Bristol-Meyers Squibb, Nippon Boehringer Ingelheim, Pfizer and Boston Scientific Japan, and accepted remuneration from Bayer Healthcare, Daiichi-Sankyo and Bristol-Meyers Squibb. KNas accepted remuneration from Johnson & Johnson K.K. TK received lecture fees from Daiichi-Sankyo, Bristol-Myers Squibb, Bayer Healthcare, Boston Scientific and Medtronic Japan. HF accepted remuneration from Daiichi-Sankyo, Bayer Yakuhin, Nippon Boehringer Ingelheim, Johnson & Johnson K.K., Abbott Medical Japan, Medtronic Japan and Japan Lifeline. SN received speaker honoraria from Bayer Healthcare, Daiichi-Sankyo, Bristol-Meyers Squibb and Medtronic Japan. WS received grants from Daiichi Sankyo Co., Ltd, and Nippon Boehringer Ingelheim; and remuneration for lectures, presentations, speakers bureaus, manuscript writing or educational events from Daiichi Sankyo, Nippon Boehringer Ingelheim, Bristol-Meyers Squibb, K.K., Bayer Yakuhin, Pfizer, Ono Pharmaceutical and Medtronic Japan. YM received lecture fees from Bayer Healthcare, Daiichi-Sankyo, Bristol-Meyers Squibb, Nippon Boehringer Ingelheim, Johnson & Johnson K.K., Japan Lifeline K.K, Medtronic Japan, Pfizer and Boston Scientific Japan. SSu received research funding from Daiichi Sankyo and remuneration from Bristol-Myers Squibb and Daiichi Sankyo. MHar received research funding from BIOTRONIK Japan, Medtronic Japan, Abbott Japan, Japan Lifeline, Nihon Kohden and Boston Scientific Japan, and accepted remuneration from Nippon Boehringer Ingelheim, Daiichi-Sankyo, Bristol-Meyers Squibb, Medtronic Japan, Japan Life Line and Abbott Japan. TY received speaker honoraria from Medtronic Japan and Abbott Medical Japan. MTo received research funding from Japan Lifeline and consulting fee from Medtronic Japan. MTa belongs to the Section of Arrhythmia, Division of Cardiovascular Medicine, Department of Internal Medicine. This section supported by an endowment from Abbott Japan, Medtronic Japan and Boston Scientific Japan. MS is affiliated with an endowed division supported by BIOTRONIK Japan, Boston Scientific Japan K.K., Medtronic Japan and Abbott Medical Japan. AO taught courses endowed by BIOTRONIK, Abbott, Medtronic, Boston Scientific Japan and Japan Lifeline. KSa accepted remuneration from Abbott Japan, Medtronic Japan and Japan Lifeline. HKi accepted remuneration from Otsuka Pharmaceutical., AstraZeneca, Bristol-Meyers Squibb, Ono Pharmaceutical, Pfizer and Novo Nordisk. KMu received honoraria for Chugai Pharmaceutical, AstraZeneca, Taiho Pharmaceutical, MSD, Kyowa Kirin, Yakult Pharmaceutical and Boehringer Ingelheim. KKus received speaker honoraria from Daiichi-Sankyo, Nippon Boehringer Ingelheim, Bayer Yakuhin, Pfizer and Medtronic Japan, and research grants from Medtronic Japan and JSR. KoM received speaker honoraria from Medtronic Japan and Abbott Japan, and research funding from Bristol-Meyers Squibb, Pfizer, Medtronic Japan, Japan Lifeline and Boston Scientific Japan., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Oxygenator exchange during extracorporeal membrane oxygenation (ECMO) is a life-threatening procedure. D-dimer has been used to predict oxygenator failure, but it is a parameter used a few days before oxygenator exchange. This study investigated parameters before and immediately after ECMO initiation that predict oxygenator exchange., Methods: This was a single-center, retrospective study of 28 patients who received veno-venous ECMO with heparin/silicone-coated polypropylene oxygenator (NSH-R HPO-23WH-C; Senko Medical Inc., Tokyo, Japan), due to acute respiratory failure, from April 2015 to March 2020. Clinical data before ECMO initiation and during the first 3 days on ECMO were compared between the patients with oxygenator exchange (exchange group) and those without oxygenator exchange (non-exchange group)., Results: Nine (32%) patients required oxygenator exchange. The exchange group had significantly higher white blood cell count (WBC) (16,944 ± 2423/µL vs 10,342 ± 1442/µL, p  < 0.05) and Acute Physiology and Chronic Health Evaluation (APACHE) II score (31 ± 5 vs 25 ± 8, p  < 0.05) before ECMO initiation than the non-exchange group. The partial pressure of oxygen at the outlet of the oxygenator (PO 2 outlet ) and activated partial thromboplastin time (aPTT) during the first 3 days on ECMO were significantly lower in the exchange group than in the non-exchange group., Conclusions: High WBC and APACHE II score before ECMO initiation, low PO 2 outlet , and aPTT during the first 3 days on ECMO were associated with oxygenator exchange during veno-venous ECMO. These parameters could be used to avoid unexpected oxygenator exchange.

Objective: To investigate the effects of discontinuing antihypertensive drugs on the characteristics of patients with frailty syndrome., Methods: This prospective pilot study was conducted between March 2016 and July 2019. Among patients who visited the frailty clinic within this period, outpatients who received antihypertensive drugs at their first visit and were followed-up for about 1 year were enrolled. Participants who discontinued or continued antihypertensive drugs during 1 year of follow-up were classified into a discontinuation group or continuation group, respectively. Each domain in the Kihon checklist (KCL), fall risk score, short physical performance battery (SPPB) score, and skeletal muscle index (SMI) were assessed at the first visit and 1-year follow-up assessment, and were compared between the two groups., Results: Among 498 patients who attended the frailty clinic, 78 were enrolled (discontinuation group, n  = 19; continuation group, n  = 59). At the first visit, SMI scores were significantly higher in the discontinuation versus continuation group. At the 1-year assessment, physical strength in the KCL for the discontinuation group and various SPPB scores for both groups were significantly improved, and the fall risk score was improved in the continuation group., Conclusion: Discontinuation of antihypertensive drugs may positively affect physical performance.

A NIMA-related protein kinase, MpNEK1, directs tip growth of rhizoids through microtubule depolymerization in a liverwort Marchantia polymorpha . The Mp nek1 knockouts were shown to develop curly and spiral rhizoids due to the fluctuated direction of growth. Still, physiological roles and mechanisms of MpNEK1-dependent rhizoid tip growth remain to be clarified. Here, we developed novel culture methods to further study rhizoid growth of M. polymorpha , in which plants were grown on vertical plates. We applied the established methods to investigate MpNEK1 function in rhizoid growth. Rhizoids of the wild-type and Mp nek1 plants grew toward the gravity. The aerial rhizoids were longer in Mp nek1 than in the wild type. When the rhizoids were grown on the surface of a cellophane sheet, rhizoid length was comparable between the wild type and Mp nek1 , whereas Mp nek1 developed more rhizoids compared to the wild type. We also applied gellan gum, which is more transparent than agar, to analyze rhizoids grown in the medium. Rhizoids of Mp nek1 displayed defect on entering into the solid medium. These results suggest that Mp nek1 rhizoids have the deficiency in invasive tip growth. Thus, stable directional growth is important for rhizoids to get into the soil to anchor plant body and to adsorb water and nutrients. Collectively, our newly designed growth systems are valuable for analyzing rhizoid growth., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Backgrounds: An adverse increased risk of atrial fibrillation (AF) can be detected by measuring the p-wave indices, including prolonged p-wave duration, the PR interval, abnormal p-wave terminal force, and abnormal p-wave axis (aPWA). Our purpose was to characterize the AF patient population with an aPWA and to identify whether the aPWA was associated with recurrence after catheter ablation of AF., Methods: This study retrospectively included 249 patients with AF who underwent catheter ablation in our hospital from October 2015 to May 2019. We measured the p-wave indices and left atrial cavity size (LAVI) before the catheter ablation. A logistic regression analysis was performed to analyze the concurrent effects of various factors on the prevalence of AF recurrence over 12 months after the ablation., Results: An aPWA was observed in 35 patients (14%). There were significantly more patients with an aPWA in the non-PAF than PAF patients (26% versus 7%, p < 0.001). The patients with an aPWA had a significantly larger LAVI values (37 ± 12 versus 45 ± 11 ml/m2, p = 0.016). In a multivariate analysis, an aPWA (odds ratio, 4.27; 95% confidence interval, 1.75-10.4; p = 0.001) and the LAVI (odds ratio, 1.04; 95% confidence interval, 1.00-1.08; p = 0.032) were independently associated with recurrence after catheter ablation., Conclusions: Our results demonstrated that measuring the aPWA in patients with atrial fibrillation before ablation was useful for identifying patients at a higher risk of recurrence after catheter ablation of AF., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Systematic reviews have identified effective strategies for increasing postal response rates to questionnaires; however, most studies have isolated single techniques, testing the effect of each one individually. Despite providing insight into explanatory mechanisms, this approach lacks ecological validity, given that multiple techniques are often combined in routine practice., Methods: We used a two-armed parallel randomised controlled trial (n = 2702), nested within a cross-sectional health survey study, to evaluate whether using a pragmatic combination of behavioural science and evidenced-based techniques (e.g., personalisation, social norms messaging) in a study invitation letter increased response to the survey, when compared with a standard invitation letter. Participants and outcome assessors were blinded to group assignment. We tested this in a sample of women testing positive for human papillomavirus (HPV) at cervical cancer screening in England., Results: Overall, 646 participants responded to the survey (response rate [RR] = 23.9%). Logistic regression revealed higher odds of response in the intervention arm (n = 357/1353, RR = 26.4%) compared with the control arm (n = 289/1349, RR = 21.4%), while adjusting for age, deprivation, clinical site, and clinical test result (aOR = 1.30, 95% CI: 1.09-1.55)., Conclusion: Applying easy-to-implement behavioural science and evidence-based methods to routine invitation letters improved postal response to a health-related survey, whilst adjusting for demographic characteristics. Our findings provide support for the pragmatic adoption of combined techniques in routine research to increase response to postal surveys., Trial Registration: ISRCTN, ISRCTN15113095 . Registered 7 May 2019 - retrospectively registered., (© 2021. The Author(s).)

The successful use of prolonged (ie, >28 days) veno-venous extracorporeal membrane oxygenation (V-V ECMO) is being increasingly reported. However, limited data are available on its outcomes. This study investigated the outcomes of acute respiratory distress syndrome (ARDS) patients on prolonged ECMO support. We retrospectively evaluated 57 patients requiring V-V ECMO for ARDS between 2015 and 2020. The patients were divided into two groups according to ECMO duration: (a) ≤28 days group (n = 43, 75%) or (b) >28 days (n = 14, 25%) group. Clinical characteristics, complications, and outcomes between these two groups were statistically compared. There were no significant differences in demographics, comorbidity, ARDS etiology, and severity scores between the two groups. However, the mechanical ventilation period before ECMO initiation was significantly longer in the >28 days group than in the ≤28 days group (10.5 days vs. 1 day; P < .05). The incidence of positive bacterial blood culture results during ECMO was significantly higher in the >28 days group than in the ≤28 days group (43% vs. 9%; P < .05). Additionally, the hospital survival rate was significantly lower in the >28 days group than in the ≤28 days ECMO group (21% vs. 60%; P < .05). Prolonged ECMO was associated with worse hospital survival outcomes. Early initiation of ECMO along with meticulous care and appropriate treatment against infection during ECMO could improve the hospital survival of ARDS patients on prolonged ECMO support., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Background: Insertable cardiac monitors (ICMs) improve diagnostic yield in patients with unexplained syncope. The most of cardiac syncope is arrhythmic causes include paroxysmal bradycardia and supraventricular tachycardia (SVT) in patients with unexplained syncope receiving ICM. Predictors for bradycardia and SVT that necessitate therapy in patients with unexplained syncope are not well known., Hypothesis: This study aimed to investigate predictors of bradycardia and SVT necessitating therapy in patients with unexplained syncope receiving ICMs., Methods: We retrospectively reviewed medical records of consecutive patients who received ICMs to monitor unexplained syncope. We performed Cox's stepwise logistic regression analysis to identify significant independent predictors for bradycardia and SVT., Results: One hundred thirty-two patients received ICMs to monitor unexplained syncope. During the 17-month follow-up period, 19 patients (14%) needed pacemaker therapy for bradycardia; 8 patients (6%) received catheter ablation for SVT. The total estimated diagnostic rates were 34% and 48% at 1 and 2 years, respectively. Stepwise logistic regression analysis indicated that syncope during effort (odds ratio [OR] = 3.41; 95% confidence interval [CI], 1.21 to 9.6; p = .02) was an independent predictor for bradycardia. Palpitation before syncope (OR = 9.46; 95% CI, 1.78 to 50.10; p = .008) and history of atrial fibrillation (OR = 10.1; 95% CI, 1.96 to 52.45; p = .006) were identified as significant independent predictors for SVT., Conclusion: Syncope during effort, and palpitations or history of atrial fibrillation were independent predictors for bradycardia and for SVT. ICMs are useful devices for diagnosing unexplained syncope., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

The 2020 summer Olympic and Paralympic Games in Tokyo were postponed to July-September 2021 due to the coronavirus disease 2019 (COVID-19) pandemic. While COVID-19 has emerged as a monumental health threat for mass gathering events, heat illness must be acknowledged as a potentially large health threat for maintaining health services. We examined the number of COVID-19 admissions and the Tokyo rule for emergency medical care, in Tokyo, from March to September 2020, and investigated the weekly number of emergency transportations due to heat illness and weekly averages of the daily maximum Wet Bulb Globe Temperature (WBGT) in Tokyo in the summer (2016-2020). The peak of emergency transportations due to heat illness overlapped the resurgence of COVID-19 in 2020, and an increase of heat illness patients and WBGT has been observed. Respect for robust science is critical for the decision-making process of mass gathering events during the pandemic, and science-based countermeasures and implementations for COVID-19 will be warranted. Without urgent reconsiderations and sufficient countermeasures, the double burden of COVID-19 and heat-related illnesses in Tokyo will overwhelm the healthcare provision system, and maintaining essential health services will be challenging during the 2021 summer Olympic and Paralympic Games.

The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted essential health services. Simultaneously, it has created opportunities for citizens to raise awareness of personal hygiene, mask wearing, and other preventive measures. This brief report aims to clarify the epidemiological trends of measles and rubella in Japan and to explore future challenges for controlling these diseases during and after the COVID-19 pandemic. Although Japan eliminated measles in 2015, the number of measles patients has gradually increased since then, and reached 744 in 2019. In the 2010s, Japan experienced two large rubella epidemics, and the majority of the patients were reported in Tokyo and other metropolitan areas. While the transmission of measles and rubella seems to be suppressed during the COVID-19 pandemic, closing the gap in routine childhood vaccination will be challenging in any country. Moreover, supplementary immunization campaigns for adults have also been disrupted, and they must be invigorated. While the pandemic has a devastating effect on a global scale, it should be utilized as a good opportunity to regain faith in vaccines, implement an evidence-based vaccination policy, and strengthen international cooperation.

Guanosine 5'-monophosphate reductase (GMPR) is involved in the purine salvage pathway and is conserved throughout evolution. Nonetheless, the GMPR of Trypanosoma brucei (TbGMPR) includes a unique structure known as the cystathionine-β-synthase (CBS) domain, though the role of this domain is not fully understood. Here, we show that guanine and adenine nucleotides exert positive and negative effects, respectively, on TbGMPR activity by binding allosterically to the CBS domain. The present structural analyses revealed that TbGMPR forms an octamer that shows a transition between relaxed and twisted conformations in the absence and presence of guanine nucleotides, respectively, whereas the TbGMPR octamer dissociates into two tetramers when ATP is available instead of guanine nucleotides. These findings demonstrate that the CBS domain plays a key role in the allosteric regulation of TbGMPR by facilitating the transition of its oligomeric state depending on ligand nucleotide availability.

Intravascular lymphoma is a rare disease that progresses to multiple organ dysfunction caused primarily by tumor cell proliferation in small blood vessels. Few studies have investigated critical care management of intravascular lymphoma. We describe a rare case of multiple organ failure due to intravascular lymphoma with severe lactic acidosis in a patient who survived. A 64-year-old man with impaired consciousness was diagnosed as having intravascular large B-cell lymphoma by means of a random skin biopsy. The patient arrived at our hospital's intensive care unit (ICU) with impaired consciousness, respiratory failure that required mechanical ventilation, and lactic acidosis that required renal replacement therapy. Mechanical ventilation and renal replacement therapy were continued in the ICU, and his respiratory status and circulatory dynamics eventually stabilized. However, his impaired consciousness and hyperlactatemia did not improve until after the start of chemotherapy with doxorubicin, cyclophosphamide, vincristine, prednisolone, and rituximab. Although he developed tumor lysis syndrome immediately after chemotherapy, his systemic condition was gradually stabilized by continued critical care management primarily comprising renal replacement therapy. He was weaned from ventilator support after a tracheotomy and moved to the general ward. Hematopoietic malignancy with hyperlactatemia has a very poor prognosis; however, hyperlactatemia and impaired consciousness were dramatically improved in this patient by critical care management and chemotherapy.

Background: Non-cardiac surgery for hypertrophic obstructive cardiomyopathy (HOCM) is considered to require meticulous perioperative care. β-blockers are considered the first-line drugs for patients with HOCM, and they play a key role in preventing cardiovascular complications in perioperative care. The bisoprolol transdermal patch has recently become available in Japan, and it is useful for patients who are unable to take oral medication during perioperative care. The aim of this case series was to assess the hemodynamic features of patients with HOCM who used the bisoprolol transdermal patch during perioperative care for non-cardiac surgery., Methods: Between August 2016 and August 2018, we retrospectively analyzed 10 consecutive cases of HOCM with the patients using the bisoprolol transdermal patch during perioperative care. Hemodynamic and echocardiographic features were evaluated before and after patients were switched from oral bisoprolol to transdermal patch therapy or started transdermal patch therapy as a new β-blocker medication. In addition, cardiovascular complications (all-cause death, cardiac death, heart failure, ventricular tachycardia, and ventricular fibrillation) during the perioperative period were evaluated., Results: There was no significant change in the patients' heart rate, blood pressure, ejection fraction, and pressure gradient in the left ventricle after switching from oral bisoprolol to the transdermal patch therapy. On the other hand, patients who started using the bisoprolol transdermal patch as a new ß-blocker medication tended to have a decreased heart rate and pressure gradient thereafter, but there was no significant difference in blood pressure or ejection fraction. No cardiovascular complications occurred during the perioperative period., Conclusions: We described the utilization of the bisoprolol transdermal patch during perioperative care for non-cardiac surgery in patients with HOCM. We determined that the hemodynamic features of these patients did not change significantly after switching to patch therapy. Further, initiation of the bisoprolol transdermal patch as a new ß-blocker medication sufficiently tended to decrease the pressure gradient. This unique approach can be an alternate treatment option for HOCM., Trial Registration: The registry was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000036703). The date of registration was 10/5/2019 and it was "Retrospectively registered".

Background : Nivolumab efficacy in patients with non-small-cell lung cancer (NSCLC) and performance status (PS) of 2-4 is unclear. We aimed to compare survival, treatment efficacy, and safety in patients with NSCLC with poor PS who received nivolumab plus best supportive care (BSC) with those in patients who received BSC alone in a palliative care unit (PCU). Patients and methods : This retrospective study included 99 consecutive patients with NSCLC who received nivolumab plus BSC or BSC alone between December 2015 and March 2018. Results : In total, 43 patients with PS of 0-1 (good PS group) and 20 patients with PS of 2-4 (poor PS group) received nivolumab plus BSC; the remaining 36 patients received BSC alone in the PCU (PC group). Median overall survival was 32 days [95% confidence interval (CI), 21-43] in the poor PS group and 31 days (95% CI, 25-37) in the PC group (hazard ratio, 0.653; 95% CI, 0.368-1.158; P = 0.137). Moreover, median overall survival in patients with PS of 3 or 4 among the poor PS group was not significantly longer than that in the PC group (HR, 1.235; 95% CI, 0.646-2.360; P = 0.516). The frequency of severe pneumonitis in the poor PS group was significantly higher than that in the good PS group (25% vs. 2%, P = 0.010). Conclusion : Survival benefit of nivolumab in patients with NSCLC with poor PS, especially 3 or 4, was not confirmed. Further studies with larger numbers of patients are required to confirm our results., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Left atrial (LA) dilation is associated with morbidity of atrial fibrillation (AF). However, little is known about pulmonary vein (PV) dilation., Purpose: We investigated the PV volume in the patients with AF., Methods and Results: We performed 3dimensional computed tomography (3DCT) in 155 patients and divided them into three groups: 19 patients without AF (non-AF group, mean age 66 ± 12 years), 50 with paroxysmal AF (PAF group, mean age 67 ± 8 years) and 24 with persistent AF (PeAF group, mean age 64 ± 10 years). The absence of AF was diagnosed in patients with a cardiac implantable electronic device for at least 1 year (mean: 59 ± 37 months). We determined the PV volume as the total volume from the orifice to the first branch of each PV. According to the echocardiographic data, the LA dimension (LAD) and LA volume index (LAVI) were largest in the PeAF group followed by the PAF and non-AF group. According to the morphometric data obtained on 3D-CT, the PV volume was similar in PeAF and PAF groups but significantly smaller in the non-AF group (median value: 24 vs 21 vs 14 mL, respectively). According to the receiver operating characteristic curve analysis, the area under the curve for the PV volume in the presence of AF was 0.80, and the optimum cut-off value was 17 mL (sensitivity 74%, specificity 80%)., Conclusion: The PV volume might be useful for predicting the presence of AF before increases in the LAD and LAVI on echocardiography., Competing Interests: The authors declare no conflicts of interest for this article.

Background: Cognitive abilities strongly influence medication adherence among elderly individuals. We aimed to evaluate the relationship between medication adherence and cognitive decline using Lawton's instrumental activities of daily living (IADL) scoring system and the Mini-Mental State Examination (MMSE)., Methods: Receiver-operating characteristic (ROC) curves were used to evaluate the IADL scores and MMSE results., Results: The ROC curve analysis of the IADL and MMSE results revealed that the shopping (MMSE cutoff = 22 points, sensitivity = 0.726, and specificity = 0.683) and responsibility for own medications (MMSE cutoff = 22 points, sensitivity = 0.759, and specificity = 0.720) categories were associated with declining IADL scores during early stage cognitive dysfunction., Conclusion: Declining IADL scores in the shopping and responsibility for own medications categories may be effective indices for predicting early-stage cognitive dysfunction in elderly individuals. Cognitive dysfunction screening at pharmacy counters may be useful., (© The Author(s) 2015.)

Background/aims: We conducted a 3-year longitudinal study concerning factors associated with changes in brain atrophy in elderly diabetic patients., Methods: We evaluated hippocampal and global brain atrophy using automatic voxel-based morphometry of structural magnetic resonance images, 4 cognitive function tests, and cerebral small vessel disease (SVD) in 66 diabetic patients., Results: During the 3-year follow-up, hippocampal and global brain atrophy advanced, and cognitive functions worsened. For changes in hippocampal atrophy, changes in estimated glomerular filtration rate (eGFR), albuminuria, and being an ApoE ε4 carrier were independent factors; change in the number of silent brain infarctions was an independent factor for changes in global brain atrophy. A significant association of changes in eGFR and albuminuria with hippocampal atrophy remained after adjusting for confounders including SVD. Both types of brain atrophy at baseline were significantly correlated with cognitive impairment at baseline and especially associated with changes in delayed word recall during the follow-up after adjusting for confounders., Conclusion: Changes in eGFR and albuminuria during follow-up were independent risk factors for hippocampal atrophy, which was associated with decline in delayed word recall, suggesting that management of chronic kidney disease may prevent the progression of hippocampal atrophy.

Typhoon Haiyan, which struck the Philippines in November 2013, was an extremely intense tropical cyclone that had a catastrophic impact. The minimum central pressure of Typhoon Haiyan was 895 hPa, making it the strongest typhoon to make landfall on a major island in the western North Pacific Ocean. The characteristics of Typhoon Haiyan and its related storm surge are estimated by numerical experiments using numerical weather prediction models and a storm surge model. Based on the analysis of best hindcast results, the storm surge level was 5-6 m and local amplification of water surface elevation due to seiche was found to be significant inside Leyte Gulf. The numerical experiments show the coherent structure of the storm surge profile due to the specific bathymetry of Leyte Gulf and the Philippines Trench as a major contributor to the disaster in Tacloban. The numerical results also indicated the sensitivity of storm surge forecast.

Disseminated non-tuberculous mycobacterium (dNTM) infection is rare in humans without human immunodeficiency virus (HIV) infection. Previous reports have shown autoantibodies to human interferon-gamma (IFN-γ), which play important roles in mycobacterium infection, in the sera of patients with non-HIV dNTM disease. Herein, we describe a 53-year-old male who was strongly suspected to have multicentric Castleman disease (MCD) based on bone marrow study and chest radiological findings. However, Mycobacterium kansasii was detected in respiratory samples including pleural effusion. We initiated anti-mycobacterial therapy under intensive care; he died on the 48(th) hospital day. We detected no hematological disorders, ruling out MCD postmortem. However, we detected M. kansasii in pulmonary, liver, spleen and bone marrow tissues. Moreover, anti-IFN-γ autoantibody was detected with strong neutralizing capacity for IFN-γ. We consider our present report to contribute to understanding of the relationship between anti-IFN-γ autoantibody and disease development.

Novel near-infrared (NIR)-sensitizing (up to 800 nm) simple asymmetric squaraine dyes (Sq 31 and Sq 33) carrying indoline moieties that did not require the introduction of any linker groups were developed. DSSCs fabricated with Sq 33 exhibited remarkable characteristics in the long-wavelength visible and NIR region (up to 800 nm), such as a conversion efficiency of 3.75% (AM 1.5G) with an incident photon-to-current conversion efficiency of 63% (650 nm), a short-circuit photocurrent density of 13.64 mA, an open-circuit photovoltage of 0.48, and a fill factor of 0.57., (© 2012 American Chemical Society)

Background: Because it remains unclear whether noninvasive ventilation (NIV) is an effective therapy for cardiogenic pulmonary edema secondary to acute myocardial infarction (AMI), we retrospectively evaluated our experience with NIV in the treatment of pulmonary edema secondary to AMI and other cardiac conditions., Methods and Results: The study group included 206 patients with cardiogenic pulmonary edema, divided into an AMI group (53 patients) and a non-AMI group (153 patients). The weaning rate from NIV was similar in the AMI and non-AMI groups (90.6% vs. 90.8%, P=0.950). Heart rate, blood pressure, and respiratory rate decreased significantly 1h after initiation of NIV in both groups, and were maintained until weaning from NIV. The frequency of endotracheal intubation after weaning from NIV was higher in the AMI group than in the non-AMI group (7.5% vs. 0.7%, P=0.016), although the overall frequency of intubation was similar in both groups. The in-hospital mortality rate was similar in the AMI and non-AMI groups (13.1% vs. 9.8%, P=0.489)., Conclusions: NIV effectively improved vital signs and oxygenation and lowered the intubation rate in patients with cardiogenic pulmonary edema of all etiologies, including AMI. The outcome in patients with AMI treated with NIV depends primarily on the severity of the course of AMI and not on the severity of acute respiratory failure.

The rostral ventromedial medulla (RVM) is a major region for the descending modulation of pain at the spinal cord level, and neurons in the RVM have been implicated in the inhibition and facilitation of spinal nociceptive transmission. Although recent studies have established that the RVM facilitation of nociceptive transmission in the spinal cord contributes to neuropathic pain, the underlying mechanisms remain largely unknown. In the present study, we investigated the effects of kainic acid (KA)-induced RVM damage on neuropathic pain behavior and the expression of molecules implicated in pain modulation. KA was injected into the RVM midline region after neuropathic pain was established by chronic constrictive injury of the left sciatic nerve. Thermal hyperalgesia, but not mechanical allodynia, was persistently suppressed in the ipsilateral paw by a single KA injection into the RVM for at least the next 7 days in a rat neuropathic pain model. KA injection alone did not affect the nocifensive responses to mechanical and thermal stimuli on the intact side. Immunohistochemical analysis revealed that KA injection into the RVM significantly reduced the number of immunoreactive neurons for μ-opioid receptors, but not tryptophan hydroxylase, in association with the analgesic effect. These results suggest that a subset of RVM neurons expressing μ-opioid receptors contribute to the maintenance of thermal hyperalgesia in neuropathic pain., (Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

The oxygen free radical scavenger edaravone is used in patients with acute ischemic stroke in Japan, but adverse reactions, especially decreased renal function, have raised concerns. To examine whether a patient's estimated glomerular filtration rate (eGFR) at admission can predict renal function deterioration after edaravone treatment, we retrospectively evaluated the effect of edaravone on eGFR in Japanese patients with acute ischemic stroke and chronic kidney disease (CKD). The baseline eGFR in the edaravone-treated group (73.5±20.3 mL/min/1.73 m(2); n=408) at admission was significantly (P < .05) higher than that in the non-edaravone-treated group (51.9±25.2 mL/min/1.73 m(2); n=41). The change in eGFR after treatment was categorized into 3 grades: nonexacerbation (≤10%), 10%-30% exacerbation, and >30% exacerbation. There was no significant difference in exacerbation grade between the edaravone-treated and non-edaravone-treated groups (χ(2) =3.134; P=.21). We next subdivided the edaravone-treated group according to eGFR at admission as either CKD (eGFR <60 mL/min/1.73 m(2); n=111) and non-CKD (n=297). No significant decrease in eGFR was seen even in the edaravone-treated CKD group (most of whom were in stage 3 CKD). Decreased eGFR in stroke patients was found to be associated with stroke subtype (cardiogenic stroke), but not with infection. The present study demonstrates that eGFR at admission is not a good predictor of renal deterioration in edavarone-treated acute ischemic stroke patients, including those with stage 3 CKD., (Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Pollen information is indispensable for allergic individuals and clinicians. This study aimed to develop forecasting models for the total annual count of airborne pollen grains based on data monitored over the last 20 years at the Mie Chuo Medical Center, Tsu, Mie, Japan., Methods: Airborne pollen grains were collected using a Durham sampler. Total annual pollen count and pollen count from October to December (OD pollen count) of the previous year were transformed to logarithms. Regression analysis of the total pollen count was performed using variables such as the OD pollen count and the maximum temperature for mid-July of the previous year., Results: Time series analysis revealed an alternate rhythm of the series of total pollen count. The alternate rhythm consisted of a cyclic alternation of an "on" year (high pollen count) and an "off" year (low pollen count). This rhythm was used as a dummy variable in regression equations. Of the three models involving the OD pollen count, a multiple regression equation that included the alternate rhythm variable and the interaction of this rhythm with OD pollen count showed a high coefficient of determination (0.844). Of the three models involving the maximum temperature for mid-July, those including the alternate rhythm variable and the interaction of this rhythm with maximum temperature had the highest coefficient of determination (0.925)., Conclusions: An alternate pollen dispersal rhythm represented by a dummy variable in the multiple regression analysis plays a key role in improving forecasting models for the total annual sugi pollen count.

A simple and rapid method was developed for measuring 10 organophosphorus pesticides (acephate, methidathion, dichlorvos, fenthion, EPN, diazinon, phenthoate, malathion, fenitrothion, and cyanophos) in the serum of acute poisoning patients by LC/MS. Following deproteinization by acetonitrile, an aliquot of the biological sample was injected into a C(18) column using 10mM ammonium formate-methanol as the mobile phase. Extraction recoveries were satisfactory and ranged between 60.0 and 108.1% in serum. The limits of detection (LODs) in serum ranged from 0.125 to 1 microg/ml, and the limits of quantitation (LOQs) ranged from 0.25 to 1.25 microg/ml. An excellent linearity was observed for these LOQs up to 8 microg/ml. Intra- and interassay precision and accuracy were satisfactory for most of the pesticides analyzed. In terms of temperature stability, of all the organophosphorus compounds analyzed, dichlorvos and malathion exhibited the most rapid degradations over 24h at room temperature. Methidathion and diazinon remained relatively stable at all temperatures during the entire 4-week testing period. The present method was successfully applied to one actual case of acute poisoning. In conclusion, this method is simple, accurate, and useful for the determination of organophosphorus pesticides and should benefit both clinical and forensic toxicology.

This paper presents a simple and sensitive chromatographic procedure for the simultaneous determination and quantification of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates in human urine by gas chromatography-mass spectrometry. This method involves enzyme hydrolysis in the presence of a deuterated internal standard, liquid-liquid extraction, and derivatization with pentafluoropropionic anhydride and pentafluoropropanol. The recovery of each compound averaged at 65.8% or more. The limits of detection determined for each compound by using a 2-mL sample volume ranged from 5 to 50 ng/mL. The calibration curves were linear to 100 ng/mL for all compounds when determined using methamphetamine-d4 and MDMA-d5 as internal standards. This method was successfully applied for the analysis of urine samples suspected to contain intoxicants such as methamphetamine and heroin.

Limited information is available about histopathological reactions to the implanted endocardial electrodes of pacemakers (PM). Gross anatomic and histologic studies of tissue reactions to PM electrodes were made in thirteen autopsy cases (nine men and four women, ages 25 approximately 89 years, mean age 71.8) who died two months to twenty-one years after PM implantation. Nine of them had complete atrioventricular (AV) block, three had sick sinus syndrome, and one had bradycardia-tachycardia syndrome. The direct causes of death were not related to their PM. The tip with projecting tines was implanted in the right ventricle in all patients. At the contact area between the electrode and the endocardium, no tissue reaction was observed in one patient with a history of over sixteen years of PM implantation. However, cardiomyocytes under the tip had been replaced by fibrotic tissue in many other patients. In two patients in particular where the electrode had been implanted at the apex of each right ventricle, all cardiomyocytes had disappeared and only fibrotic tissue and adipose tissue were observed under the tip. These findings suggest that mechanical stress caused by attaching the tip tightly damages cardiomyocytes and brings about changes in the pacing thresholds. In three patients, a space was seen between the tip and the endocardium. A fibrous sheath covering the electrode extended to the tip and formed a thick fibrous cap. This non-excitable fibrous cap acted as a virtual electrode and possibly affected the elevation of the threshold in these patients. In four patients, extensive myocardial fibrosis due to disease, e. g. previous myocardial infarction, dilated cardiomyopathy, amyloidosis, or sarcoidosis, was found in the area surrounding the tip and also might affect the elevation of the threshold. We concluded that elevation of pacing thresholds after PM implantation is not due to reactive endocardial thickening. The space between the tip and the endocardium is occupied by a fibrous sheath, and an overly tight attachment damages cardiomyocytes causing replacement fibrosis. Thus, it is not desirable in some patients to insert the electrodes into the apex, where the myocardium is thin. To avoid the elevation of thresholds, development of further devices is necessary to allow electrode fixation to the endocardium with a more suitable pressure level.

A diabetic patient with hemoglobin (Hb) J-Meerut and low HbA1C levels is reported. An automatic glycohemoglobin analyzer used for the determination of HbA1C revealed an abnormal peak of the peripheral blood obtained from a Japanese female with diabetes. She showed a lower HbA1C level (3.7%) than expected from her fasting plasma glucose (172 mg/dl). High performance liquid chromatography and isoelectric focusing indicated that her abnormal hemoglobin was Hb J-Meerut [alpha 120(H3)Ala-->Glu] and it accounted for 28.3% of the total hemoglobin. Abnormal hemoglobinemia should be considered when a major discrepancy between the levels of HbA1C and fasting plasma glucose is observed.

A simple and reproducible high performance liquid chromatographic (HPLC) method using an internal standard (I.S.) was developed for the determination of an anticancer drug, paclitaxel, in biological fluids. The sample preparation involves a solid-phase extraction step. HPLC was performed on an ODS column using acetonitrile-2 mM phosphoric acid (45:55) as a mobile phase with detection at 227 nm. A linear relationship was obtained in the range of 0.02-2.0 micrograms/ml in the rat plasma and urine. Since the recovery of the drug was as high as that of I.S. (> 96%), a standard curve generated from the solution of the drug with I.S. in the mobile phase could be used for determination. The method could be applicable for human and dog plasma as well as rat plasma, and the intra- and interday coefficients of variation at 0.05, 2.0 and 10.0 micrograms/ml were less than 7%. This method is useful for pharmacokinetic studies of paclitaxel.

The plasma disposition of paclitaxel in rabbits (7 mg/kg, 1 h i.v. inf.) was biphasic with half-lives of 0.36 and 6.36 h, and AUC was 9.46 micrograms.hr/ml. K12 value was larger than K21 and V2 was larger than V1, suggesting that paclitaxel had a favorable distribution profile in tissues. In S 180 bearing male ICR mice (30 mg/kg, i.v. bolus), the biphasic plasma disposition was also observed. The half-lives and AUC were 0.25 h, 2.23 h and 117.93 micrograms.hr/ml. Paclitaxel distributed widely in plasma rather than blood cells. The biliary level of paclitaxel in the enlarged gallbladder of ICR mice was markedly high, about 10-fold higher than the urinary level and 100-fold higher than the plasma level. The bioavailability with oral administration to ICR mice was poor. AUC(oral)/AUC(i.v.) ratio in the bile, liver, tumor and plasma was 18.91, 6.71, 0.83 and 0.45%, respectively.

In S 180 bearing male mice, paclitaxel was rapidly distributed to various tissues within 10 minutes. The highest AUC was seen in the liver, and relatively high in the pancreas, kidney, thymus, intestine, stomach and lung. The concentration of paclitaxel in tumor tissue was not so high early time after administration, but was sustained for a long time with a half life of 12.3 hr. Elimination from the testis and thymus was also slow. The drug level in the brain was very low. In M 109 bearing female CDF1 mice, the distribution and elimination profile of paclitaxel was comparable to that in S 180 mice. The concentration of paclitaxel in the ovary, lung and uterus decreased slowly. In M 109 tumor, which was very sensitive to paclitaxel, the drug had a higher and long lasting distribution compared with S 180 tumor. In S 180 tumor bearing mice pretreated with CCl4, the paclitaxel level was found to be lower in the liver and higher in the other tissues including tumor, plasma, urine and bile than in non-treated mice.

The pharmacokinetics of carboplatin were investigated in cancer patients after single, IV infusion doses of 75, 150, 247.5, 300, 375, and 450 mg/m2. Total plasma and urine platinum and plasma ultrafilterable platinum concentrations were determined by atomic absorption spectrometry. Carboplatin was analyzed in plasma by a specific high-performance liquid chromatography (HPLC) procedure. Total plasma platinum, which represented free carboplatin, protein-bound platinum and metabolites, declined triexponentially; plasma half-lives (t1/2 lambda 1, 0.2 to 0.4 hr; t1/2 lambda 2, 1.3 to 1.7 hr; t1/2 lambda 3, 22 to 40 hr) and total body clearance (CLTB 2.8 +/- 0.5 L/m2/hr) were dose independent. Maximum plasma concentrations (Cmax) and area under the plasma concentration time curve (AUC) increased proportionally with dose. Plasma ultrafilterable platinum and carboplatin concentrations at doses of 375 and 450 mg/m2 declined in a biphasic manner. Plasma carboplatin elimination (t1/2 lambda 1, 0.50 hr; t1/2 lambda 2, 2.2 hr) and CLTB (4.4 to 5.6 L/m2/hr) were also independent of dose; AUC and Cmax increased proportionally to dose. Plasma free platinum was essentially all carboplatin for 8 or 12 hours after administration. Carboplatin did not bind to plasma protein in vitro but did degrade (t1/2-26 hours) to yield a reactive intermediate that bound rapidly and irreversibly to protein. The long terminal elimination half-life of plasma platinum was associated with irreversible binding of a platinum metabonate to plasma protein. The urinary excretion of platinum (0 to 24 hours) accounted for 58 to 72% of doses in 12 to 24 hours. The remainder of the dose is slowly excreted. The pharmacokinetics, in vivo stability, protein binding, and elimination of carboplatin are distinct from the first-generation analog cisplatin.